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Monday, February 6, 2023

Practice

How the End of the Public Health Emergency (PHE) Will Affect You and Your Patients
The White House recently announced it will end the Public Health Emergency (PHE) on May 11, 2023. What does this mean for allergists? Fortunately, the Omnibus Bill passed at the end of 2022 extended all the telehealth flexibilities until the end of 2024. Vaccines will remain covered under the Affordable Care Act and Medicare because the Advisory Committee on Immunization Practices (ACIP) included them on the recommended vaccine list. Testing and medications, however, will be subject to commercial and Medicare insurance coverage. The CDC launched a special website to help people find no cost testing, at least in the short term.

Vaccines

Bivalent Booster Study Results Vary
Studies to date on the bivalent booster have brought mixed results. Some have indicated that the bivalent booster offers marginal benefit compared to the monovalent booster, as reported in our last message. Since then, however, additional published data is more favorable to the bivalent vaccine.

Data from the Increasing Community Access to Testing (ICATT) national pharmacy program for SARS-CoV-2 testing were analyzed to estimate VE of updated (bivalent) mRNA COVID-19 vaccines against symptomatic infection caused by BA.5-related and XBB/XBB.1.5-related sublineages among immunocompetent adults from December 1, 2022–January 13, 2023. Reduction or failure of spike gene (S-gene) amplification (SGTF) in RT-PCR was used as a proxy indicator of infection with likely BA.5-related sublineages, and S-gene target presence (SGTP) of infection with likely XBB/XBB.1.5-related sublineages. Among 29,175 nucleic acid amplification tests (NAATs) with SGTF or SGTP results available from adults who had previously received 2–4 monovalent COVID-19 vaccine doses, the relative vaccine effectiveness of a bivalent booster dose given between two and three months earlier compared with no bivalent booster in persons aged 18–49 years, was 52% effective against symptomatic BA.5 infection and 48% effective against symptomatic XBB/XBB.1.5 infection.  

Another study involving adults older than 55 years, who had received three doses of monovalent vaccine, and a fourth dose of either monovalent or bivalent booster, showed:
•    The bivalent BA.4–BA.5 vaccine consistently elicited higher neutralizing responses against BA.5-derived sublineages (BA.4.6, BQ.1.1, and XBB.1) and the BA.2-derived sublineage (BA.2.75.2) than the original BNT162b2 vaccine when administered as a fourth booster dose, regardless of the participants’ history of SARS-CoV-2 infection.
•    After the fourth dose, higher neutralizing titers developed in participants with a history of SARS-CoV-2 infection than in those without a history of infection.
•    For each tested omicron sublineage, the difference between the original and bivalent neutralizing geometric mean factor increase was greater in the serum samples obtained from participants without previous infection than in those obtained from participants with previous infection.

Data from a large cohort study involving patients over the age of 12 years looking at vaccine effectiveness against severe infection compared data over time when the bivalent booster was administered to a similar period when the monovalent boosters were in use. They found that the VE against severe infection resulting in hospitalization was 33.5% higher after the bivalent booster, and the VE against severe infection resulting in hospitalization or death was 36.9% higher after the bivalent booster. Similar results were noted when the analysis was restricted to participants who were 18 years or older or 65 years or older.

Among nursing home residents in two states, SARS-CoV-2 antibody levels waned within months after vaccination, irrespective of previous SARS-CoV-2 infection, after monovalent booster vaccination, according to this study. Antibody response broadened after the COVID-19 bivalent booster for vaccinated nursing home residents among those with and without previous infection.

From a clinical standpoint, nursing home residents who were not up to date with recommended COVID-19 vaccines had a 30-50% higher risk for infection compared to those who were up to date with COVID-19 vaccines, this study points out. If this is seen in a very vulnerable population in a congregate living arrangement, one would expect similar or better results in the regular population.  
 
Results from the FDA’s Vaccine and Related Biologics Products Advisory Committee (VRBPAC) Meeting
This information comes from a variety of sources. The VRBPAC unanimously agreed on using the bivalent vaccines for all doses, including first doses, retiring the original mRNA vaccines. The FDA reportedly wants to simplify COVID-19 vaccination by offering a single fall booster, with the strain to be contained in the vaccine determined in June of the same year, but several members of the committee were reluctant citing lack of data on the duration of the vaccine. The decision also depends on the ACIP. The committee also looked at data for a second bivalent booster for immunocompromised people.
 
Post-Vaccine Stroke Concern Not Supported By Data
Recent concern about post-vaccine stroke in the elderly that was first reported in VAERS has not been evident in any of the other safety monitoring systems in the US and internationally.
 
Duration of Protective Effect of Hybrid Immunity
In this systematic review and meta-regression study the effectiveness of previous infection against hospital admission or severe disease was 74·6% (95% CI 63·1–83·5) at 12 months. The effectiveness of previous infection against reinfection waned to 24·7% (95% CI 16·4–35·5) at 12 months. The effectiveness of hybrid immunity against hospital admission or severe disease was 97·4% (95% CI 91·4–99·2) at 12 months with primary series vaccination and 95·3% (81·9–98·9) at 6 months with the first booster vaccination after the most recent infection or vaccination. Against reinfection, the effectiveness of hybrid immunity following primary series vaccination waned to 41·8% (95% CI 31·5–52·8) at 12 months, while the effectiveness of hybrid immunity following first booster vaccination waned to 46·5% (36·0–57·3) at 6 months. Limitations of the review include the fact that many papers have a high risk of bias and the included studies covered periods involving a variety of variants.

Infection

Variant Roundup

The XBB.1.5 variant remains the dominant variant, with an estimated prevalence of 66.1%, with all other variants and subvariants in decline. To help people visualize how variants emerge, disappear, and persist, CDC’s COVID Data Tracker added a dendrogram (tree diagram) to the Summary of Variant Surveillance and Variant Proportions pages. Dendrograms are like variant family trees, showing the genetic relationships between the lineages displayed on the COVID Data Tracker genomic surveillance pages.

Counting COVID-19 Deaths

Opinions that the CDC is overestimating deaths from COVID-19 continue to circulate. In response, the CDC, in their COVID Data Tracker Weekly Review, explained how they count deaths. Death data include only the deaths in which COVID-19 played a “meaningful role.” Data comes from health departments and death certificates and includes COVID-19 as a primary or secondary cause of death. People who have COVID-19 at the time of death, but it is unrelated to the cause of death, should not be listed on death certificates.

 
Testing

FDA Removes Positive Test from EUA for Oral Anti-Viral

The FDA recently removed the requirement for a positive COVID-19 test before prescribing Paxlovid or molnupiravir. This allows practitioners who diagnose patients with symptoms or exposure and negative tests to prescribe these medications. This will increase the likelihood that patients will get timely prescriptions, rather than waiting 48 hours or more for repeated testing.

 
Treatment

FDA Announces Removal of Evusheld EUA

On January 26th, the FDA revised the Emergency Use Authorization (EUA) for Evusheld (tixagevimab co-packaged with cilgavimab) to limit its use to when the combined frequency of non-susceptible SARS-CoV-2 variants nationally is less than or equal to 90%. Based on this revision, Evusheld is not authorized for use in the U.S. until further notice by the Agency. The CDC strongly recommends that we, as allergists, should be counseling our immunosuppressed patients to get vaccinated, improve ventilation, do activities outdoors when possible, wear masks and maintain distance in crowded spaces, get tested with exposure or symptoms and create a COVID-19 action plan. Such an action plan would include identifying testing as well as treatment locations before exposure or getting sick. They also recommend having a list of medications available with drug-drug interactions checked for Paxlovid before you need it.  
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,
 
Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, January 24, 2023

Vaccines

FDA Committee to Meet January 26 to Discuss Future COVID-19 Vaccine Regimens
The FDA’s Vaccines and Related Biological Products Advisory Committee will meet in open session this Thursday, January 26 from 8:30 am to 5:30 pm ET to discuss future vaccination regimens addressing COVID-19. You can watch this meeting online.
 
Immunogenicity of BA.5 Bivalent mRNA Vaccine Boosters
This very small study compared the neutralizing antibody titers after monovalent boosting in 15 participants and after the bivalent booster in 18 participants. Results: Both monovalent and bivalent mRNA boosters markedly increased antibody responses, but did not substantially augment T-cell responses. Neutralizing antibody titers against the ancestral strain of SARS-CoV-2 were higher than titers against BA.5 after both monovalent and bivalent boosting. The median BA.5 neutralizing antibody titer was similar after monovalent and bivalent mRNA boosting, with a modest trend favoring the bivalent booster by a factor of 1.3.
 
Similar findings were reported in a second small study comparing participants who had three monovalent vaccines plus the bivalent compared to those with three doses of monovalent, four doses of monovalent and participants who had a breakthrough infection after three monovalent vaccines. There was no significant difference in neutralizing titers against a variety of subvariants between the bivalent group and the four monovalent group. The highest titers were in those who had been infected after three vaccine doses.
 
In an accompanying editorial, Paul Offit, MD, suggested that this was most likely due to immunological imprinting. “The immune systems of people immunized with the bivalent vaccine, all of whom had previously been vaccinated, were primed to respond to the ancestral strain of SARS-CoV-2. They therefore probably responded to epitopes shared by BA.4 and BA.5 and the ancestral strain, rather than to new epitopes on BA.4 and BA.5.” He offered that this could possibly be corrected by immunizing with the BA.4/5 mRNA alone or using a higher dose of BA.4/5 mRNA. He also made suggestions about vaccine indications. Read the article for his comments on boosters for low-risk people.
 
In contrast, another study that was reviewed in an earlier COVID-19 Response Task Force message noted that the bivalent booster produced about two to 10 times the neutralization activity compared to the monovalent vaccines against BA.4/5 as well as BA.2.75.2, BQ.1.1 and XBB.
 
Latest Safety Data on Bivalent Vaccines in Children Ages 5-11
Based on VAERS and V-Safe reporting data after about 950,000 bivalent vaccine doses in this age group, the CDC reported:"Early safety findings from v-safe and the Vaccine Adverse Event Reporting System (VAERS) for bivalent booster vaccination in children aged 5–11 years are similar to those described for monovalent booster vaccination. Most VAERS reports represented vaccine errors rather than adverse events. Neither myocarditis nor death were reported after bivalent booster vaccination."
 
Developing Future Vaccines For Respiratory Viruses
Why do vaccines against measles, mumps and rubella provide protection that lasts decades, but those against influenza and SARS-CoV-2 lose effectiveness over short periods of time? In this review, the authors suggest that the short incubation periods, rapid transmission and replication in the nasal mucosa are characteristics of respiratory viruses that lead to re-infections. This non-systemic replication, in contrast to the other viruses mentioned, does not allow enough time for the viruses to stimulate the full force of the adaptive immune system. “Over time, these interactions have evolved and led to 'immune tolerance,' wherein the human host tolerates transient, limited infections by viruses that are generally non-lethal to avoid the destructive consequences of an all-out immune system attack.” Understanding this interaction is vital to the development of future vaccines for respiratory viruses.
 
Class Switched Memory B Cells After mRNA Vaccines
The initial antibody response following mRNA vaccination consists mainly of IgG1 and IgG3 subclasses. Several months later, IgG4 antibodies become more prevalent, further boosted by a third mRNA vaccine and/or breakthrough infections. This class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition, both critical for antiviral immunity. These findings may have implications for choice and timing of vaccination which have not been worked out. Of note, the same class switch does not occur after adenoviral vaccines.

Infection

Current Variant Status
As of January 21, XBB.1.5 represents 49.1% of all variants in the United States in general, followed by BQ.1.1 at 26.9% and BQ.1 at 13.3%. Remember, these are estimates based on limited data and may change as more data becomes available in the following weeks. There are nine additional subvariants at less than 5%. All are Omicron subvariants, as we have not seen any new variants emerge in the past year.
 
New CDC Data Resources
The CDC announced several new tools to help track the impact of respiratory viruses on the healthcare system. The COVID Data Tracker’s Hospital Capacity and Utilization page will be updated daily, the Respiratory Virus Hospitalization Surveillance Network will be updated weekly, and the National Emergency Department Visits for COVID-19, Influenza and RSV dashboards will be updated weekly.

Treatment

NIH Updates Treatment Guidelines For Evusheld
This update was released on January 10: "In the United States, the prevalence of subvariants likely to be resistant to tixagevimab plus cilgavimab (Evusheld) is more than 91%. Although tixagevimab plus cilgavimab is still authorized by the Food and Drug Administration for COVID-19 PrEP, it is unlikely to be effective at preventing COVID-19 in the vast majority of individuals. However, no alternative options for PrEP are available, and clinicians could still administer tixagevimab plus cilgavimab after considering an individual patient’s risks and the regional prevalence of resistant subvariants."
 
Alternative treatments for COVID-19 remain underutilized, due partially to poor understanding about indications and drug-drug interactions. This interesting perspective points out many of the issues, and patients may seek treatment from trusted physicians other than their PCP, like their allergist. Please bookmark and remember the NIH Treatment Guidelines page, where you can also find several resources to help you with the drug-drug interactions.
 
Real-Life Paxlovid Efficacy
The initial clinical trials for Paxlovid were done in unvaccinated participants during the Delta surge and showed 90% effectiveness in reducing hospitalization and death in the groups at risk for severe disease. This population-based cohort study in a large health system involved 44,551 nonhospitalized adults (90.3% with three or more vaccine doses) aged 50 and older with COVID-19 and no contraindications for Paxlovid. The use of the drug resulted in a 44% reduction in the composite outcome of hospitalization or death compared to those who were not treated.
 
Fluvoxamine Not Effective After All
An early pilot study, reported in one of our COVID-19 Response Task Force messages, suggested that fluvoxamine might be useful in the treatment of COVID-19. This randomized clinical trial in 1,288 adults with symptomatic mild-to-moderate COVID concludes that it is no more effective than placebo in shortening the duration of symptoms.
 
Nasal Spray to Block Viral Entry
Investigators at Johns Hopkins have developed a nasal spray containing ACE2 receptors bound to supramolecular filaments that have been able to bind SARS-CoV-2 and influenza viruses and prevent or delay entry into cells, at least in mouse models. The idea is that this spray could be used just before possible exposure in a public setting.

Long COVID

Symptoms Three Months After COVID Compared to COVID-Negative Patients With Similar Symptoms
This prospective cohort study evaluated adults with active symptoms who tested negative for COVID-19 with those who tested positive. Approximately half of the COVID+ participants had persistent symptoms after three months compared to one-quarter of those who were COVID-19 negative. The most common symptoms included upper respiratory tract symptoms (37%), constitutional (28.8%), musculoskeletal (19.5%), pulmonary (17.9%), cardiovascular (10%) and GI (8.7%).
 
65 Million People Worldwide Have Long COVID
This current review estimates that 10% of people infected with COVID-19 will develop long COVID. The authors explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. A recently published survey of U.S. patients estimated that 7.3% of all respondents reported long COVID or about 19 million people. Prevalence was higher among females, those with comorbidities, and those who were not vaccinated or were not boosted.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,
 
Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, January 9, 2023

Vaccines

Vaccines and Infection Reduces Infectiousness in Congregate Settings
This study was performed across 35 California state prisons from December 2021 to May 2022 and estimated that any vaccination, prior infection alone, and both vaccination and prior infection reduced an index case’s risk of transmitting infection by 22%, 23% and 40% respectively. Limitations: The study was performed in a prison setting, so the findings may not be generalizable, and these results preceded the current more infectious subvariants.
 
COVID-19 Vaccine Safe After MIS-C
This cross-sectional study included 22 medical centers participating in the NHLBI’s Long-Term Outcomes after the Multisystem Inflammatory Syndrome in Children (MIS-C) Study and involved 385 children 5 years of age and older with prior MIS-C. Within this group, 185 (48.1%) received at least one vaccination. Adverse effects were similar to the general population and there was no myocarditis or recurrence of MIS-C.

Infection

Updates on Subvariants and Cases
As of January 7, according to the Nowcast projections on the CDC’s COVID-19 Data Tracker BQ.1.1 remains the most common subvariant in the United States at 34.4%, with XBB.1.5 second at 27.6%. BQ.1 is at 21.4 % and XBB at 4.9%. The numbers for XBB.1.15 are much higher in the Northeast. You may have noted different numbers in the media, so the CDC sent out additional information on how they report this information: “CDC uses two methods to display variant proportions: weighted estimates and Nowcast estimates. Weighted estimates for each circulating lineage are very precise, but it takes two to three weeks for sample collection, specimen treatment, shipping and analysis to occur. CDC uses Nowcast to forecast variant proportions before the weighted estimates are available.” When you look at the graphic on their COVID-19 Data Tracker page, you will notice the header “Nowcast” over the latest three weeks of reporting. Previous reports are weighted estimates and more accurate. When the CDC first reported XBB.1.15 separately from XBB at the end of December, based on its rapid growth rate, the prediction (Nowcast estimate) was for 41% on December 31, but with additional data the prediction for the end of December was revised downward to 18%. Weekly cases have been stable in the upper 400,000 for the past four weeks. Hospitalizations have been increasing in all age groups since the end of November, from 1.29 to 1.96/100,000 on January 6. Hospitalizations are highest in those over 70 years at 9.57/100,000 on January 2. In November 2022 (latest data available) hospitalizations were 16 times higher in unvaccinated people compared to those who had received the bivalent booster. Hospitalizations were almost three times higher in those with vaccinations but not a bivalent booster.

Treatment

Update to NIH Treatment Guidelines
Although the basic information has not changed since early December, the NIH Treatment Guidelines website has revised several sections of the guidelines related to outpatient management. Due to the resistance of the current circulating subvariants noted above, the Panel recommends against the use of the monoclonal antibody betelovimab for treatment of nonhospitalized patients. The current recommended therapy for outpatients with COVID-19 at high risk of progression to severe disease include (in order of preference) Paxlovid, remdesivir and molnupiravir. The CDC currently lists the following conclusive risk factors for progression: age over 65 (perhaps even over 50), asthma, cancer, cerebrovascular disease, chronic kidney disease, COPD, interstitial lung disease, bronchiectasis, chronic liver disease, CF, diabetes Type I and II, disabilities, heart conditions, HIV, mood disorders, schizophrenia, dementia, obesity (BMI >29 kg/m2), physical inactivity, pregnancy and recent pregnancy, inborn errors of immunity, smoking, solid organ or stem cell transplant, tuberculosis, use of corticosteroids or other immunosuppressants. (The AAAAI COVID-19 Response Task Force does not agree with the CDC with respect to asthma as a risk factor). Even though most of the subvariants are resistant to Evusheld, the NIH Panel has not removed the indication for its use as pre-exposure prohpylaxis, but patients will need to be vigilant about notifying their providers early if they suspect symptoms.
 
Oral Version of Remdesivir Not Inferior to Paxlovid
This multicenter, single-blinded, randomized controlled trial compared VV116, an oral analogue of remdesivir to Paxlovid in symptomatic participants who were at high risk of progression to severe COVID-19 and found VV116 to be non-inferior in efficacy at prevention of severe disease with less drug interactions.
 
NIH Launches Home Test to Treat
The NIH announced on January 5 that in collaboration with the Administration for Strategic Preparedness and Response (ASPR) at HHS, they launched the Home Test To Treat program, an entirely virtual community health intervention that will provide free COVID-19 health services—at-home rapid tests, telehealth sessions and at-home treatments—in selected communities. Participants can sign up for the program, report symptoms, receive telehealth and antiviral treatment delivery, and coordinate telehealth enabled test kits. The program will launch in Berks County, Pennsylvania. The plan is to evaluate and revise the program based on the experience at this site and then expand it nationally.

Long COVID

MIS-C More Common and Severe
MIS-C is the most severe post-COVID condition occurring in childhood. Prior to 2021, the CDC relied on voluntary reporting of the condition. In 2021, an ICD-10-CM code was published for MIS-C and this study was able to use quarterly inpatient data from 4,057 community hospitals in 31 states, representing 77% of the U.S. population. Most of the diagnoses of MIS-C were made in teaching hospitals. Hospitalization rate was 1.48 per 100,000 children with a 2-fold increase in Black children compared to White. More children with MIS-C had multiple organ systems involved compared to COVID-19 and outcomes worsened with more organ system involvement, with mortality increasing to 5.8% if six to eight organ systems were involved. Multi-organ involvement was more common in Black children.

Practice

Omnibus Bill Extends Telehealth
The Omnibus package just signed by the President has a provision to extend all Medicare telehealth flexibilities that are currently in place until the end of 2024.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,
 
Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Tuesday, December 27, 2022

Vaccines

Neutralizing Activity of Vaccines Against BQ.1.1 and XBB
This small study compared the serum neutralizing activity against the wild-type variant, BA.1, BA.5, BA.2.75.2, BQ.1.1 and XBB in participants who had received one monovalent booster (12), two monovalent boosters (11) or one bivalent booster (12). Compared to the wild-type variant, neutralizing activity against BA.1/5 were 5 to 9 times as low and activity against BA.2.75.2, BQ.1.1 and XBB were 23 to 63 times as low in those who had monovalent boosters. In those with the bivalent booster, activity was 4 times as low against BA.1/5, and 12 to 16 times as low and 12 to 26 times as low against BQ.1.1 and XBB, respectively.

Bivalent Vaccine Effectiveness (VE) in Preventing Hospitalization  
Among immunocompetent adults aged 65 years or older hospitalized in the multistate IVY Network, a bivalent booster dose provided 73% additional protection against COVID-19 hospitalization compared with two or more past monovalent mRNA vaccination only. Compared to unvaccinated persons, the VE was 84%.

Bivalent booster doses also provided additional protection against ER/Urgent Care encounters in patients who previously received two, three or four monovalent vaccine doses. Relative effectiveness of bivalent vaccines was higher with increased time since the previous monovalent vaccine.

Despite these positive outcomes, only 14% of those eligible for a bivalent booster have received one.

Overall Prevention of Death Due to Vaccines  
From December 2020 through November 2022, the COVID-19 vaccination program in the U.S. prevented more than 18.5 million additional hospitalizations and 3.2 million additional deaths, according to The Commonwealth Fund, which used a computer model of disease transmission to estimate hospitalizations and deaths. Without vaccination, there would have been nearly 120 million more COVID-19 infections. The vaccination program also saved the U.S. $1.15 trillion (Credible Interval: $1.10 trillion–$1.19 trillion) in medical costs that would otherwise have been incurred.

New Nasal Vaccines Show Some Promise  
A previous message reported disappointing results using the current IM vaccines introduced nasally. Two recent NIAID animal model studies using attenuated live virus vaccines (avian paramyxovirus and bovine/human parainfluenza virus) showed protection of the respiratory system from infection and the parainfluenza virus showed strong blood antibody and white cell responses.

No Increase in Herpes Zoster After mRNA Vaccine
There was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, despite some case reports of herpes zoster occurring after receipt of the mRNA vaccines, this study found. These finding may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.
 
FDA Committee to Hold Open Meeting January 26, 2023  
The FDA’s Vaccines and Related Bilogical Products Advisory Committee (VRBPAC) will be meeting in open session January 26, 2023, from 8:30 am to 5:30 pm ET to discuss future vaccination regimens addressing COVID-19. You may join this meeting online.

Infection

The Tripledemic
RSV, influenza and COVID-19 have all arrived in force this fall. RSV is plateauing, influenza is rapidly increasing and COVID-19 is following in hospitalizations after the Thanksgiving holiday. Influenza hospitalizations are highest in those over age 65 at 67 per 100,000, but children 0-4 are close behind at 42.3 per 100,000. This compares to COVID-19 hospitalizations, which are 0.25/100,000 for children and 6.93/100,000 for those over age 70. Infectious disease and public health officials are recommending masking indoors in crowded spaces for all, and on public transportation. Vaccinations are also crucial, but won’t do much to reduce mild disease, and such people can spread the infection to those most vulnerable.

Latest Numbers on Circulating Variants
As of December 24, 2022, BQ.1.1 is at 35.7%, BQ.1 is at 27.4%, XBB is 18.3%, and BA.5 at 6.9%. There are a variety of other subvariants at <5%. BQ.1.1, BQ.1 and XBB are increasing with XBB now showing large increases week to week.

Influenza and COVID-19 Coinfection in Pediatrics
During the 2021-22 influenza season, 6% of hospitalized pediatric influenza patients also had SARS-CoV-2 coinfection, according to this report, which describes characteristics and prevalence of laboratory-confirmed influenza virus and SARS-CoV-2 coinfections among patients aged <18 years who had been hospitalized or died with influenza as reported to three CDC surveillance platforms during the season. A higher percentage of patients with coinfection required invasive or noninvasive respiratory support compared with those with influenza only. Among influenza-associated pediatric deaths, 16% had SARS-CoV-2 coinfection; only one co-infected decedent received influenza antivirals, and none were fully vaccinated against influenza. Take away: Coinfection is rare, but can lead to more severe disease. Get immunized for both, test for both and use anti-virals.

Patient Guide to Testing For COVID-19
With increasing numbers of infections and anticipated holiday gatherings, there is a lot of talk related to testing for COVID-19, but still a lot of confusion. The FDA has developed a website that offers step-by-step guidance on when to test and how to interpret the results.

Can We Bring This Pandemic to an End?  
This consensus study advances a global vision of informed decision-making on how the world can end COVID-19 as a public health threat without a return to sweeping limitations on civil liberties, without risking the health and lives of vulnerable groups, and without exacerbating economic burdens. A multidisciplinary panel of 386 academic, health, non-governmental, government and other experts in COVID-19 response from 112 countries and territories has developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communications, health systems, vaccination, prevention, treatment and care, and inequities. Three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches, while maintaining proven prevention measures using a vaccines-plus approach that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities in the management of pandemic responses.

NFL Game Attendees At Increased Risk For COVID-19
In this cross-sectional study of NFL games attended by a total 1.3 million fans, the presence of large numbers of fans at NFL games was associated with increases in the incidence of COVID-19 cases both in the counties in which these venues were located and contiguous counties. Specifically, NFL games that had 20,000 fans in attendance had 2.23 times the rate of spikes in COVID-19, but NFL games with fewer than 5,000 fans in attendance did not generate any spikes.

Long COVID

Death From Long COVID
Using literal text of death certificates, this study identified 3,544 deaths related to long COVID, for an age-adjusted death rate of 6.3 per million population. Death rates were highest among adults over 85, non-Hispanic American Indian or Alaskan Native peoples, and males.

Practice

COVID-19 Flexibilities Also Apply to RSV and Flu  
On December 2, 2022, HHS clarified that existing regulatory and administrative authorities provided by the COVID-19 public health emergency declaration also apply to RSV and flu. This new legal clarification allows states and providers to use the flexibilities that have been available under the federal public health emergency for the current crisis.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,
 
Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, December 12, 2022

Vaccines

FDA Authorizes Bivalent Vaccines for Young Children
The FDA has authorized bivalent COVID-19 vaccine boosters for children 6 months and older. However, the authorization differs for Moderna and Pfizer because the approval ages and vaccine series schedule differs between the two.
 
Children ages 6 months to 4 years who have received up to two of the three doses of the Pfizer-BioNTech COVID-19 three-dose primary series, can receive the updated (bivalent) Pfizer-BioNTech COVID-19 vaccine as the third dose. However, children in this age group who have already completed their three-dose primary series will not be eligible for a booster dose of the bivalent vaccine because they are expected to have protection against the most serious outcomes from the currently circulating Omicron variant. The data to support giving an updated bivalent booster dose for these children are expected in January.
 
Children 6 months through 5 years who received the Moderna two-dose primary series are eligible to receive a single bivalent booster two months after completing a primary series.
 
Clinical Characteristics of Post-Vaccine Myocarditis: A Recent Review
This systematic review and meta-analysis of 23 studies including 854 patients ages 12-20 years with vaccine-associated myocarditis found that 74.4% of cases occurred after the second dose, most patients (84.4%) had preserved left ventricular (LV) function. Of those with LV dysfunction, most were mild with 1.3% having severe LV dysfunction. Although 92.6% were hospitalized and 23.2% required ICU admission, inotropes were used in only 1.3%, there were no deaths or required mechanical support and hospital length of stay was 2.8 days.

In contrast, a retrospective cohort study in Hong Kong comparing post-vaccination myocarditis with viral infection-related myocarditis pre-COVID found one death of 104 patients with post-vaccine myocarditis compared to 11% of 762 patients with viral infection-related myocarditis. One case (1.0%) of cardiomyopathy and two cases (1.9%) of heart failure were noted in the post-vaccination group compared to 28 cases (3.7%) and 93 cases (12.2%) in the viral infection-related group, respectively. Adjusted analysis showed that the post-vaccination group had a 92% lower mortality risk. It should be noted that this was not a comparison to unvaccinated COVID-related myocarditis.
 
Autoantibodies Against Soluble IL-1RA May Be the Cause of Post-Vaccine Myocarditis
In a study of 69 patients with clinically suspected myocarditis after vaccination, among patients with histologically confirmed myocarditis, anti–IL-1RA antibodies were found in nine of 12 patients (75%) younger than 21 years of age, as compared with three of 28 patients (11%) 21 years of age or older. Anti–IL-1RA antibodies were not detectable in the 21 patients in whom biopsy ruled out the diagnosis of myocarditis. These same antibodies have been found in patients with myocarditis following SARS-CoV-2 infection. IL-1RA inhibits IL-1 signaling and inflammation. The IL-1RA levels correlated with markers of cardiac damage and inflammation.
 
Nasal Vaccine Results Disappointing
This U.K. study using the IM version of the adenovirus-vector vaccine intranasally showed a mucosal antibody response in only a minority of patients and a weak systemic response. There are a number of other nasal vaccines in development and another type of vaccine may be more efficacious. Anthony Fauci, MD, FAAAAI, Director of the NIAID and Chief Medical Advisor to President Joe Biden, has opined that future vaccination campaigns may utilize both intranasal and systemic vaccines for the best mucosal and systemic immunity.

Infection

COVID-19 Mortality and All-Cause Mortality in the United States Compared to Others
U.S. COVID-19 mortality and all-cause mortality were compared to peer countries and also state subgroups based on vaccination uptake in this study. The U.S. mortality in both cases exceeded those of peer group countries overall, but states with vaccination uptakes >73% had significantly lower rates.
 
COVID-19 “Plan” For Patients
The CDC has developed a plan for patients who are at high risk for severe disease that you can download here and give to appropriate patients. It talks about risk, prevention, symptoms (and what to do if you have them), testing (and what to do with the results), things to consider if you are sick and need to isolate, places to list testing centers, vaccinations and more.
 
Gut Dysbiosis in COVID-19 Infection
Samples collected from 96 COVID-19 patients at two different clinical sites revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.

Treatment

NIH COVID-19 Treatment Guideline Update
The FDA revoked the EUA for bebtelovimab on November 30 because of resistance to this monoclonal antibody by the newer variants. In response, the COVID-19 Treatment Guidelines Panel has published a new statement recommending against the use of bebtelovimab for the treatment of nonhospitalized patients with COVID-19 who are at high risk of progression. Ritonavir-boosted nirmatrelvir (Paxlovid), remdesivir and molnupiravir remain available for treatment.
 
Antiviral Agents and BQ.1.1 and XBB Variants
This study looked at the efficacy of monoclonal antibodies and antivirals against BQ.1.1 (a subvariant of BA.5), which comprises about 30% of isolates in the United States and XBB (a subvariant of BA.2), which comprises about 5.5%. Using a live virus neutralization assay, the investigators found that none of the monoclonal antibodies or antibody combinations available neutralized these subvariants. Fortunately, both subvariants were susceptible to remdesivir, molnupiravir and nirmatrelvir (Paxlovid). This study did not involve the BQ.1 variant, but one has to assume results would be similar. BQ.1 now comprises about 32% of isolates in the United States.
 
Rebound After Treatment With Molnupiravir and Nirmatrelvir-Ritonavir
Data on the frequency of rebound after viral treatment has been confusing, perhaps related to the different study designs and testing methods. This study out of Hong Kong used viral load data, defining viral rebound as a cycle threshold on RT-PCR >40 that decreased to <40, in 12,629 adults who were hospitalized and had serial cycle thresholds measured. Viral rebound as defined occurred in 0.6% of untreated patients, 1.0% of nirmatrelvir-ritonavir treated patients and 0.8% of molnupiravir treated patients. Readers should know that cycle thresholds of 40 indicate very low viral loads, so this definition would have identified patients that would likely have had negative antigen tests.

Long COVID

Prolonged Symptoms May Accompany Other Respiratory Viral Infections
In this cohort study of 1,000 U.S. adults with symptomatic illness, poor well-being scores at follow-up were common in both those who tested positive and negative for SARS-CoV-2 infection. Despite some improvements over time, 39.6% of COVID-19–positive and 53.5% of COVID-19–negative patients reported residual symptoms. These findings emphasize the importance of including a concurrent control group when studying sequelae of COVID-19 illness.

More Looking Back

Vaccination Campaigns and Return on Investment
In this decision analytical model study of a citywide initiative, every $1 invested in the New York City vaccination campaign yielded an estimated $10.19 in cost savings from lower infection and mortality rates, fewer productivity losses and averted healthcare use.
 
Masking and Distancing on Airplanes
Universal masking on all airplanes and vacant middle seats on some were non-pharmaceutical interventions used/required from January of 2021. In April of 2022, the CDC removed that requirement and quickly mask wearing became the exception rather than the rule. This study estimated airborne virus exposure and infection reductions when middle seats are vacant compared to full occupancy and when passengers wear surgical masks in aircraft, using tracer particle data reported by the U.S. Transportation Command and simulations on cabin airflow reported by Boeing, along with NIOSH data to build models. Results of the modeling estimates suggested that distancing alone (vacant middle seats), masking alone and both together reduced SARS-CoV-2 exposure risk in increasing order of effectiveness when an infectious passenger is present.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,
 
Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, December 5, 2022

Vaccines

Effectiveness of Bivalent Vaccine Against Symptomatic Infection
Previous clinical efficacy data was based on a bivalent vaccine directed at the original strain and BA.1. In this study, effectiveness of the bivalent (Omicron BA.4/BA.5–containing) booster formulation against symptomatic SARS-CoV-2 infection was examined. Relative vaccine effectiveness (rVE) of a bivalent booster dose compared with that of two or more monovalent vaccine doses among persons for whom 2–3 months and 8 months or more had elapsed since their last monovalent dose was 30% and 56% among persons aged 18-49 years, 31% and 48% among persons aged 50-64 years, and 28% and 43% among persons aged 65 years and older, respectively. The CDC’s COVID Data Tracker now includes early data showing that people ages 12 years and older who got an updated (bivalent) booster were 15 times less likely to die from COVID-19 compared with people who were not vaccinated. Also, 48.3% of the total booster-eligible population has not yet received a booster dose.
 
Strategies to Increase Vaccine Intention and Reasons for Hesitancy
Online surveys conducted at several time periods during 2020 and 2021 involving up to 33,000 adults per survey noted an increase in vaccine intention from 46% to about 80% from October 2020 to October 2021. Unvaccinated participants were placed into treatment groups to evaluate various strategies to increase intention to get vaccinated (IGV). The most effective strategy was a work requirement for vaccination, which increased IGV by 35.4%, followed by financial incentives 12.3% to 18.9%, vaccine requirements for sporting events or travel 7.8 to 9.1%, and reducing need for masking and social distancing 6.4%. Endorsements had no effect. Reasons for hesitancy included concerns about vaccine safety (52.5%), side effects (51.6%), trust in the government’s motives (41.6%) and concerns about vaccine effectiveness (37.6%). Although feelings may have changed since the end of this study, these findings may present a starting point for improving intent.
 
Young Children at Increased Risk of Hospitalization If Parents Unvaccinated
In this study performed before vaccines were approved for those younger than 5 years, the association of SARS-CoV-2 hospitalizations in children younger than 5 years with vaccinated versus unvaccinated parents showed that HRs were 0.03 (95% CI, 0.02-0.06) during the Delta period and 0.21 (95% CI, 0.14-0.33) during the Omicron period.
 
Increased Pediatric Vaccinations Could Prevent Thousands of Hospitalizations
An analysis by the Commonwealth Fund and the Yale School of Public Health estimated that if all school-age children were vaccinated with the updated booster at the same rate that they were vaccinated against influenza last year (50-60% coverage), at least 38,000 pediatric hospitalizations could be averted. If booster coverage reached 80%, more than 50,000 hospitalizations could be averted.

Infection

COVID-19 Infection in Patients With Atopic Dermatitis on Tralokinumab
This study evaluated a subset of adults enrolled in the ECZTEND Trial with atopic dermatitis who were on tralokinumab. Seventy-seven of the 300 patients developed COVID-19 during the trial. COVID-19 was considered to be mild in 68% and moderate in 30%. All but one patient was unvaccinated. Although there are no studies reporting COVOD-19 vaccine response in patients on tralokinumab, studies with Tdap and meningococcal vaccines in such patients have demonstrated a good response to vaccination [“Tralokinumab does not impact vaccine-induced immune responses: Results from a 30-week, randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis”: J Am Acad Dermatol 2021; 85(1):71)] and this study would imply the same for COVID-19 vaccines. As of April 2021, 231 patients in this trial have been vaccinated without adverse events.
 
Limited Benefit For COVID-19 Entrance Screening
This study was performed at a single academic medical center (Yale-Newhaven) from March 2020 to April 2021 and involved 950,000 screenings. Screening failures were highest during the first wave of infections, at 0.69%, but were stable during subsequent times of high and low community case rates at 0.035%. It took 29.5 FTE employees to conduct the screening at an annual compensation cost of over $1.2 million dollars: Conclusion: Entrance screening has limited benefit.
 
Pouring Through Poo
This article in Nature is an interesting read on how wastewater surveillance can help scientists keep tabs on SARS-CoV-2 variants. One researcher who had been tracking a heavily mutated variant for about one year, had been able to track the source to a single business. Nasal swabs from most of the employees there were negative, but there is a question about whether someone with immunocompromise was harboring the virus in their gut since this lineage had been present in the wastewater in large amounts for about eight months. They often find new lineages in wastewater, but most of them do not spread.

Treatment

Real World Paxlovid Effectiveness
Among 699,848 adults aged 18 years and older eligible for Paxlovid during April-August 2022, 28.4% received a Paxlovid prescription within five days of COVID-19 diagnosis. Being prescribed Paxlovid was associated with a lower hospitalization rate among the overall study population (adjusted hazard ratio [aHR] = 0.49), among those who had received three or more mRNA COVID-19 vaccines (aHR = 0.50) and across age groups (18-49 years: aHR = 0.59; 50-64 years: aHR = 0.40; and 65 years and older: aHR = 0.53). Conclusion: Paxlovid should be prescribed to eligible adults to reduce the risk of COVID-19–associated hospitalization. These results differ from those from Israel in healthcare workers, which did not document a benefit for younger ages (<65). A meeting with the White House COVID-19 Task Force attended by the AAAAI and several other medical societies discussed barriers to use of Paxlovid and how to overcome them.
 
Major Update to NIH Treatment Guidelines
Although there may be some regional variations, the most common variants of interest in the United States now are BQ.1 and BQ.1.1, which represent 62.8% of all variants. BA.5 is now down to 13.8%. (Look up your region here.) Since the BQ variants are resistant to betelovimab, the FDA has removed the EUA for that monoclonal antibody to protect against severe disease. These variants are also resistant to Evusheld, although the NIH continues to recommend its use. Other changes to the Treatment Guidelines include recommendation against the use of metformin for nonhospitalized patients, the use of remdesivir for patients who cannot take Paxlovid and: “There is currently insufficient evidence for the Panel to recommend either for or against the use of high-titer COVID-19 convalescent plasma (CCP) for the treatment of COVID-19 in hospitalized or nonhospitalized patients who are immunocompromised. However, some Panel members would use CCP to treat an immunocompromised patient with significant symptoms attributable to COVID-19 and with signs of active SARS-CoV-2 replication and who is having an inadequate response to available therapies.”

Long COVID

How Long is Long COVID?
A cross-sectional study in approximately 700 individuals found that the proportion with at least one post-COVID-19 symptom two years after acute infection was 59.7% for those hospitalized and 67.5% for those not requiring hospitalization, without significant differences between hospitalized and non-hospitalized patients.

Testing

NIH Establishes Website For Self-Reporting COVID-19 Test Results
In an attempt to get a better handle on cases, the NIH is trying to make it easier to report the results of home tests for COVID-19 at MakeMyTestCount.org.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, November 21, 2022

Vaccines

Response to mRNA-1273 (Moderna) in Children Six Months to Five Years
In part 2 of a phase 2-3 trial, 3,040 two to five year-old children and 1,762 six months to two years were given two 25mcg injections of this vaccine four weeks apart. Median duration of follow-up was about 70 days after the second injection. Neutralizing antibody geometric mean titers were slightly higher than those achieved in young adults, with a better response in the younger age group. Estimated vaccine efficacy against infection was 50.6% in the younger age group compared to 36.8% in the older age group during the early Omicron surge. As noted in an earlier message, reactogenicity was largely mild and transient and no new safety concerns were identified.
 
Six Month Follow-up of a Fourth Dose of the Monovalent Pfizer Vaccine
A prospective cohort study in Israel analyzed antibody response (IgG and neutralizing) and vaccine effectiveness (VE) among health care workers without evidence of previous infection after a fourth dose of BNT162b2. The study included 6,113 workers in the analysis of the humoral response and 11,176 in the analysis of VE. Antibody response peaked at four weeks, waned to levels seen before the fourth dose by 13 weeks, and remained stable thereafter. Throughout the 6-month follow-up period, weekly antibody levels were similar after receipt of the third and fourth doses and were markedly higher than levels seen after the second dose. VE was higher after the fourth dose than that afforded by three doses but waned from 52% during the first five weeks to -2% at 15-26 weeks. Protection against severe disease was not measurable since none of the workers had severe disease.
 
Response to mRNA Bivalent Vaccines
There is no peer-reviewed published data, but Moderna and Pfizer both recently announced that the new BA.5 bivalent vaccines increase Omicron-fighting antibodies. Moderna said that post-vaccine antibody titers following its BA.5 bivalent vaccine increase 15 times the pre-booster level. In a smaller number of patients, preliminary analysis showed some potency loss against BQ.1.1 but levels were still protective. Pfizer said its bivalent booster showed a 9.5-fold increase in adults <55 and 13.2-fold increase in those older. Only about 10% of eligible patients over age five years have gotten the vaccine. HHS announced their VAX up America Tour last week as well.

Infection

Additional Risks Following Reinfection
Using the VA National Healthcare Database, these researchers compared individuals with one infection, two or more infections and non-infected controls. Compared to no reinfection, reinfection contributed additional risks of death (hazard ratio (HR) = 2.17, 95% confidence intervals (CI) 1.93–2.45), hospitalization (HR = 3.32, 95% CI 3.13–3.51) and sequelae including pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders. The risks were evident regardless of vaccination status. The risks were most pronounced in the acute phase but persisted in the postacute phase at six months. Compared to noninfected controls, cumulative risks and burdens of repeat infection increased according to the number of infections. The study included 443,588 patients with one infection, 40,947 with two or more infections, and over 5,000,000 controls.
 
Infection in Those Under Six Months Surged During Omicron; Masking Best Defense Against COVID and RSV in This Group
Data from COVID-NET in 13 states noted that hospitalization among children <6 months of age were higher than in any other pediatric age group during the Omicron wave, compared to the Delta wave. Since we do not have vaccination for this age group, other preventative measures include masking in caregivers and siblings, vaccination in siblings and vaccination during pregnancy.
 
As we experience a wave of RSV in our hospitals currently, it is important to note that RSV-associated acute respiratory infection causes substantial morbidity, leading to the hospitalization of one in every 56 healthy term-born infants in high-income settings and masking has shown effectiveness against the spread of RSV in the early stages of the COVID pandemic.  

Treatment

NIH COVID-19 Treatment Guidelines Updated Again
Based on the likelihood of resistance to Evusheld for most of the circulating subvariants other than BA.5 and the BQ.1 and BQ.1.1 resistance to beptelovimab, the NIH Treatment Guidelines Panel has published a statement that provides interim recommendations on the use of these therapies. Both of these therapies are still recommended depending on the prevalence of these subvariants in your area, which can be found on the CDC’s COVID-19 Tracker pages. This statement also provides strategies to facilitate the use of Paxlovid and Remdesivir in patients with COVID-19. Remember that most patients with inborn errors of immunity respond to some extent to the vaccines, so vaccination is still the first step. Secondary immune deficient patients also seem to respond to the vaccine, with those with solid organ transplants the least likely to respond. For those who live with immunosuppressed patients, other non-pharmacologic methods of prevention remain important as well.

 
Long COVID

Possible Mechanism Behind “Brain Fog”
Using a mouse model, researchers found elevated levels of inflammatory cytokines in the blood and CSF following infection, many of which persisted. Also noted were increases in microglial/macrophage activity. Human brain tissue samples from nine subjects who had died with positive COVID-19 tests at the time of death (but not necessarily from COVID and none were in the ICU and none died in the hospital) showed elevated microglial/macrophage reactivity compared to controls without COVID-19. Virus was not found in the brain in the mouse model. Increased microglial activity is associated with deficits in learning and memory.  


Practice

PHE to be Extended Past January
The White House announced that they plan to extend the PHE for another 90 days following its current expiration date in mid-January, in keeping with their promise to provide 60 days warning before ending the PHE.

 
Looking Back

Did Those State-Issued Non-pharmaceutical Interventions (NPI) Make Any Difference?
Using seroprevalence data from a nationwide blood donor serosurvey from August 2020 to March 2021, this study measured the association of seropositivity and state-issued, county specific NPIs for masks mandates, gathering bans and bar closures. Compared with individuals living in a county with all three NPIs in place, the odds of having anti-nucleocapsid antibodies were 2.2 (95% confidence interval [CI]: 2.0-2.3) times higher for people living in a county that did not have any of the three NPIs, 1.6 (95% CI: 1.5-1.7) times higher for people living in a county that only had a mask mandate and gathering ban policy, and 1.4 (95% CI: 1.3-1.5) times higher for people living in a county that had only a mask mandate. This data does not apply to any variants present after March of 2021.  
 
What About School Mask Mandates?
Following the rescinding of school mask mandates in Massachusetts in February 2022, two school districts in the greater Boston area retained masking requirements to the end of the school year while others stopped in February allowing for comparisons of the effect of masking. The lifting of mask requirements was associated with an additional 44.9 cases per 1,000 students and staff. That corresponded to an estimated 11,091 cases and to 29.4% of the cases in all districts during that time despite the fact that schools that maintained the mask requirement were older, more crowded, less well ventilated and had higher percentages of lower income students, students with disabilities and higher numbers of minority students and staff.  
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, November 7, 2022

Vaccines

Effectiveness of Monovalent mRNA Vaccines Against Hospitalization During BA.1/BA.2 and BA.4/BA.5 Predominant Periods
Data from the IVY Network of 21 hospitals in 18 states showed that in adults three-dose monovalent mRNA vaccine effectiveness (VE) estimates against COVID-19–associated hospitalization decreased with time since vaccination. Three-dose VE during the BA.1/BA.2 and BA.4/BA.5 periods was 79% and 60%, respectively, during the initial 120 days after the third dose and decreased to 41% and 29%, respectively, after 120 days from vaccination. Take home: Good idea to get the bivalent vaccine booster.

Effectiveness of the Monovalent mRNA Vaccine Against Hospitalization in Immunocompromised Adults During Omicron
Data from the VISION Network of hospitals showed that among immunocompromised adults hospitalized with a COVID-like illness, two-dose monovalent mRNA COVID-19 VE against COVID-19–associated hospitalization during Omicron predominance was 36%. VE was 67% at least 7 days after a third dose during BA.1 predominance, but declined during BA.2/BA.2.12.1 and BA.4/BA.5 predominance to 32% at least 90 days after dose three and 43% at least seven days after dose four. Same take home: Based on the response to a three-dose vaccine regimen, the bivalent booster may be helpful, although we don’t have data on the response to this vaccine in this population.

Adverse Reactions to mRNA Vaccines Correlate With Immune Response
Two studies (here and here) have now noted that patients with systemic reactions to vaccination such as fever, myalgias and fatigue tend to have higher anti-spike antibody titers in response to the vaccine compared to those with local or no reaction.

Early Safety Data on Bivalent Boosters in Those 12 Years and Older
Early safety findings from v-safe and the Vaccine Adverse Event Reporting System (VAERS) for bivalent booster doses administered to persons aged 12 years and older during the first seven weeks of vaccine availability are similar to those previously described for monovalent vaccine booster vaccines. Among 251 VAERS reports (out of 22.6 million doses) classified as serious, five were reports of myocarditis, four were reports of pericarditis and 20 were reports of COVID-19 disease. The age range of those who experienced myocarditis or pericarditis was 12-78 years and 46-78 years, respectively.

Bottom Line: If You Haven't Had the Bivalent Booster and You Are Over the Age of 5, Get One
Three matched, retrospective target-trial cohort studies performed in Qatar in children ages 5-11 (one trial) and 12-17 (two trials) compared VE of the Pfizer mRNA vaccine and durability compared to unvaccinated children and adolescents before and after the Omicron surge. In ages 5-11, VE against Omicron was 49.6% right after receipt of the second dose, lower in ages 8-11, waning to negligible levels after three months. In adolescents, many of whom had been vaccinated months earlier, the VE was 30.6%, lower in ages 15-17. Even though severe infections and hospitalizations are rare in children, they can spread the virus to the more vulnerable and families will all be gathering for the holidays.

Infection

“Variant Soup”
Most prior surges of infection have been associated with a single variant or subvariant, but now, for the first time, infections in the United States are due to a variety of subvariants of BA.2 and BA.5, with differing potentials for infectiousness and immune evasion. This makes any predictions on the future course of the pandemic difficult at best. Current percentages in the United States as of November 5 show that BA.5 is the cause of 39.2% of infections, down from 49% the week before. BQ.1 and BQ.1.1 are increasing and now cause an estimated 18.8% and 16.5% of infections, respectively. BA.4.6 and BF.7 are causing 9.5% and 9%. BA.5.2.6, BA.2.75 and BA.2.75.2 are all 3% or less. This could mean that over 50% of infections could be resistant to Evusheld and bebtelovimab.

Rebound Symptoms During Infection
We know that a small percentage of patients who are treated with Paxlovid experience rebound symptoms, but how does that compare to patients without such treatment? This study analyzed daily symptoms for 28 days in the placebo group of a phase 2/3 clinical trial on therapeutics for COVID-19 to assess the frequency of targeted symptom recurrence after symptom resolution and found that 30% of 158 participants subsequently reported at least one of 13 symptoms by the end of the 28-day period. Eighty-five percent of the symptoms were mild. These results would suggest that rebound after Paxlovid is actually less common than occurs without treatment.

Long COVID

Global Proportions of Individuals With Prolonged Symptoms
An observational analysis of 54 studies and two medical record databases for 1.2 million individuals from 22 countries with a history of symptomatic COVID-19 estimated that 6.2% had at least one of the three self-reported long COVID symptoms clusters three months after infection. The most common symptom cluster was ongoing respiratory problems at 3.7%, followed by persistent fatigue with myalgias or mood swings at 3.2% and 2.2% with cognitive problems. In a cross-sectional study of more than 16,000 individuals, 15% of U.S. adults with a prior COVID-19 positive test reported current symptoms of long COVID. Those who had completed a primary vaccination series prior to infection were less likely to report. These two studies demonstrate a varied risk among individuals. Since there are no clinical or laboratory tests that identify long COVID, some of the symptoms reported could be due to other diseases.

Long-Term Neurologic Outcomes of COVID-19
Using the national healthcare databases of the Veteran’s Administration, this study analyzed a cohort of 154,068 individuals with COVID-19 compared to over 5,000,000 contemporary controls and similar numbers of historical controls with respect to neurologic sequelae at 12 months. Overall the hazard ratio of any neurologic sequelae at 12 months in the COVID-19 patients compared to contemporary controls was 1.42 per 1,000 persons. The most common sequelae were cognition and memory disorders, peripheral neuropathy, migraines and seizures. Although the risks were greater in people with severe disease, sequelae occurred in those with mild disease as well and across the age spectrum, perhaps even stronger in young adults.

VA Guidebook on Long COVID
The Department of Veterans Affairs published a new guidebook on caring for veterans with long COVID. Titled the Whole Health System Approach to Long COVID, the guidebook provides information about signs, symptoms and treatments for the illness. The guidebook also includes metrics, such as surveys, to assess autonomic symptoms. This is an excellent resource when confronted with a patient with potential long COVID.

Treatment

Most Eligible Patients Are Going Untreated
Representatives from the AAAAI, along with other healthcare organizations, met with the White House COVID-19 Response team on November 1. Their concern relates to data that show that only 20% of eligible patients are getting antivirals or monoclonal antibodies for treatment of COVID. As allergists, we need to educate our patients about symptoms that are consistent with COVID-19, the importance of testing early to identify an infection so they can be treated if at elevated risk and that treatments are readily available at most pharmacies. This is especially important for immunosuppressed patients because of increasing resistance to Evusheld (see above).

Racial Differences in Treatment
A retrospective cohort study conducted in 130 Department of Veteran’s Affairs Medical Centers included 43,222 veterans hospitalized with COVID-19. The findings suggest that Black veterans hospitalized with COVID-19 were less likely to be treated with evidence-based COVID-19 treatments, including systemic steroids, remdesivir and immunomodulatory drugs. Other studies have shown a decreased availability of Paxlovid in underprivileged neighborhoods as well as a lower prescription of this drug to racial minorities.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, October 24, 2022

Vaccines

ACIP Adds COVID-19 Vaccine to the Child, Adolescent and Adult Immunization Schedules
The Advisory Committee on Immunization Practice’s (ACIP) recommendation to add COVID-19 vaccinations to the immunization schedules will not have any effect on school mandates, which are determined on a state and local basis, but will allow for commercial and Medicare insurance payment for these vaccines. The ACIP also added COVID-19 vaccines to the Vaccines for Children (VFC) Program, which provides free vaccines for Medicaid-eligible, uninsured, underinsured and American Indian/Alaska Native children.
 
Updated Data on Post-vaccine Myocarditis/Pericarditis
Using data from the Vaccine Safety Datalink (VSD), a collaborative of eight integrated health care delivery systems, 320 potential cases of myocarditis/pericarditis among patients ages 5-39 years of age were identified one to 98 days after 6,992,340 vaccine doses, 70% of which were verified. Incidence was highest for male adolescents 12-17 years of age following dose two (1 in 30,000 doses). The incidence after the first booster was 1 in 50,000. A study from Israel involving 182,605 adolescents identified an incidence of 4.8 per 100,000 vaccinations.  
 
Safety of mRNA Vaccines Compared to Other Approved Vaccines in Children <5 Years Old
In this cohort study based on a survey of guardian-reported safety profiles of BNT162b2 in 7,806 children, higher dosages of BNT162b2 were significantly associated with injection-site reactions. Compared with approved non–SARS-CoV-2 vaccines, BNT162b2 was associated with significantly more frequent injection-site, musculoskeletal, dermatologic, or otolaryngologic symptoms but fewer general symptoms and fever after vaccination. The overall frequency of adverse events after vaccination with BNT162b2 was comparable with the frequency of adverse events after vaccination with approved non–SARS-CoV-2 vaccines in children younger than five years. Similar results were noted in a clinical trial in over 4,000 children six months to five years with Moderna’s mRNA-1273 vaccine. Neither of these studies enrolled a sufficient number of patients to identify rare events. The last ACIP review of myocarditis in this age group was done in September and found no increased incidence following vaccination.
 
Severe Disease After Vaccination, a Closer Look
This retrospective cohort study included 1,610,719 participants receiving care at Veterans Health Administration facilities, followed up for 24 weeks (July 1, 2021, to May 30, 2022) after completing a COVID-19 vaccination series and booster. Almost 75% were over age 65, and 70% had a pre-existing condition that rendered them high-risk. Findings: about 1% had a breakthrough infection, <0.1% died or were hospitalized for COVID pneumonia. Hospitalization or death occurred in 0.3% of immunocompromised, 0.07% of those with pre-existing conditions, 0.01% of otherwise healthy people over 65.  
 
Effect of mRNA Vaccination on Clinical and Virologic Features of COVID-19
In this prospective cohort study which included 1,199 participants with SARS-CoV-2 infection, receipt of two or three mRNA vaccine doses before Delta infections and three mRNA vaccine doses before Omicron infections, was significantly associated with milder COVID-19 (less frequently symptomatic, febrile, or medically attended or shorter duration of illness) compared with being unvaccinated. Receipt of two mRNA vaccine doses 14 to 149 days prior to either Delta or Omicron infection was significantly associated with lower viral RNA load.
 
Novavax Booster Granted EUA
On October 18, the FDA authorized and the CDC agreed to allowing the Novavax vaccine to be given as a booster six months after a primary series with any of the vaccines, for those 18 years of age or older who cannot get the bivalent Pfizer or Moderna vaccine, or otherwise would not get a booster at all.

Infection

Update on Variants
As of October 22, BA.5 remains the most common variant in the U.S. at 63.2% of infections. The next most common is BA.4.6 at 11.3%, which has declined over the last week. BQ.1 is now at 9.4%, almost double last week’s percent and BQ.1.1 is up to 7.2% (BQ.1.1 was at 1% on 10/1). BF.7 is close behind at 6.7%. BA.2.75.2 and BA.2.75 are at 1.6% and 1.3%, respectively and these three have been relatively stable. BQ.1 and BQ.1.1 appear to have a growth advantage over BA.5. BA.4.6, BA.2.75.2, BQ.1, BQ1.1 and BF.7 all have evidence for immune evasiveness against monoclonal antibodies including Evusheld. Here's the Summary of Variant Surveillance. Since these are all subvariants of BA.5, the new bivalent boosters should offer benefit. A small study in two groups of patients, one with prior infection and another with primary and booster vaccination, showed that median pseudovirus neutralizing antibody titers against BA.4.6 were reduced 2-2.7-fold compared to BA.4/5. (See also the statement concerning these subvariants and treatments with bebtelovimab and Evusheld on the NIH COVID-19 Treatment Guidelines.) In brief, currently the prevalence of these subvariants is low to moderate, and the panel has not changed its recommendations. If the prevalence continues to increase, the panel’s recommendations for bebtelovimab and for tixagevimab plus cilgavimab may be updated.
 
Latest Update on Pediatric Seroprevalence
This repeated, cross-sectional study conducted across all 50 states, the District of Columbia, and Puerto Rico used a convenience sample of residual serum specimens provided by persons of all ages that were originally submitted for routine screening or clinical management from two private clinical commercial laboratories. Over 27,000 samples were tested. Current estimates are that 86.3% of children <17 have evidence for at least one prior infection.
 
So is Infection With BA.1 or BA.2 Protective or Not?
The literature on this issue has been contradictory, which may relate to what is being measured. Some research at the antibody, B-cell and T-cell level suggests that a history of infection could have a negative effect on subsequent protective immunity. This study from Qatar on the incidence of reinfection after an earlier infection with a pre-omicron variant or omicron was 2.1% in those with a single past infection and 1.1% in those with two prior infections.
 
Should we Test Before Ending Quarantine?
The debate over the need to test before ending quarantine continues to generate some controversy. The CDC says no, citing a lack of evidence that repeat testing reflects contagiousness and the lack of data to support using rapid antigen testing for this purpose. One study cited in an earlier message found that a positive test at six days was only 50% predictive of a positive culture. In this study, 268 college athletes who tested positive for COVID-19 underwent rapid antigen testing starting seven days after the initial positive test. At seven days, 27% still had a positive test, with a higher percent positive in symptomatic individuals (35%) and those infected with BA.2 compared to BA.1(40%).  

Treatment

Study Suggests COVID-19 Rebound After Paxlovid not Due to Impaired Immune Response
This small study funded by the NIAID of eight patients who experienced rebound after Paxlovid, compared to those with rebound who had not taken Paxlovid, and six control patients with COVID-19 who did not experience rebound, showed no evidence of infection by resistant virus or delay in antibody response. T cell response was robust in those with rebound, suggesting that rebound symptoms could be partially driven by the robust cellular immune response.

Testing

First OTC Molecular Test Granted an EUA
On October 18, the FDA issued an emergency use authorization (EUA) for the first over-the-counter molecular test authorized for use with saliva specimens to Aptitude Medical Inc. for their Metrix COVID-19 Test, a single-use molecular in vitro diagnostic test for the detection of SARS-CoV-2. This test is authorized for non-prescription at-home use with anterior nasal (nares) swab and saliva sample, self-collected from people aged 14 years or older, or adult-collected from people aged two years or older, including people without symptoms or other epidemiological reason to suspect COVID-19. Comparison with lab-performed NAATs are not available. Negative results are considered presumptive and confirmation with lab performed NAAT tests may be indicated. This test does target more than one viral gene, so may be more sensitive than single target tests and more accurate with mutated variants. View In Vitro Diagnostics EUAs – Molecular Diagnostic Tests for SARS-CoV-2.
 
Accuracy of Rapid Tests With Omicron Variant
Members have asked whether rapid testing is less sensitive against Omicron. According to NIH research, no (see previous message). This study in Europe, using three different at-home rapid tests performed as self-tests with either nasal swabs or oropharyngeal and nasal swabs performed in adolescents showed a mild decrease in sensitivity that was only significant for one of the three, with improved sensitivity when both oropharyngeal and nasal swabs were used. This study was performed when omicron was responsible for >99% of infection, but most likely was BA.1 or BA.2 based on the time of year. The makers of the test with the lowest sensitivity stated that their engineers doubted that there would be any difference. This test is available in the U.S., but not approved for oropharyngeal use. In a study comparing symptoms during the pre-Delta, Delta and BA.1 surges, rapid antigen testing positivity during Omicron was 80% at five days after symptom-onset.  
 
Accuracy of NAAT Tests For Diagnosis of COVID-19
This study on over 17,000 patients in Canada, who presented to the ER with COVID-19 symptoms, found the sensitivity of Nucleic Acid Amplification Testing (NAAT) remained high for at least 14 days after onset of infection. The sensitivity was 97.7% on day two of symptoms and declined to 90.4% on day 11. Implications: a single negative NAAT test can rule out infection, and repeat testing is not needed except in those with a high pre-test probability of infection.
 
White House Reports Inadequate Supply of PPE and Tests for the Winter
Plans were to have a stockpile of these items but the money dedicated for the stockpile had to be pulled to ensure enough vaccines. Let’s hope the vaccines don’t go to waste. U.S. without ‘adequate’ Covid-19 tests this winter due to congressional inaction, White House says.
 
COVID-19 AG Rapid Test Device Recalled
FDA announced this Class 1 recall of the Jiangsu Well Biotech Co., Ltd CVOID-19 Ag Rapid Test Device because it has been distributed in the US without adequate validation data submitted to the FDA.  

Practice

Public Health Emergency Extended to January 11
Biden administration announced an extension of the PHE until January 11, and continues to promise 60-day notice prior to ending the PHE.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,
 
Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, October 10, 2022

Vaccines

Odds of Decreased Hospitalization Following COVID-19 Booster Vary Based on Timing of Shot
We know from previous studies that boosters reduce the risk for hospitalization and that protection wanes over time. A new study gives us a more quantitative review which may help in patient counseling. In the study, 3,062 adults who were hospitalized for COVID-19 were compared to matched controls for two versus three doses of mRNA vaccine and the time since vaccine. Overall the odds ratio for hospitalization in those with three doses of vaccine was 0.41 versus controls. The OR varied with the time since the booster: 0.24 if <100 days, 0.47 if 101-150 days and 0.72 if >150 days.
 
Many Adults Profess Minimal Awareness of the New COVID-19 Bivalent Booster
The latest addition of the Kaiser Family Foundation Vaccine Monitor notes that 50% of U.S. adults have little or no awareness of the new boosters and whether they should get one. Allergists should review COVID-19 vaccine status with their patients and the CDC recommendation that all people 12 years of age and older get the updated bivalent booster if it has been two months or more since their last vaccine. A projection by the Commonwealth Fund predicted that if 80% of the eligible population received a booster vaccination by the end of 2022, an additional 15,000 lives and almost 200,000 hospitalizations could be averted, compared to a continuation of the current rate of vaccine booster uptake. This would result in direct medical savings of an additional $12 billion.
 
Pfizer and Moderna Ask FDA for Approval for Boosters for Younger Children
Pfizer has requested authorization for its bivalent booster for those ages 5-11. Moderna has requested authorization for ages 5-11 and 12-17.
 
Hybrid Immunity Effects With Different SARS-CoV-2 Variants
This article provides a good discussion on the impact of hybrid immunity (infection plus vaccination) on protection against some of the newer Omicron sublineages. Subjects covered include the impact on memory B and T cell clones. A BA.1 breakthrough infection elicits a broad cross-variant neutralizing activity against, for example, the ancestral WA1 and Delta variants, whereas BA.1 infection in the absence of prior vaccination only induces neutralization of BA.1. But titers are lower overall: anti-BA.1 neutralizing titers elicited by a BA.1 breakthrough infection average six-fold lower than the anti-Delta neutralizing titers elicited by a Delta breakthrough infection. Consequently, newly emerging Omicron variants, including BA.2.12.1, BA.4 and BA.5, show neutralization escape when tested with sera from BA.1-infected individuals. In contrast, a study from Qatar looking at the protective effect of an infection after the occurrence of Omicron (likely BA.1 and BA.2) showed 78% effectiveness against symptomatic infection caused by BA.4 and BA.5.
 
Split Vaccine Dosing Offers Comparable Immune Response
This small study of 30 patients with a history of vaccine allergy concerns were given the second dose of vaccine either as a split dose (0.05 mL then remainder) or full dose. Split dose recipients were also pre-treated with antihistamines and acetaminophen. There were no differences in receptor-binding domain and S1 antibody between the groups. As a side note, in most of the studies to date, patients with previous allergic reactions to mRNA vaccines tolerated second doses given as the full dose, but if this approach encourages more vaccine hesitant patients to proceed, then it is reassuring to know that the response is equivalent.

Infection

Predictions for Fall and Winter
Several epidemiologic experts are predicting an increase in cases and hospitalizations for the fall and winter. Hospitalizations are currently increasing across western Europe, which typically precedes what happens in the United States. The most common isolate has been BA.5, but genome sequencing has markedly declined so we don’t know for sure. The subvariant BQ.1.1, a direct descendant of BA.5 is the most common of the new subvariants in Europe. Although U.S. wastewater monitoring has shown declines recently, it is starting to plateau. Based on the data from Europe, the new bivalent booster, which is focused on BA.5 should help, but the immunocompromised and elderly need to do additional non-medical mitigations.

Treatment

NIH Treatment Guidelines Updated Again
Topics updated in the guidelines include pulse oximetry limitations, approach to non-hospitalized adults with respect to supplemental oxygen, discussion about Paxlovid rebound, additions to the Paxlovid drug-drug interaction tables, recommendation against the use of molnupiravir in pregnant patients and discussion of potential influenza-COVID-19 co-infections. They do mention that there are no significant drug interactions between Paxlovid and influenza anti-virals.
 
EVUSHELD Less Effective Against Some Omicron Subvariants
As we mentioned in last week’s message, the subvariants BA.4.6, BF.7 and BA.2.75.2 contain spike mutations that reduce the susceptibility to EVUSHELD, and in the case of BA.4.6 this shows >1,000-fold reduction. The FDA released additional information on this on October 3. BA.4.6. currently is the second most common subvariant in the United States, with 12.8% of isolates and is slowly rising. BF.7 is at 3.4% and BA.2.75.2 is not listed as a separate subvariant. The current recommendations are to continue to use EVUSHELD, but advise patients if they have symptoms to get tested immediately and seek treatment if positive. Details are in the updated Fact Sheet for Healthcare Providers.

Long COVID

NIH Resource for Patients
Here is a nice resource for patients about long COVID.
 
Prognosis and Persistence of Loss of Smell and Taste
This systematic review and meta-analysis found that loss of smell persisted in 5.6% and taste in 4.4% 180 days after recovery from COVID-19. Women were less likely to recover than men.
 
Incidence and Clinical Features in Children
A cohort study involving 59,893 children <21 years of age with a positive test for COVID-19 revealed that, in comparison to matched children without COVID-19, the most common symptom was loss of taste/smell (aHR 1.96); the most common condition was myocarditis (aHR 3.10); and the most common medication taken were cough and cold preparations (aHR 1.52). The difference in incidence of at least one symptom, condition or medication feature between the infected cohort and the uninfected cohort was 3.7%. Bottom line: Long COVID is uncommon in children and the features are different than adults. The results of symptoms and medication use suggest that many of these patients may present to the allergy office.
 
Persistent Pulmonary Abnormalities in Children and Adolescents After COVID-19
A cross-sectional, prospective clinical trial using low-field MRI in 54 children and adolescents found persistent pulmonary dysfunction (V/Q mismatch). This finding was present in both the 29 who had recovered from infection, and the 25 who were diagnosed with long COVID. These abnormalities persisted for up to one year. Long COVID is rare in children, but these findings occurred even in those who had recovered.

Practice

CDC Updates Infection Prevention and Control Recommendations for Healthcare Personnel for COVID-19
The CDC quietly updated their guidelines for healthcare workers on September 23. Updates: vaccination status is no longer used to inform source control, screening testing or post-exposure recommendations; screening testing of asymptomatic healthcare workers is at the discretion of the healthcare facility (depending on the Community Transmission metric and not the Community Level metric used for non-healthcare settings); use of source control (e.g. masks, respirators) is optional when community transmission levels are not high except for those with symptoms or close contact; and many others too numerous to be mentioned here. Everyone should be familiar with these updates and review office protocols to be sure they are consistent.
 
Emotional Exhaustion and Burnout Among Healthcare Workers During the Pandemic
In this three-year survey study with an overall sample of 107,122 responses from U.S. healthcare workers before (2019) and twice during (2020 and 2021-2022) the COVID-19 pandemic, increases were reported in assessments of emotional exhaustion in oneself and in one’s colleagues overall and for every role; nurses reported increases each year, but physicians reported decreases in 2020 followed by sharp increases in 2021. Exhaustion score clustering in work settings was suggestive of a social contagion effect of exhaustion. In part two of the Physician Foundation 2022 Survey of America’s Physicians based on 1,509 responses, six in 10 physicians have felt inappropriate feelings of anger, tearfulness or anxiety, one-third have felt hopelessness and half report withdrawing from family/friends/co-workers. Feelings of burnout have increased from 40% in 2018 to 63% of physicians in 2022. Additional key findings can be found on their website.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, September 26, 2022

Treatment

LABAs and Paxlovid
According to the University of Liverpool Interaction Checker, based on route of metabolism but no direct studies, salmeterol should not be co-administered with Paxlovid. Vilanterol, formoterol and albuterol are OK. Change your patient’s controller medication accordingly for the duration of Paxlovid and for another three days after.
 
Rebound After Paxlovid Similar to Placebo
Data on the occurrence of viral load rebound from a phase 2-3 double-blind, randomized controlled trial which enrolled 2,246 symptomatic, unvaccinated outpatient adults with COVID-19 and elevated risk of severe disease showed rebound in 2.3% of the treated group and 1.7% in the placebo group. Swabs for viral load were collected on days five, 10 and 14. No predisposing factors were found. The study was conducted during the Delta variant surge.

Vaccines

Boosters Encouraged for Those Over 5
The new bivalent boosters from Pfizer are recommended for all those 12 and older if it has been more than two months since their last vaccination. Moderna is authorized for 18 years and older. The monovalent booster is recommended for 5-11-year-olds currently and is no longer authorized for those 12 and older. There are no boosters authorized or recommended for those younger than 5 years. While deaths are trending downward for COVID-19, there are still about 400 people dying every day in the United States, and most of these deaths are preventable. Thirty percent of those over 65 have not received any boosters and 60% have not received a second booster. The numbers for younger people are about 50% and 65% respectively. Unvaccinated people over the age of 50 are about six times as likely to die from COVID-19 compared to those who have had 2+ booster shots. Considering that most unvaccinated people have been infected, these numbers are even more concerning. Vaccine effectiveness against hospitalization is 92% in adults for up to 120 days after three doses. If approved by the FDA, the CDC anticipates recommending the bivalent vaccine for 5-11-year-olds in early to mid-October.
 
Vaccine Effectiveness (VE) and Effects of Previous Infection in 5-11-Year-Old Children During Omicron
This large cohort study performed over a six-month period during Omicron found that the VE among previously uninfected children reached 63.2% four weeks after the first dose of Pfizer vaccine and declined to 15.5% at 16 weeks, whereas in previously infected children, VE was 69.6% at four weeks after the first dose and declined to 22.4% at 16 weeks. Not all children had two doses of vaccine. Among unvaccinated children, previous Omicron infection was 90.7% protective of reinfection at two months and 62.9% at four months. Among vaccinated children, the estimated effectiveness of Omicron infection alone against reinfection was 94.3% at two months and 79.4% at four months.
 
VE of Pfizer During BA.4 and BA.5 in South Africa
Among 5,900 patients of a large health system in South Africa who were SARS-CoV-2 positive, waning of effectiveness against hospitalization was evident as early as three to four months after vaccination. VE was 47.4% after two doses. Boosting with a third dose maintained VE against severe disease at one to two months, but decreased to 46.8% by three to four months.
 
VE of Moderna mRNA1273.214 Against BA.4 and BA.5
These are interim results from an ongoing phase 2-3 study comparing the original Moderna vaccine (mRNA1273) to the bivalent vaccine (mRA1273.214) containing Wuhan and BA.1 mRNA in 800 adults who had received a primary series and one booster from the original Moderna vaccine and no history of severe disease. The bivalent booster resulted in neutralizing antibody titers against BA.1 that were 1.6 times those of the original vaccine and titers against BA.4 and BA.5 that were 1.5 times as great. The titers against BA.4 and BA.5 were about 3.5-fold lower than against BA.1. Note that the bivalent vaccine that is currently approved contains BA.4 and BA.5 mRNA rather than BA.1.
 
Neutralization of BA.2.75 After Moderna Monovalent Vaccine
In this small phase 2 clinical study of 20 adults, neutralization of BA.2.75 one month after a booster dose of Moderna mRNA-1273 was 2.5 times higher than against BA.5 and more closely resembled titers against BA.1. BA.2.75 is 4.2 times less sensitive to the vaccine compared to the prototypic D614G variant. A nice review on variants and vaccines can be found in the September 12 issue of NEJM.

Infection

Latest Attitudes About the Pandemic
The final Axios-Ipsos Coronavirus Index published on September 13 finds a decline in perceived risks from COVID-19, increased support for ending mandated COVID-19 restrictions but continued support for federally funded at-home tests and free access to vaccines and treatment. The number of people who are “somewhat concerned about COVID-19” has declined to 57%, although the numbers have been fairly stable since April. Those that have returned to their pre-pandemic lives has increased to 46%, up from 42% in June. Thirty-seven percent wear a mask outside the home at least sometimes. More details can be found in the article.
 
New Variants
Subvariants that the CDC are monitoring include BA.4.6, BA.2.75, BA.2.75.2 and BF.7. BA.4.6 is increasing in the United States according to wastewater levels in the Northeast and represents 5-20% of isolates depending on the state. BA.4.6, BF.7 and BA.2.75.2 contain a mutation that causes increased immune evasion and decreased efficacy with Evusheld, but BA.2.75 is still responsive. BA.2.75 constitutes a very small number of cases globally, but is doubling every week. BF.7 represents about 1.7% of isolates. These are all Omicron subvariants and the bivalent boosters should have at least some effect, but data is lacking. For treatment, remdesivir, Paxlovid, molnupiravir and bebtelovimab are still effective against these subvariants. Sources of information: Your Local Epidemiologist by Katelyn Jetelina, PhD, CDC and Infectious Diseases Society of America.

Long COVID

Mild Disease Associated With Long-Term Cardiac Pathology
A prospective cohort study in 346 previously well individuals with mild initial COVID-19 disease found that 57% had persistent cardiac symptoms at follow-up 329 days after infection. Symptoms included exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%). Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare, but imaging indicated ongoing cardiac inflammation.
 
Resources for Respiratory and Cardiovascular Symptoms Associated With Long COVID (PCC, PASC)
A recent CDC Clinician Outreach and Communication Activity (COCA) call presented a good overview of cardiovascular symptoms following COVID-19 with suggestions on evaluation and support. These patients may present with cough and dyspnea. Females, older age and more severe disease are risk factors, but can occur even with asymptomatic infection. The incidence is 17%, 8-14% with some activity limitation. As allergists, we need to evaluate possible pulmonary co-morbidities that might be contributing. Slides from the call can be found here. PASC Consensus Guidance statements from the American Academy of Physical Medicine and Rehabilitation on breathing discomfort and respiratory sequelae can be found here and on cardiovascular disease here. Get information here on the NIH Recover Initiative to learn more about long-term effects of COVID, find a study near you or to encourage your patients with long-COVID to volunteer.
 
Preinfection Psychological Distress Associated With Increased Risk of Post-COVID Conditions
Depression, anxiety, perceived stress, loneliness and worry about COVID-19 were prospectively associated with a 1.3- to 1.5-fold increased risk of self-reported post-COVID-19 conditions, as well as increased risk of daily life impairment related to post-COVID-19 conditions, in this cohort study involving primarily females.

Testing

United States Orders >100 Million At-Home Tests for Fall and Winter Demand
Although no longer providing free tests via the U.S. Postal Service, the United States will boost its stockpile of rapid antigen tests in anticipation of a fall or winter surge. The White House stated that this purchase will still fall short of replenishing the existing stockpile.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, September 12, 2022

Government Support for COVID-19 Care Declining
The federal government already announced that they were stopping the supply of free home tests on September 2, as Congress has not appropriated additional funds to pay for tests and they wanted to have an emergency supply in case of a fall surge. A recent Bloomberg report stated that the government anticipates that it will stop purchasing and providing COVID-19 shots as soon as January due to the same lack of funding. This means that payment for vaccines and therapeutics will transition to the commercial market.

Vaccines

mRNA Vaccines Safe in Patients With a History of Kawasaki Disease
Because of the similarities between Kawasaki disease and Multi-Inflammatory Syndrome (MIS) following COVID-19 infection, concerns have been expressed that mRNA vaccination or COVID-19 infection in people with a history of Kawasaki disease might increase the risk of adverse outcomes. This study of 153 patients in a vaccination cohort and 37 patients in an infection cohort showed no clinically severe adverse outcomes occurred in the vaccinated cohort and none of the 37 infection cohort patients required hospitalization. The numbers in this study were too small to identify any rare adverse vaccine events, although this information may help in shared decision making, and the number of infected patients doesn’t allow for meaningful conclusions. There is also evidence that vaccination reduces the risk of MIS-C.
 
PEG and Vaccine Skin Tests in Patients With an Immediate Reaction to mRNA Vaccine
Based on several reports, skin testing with PEG-containing compounds has not been predictive of future reactions to vaccination in those with initial hypersensitivity reactions. Skin testing with the vaccine has not been widely reported. This study from Israel looked at 51 patients with a history of an allergic reaction to the Pfizer vaccine, 18 of whom had experienced anaphylaxis per the Brighton criteria. Skin testing was performed with PEG-containing medications and whole vaccine (full strength prick, then 1:100 and 1:10 ID). Thirty-eight out of 51 had negative skin tests and went on to subsequent Pfizer vaccine doses, and half of those had clinical reactions, although generally milder than the initial reaction. Seven out of 51 had negative skin tests but a clinical reaction (six out of seven with persistent cough) during testing that required treatment. Four of these went on to have subsequent Pfizer doses. There were only six patients with positive skin tests to PEG-containing medications and/or vaccine with three out of six having reactions to both. Two of the six patients with positive skin tests to PEG-containing medication and/or vaccine were also skin test positive to the AstraZeneca vaccine. Patients with a history of anaphylaxis were more likely to have positive skin tests. Take home message: Positive skin tests, even with vaccine, are uncommon following initial allergic reactions and have poor negative predictive values for subsequent reactions. None of the skin test positive patients were given subsequent doses of the Pfizer vaccine, so we can’t calculate the positive predictive value.
 
Are Mosaic Vaccines the Answer?
Current vaccines have been successful at reducing severe disease, but the rapid antigenic changes of the SARS-CoV-2 virus has made prevention of infection difficult. These NIH-funded investigators developed a nanoparticle vaccine containing proteins from the receptor-binding domain of several different coronaviruses. The resulting “mosaic vaccine” resulted in the production of antibodies that recognized a range of coronaviruses, including some not contained in the vaccine. Human clinical trials are soon to follow.

Infection

Hospitalizations Among Adults During BA.2 Predominance
According to this CDC report, increased hospitalization rates among adults aged 65 years and older compared with rates among younger adults were most pronounced during the Omicron BA.2-predominant period. Among hospitalized nonpregnant patients, 44.1% had received primary vaccination and at least 1 booster or additional dose. Hospitalization rates among unvaccinated adults were approximately triple those of vaccinated adults. Take home: Vaccination by itself is not enough to prevent hospitalization in those over 65, other mitigation measures (nonpharmaceutical and medical) should be used (e.g., masking, social distancing, antivirals, monoclonal antibodies).
 
Risks of Acute Venous Thromboembolism (VTE) in Ambulatory Patients With Acute COVID-19
Most of the data reported to date relates to hospitalized patients with COVID-19 infection. This retrospective population based-cohort study involved 18,818 outpatients with COVID-19 matched with COVID-19-naive patients from the same time period. The hazard ratio for VTE in the 30 days post-infection in infected versus uninfected patients was 21.42 (incidence rate of 50.99 compared to 2.37 per 1,000 person-years). Vaccination reduced the hazard ratio to 5.95. Risk factors included older age, male sex, obesity and inherited thrombophilia.
 
Mechanisms for COVID-19-Associated Coagulopathy (CAC): Current Understanding
CAC is a life-threatening complication of SARS-CoV-2 infection. Compared with diseases caused by other common respiratory viral infections, patients with COVID-19 have a higher frequency and severity of clotting events, which in most cases are associated with elevated plasma levels of D-dimer, C-reactive protein, P-selectin and fibrinogen. CAC can manifest as microthrombi and macrothrombi, resulting in damage to multiple organs, including the lungs, heart, brain and kidneys. This article discusses the current understanding of the mechanisms underlying CAC, which include vascular endothelial cell dysfunction, a hyper-inflammatory response and hypercoagulability.
 
COVID-19 Outcomes in Patients With Primary Immunodeficiency (PIDD)
This systematic review of 68 articles includes 459 people with PIDD and COVID-19. Case fatality rate was 9%, with a hospitalization rate of 49%. Vaccination was less effective at prevention of hospitalization, although a number showed at least some response to vaccination. Overall symptom duration was similar to those without PIDD, but patients with B-cell defects were reported to have prolonged infections.
 
Varying Incubation Periods Over Time
In this systematic review and meta-analysis of 141 articles, the pooled incubation period was 6.57 days. The incubation periods of COVID-19 caused by the Alpha, Beta, Delta and Omicron variants were 5.00, 4.50, 4.41, and 3.42 days, respectively.
 
Orphanhood and Caregiver Loss Globally
Based on new global excess COVID-19 death estimates, 10.5 million children lost parents or caregivers and 7.5 million experienced orphanhood through May 2022. Little is being done to care for the children left behind, although the United States has made a national commitment to address the issue. We should all make sure that this happens.

Testing

Children Can Successfully Self-Test
In a cross-sectional study of 197 symptomatic children and adolescents ages 4 to 14 years, self-collected nasal swabs that were positive for SARS-CoV-2 agreed with results from healthcare worker-collected swabs in 97.8% of participants, while self-collected swabs that were negative agreed with healthcare worker-collected swabs in 98.1% of participants. The median age in the study was 9 years (IQR, 6-11). Instructional material consisted of a short video and a handout with written and visual steps.

Emerging Infections

Monkeypox
Allergists are not likely to be involved with these cases, except perhaps for those that care for HIV patients. The CDC has information on monkeypox prevention, diagnosis and treatment.
 
Polio
The recent case in New York State reminds us that this virus is no longer absent from the United States. With global travel, people who have been immunized with oral polio vaccine travel or move to the United States. They shed attenuated virus in their stool, which can circulate in an under-vaccinated population, such as the one in New York, and revert to a paralytic form. Since 75% of patients infected with polio are asymptomatic, silent circulation is possible. Although paralytic polio only affects one in 200 or one in 2,000 infected patients, our immunosuppressed patients may be at greater risk. As allergists, we should continue to ask our patients about their immunization status, now particularly against polio. Read the following for more information:
•    What All Physicians Need to Know About the Polio Resurgence in New York State
•    Polio in New York: How to Recognize and Report Polio, and Reinforce Routine Childhood Polio Vaccination
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, August 29, 2022

Vaccines

Bivalent Vaccines Poised for Fall Debut
Both Pfizer and Moderna have submitted data on bivalent vaccine boosters containing a wild-type and BA.4 and BA.5 component to the FDA for authorization. Pfizer, with their 30mcg dose (same as the initial series dose), has requested authorization for those 12 and older, Moderna, with a 50mcg dose (half the initial series dose), for those 18 years and older. The data submitted is based on animal studies, and human trials are just beginning. Updates to influenza boosters are based on animal data as well. The Vaccines and Related Biologic Products Advisory Committee (VRBPAC) is scheduled to meet September 1 and 2, and if authorization is granted, the CDC will offer their recommendations shortly afterwards. According to HealthDay News, the UK Medicines and Healthcare Regulatory Agency approved the Moderna Omicron-targeted vaccine for adults 50 years of age and older beginning this fall.
 
Novavax Authorized for Ages 12-17
The FDA extended the Novavax EUA to include teens ages 12-17 on August 19.The CDC recommended the vaccine be given to this age group on August 22.

Infection

Awareness of Omicron Infection in Adults
Among adult employees and patients of an academic medical center in Los Angeles who had serologic evidence for a recent Omicron infection, 56% reported being unaware of their infectious status. Ten percent of these had mild symptoms that they attributed to a common cold or another infection. Thus nearly half were asymptomatic, which certainly contributes to the rapid spread of infections. Placing emphasis on testing for cold symptoms will not have much impact.

Long COVID (PCC, PASC)

Health Impairments in Children and Adolescents After Hospitalization for Acute COVID-19 Or MIS-C
Two-to-four-month follow-up data on patients hospitalized between May of 2020 and May of 2021 conducted in 25 U.S. pediatric hospitals revealed readmission occurred in 11% and 8% of COVID-19 and MIS-C patients respectively. Also, 26.9% of patients with acute COVID-19 had persistent symptoms (22.7%) or activity impairment (14.3%) compared to 30% of MIS-C patients. For patients with acute COVID-19, persistent symptoms and activity limitations were associated with the number of organ systems involved; for MIS-C patients, pre-existing respiratory conditions were associated with persistent symptoms, and obesity with activity impairment. In a retrospective cohort study of 659,286 children with confirmed infection, loss of taste and smell, and myocarditis were the most common PASC symptoms or condition, and cough and cold preparations were the most commonly prescribed medications post COVID-19. Overall about 3.7% of children had post-COVID symptoms and increased rates were related to disease severity, age <5 years and medical complexity.
 
Neurologic and Psychiatric Sequelae After Two Years
An analysis of two-year retrospective cohort studies involving 1,284,437 patients from multiple countries (most from the United States) matched with a contemporaneous cohort of patients with any other respiratory infection found that risks of cognitive deficit, dementia, psychotic disorders and epilepsy or seizures were still increased at the end of two years. Children had an increased risk of cognitive deficit, insomnia, intracranial hemorrhage, ischemic stroke, neuropathy, psychotic disorders and seizures, although the cognitive deficits were equal to the comparison group by 491 days. Risk profiles were higher with Delta, but Omicron and Alpha variants had similar risk profiles. Mood disorders and anxiety were short-lived in adults and not increased in children.
 
Information for Your Patients on Long COVID
The NIH has a website for patients on Long COVID, symptoms, duration and research.

Treatment

Real World Effectiveness of Paxlovid During Omicron
Clinical trials have indicated that Paxlovid is 93% effective at reducing severe COVID-19 due to the Delta variant. This study from Israel involving 3,902 adults 40 years and older who received Paxlovid for treatment found in those over age 65 an adjusted hazard ratio (aHR) for hospitalization of 0.27 for treated patients compared to untreated patients, and an aHR of 0.21 for death. There was no apparent benefit for those ages 40-64.
 
Randomized Trial of Metformin, Ivermectin and Fluvoxamine for COVID-19
A phase-4, double blind, randomized placebo-controlled trial found that none of these drugs were effective in preventing serious SARS-CoV-2 infection in non-hospitalized adults who had been enrolled within 3 days of confirmed diagnosis and less than 7 days after onset of symptoms. All patients had at least one comorbidity.
 
NIH COVID-19 Treatment Guidelines Updates for Monoclonal Antibodies
For non-hospitalized adults at high risk, the Panel recommends using bebtelovimab 175mg IV as an alternative therapy ONLY when Paxlovid and remdesivir are not available or feasible to use. Treatment should be initiated as soon as possible and within 7 days of symptom onset.

Testing

How Does Low Self-Reporting of Tests Affect Determination of Case Numbers?
The popularity of self-testing for COVD-19 has made ascertainment of case levels difficult, presumably because of lack of reporting. In a CDC analysis of COVID-19 self-test result data voluntarily reported by users of four brands of tests, while these four manufacturers produced 393.4 million self-tests (15.3% of all self-tests produced for the United States), users voluntarily reported 10.7 million test results (3% of all tests produced). During the same time there were 361.9 million laboratory and point-of-care tests reported. Fortunately overall trends in reporting volume and percentage of positive results were similar across test types. Clearly self-test reporting is insufficient to help case tracking.

Practice

Mental Health Conditions and Suicidal Ideation Among Public Healthcare Workers
In this report from the CDC, 26,069 STLT (State, Tribal, Local and Territorial) public health workers responded to a survey during March 14–25, 2022. Overall, approximately one half of respondents (48.0% [95% CI = 47.3%–48.7%]) experienced symptoms of at least one of the mental health conditions of depression, anxiety, or PTSD. The most commonly reported mental health condition was PTSD (28.4%) followed by anxiety (27.9%), depression (27.7%), and suicidal ideation (8.1%). These symptoms declined from 2021 to 2022, but the prevalences of symptoms of suicidal ideation, anxiety, depression, and PTSD remained high among those who worked >60 hours per week (range = 11.3%–45.9%) and those who spent 76% or more of their work time on COVID-19 response activities (range = 9.0%–37.6%). Respondents were less likely to report mental health symptoms if they could take time off (prevalence ratio [PR] range = 0.48–0.55), or if they perceived an increase in mental health resources from their employer (PR range = 0.58–0.84).
 
Extension of Public Health Emergency (PHE) Likely
The Biden administration pledged to provide 60 days warning before ending the PHE. Since that time has passed, we anticipate that the PHE will be extended for another 90 days beyond the current expiration date of October 13. Since policy has already been established that telehealth waivers will be extended at least 150 days beyond the end of the PHE, this means that we will continue to benefit from those waivers until at least June of 2023. There are bills in Congress that propose to extend that even further. Here are resources from CMS on what waivers will end with the end of the PHE:
•    COVID-19 Emergency Declaration Blanket Waivers for Healthcare Providers
•    Physicians and Other Clinicians: CMS Flexibilities to Fight COVID-19
•    Teaching Hospitals, Teaching Physicians and Medical Residents: CMS Flexibilities to Fight COVID-19
 

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,
 
Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, August 15, 2022

Vaccines

Booster Alternatives for People With Allergy to mRNA Vaccines Who Refuse Administration Under Observation
Novavax is not authorized as a booster under its current EUA, and physicians cannot prescribe “off-label” for drugs/vaccines which have an EUA. The J&J vaccine’s EUA was recently restricted to those who are unable to tolerate any other option. This study done at a single site in Boston showed that using Ad26.COV2.S (J&J) vaccine as a booster after a primary series of Pfizer had a more durable response with only a 2.1-fold decline in neutralization against Omicron at 4 months compared to a 6.9-fold reduction after a Pfizer booster. This could be a consideration in people who are not at risk for the thrombosis with thrombocytopenia syndrome that occurs in middle-aged females.

Infection

CDC Makes Major Changes in COVID-19 Guidance
On August 11, the CDC revised their guidance for minimizing the impact of COVID-19. Key points (changes from prior guidelines in bold): Know your risk, protect yourself, take action if exposed, and take action if you are sick or test positive. Vaccination for all and pre-exposure prophylaxis for those with immunosuppression or unable to be vaccinated are still recommended. Patients at high risk (over 65, pre-existing conditions, immunosuppression) should have plans for testing and treatment if symptomatic or exposed. Monitor community levels of COVID-19 to guide prevention efforts. Those at high risk should wear a well-fitting N95, KN95 or KF94 indoors in public when community levels are medium or high. All should wear such masks indoors in public at high community levels. Isolation recommendations for those infected have not changed, although there are new guidelines if one chooses to use testing to discontinue masking: wait to take the first test until at least day six and they are without a fever for at least 24 hours without the use of fever-reducing medication and all other symptoms have improved. Use of two antigen tests with at least 48 hours between tests provides more reliable information because of improved test sensitivity. Two consecutive test results must be negative for persons to discontinue masking. If either test result is positive, persons should continue to wear a mask around others and continue testing every 48 hours until they have two sequential negative results. Persons who choose to use testing to determine when to discontinue masking can end isolation after day five even if they receive a positive test result. Persons who had moderate illness from COVID-19, including those who show evidence of lower respiratory illness such as shortness of breath or difficulty breathing, should isolate for at least 10 days. For managing exposures: Persons who have had recent confirmed or suspected exposure to an infected person should wear a mask for 10 days around others when indoors in public and should receive testing at least five days after exposure (or sooner, if they are symptomatic), irrespective of their vaccination status. In light of high population levels of anti–SARS-CoV-2 seroprevalence, and to limit social and economic impacts, quarantine of exposed persons is no longer recommended, regardless of vaccination status. Masking is still recommended in healthcare settings. Changes were also made to school guidance, with masking recommended for all when community levels are high. Cohorting is no longer recommended, nor routine screening except perhaps in high-risk settings when community levels are high, test to stay is no longer needed. All the other recommendations for the general public also apply. Allergists may need to be familiar with these guidelines to counsel parents/caregivers of school-aged immunocompromised individuals.
 
Rapid Antigen Tests and Infectiousness During Isolation
This small study out of Boston enrolled 40 patients with confirmed COVID-19 infection during the Omicron BA.1 surge, where 90% were up to date on vaccines. Only 25% were negative on rapid antigen testing (RAT) on day six, and all had negative tests on day 14. The mean (SD) day of first negative RAT result in the seven never-symptomatic participants versus the 33 ever-symptomatic participants was 8.1 (3.0) versus 9.3 (2.4) (P = .14). Positive RAT results were frequent (61 of 90 tests [68%]) on days six to 14 among individuals reporting no symptoms that same day. Seventeen had viral cultures performed on day six, 12 of whom also had a (+) RAT. Only six of 12 had positive cultures, two with unchanged symptoms, two with improving symptoms and two had been asymptomatic. Seven of nine who were asymptomatic on day six had negative cultures. Limitations of the study are the small sample size, but this would suggest that perhaps about half of those with positive RAT results on day six are actually infectious.
 
Upper Airway Infections (Epiglottitis, Croup) During Omicron Infection
This cross-sectional study from 43 U.S. Children’s Hospitals identified 5,152 children with COVID-19-related croup. The proportion of children with croup was much higher during the Omicron period (10.9%) compared to Alpha and Delta. Odds of hospitalization or ICU admission were not significantly different. This study from another database provides additional information.
 
Hospitalization Rates for Children Ages 6 Months and Younger Highest Among All Pediatric Age Groups  
CDC’s Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET) shows that for the week ending July 16, the rate of COVID-19-associated hospitalizations (per 100,000 population) for children ages 6 months and younger, who are not eligible for vaccination, is 26.0, more than 10 times the rate of 2.0 for the week ending April 9.
 
Immune Response After Mild Infection
In this cohort study of 252 family clusters with COVID-19, anti–SARS-CoV-2 spike receptor-binding domain IgG persisted until 12 months after infection in all age groups, showing significant higher antibody peaks for younger individuals at every follow-up time point. Children younger than 3 years were found to develop higher levels of binding antibodies compared with adults older than 18 years. Another study on T-cell reactivity in 30 patients with confirmed COVID-19 infection showed a two-phase response. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until about 70 days after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-gamma remained stable and highly correlated at 3 to 21 months after infection.
 
Differential Viral Replication May Explain Changes in Pediatric Hospitalizations During Omicron
This study from Australia using primary nasal epithelial cells from children and adults demonstrated that viral replication in these cells after infection by the ancestral strain and Delta strains was lower in children compared to adults, which was associated with a heightened antiviral response in children. This difference was markedly less with Omicron infection.
 
Olfactory Dysfunction With Mild Infection Less With Omicron
This retrospective study from Brazil reported that olfactory dysfunction occurred in 52.6% of those with mild infection due to original lineages, 42.1% during Delta and 5.8% during Omicron.

Post-COVID Conditions

Neuropsychiatric Sequelae
Preliminary results on 200 patients from a prospective study of COVID-19 positive adults (average 125 days post infection) in Georgia showed that fatigue was most common (68.5%), with hyposmia and hypogeusia in 30%. Self-reported neurologic dysfunction did not correlate with dysfunction on quantitative neurologic testing. Additionally, self-reported symptoms and comorbidities were associated with depression and anxiety.
 
HHS to Create an Office of Long COVID Research and Practice
This was reported in Bloomberg Law and noted in AMA Morning Rounds on August 4. The new "Office of Long COVID Research and Practice will fall under the Health and Human Services (HHS) assistant secretary for health, according to the White House’s National Research Action Plan on Long COVID released Wednesday.” This plan “makes long COVID a high-level priority by creating a permanent leadership within the department.”

Treatment

Major Update to NIH COVID-19 Treatment Guidelines
Included in this update are: a new section on Special Considerations in People Who Are Immunocompromised, three new sections that focus on therapeutic management in children, Pediatric Clinical Management Summary, Therapeutic Management of Nonhospitalized Children with COVID-19, and Therapeutic Management of Hospitalized Children with COVID-19, revised sections on Special Considerations in Children, Clinical Spectrum of SARS-CoV-2 Infection, Therapeutic Management of Nonhospitalized Adults with COVID-19 and Therapeutic Management of Hospitalized Adults with COVID-19, and a section on Kinase Inhibitors (JAK and BTK) for treatment of COVID-19.

Testing

FDA Issues New Guidance on Testing
Serial testing is now recommended for rapid antigen tests. If symptomatic but test is negative, repeat again in 48 hours for a total of two tests. If exposed but asymptomatic, and first test is negative, repeat in 48 hours and if again negative, repeat in another 48 hours for a total of three tests. Positive tests indicate that a person is most likely infected.
 
Oral Rapid SARS-CoV-2 Rapid Antigen Test Kits Recalled
North American Diagnostics is recalling these kits because they were distributed without authorization, clearance or approval by the FDA.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, August 8, 2022

Vaccines

Boosters and BA.4/5
This study using serum from vaccinated patients and pseudoviruses and target cell lines showed that a single booster markedly increases neutralizing antibody titers and breadth against BA.4/5. Boosters are recommended for all people ages 5 years and older, but only 2.8% of 5-to-11-year-olds who are eligible have received a booster dose, only 16.7% of those 12-17 years, and 27.2% of those 18-49 years. Of those ages 50-64, 45.3% have received a first booster but only 9.7% have received a second booster. Of those 65 years and older, the numbers are 64.7% and 23.6%. These numbers are from the CDC's COVID Data Tracker. Media coverage about breakthrough infections may have contributed to these low numbers, but it is important for allergists to remind patients that being up to date on vaccination (primary series plus booster(s) for which they are eligible) prevents hospitalization and death. The Biden administration has recently announced that second boosters for those under age 50 are on hold in hopes of getting a BA.4/5 focused booster out by mid-September.
 
Experience With Allergic Reactions to mRNA Vaccines in Israel
Allergists should be well aware of the concerns about allergic reactions to mRNA vaccines since their debut in December of 2020. This report from Israel looks at the reporting of such reactions from December of 2020 to September 2021. The reporting rate was 106 per million in December of 2020, declining to 66, 18, 14, 8 and 0 per million over the ensuing 5 months. Validated immediate allergy was observed in only 37 patients (8% of those reporting a reaction) and a history of allergy was associated with high false reporting of immediate reactions (83%). As we have reported, subsequent studies have shown that second and further doses of vaccine are well tolerated in the overwhelming majority of those with reactions to the first dose and in this group there was no effect on adherence to second and subsequent doses of vaccine in these patients.
 
Risk of Myocarditis in 5-to-11-Year-Olds
This study from Denmark involving 208,088 children who had received at least one dose of an mRNA vaccine found the rate of myocarditis in the 4 weeks after vaccination to be 4.8 per 1,000,000 doses, much lower than the 12-to-17-year-old group. Limitations of the study include the relative size of the population studied compared to the risk, which could result in underestimation, and the fact that most cases occur after the second dose.
 
Factors Associated With Severe Outcomes Among Hospitalized Immunocompromised Adults
Immunocompromised adults comprise 12.2% of all adult hospitalizations, compared with an estimated 2.7% of the U.S. population. From March 2020 to February 2022, immunocompromised patients had a higher risk of ICU admission and in-hospital death compared to non-immunocompromised, and vaccinated patients had a higher risk than the unvaccinated, but from March 2021 to February 2022, there was no difference between groups with respect to odds of death. Very small numbers of PIDD patients were included in this study. Take home: Immunocompromised patients need more than vaccination to protect them:  improved ventilation, masking, EVUSHELD.
 
Vaccination May Reduce Post-COVID MI and Stroke
This restrospective cohort study from Korea included 231,037 patients, speficially 62,727 were never vaccinated and 168,310 were fully vaccinated (two doses). The adjusted hazard ratio (aHR) for acute MI and ischemic stroke 31-120 days after COVID-19 infection were significantly lower for the vaccinated patients (aHR 0.48 and 0.40 respectively).
 
Vaccination After Infection Provides Protection Against Reinfection  
In this cohort study of more than 95,000 Rhode Island residents from March 2020 to December 2021, including residents and employees of long-term congregate care (LTCC) facilities, completion of the primary vaccination series after recovery from COVID-19 was associated with 49% protection from reinfection among LTCC residents, 47% protection among LTCC employees, and 62% protection in the general population during periods when wild type, Alpha, and Delta strains of SARS-CoV-2 were predominant. Reinfection with the Omicron sublineages BA.4/5 are much more common and we don’t know if these results would apply, but vaccination is still recommended after infection.

Post-COVID Conditions (PCC) (PASC, Long-COVID)

PCC in Children
This prospective multinational cohort study of 1,884 children infected with SARS-CoV-2 tested in the ED with 90-day follow-up noted that 5.8% of patients, including 9.8% of hospitalized children and 4.6% of ED-discharged children, reported PCCs. Factors associated with PCCs include hospitalization for more than 48 hours, and four or more symptoms at presentation. The most common symptoms included respiratory complaints, fatigue and weakness. While the percentages are small, 13.9 million children have tested positive for COVID-19 since the pandemic started, so over 800,000 children could have PCCs. Allergists may very well see some of these patients with respiratory complaints. In a study using a medical claims database, the CDC reported that compared with patients aged 0–17 years without previous COVID-19, those with previous COVID-19 had higher rates of acute pulmonary embolism (adjusted hazard ratio = 2.01), myocarditis and cardiomyopathy (1.99), venous thromboembolic event (1.87), acute and unspecified renal failure (1.32), and type 1 diabetes (1.23), all of which were rare or uncommon in this study population.
 
Symptoms and Risk Factors in Non-Hospitalized Adults
In this retrospective matched cohort study from the UK, among 486,149 adults with confirmed infection matched with 1,944,580 matched adults with no evidence for infection, a total of 62 symptoms were significantly associated with infection. The largest adjusted hazard ratios (aHR) were for (symptoms of interest to allergists in bold): anosmia (aHR 6.49), hair loss (aHR 3.99), sneezing (2.77), ejaculation difficulty (2.63), and reduced libido (2.36). Risk factors included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and comorbidities. Note that these symptoms may differ from those who have been hospitalized. In the “Listening Session” discussed below, the prevalence of PCC was 18.9% in adults who ever had COVID-19, one in five of those over 18 had a PCC, and one in four of those over 65. The most common reported symptoms are fatigue, dyspnea, sleep disturbances, cognitive dysfunction and chest pain.

Testing

Recent Updates
The AAAAI participated in a recent “Listening Session” with the CDC and the Council for Medical Specialty Societies. Guidelines for testing for SARS-CoV-2 were discussed during the session. When to test: 1) if symptomatic, 2) 5-7 days after known exposure if asymptomatic (repeat in 2 days if negative), or 3) for peace of mind before visiting someone at high risk (in this situation, pre-test probability is low so may be false negative). Testing to end isolation is not recommended. A negative test does not equate to being non-infectious. Special note: Not all infectious disease experts agree with this. What if a rapid test is positive: 1) if symptomatic, or known exposure, confirms infection; 2) if no symptoms or known exposure, retest with a PCR test and quarantine until results are back. What if the rapid test is negative in someone who is symptomatic or exposed: Check a PCR test and quarantine until results are known.

Treatment

Recent Updates
During the same listening session noted above, treatment issues were reviewed. Current NIH Treatment Guidelines (in order of preference): Paxlovid, remdesivir, bebtelovimab, molnupiravir. Dexamethasone is not recommended for outpatient treatment. The best resource for checking for Paxlovid interactions is from the University of Liverpool and can be found here. Rebound after Paxlovid: No evidence for re-treatment or increasing dose but restart isolation at onset of symptoms or positive test, and end isolation after 5 days but keep masking for a total of 10 days. Remember that day of symptom onset or positive test is day zero.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, July 25, 2022

Vaccines

FDA Authorizes Emergency Use for the Novavax Vaccines
The FDA issued the EUA for the Novavax vaccine July 13. A prior message commented on the Advisory Group recommendation for this authorization, but the FDA had to confirm manufacturing performance which it has done. Novavax is a protein subunit nanoparticle vaccine (containing a portion of the spike protein) combined with a proprietary adjuvant. This is administered as a two-dose series, three weeks apart. This vaccine is made with a more conventional technology (recombinant protein) for those concerned about the mRNA technology. The spike protein is grown in insect cells, not fetal cells. The Matrix-M adjuvant contains saponin extracts from the bark of the Soapbark tree which is native to Chili. In the initial trials in the U.S. and Mexico, the vaccine was 90.4% effective in preventing mild, moderate or severe disease, but this preceded the delta and omicron variants. Side effects of the vaccine were no different than those following the mRNA vaccines, and there is a suggestion of an increased risk of myocarditis and pericarditis. The vaccine only requires refrigeration for storage. ACIP has also recommended this vaccine be used for those 18 years of age and older. Additional information on the vaccine and current trials from the NIH and BARDA can be found here.

Safety of Vaccine Administration in 5-11-year-olds Following an Initial Vaccine Reaction or History of PEG or Polysorbate Allergy
Several studies have documented the safety of second doses in adults with a history of an allergic reaction after the first dose or in those individuals with a history of PEG or polysorbate allergy. This small study, published in JACI: In Practice, shows the same outcomes for 5-11-year-old children. Single-dose second vaccine administration was safe, and individuals with a history of allergy to the vaccine components did not have a reaction. Testing for PEG or polysorbate allergy was not performed.
 
Effectiveness of Two, Three and Four Doses of mRNA Vaccine During the Omicron BA.1, BA.2/BA.2.12.1 Sublineage Periods
The VISION network examined 214,487 emergency department/urgent care (ED/UC) visits and 58,782 hospitalizations with a COVID-19–like illness diagnosis among ten states from December 18, 2021 – June 10, 2022, to evaluate vaccine effectiveness (VE) of two, three and four doses of mRNA COVID-19 vaccines (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) compared with no vaccination among adults without immunocompromising conditions. The study found VE against COVID-19–associated hospitalization 7 – 119 days and ? 120 days after receipt of dose three was 92% (95% CI = 91%–93%) and 85% (95% CI = 81%–89%), respectively, during the BA.1 period, compared with 69% (95% CI = 58%–76%) and 52% (95% CI = 44%–59%), respectively, during the BA.2/BA.2.12.1 period. Patterns were similar for ED/UC encounters. Among adults aged ? 50 years, VE against COVID-19–associated hospitalization ? 120 days after receipt of dose three was 55% (95% CI = 46%–62%) and ? seven days (median = 27 days) after a fourth dose was 80% (95% CI = 71%–85%) during BA.2/BA.2.12.1 predominance. There is also evidence that the effectiveness of the booster doses declines significantly after three months against all omicron sublineages, including BA.5.  

Safety of Booster Doses in Immunocompromised Teens and Adults
Using data from v-safe and VAERS on over 500,000 booster doses given to immunocompromised individuals 12 years of age and older, local and systemic reactions were less than after the primary series. Only 17 severe adverse events were reported to VAERS. As a reminder, immunocompromised persons ages 12 years and older should receive a first booster three months or more after a three-dose primary series and a second booster four or more months after the first booster.  

Using T-cell Immunity to Guide Revaccination Strategy
One of the limitations of research related to booster strategies has been the reliance on neutralizing antibody levels, which naturally decay over time. Perhaps a focus on T-cell immunity would help to better refine the strategy. To date, T-cell immune studies have been based on small numbers of patients, but recently researchers from Oncology at Icahn School of Medicine in New York have developed PCR-based assays that allow for “large scale monitoring of the magnitude and duration of functional T-cell immunity to SARS-CoV-2, thus helping to prioritize revaccination strategies in vulnerable populations.”  

Update on Myocarditis/Pericarditis Following mRNA Vaccine
During the ACIP meeting to discuss recommendations concerning the Novavax vaccine, the CDC provided an update on myocarditis/pericarditis following mRNA vaccine. While the data on numbers has not been updated since late May, there is more information on follow-up of the cases. Using information from VAERS and Vaccine Safety Datalink (VSD), with confirmation of reports on VAERS, there have been 1,321 confirmed cases of myocarditis/pericarditis among 491.9 million primary series and booster doses. Case rates are highest in males ages 16-17 (case rate 75.9 per one million doses after the second dose and 24.1 per million after a booster dose), followed by 12-15 year olds (46.4/15.3), 18-24 year olds (38.9/9.9) then 25-29 year olds (15.2/4.8). Female case rates are about 10-fold lower and follow the same age pattern. The background incidence in all children is about eight per million patient years and 18 per million patient-years in those 15-18 years old. Of the 398 patients whose follow-up data from cardiologists is known, 81.7% are fully recovered or probably fully recovered at 90 days, 1% are unchanged and the remaining are improved but still some abnormalities. The majority are hospitalized but median LOS is one day. Compared to myocarditis/pericarditis caused by viral infection, ICU stays and need for additional cardiac support are rare.

Effect of Suspension of Methotrexate on Vaccine Response
This prospective, randomized study in the UK involved 254 patients with a variety of immune-mediated inflammatory conditions, including atopic dermatitis, who were on 25mg per week or less of methotrexate. All had received their primary series of vaccine. One group continued therapy and the other stopped the methotrexate for two weeks immediately following their booster dose. The S1-receptor binding domain antibody titers were 2.19 times higher in the suspended therapy group compared to the continued therapy group.

Infection

FDA Warns Against Certain Ultraviolet Wands For Disinfection
Some ultraviolet wands used to disinfect surfaces give off high levels of ultraviolet-C (UV-C) light that can damage skin and eyes of the users and people nearby. The list of wands that the FDA identified can be found here.

Practice

Provider Relief Fund Reporting Period Three Now Open: Submit Your Report Before September 30, 2022
For physicians who received more than $10,000 in the aggregate from January 1, 2021, to June 30, 2021, the PRF Reporting Portal is now open and will remain open through Sept. 30, 2022, at 11:59 pm eastern time.
 
HHS to Extend the Public Health Emergency
The current PHE is scheduled to end in mid-July, but HHS announced recently that they intend to extend it for another 90 days, so it would last until at least mid-October.

Tests

FDA Recalls ACS COVID Test Kit Nonsterile
The FDA has recalled ACS COVID test kits. These kits were assembled in an uncontrolled facility by people without proper training.  
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, July 11, 2022

Vaccines

Vaccine Efficacy (VE) of BNT162B2 (PFIZER) in 5-11-Year-olds During Omicron
Data from Israel notes VE of 51% against documented infection 7-21 days after the second dose of vaccine, 48% for symptomatic infection. There was a trend toward higher VE in the 5- or 6-year age group compared to the 10- or 11-year-old group. Limitations of the study include that not all patients in the vaccinated group had received the second dose within the follow-up study and effectiveness against hospitalization could not be calculated due to very rare hospitalizations among the study participants. Other studies have suggested that the booster increases the VE to 70% at least shortly after the second dose.
 
CDC Updates Vaccination Page
The CDC updated their page on the use of COVID-19 vaccines in the U.S. on June 30, which has a number of helpful sections for allergists, including schedules and doses for different age groups, considerations for intervals for primary series, and guidance for people with moderate or severe immunodeficiency including a description of moderate and severe immunocompromising conditions. The link will be updated on the AAAAI COVID-19 web page.
 
FDA Advisory Committee Fall Booster Recommendations
On June 28 the Vaccines and Related Products Advisory Committee of the FDA (VRBPAC) recommended that the FDA seek to approve boosters aimed at the omicron variants and subvariants for administration in the fall. The manufacturers of the Pfizer and Moderna vaccines presented their data, and the CDC and WHO weighed in on the decision. There was some data presented by the CDC on the effectiveness of the second booster in those >50 years old. People with one booster dose had 4 times the risk of dying compared to people with 2 booster doses. There was some discrepancy between manufacturers. Both companies showed that a bivalent vaccine using a BA.1/2 formula plus the original vaccine was effective against BA.4/5, although with some reduction. But there were differences in durability of the vaccines, with the Moderna bivalent showing improved durability compared to the monovalent, but the data from Pfizer demonstrated the opposite. The WHO feels that the goal isn’t to chase the current variant, as is usually done with the influenza vaccine, but rather try to broaden protection with a fall booster. Based on the Advisory Committee recommendation and available evidence “FDA has advised vaccine manufacturers seeking to update their COVID-19 vaccines that they should develop modified vaccines that add an Omicron BA.4/5 component to their current vaccine compositions to create two component (bivalent) booster vaccines.”  
 
Impact of the First Year of Vaccines
Using a mathematical model of COVID-19 transmission and vaccination separately fit to reported COVID-19 mortality and all-cause mortality in 185 countries and territories, these investigators estimated that the first year of vaccinations prevented 14.4 million deaths based on official reports of death and 19.8 million based on excess deaths reports. Inadequate access to vaccines in low-income countries has limited the impact in these settings, however. Global impact of the first year of COVID-19 vaccination: a mathematical modelling study.
 
Epidemiology of Post Vaccine Myocarditis/Pericarditis
A population-based cohort study involving 297 individuals with myocarditis or pericarditis following mRNA vaccination found that the highest rate was observed in males ages 18-24 following the second dose of mRNA-1273 (Moderna) at 299.5 cases per 1,000,000 doses, whereas the rate following a second dose of BNT162b2 (Pfizer) was 59.2 cases per 1,000,000 doses. The difference for those with interdose intervals of 30 or fewer days was much smaller (mRNA1273 83.9, BNT162b2 52.1) and the rates overall were much lower when the interdose interval was 56 or more days (mRNA1273 16.2, BNT162b2 9.6). You might find this information useful when counseling your adolescent and young adult males about vaccination.  
 
FDA Gives Full Approval For Pfizer mRNA Vaccine (Comirnaty)
On July 8, the FDA granted full approval for the Pfizer vaccine for 12-15 year olds.

Infection

BA.5 And BA.4 Now 70% of Infections
In the latest data from the CDC COVID Data Tracker, BA.5 comprises 53.6% of COVID-19 infections, and BA.4 16.5%. BA.2.12.1 is responsible for 27.6% of infections, down from 50% in mid-June. Both BA.5 and BA.4 are more immune evasive and more transmissible than other omicron sublineages. As a result, the CDC is recommending the use of masks indoors in more counties across the U.S. View the variant proportions. A new sublineage, BA.2.75, is now the cause of 25% of cases in India and has also been identified in low numbers in Australia, New Zealand, the UK and Germany. This appears slightly more transmissible than BA.5.

Reinfections
Data from the UK and New York indicate that about 25% of current cases are reinfections. The CDC uses a 90-day window to exclude counting new infections as reinfections, but there are case series suggesting that reinfection can occur as early as 20 days. Most data from the pre-omicron era suggest that reinfections are less severe but there are minimal peer-reviewed studies to date on reinfections with omicron.

Viral Dynamics of Omicron And Delta
This small longitudinal study conducted on a university campus where daily nasal swabs were collected for at least 10 days for RT-PCR and culture, and rapid antigen tests in a subset. In 92 students who tested positive (80% omicron) 17% had positive cultures beyond day five from symptom onset with the latest on day 12. For the 14 students who had rapid antigen tests sensitivity and specificity of day 4-6 were 100% and 86% respectively. Take home: rapid antigen testing on day five may be helpful, continued masking for days 6-10 important. In another small study involving 66 outpatients with COVID-19, the median time from initial PCR positive to negative culture was five days in the omicron group (interquartile range, 3 to 9) and the median time from symptom onset or positive PCR (whichever was earlier) was eight days (5-10). All of these studies are small and could be influenced by a number of factors, although attempts to control for these factors are made. The clinical correlation with infectivity is not known.

Persistent Positive Rapid Antigen Tests – What do They Mean?
There are no good studies to cite but there is considerable discussion about the meaning and implication of positive antigen tests beyond the isolation time. In interviews with the press, some infectious disease experts would continue isolation as long as the tests are positive, while others would not test after five days if afebrile and improved symptoms. Some have suggested a tiered approach, in other words, continue masking, avoid close contact with anyone at high risk but don’t worry about going to the grocery store if you test positive on day five. One key point made in these interviews is that the rapid antigen test was not designed or evaluated for the purpose of clearing isolation and the clinical significance (as discussed above) is not known. More studies are needed.

Seroprevalance Studies May Underestimate People With Infection
We have reported on seroprevalence studies in the past, with one study using blood bank data being prominent. The presence of anti-nucleocapsid antibodies (anti-N Ab) has been used as evidence of prior infection. This study on participants in the mRNA-1273 (Moderna) trials found that among 700 patients with PCR-confirmed COVID-19 illness during the blinded phase of the trial, seroconversion to anti-N Abs occurred in 21/52 vaccinated participants compared to 605/648 placebo participants.

Post COVID Conditions (PCC) (Long COVID)

Theories on Pathogenesis
Research on PCC has been hampered by the lack of a definition, biomarkers and knowledge about the cause. This article in Science discusses three possible theories, none of which are mutually exclusive: 1) minute blood clots in some organs, 2) persistent virus, and 3) persistent abnormal immune response.

PCC in Children
A nationwide cross-sectional survey study from Denmark included 10,997 COVID-19 positive children and 33,016 matched controls. Cases had 78% higher odds of reporting at least one symptom lasting longer than two months in the 0-3-year-old group compared to controls, 23% higher odds in the 4-11-year-olds, and 21% higher in the 12-14-year-old group. The three most common symptoms in the 0-3-year-old group were nausea, fever and cough. In the 4-11-year-old group, sore throat, dizziness and trouble breathing were the top three. In the 12-14-year-olds, sore throat, chest pain, and fever. Despite this, quality of life scores (ages 4-11 and 12-14) and social functioning scores (ages 12-14) were higher in the cases compared to controls.  

More Data on Vaccine Effect
A large VA study recently cited in our messaging suggested that vaccination was only 15% effective at reducing long COVID, but limitations included low numbers of females and suboptimal vaccination regimens. This observational cohort study in Italy involving health care workers found an incidence of long COVID of 31% during the wild-type virus surge, 35.9% during the alpha variant surge and 16.5% in the delta and omicron surge. The OR for long COVID (compared to unvaccinated females during the wild-type surge) in those with two vaccine doses was 0.25 (95% CI, 0.07-0.87) and 0.16 (95% CI, 0.03-0.84) in those with three doses suggesting a much higher benefit from the vaccine in those with outpatient infections. ICD-10 CODE FOR LONG COVID IS U09.9 PER CMS.

Treatment/Prophylaxis

FDA Authorizes Pharmacists to Prescribe Paxlovid
On July 6, the FDA revised the EUA for Paxlovid to authorize state-licensed pharmacists to prescribe Paxlovid to eligible patients with certain limitations to ensure appropriate patient assessment and prescribing of Paxlovid. Community pharmacists not already participating as a Test-to-Treat site can decide if or how they will offer this service. Patients must provide recent lab results showing liver and kidney function and a list of all medications currently being taken. Most pharmacist practices are determined by their state pharmacy board and currently only seven states allow pharmacists prescriptive authority beyond birth control, naloxone, smoking cessation and PrEP and PEP for HIV (those states are New Mexico, Oregon, Idaho, Florida, California, North Carolina and Montana). Apparently this FDA authorization will supersede state board of pharmacy rules.  

FDA Extends Expiration Date For Some Lots of Evusheld From 18 to 24 Months
Based on review of evidence provided by AstraZeneca, the FDA has extended the expiration date of some lots of EVUSHELD. The FDA has also revised the Factsheet for health care practitioners to advise repeat dosing every six months in those patients with ongoing need.  

More Data on Immunoglobulin and SARS-CoV-2 Antibodies
In an earlier message we commented on a study that showed that more recently produced immune globulin for patients with antibody deficiencies had increasing amounts of anti-spike IgG antibody. This study from Germany and Switzerland found the same, and also noted correlating levels of anti-RBD and anti-nucleoprotein IgG. The article has a table that lists the antibody concentrations in different products, but the point is that there isn’t a significant difference in manufacturer but the date of production is important. Using a single patient with absent B cells and no response to vaccine, and PK modeling they were able to demonstrate serum neutralization of earlier variants but poor effect against omicron. The level of antibodies increased with time, and included non-neutralizing antibodies as well which may provide additional protection.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,


Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, June 27, 2022

Vaccines

Both Pfizer And Moderna Vaccines Are Available For Anyone Over The Age of Six Months
As you know, the FDA granted an EUA to Moderna and Pfizer last week and the CDC approved the vaccines for infants, toddlers and preschoolers as well as children and teens for Moderna. The Moderna vaccine is given as two 25mcg doses 28 days apart. The Pfizer vaccine is a three dose regimen, each dose is 3mcg. The first two doses are 21 days apart and the third dose is eight weeks or more after the second dose. Immediate side effects are similar to other age groups, antibody titers are also similar to older age groups. There is an increase in myocarditis cases compared to controls for the Moderna vaccine in older teens, but it is rare and both the FDA and ACIP felt that the benefits outweigh the risk. The FDA Advisory Panel meeting on June 15 pointed out that the deaths due to COVID-19 in the six months to four-year-old group is higher than any of the other vaccine-preventable diseases. We are on pace to exceed the total pediatric deaths in 2022 to date compared to all of 2021 (147 vs. 221). Children six months to four years had the highest hospitalization rate compared to other pediatric age groups, and one in four ended up in the ICU, particularly during the omicron surge. Vaccine effectiveness (VE) of Moderna against symptomatic infection in two to five-year-old children was 36.8-46.4% (depending on definition of symptomatic infection) and 31.5-50.6% in six months - two years. Pfizer reported a VE of 80.3%, however the number of children infected during the Pfizer trial was low. You can find videos and slides here.
 
Vaccine And Previous Infection Effects on Symptomatic Omicron BA.2
A study in Qatar from December 23, 2021-February 21, 2022, involving over 1.3 million people noted 46.1% effectiveness of previous infection against symptomatic BA.2 infection. Two doses of Pfizer vaccination and no previous infections had negligible effectiveness for symptomatic infection (almost all were >6 months post primary series), effectiveness of three doses of Pfizer and no infection was 52.2%, for previous infection plus two doses of Pfizer effectiveness was 55.1%, for previous infection and three doses of vaccine, 77.3%. The median date of the third dose of vaccine was December 25, 2021. Previous infection alone, vaccination alone and hybrid immunity all showed >70% effectiveness against severe disease or death.
 
Neutralizing Antibody Against BA.2.12.1, BA.4/5 in Boosted Individuals
This small study from The Ohio State University showed that booster vaccination provided sufficient neutralizing antibody titers against the BA.4/5 and BA.2.12.1 omicron subvariants, and to a slightly lower extent than against BA.1/2. The omicron sublineage BA.2.12.1 currently is 56% of all sequenced isolates, with lineage BA.5 23.5%, BA.4 11.4% and BA.2 9.1%. BA.4 and BA.5 have been increasing over the past 6 weeks. View variant proportions.
 
Vaccinated Patients Have Shorter Duration of Viral Shedding and Lower Secondary Transmission
This small study involving 173 (50 with breakthrough infection) showed a secondary transmission rate of 7% in the breakthrough infection group compared to 26% in the non-breakthrough infection group. In a viral shedding kinetics study involving 45 patients infected with the delta variant the initial viral load was similar in both vaccinated and unvaccinated but fully vaccinated patients shed virus for four days after onset of symptoms compared to 10 days after onset of symptoms in the unvaccinated.  

Infection

Omicron Immune Evasion and Infectioness
Several studies published this past week illustrate how readily omicron evades our immune system and how readily it infects people. Results have shown higher hospital-onset infections during the omicron surge compared to the previous year in Boston despite vaccinations and precautions among workers. In New York, researchers documented a reduction in vaccine efficacy against infection and hospitalization from early December 2021 to late January 2022 in children and adolescents compared to the unvaccinated. Similar results were noted in a national study among children and teens although a booster dose in teens increased the vaccine effectiveness five-fold. In an ongoing seroprevalence study using samples from blood bank donations, the combined infection and vaccine-induced seroprevalence was 94.7% in the U.S. at the end of December yet there was a huge surge in infections from December 2021-February 2022. Finally, a small study from Boston on neutralizing antibodies in vaccinated and vaccinated/infected patients showed that vaccinated but not infected patients had a median titer that was lower by a factor of 14.1 against BA.2.12.1, and a factor of 21 against BA.4/5 compared to the wild type virus. Vaccinated and infected patients had reduced titers by a factor of 9.6 against BA.2.12.1 and 18.7 against BA.4/5. Here is an additional study on neutralizing antibodies and these sublineages of omicron.

Less Risk Of Long COVID Following Omicron Infection
A study from the UK found a reduction in odds of long COVID with the omicron variant vs. the delta variant of 0.24-0.50 depending on age and time since vaccination.

Treatment

Rate of ED Encounters and Hospitalization Very Low After Paxlovid Treatment
There have been increasing reports of rebound symptoms after Paxlovid treatment but little data on the frequency of occurrence. This study from Kaiser Permanente of Southern California, a large integrated health care system, reported <1% of Paxlovid-treated patients had such encounters in the five-15 days after treatment.

EVUSHELD For Treatment Of Early COVID-19
EVUSHELD is not approved for this use. An ongoing phase 3 randomized, double-blind, placebo-controlled trial in the U.S., Latin America, Europe and Japan studied 910 unvaccinated adults with a confirmed positive test for SARS-CoV-2 three days or less prior to enrollment with mild-to-moderate symptoms. Treated patients were given a single 600mg tixagevimab-cilgavimab dose seven days or less from onset of symptoms. A total of 89% of participants were at high risk for severe disease. Severe COVID-19 or death occurred in 4% of treated patients and 9% of placebo-treated patients for a relative risk reduction of 50.5%. The treatment did not appear to be efficacious for those over age 65 although the numbers were small.

EVUSHELD in BA.2 Infection
In this small study from France, of 29 immunocompromised individuals who received EVUSHELD all achieved neutralizing titers against BA.2 although they were reduced 8-fold compared to delta.  

Dispensing Of Oral COVID-19 Drugs Lowers in Areas Of High Social Vulnerability
Despite having the highest number of dispensing sites, zip codes with the highest social vulnerability had the lowest dispensing rates compared to zip codes with low or medium social vulnerability.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,
 
Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, June 13, 2022

Vaccines

CDC Clarifies “Up to Date” For Vaccines
The CDC has been using the term “up to date” for vaccines for some time now and updated the term to mean the receipt of the primary series and all boosters for which an individual is eligible. This is important to understand as it impacts quarantine recommendations. Stay Up to Date with Your COVID-19 Vaccines.
 
FDA Advisory Panel Recommends EUA For Novavax, But…Also Meeting on Vaccines For Young Children
The advisory panel (VRBPAC) recommended approval but the FDA is still awaiting review of manufacturing facilities before granting it. The Advisory Panel will be meeting this week to discuss the Pfizer and Moderna vaccines for those <5 years and the Moderna vaccine for 5–17-year-old children.
 
Expectations For a Vaccine For Those Ages Six Months to Five Years by June 20
The White House announced plans for rollout of a vaccine for children under 5, partnering with state and local governments, health care providers, federal pharmacy partners and national and community-based organizations. The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) is to meet this week to discuss an extension of the EUA for both Pfizer and Moderna vaccines to be followed by a meeting of the Advisory Committee on Immunization Practices (ACIP), if the FDA grants this extension.
 
Multisystem Inflammatory Syndrome (MIS-C) in Children During the Omicron Surge
You may not see patients with MIC-C, but this information may be useful in shared decision making when counseling patients about vaccination. A population-based cohort study in Denmark found that the phenotype of MIS-C was the same during the omicron wave compared to the delta wave, but the risk was 88% lower (RR, 0.12; 95% CI, 0.06-0.23). Vaccinated patients were 89% less likely to develop MIS-C compared to unvaccinated children (RR, 0.11; 95%CI, 0.01-0.83).
 
Vaccination After Infection Slightly Reduces Long COVID
This study from the UK reinforces a previous study highlighted in an earlier Task Force message of a 15% reduction. This study on 28,356 patients who had received at least one dose of vaccine after confirmed infection had a 12.8% reduction in Long COVID symptoms after one dose, with sustained improvement after a second dose.

Infection

Racial and Ethnic Discrepancy in Pulse Oximetry
In a retrospective cohort study of 7,126 patients, an analysis of 1,216 patients with oxygen saturation levels that were concurrently measured by pulse oximetry and arterial blood gas demonstrated that pulse oximetry overestimated arterial oxygen saturation among Asian, Black, and Hispanic patients compared with White patients. Separately, among 6,673 patients with pulse oximetry measurements and available covariate data, predicted overestimation of arterial oxygen saturation levels by pulse oximetry among 1,903 patients was associated with a systematic failure to identify Black and Hispanic patients who were qualified to receive COVID-19 therapy and a statistically significant delay in recognizing the guideline-recommended threshold for initiation of therapy.

Children With Food Allergies at Lower Risk For COVID-19 Infection
This prospective study of 1,394 households (4,142 participants) performed biweekly nasal swabs and weekly surveys for six months from May 2020 - February 2021 to determine the incidence of infections in households with children, and whether self-reported asthma and/or other allergic disorders affected the incidence. There were no age differences in incidence and more children were asymptomatic compared to adolescents or adults. Asthma and eczema were not risk factors for infection, but self-reported, doctor-diagnosed food allergy was associated with 50% less risk of infection (OR 0.50, 95%CI 0.32-0.81).

Health Outcomes Two Years After Hospitalization For COVID-19
A longitudinal study of 1,192 patients in China at two years following discharge, compared to non-infected controls, noted an improvement in post-COVID-19 sequelae between one and two years, but 55% still had at least one symptom after two years with fatigue and muscle weakness most common. In all, 14% still had abnormal dyspnea scale findings and lower six minute walking distance (but improving) while 89% had returned to work. In those that had received higher levels of respiratory support during hospitalization, abnormalities in diffusion capacity and lung volumes were present in over 60%.

Treatment/Prophylaxis

Reminder on Which Outpatients With COVID Should Receive Treatment
The CDC has a page on risk factors for severe disease that allergists could use for shared decision making with their patients who test positive for COVID-19 but only have mild symptoms. Higher risk factors relevant to allergists include age over 65, COPD, bronchiectasis, Cystic Fibrosis, primary immunodeficiency, smoking (current and former), and use of corticosteroids. Suggestive risk factors include BMI between 25 and 30 kg/m2.

New Version of NIH COVID-19 Treatment Guidelines
The NIH COVID-19 Treatment Guidelines newest version includes more information on management of critically ill children and transplant patients.

Duration of Protection With Evusheld and Performance For Omicron
Primary analysis of an ongoing phase 3 trial at 183 days showed a relative risk reduction for symptomatic infection of 82.8% after a median of six months. There were no cases of severe or critical disease or death in the treated group. It should be noted that this study included patients at increased risk for a poor response to vaccination and also patients who were at increased risk of exposure. An accompanying editorial pointed out some additional factors based on other studies. Serum neutralizing titers are higher for up to nine months than those usually detected in convalescent serum. The phase 3 trial enrolled all patients before the emergence of the omicron variant and the antibodies in Evusheld (tixagevimab and cilgavimab) are differentially affected by omicron mutations in cell-based assays. Tixagevimab loses substantial activity against most omicron subvariants whereas cilgavimab retains some activity. So against omicron subvariants, Evusheld may behave more like a single monoclonal antibody. The clinical impact of this is currently unknown. The FDA did recommend a doubling of the dose for this reason.  

CDC COCA Call to Focus on Therapeutic Options
On Thursday, June 16 from 2:00 - 3:00 pm ET, the CDC Clinician Outreach and Communication Activity (COCA) will host a webinar on treatment options for COVID-19. These are very useful webinars. If you can’t make it, the recording will be available here. The slides for the webinar will be available on the day of the call. Look at the same webpage under Call Materials. The Zoom link for the call is also on the webpage.

Research

Pfizer Issues RFP for COVID-19 Vaccine Hesitancy Research
Projects considered for support will focus on a meta-analysis of current behavioral and social science research of COVID-19 vaccine confidence/hesitancy in groups/subgroups (may be single group or subgroup) who are most at risk due to disparities and social determinants of health, and attitudes on vaccine confidence/hesitancy. Applications due June 27. Find the full RFP here.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,


Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Tuesday, May 31, 2022

Vaccines

Pfizer Reports Promising Efficacy for Vaccine in Those 6 Months to 5 Years
Data is still preliminary and not peer-reviewed, but analysis of the data to date shows that the Pfizer vaccine has 80% efficacy after three doses in children between the ages of 6 months and 5 years. The company hopes to have the complete data submitted this week, and the FDA Advisory Committee (VRBPAC) will meet on June 14 and 15 to discuss that application. It should be noted that these vaccine efficacy data come from exposures during the Omicron surge.
 
Homologous and Heterologous Vaccine Efficacy (VE) During Omicron
Using data from a nationwide pharmacy chain that performed rapid and lab-based nucleic acid amplification tests (NAATS) from 7,036 testing sites across 49 states, Washington, DC, and Puerto Rico from January 2 through March 23, 2022, and had vaccine records, the researchers found that VE against symptomatic infection varied between vaccine types and regimens. VE was measured at 14 days to 1 month after the last dose and 2-4 months after the last dose. For J&J primary only, VE was 17.8% and 8.4% respectively, for J&J primary and booster 27.9% and 29.2%, for J&J primary and mRNA booster 61.3% and 54.3%, and for mRNA primary and booster 68.9% and 62.8%.
 
Myocarditis After Vaccine in 5-11-Year-Olds
Data was presented during the ACIP meeting on boosters for 5-11-year-olds on the occurrence of myocarditis after vaccination. Based on VAERS data, after 18.1 million doses of mRNA vaccines in this age group, there have been 20 cases of myocarditis, for a rate after the second dose of 2.7 per 1 million doses. 17/20 were hospitalized, and 14 had fully recovered by last week. There was one death that is being investigated. The estimated background rate for myocarditis in 5-11-year-olds is 0.2 to 2.2 per million, so the risk after vaccination is only slightly higher. The highest reported rate for this complication is in 16-17 year olds, at 74.2 cases per million doses.
 
More Evidence That Second Doses of mRNA Vaccines Are Safe in Those With Reactions to the First Dose
The allergy group at McGill University in Canada evaluated 44 patients with either a first dose reaction to an mRNA vaccine or a history of allergy to PEG or polysorbate, 40 of which had reacted to the first dose of vaccine. All had skin testing to PEG and polysorbate, and five had positive skin tests. Thirty-nine patients went on to have the second dose, and two had non-severe allergic reactions. Eighteen received a single full dose, 20 underwent a 2-dose regimen and six a more graded approach. A retrospective review was done of patients referred to several military medical center allergy clinics with reports of an immediate hypersensitivity reaction to the first dose of vaccine. Twenty-six patients had skin testing to PEG, polysorbate or the Pfizer vaccine, where one was positive to the vaccine and all others were negative. Twenty-seven of the patients met Brighton criteria for anaphylaxis. Fifty-three underwent vaccine challenge, 89% had no symptoms after the second dose, 11% had recurrence of symptoms, one was given epinephrine for subjective symptoms, two had minor pruritis and urticaria, and three had symptoms of throat closure that turned out to be confirmed laryngeal dysfunction.
 
Reminder for FDA VRBPAC Meeting
The Vaccines and Related Biologic Products Advisory Committee (VRBPAC) will meet on June 7 from 8:30 am to 5:00 pm ET to discuss an EUA for Novavax. Find more information here.
 
Current and Future Vaccine Strategy
This article provides a nice discussion of the development of vaccines for SARS-CoV-2, the limitations of current vaccines, and candidates for future use.
 
Allergists Are the Best Referral for the Vaccine Hesitant
Hong Kong set up a vaccine allergy safety clinic to assess people at increased risk for vaccine-associated allergies at the time they began their vaccination program. They used a “Hub-and-Spoke” model, where the hub was allergist-led and the spokes were non-allergist-led clinics. Using data from the busiest Hub-and-Spoke clinic, of 2,725 patients, 85.3% were recommended to proceed with vaccination, with allergists recommending almost 22 times as many as non-allergists. Among those in whom vaccination was recommended, 4 times as many patients who were recommended by allergist received their first dose.

Infection

Post-COVID Conditions (PCC, Long COVID or PASC)
EHR data from March 2020-November 2021 were used to assess the incidence of 26 conditions often attributable to post-COVID in adults who had received a previous COVID-19 diagnosis, compared to matched controls who were not infected. Patients were followed for 30-365 days. Thirty-eight percent of patients experienced an incident condition compared to 16% of controls. Conditions affected multiple systems, and included cardiovascular, pulmonary, hematologic, renal, endocrine, GI, musculoskeletal, neurologic and psychiatric signs and symptoms. Incident conditions were more common in those >65 compared to controls. The highest risk ratios were for acute pulmonary embolism (2.2) and respiratory signs and symptoms (2.1). These findings translate to one in five COVID-19 survivors aged 18–64 years, and one in four survivors aged 65 years and older experiencing an incident condition that might be attributable to previous COVID-19. Baseline findings from an evaluation of 104 patients with symptoms consistent with post-COVID conditions noted an absence of physical findings and laboratory results compared to a control group, without evidence of persistent viral infection, autoimmunity or abnormal immune activation. Data from the U.S. Department of Veteran’s Affairs national healthcare database found that people with breakthrough infections after vaccination were 15% less likely to develop post-acute sequelae, indicating only partial protection from vaccination before infection. A prospective cohort study on cardio-renal post-acute sequelae found: “Compared to controls (n = 29), at 28–60 days post-discharge, people with COVID-19 (n = 159; mean age, 55 years; 43% female) had persisting evidence of cardio-renal involvement and hemostasis pathway activation. The adjudicated likelihood of myocarditis was ‘very likely’ in 21 (13%) patients, ‘probable’ in 65 (41%) patients, ‘unlikely’ in 56 (35%) patients and ‘not present’ in 17 (11%) patients. At 28–60 days post-discharge, COVID-19 was associated with worse health-related quality of life (EQ-5D-5L score 0.77 (0.23) versus 0.87 (0.20)), anxiety and depression (PHQ-4 total score 3.59 (3.71) versus 1.28 (2.67)) and aerobic exercise capacity reflected by predicted maximal oxygen utilization (20.0 (7.6) versus 29.5 (8.0) ml/kg/min) (all P < 0.01)”.
 
NHLBI Offers Free Workshop on Sex/Gender-Specific COVID-19 Outcomes and Management
A virtual NIH workshop, hosted by NHLBI, will be held on June 16-17 from 11:00 am to 5:30 pm ET.  This workshop brings together basic and clinical scientists to review the state of the science in sex/gender differences in COVID-19 outcomes relevant to heart, lung, blood, and sleep (HLBS) disorders. Specifically, the workshop aims to identify key knowledge gaps and explore research opportunities to improve our understanding of these differences in COVID-19 outcomes.

Treatment

COVID-19 Rebound After Paxlovid Treatment
The CDC issued a Health Alert Network (HAN) Health Advisory on May 24 on the potential for recurrence of COVID-19 or “COVID-19 rebound” following treatment with Paxlovid. This has been reported to occur between 2 and 8 days after initial recovery and is characterized by a recurrence of COVID-19 symptoms or a new positive viral test after having tested negative. According to the CDC, “A brief return of symptoms may be part of the natural history of SARS-CoV-2 (the virus that causes COVID-19) infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status. Limited information currently available from case reports suggests that persons treated with Paxlovid who experience COVID-19 rebound have had mild illness; there are no reports of severe disease. There is currently no evidence that additional treatment is needed with Paxlovid or other anti-SARS-CoV-2 therapies in cases where COVID-19 rebound is suspected.” Isolation precautions should be utilized with recurrence of symptoms or a positive test. “Paxlovid continues to be recommended for early-stage treatment of mild to moderate COVID-19 among persons at high risk for progression to severe disease.”
 
FDA Updates Consumer Website for COVID-19 Treatments
Allergists can refer their patients to this website for details on FDA-authorized treatments for COVID-19.
 
Administration Test-to-Treat Program for Paxlovid Begins Rollout
The White House announced this past week that the first site will open in a clinic in Providence, Rhode Island where the federal government will reimburse the clinic for the test and the cost of Paxlovid. Next up are some of Minnesota’s state-run testing sites which will be converted to test-to-treat locations over the coming days, as well as sites in New York and Illinois.
 
FDA Updates EUA for EVUSHELD
The FDA revised the EUA, and subsequently the prescriber information sheet, to note that the product contains polysorbate 80 and may cross react with COVID-19 vaccines. They are recommending referral to an allergist/immunologist for patients with a history of a severe allergic reaction to a COVID-19 vaccine. They are also recommending that EVUSHELD be administered in a setting where treatment of anaphylaxis is immediately available and that patients be observed for one hour after administration. As a reminder, polysorbate 80 is present in the J&J vaccine, but not in the two mRNA vaccines. The mRNA vaccines contain PEG, which may cross-react with polysorbate 80. Most studies to date suggest that anaphylactic reactions to COVID-19 mRNA vaccines are not IgE mediated.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, May 23, 2022

HHS Announces Extension of the Public Health Emergency (PHE)
The administration promised that it would announce its intention to extend or end the PHE 60 days before the expiration date. The current expiration date is mid-July. On May 16, they announced that the plan is to extend it past mid-July. Since the declaration is usually for 90 days, the anticipated extension should last until mid-October.

Infection

COVID-19 Mortality and Its Impacts
The COVID death toll in the United States surpassed 1,000,000 two weeks ago. COVID-19 was the third leading cause of death in the United States in 2021, behind heart disease and cancer. An analysis by the National Academy of Sciences estimated that 9,000,000 family members may be grieving the loss of a loved one killed by the virus. More than 241,000 children lost a parent or caregiver. Many racial and ethnic minority groups, older adults, people with disabilities and people living in rural areas have been disproportionately impacted.
 
Risk of Serious COVID-19 Outcomes in Asthmatics
As noted in several previous messages, there have been multiple publications on COVID-19 and asthma, with the overwhelming majority showing that asthma patients are not at increased risk for severe disease. Notable exceptions have been reported from the UK, particularly Scotland, but the reasons behind the differences are not clear. This “urgent analysis” was undertaken to inform the UK health authorities on which patients with asthma should be given priority for booster vaccination. The national incident cohort study was done in all adults in Scotland aged 18 years and older who were included in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). They used data from EAVE II to investigate the risk of COVID-19 hospitalization and the composite outcome of intensive care unit (ICU) admission or death from COVID-19 among adults with asthma. The study found that adults with asthma were about 25% more likely to be hospitalized than those without asthma. This increased up to 54% in those with a prior history of oral corticosteroid use in the preceding 2 years. The risk for ICU admission/death was also increased in those with asthma, more so with prior history of oral corticosteroid use.
 
Omicron Infection Induces Limited Immunity
A study performed in mice and humans indicates that Omicron infection in unvaccinated patients produces immunity only to the Omicron variant, but infection in vaccinated humans induces higher neutralization titers against all variants of concern. Limitations are that the abstract (all that is currently available) does not indicate how many humans were studied.

Vaccines

Implications of Adverse Reactions to Vaccines
This review of adverse reactions reported with SARS-CoV-2 vaccines provides an excellent summary and resource for allergists to use in shared decision making. With the variety of vaccines available, there are few, if any, contraindications to vaccination.
 
Graded Vaccine Dosing Appears Equally Immunogenic
There have now been several case reports and systematic reviews noting that most patients with allergic reactions to the first dose of an mRNA vaccine can tolerate a second full dose, although many of the patients underwent a graded challenge. Many patients who are presented with the data concerning the safety of a second full dose still decline that option but may consent to a graded dose. The question has arisen whether such graded dosing is effective. In this small study, patients were administered either Moderna or Pfizer vaccine in a three or four dose graded protocol and had spike protein antibodies measured 6 months after the graded dose. In the six patients studied, titers were greater than a matched health control.
 
Evidence for Waning Immunity in Children
In a test-negative, case-control study conducted from December 2021 to February 2022 during Omicron variant predominance that included 121,952 tests from sites across the United States, estimated vaccine effectiveness against symptomatic infection for children 5 to 11 years of age was 60.1% 2 to 4 weeks after dose two and 28.9% during month 2 after dose two. Among adolescents 12 to 15 years of age, estimated vaccine effectiveness was 59.5% 2 to 4 weeks after dose two and 16.6% during month 2; estimated booster dose effectiveness in adolescents 2 to 6.5 weeks after the booster was 71.1%. This study from New York state demonstrates the results of the waning immunity. In comparing the rates for cases and hospitalizations among over 350,000 unvaccinated and vaccinated children 5-11 years of age and 12-17 years of age, the incidence rate ratio (IRR) (comparing unvaccinated versus vaccinated) for adolescents declined from 6.7 prior to Omicron to 2.0 toward the end of the Omicron surge. For those ages 5-11, the decline was from 3.1 to 1.1. For hospitalizations, the IRR was 1.9 for ages 5-11 at the end of Omicron and 3.7 for teens, reflecting continued protection against severe disease.
 
Booster Doses Remain Effective Against Severe Disease
Using data from March 2022, the CDC notes that adults aged 18 years or older who were unvaccinated were about 5 times more likely to be hospitalized with COVID-19 compared to those who are up to date (boosted). People aged 12 years and older who were unvaccinated were 17 times more likely to die of COVID-19 compared to those up to date.
 
FDA Amends EUA for Pfizer Vaccine Booster Dose for Ages 5-11, CDC Approves
On May 17, the FDA amended the emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine, authorizing the use of a single booster dose for administration to individuals 5 through 11 years of age at least 5 months after completion of a primary series with the Pfizer-BioNTech COVID-19 vaccine. On May 19, the ACIP voted 11-1 to recommend the booster dose.
 
Neutralization of Deltacron and BA.3 Variants
This small study of 10 healthcare workers from Wexner Medical Center at The Ohio State University and 18 patients who had been admitted to the ICU after infection with the Delta variant looked at neutralizing antibody titers (NTAb) in serum using a pseudotyped virus neutralization assay. Two doses of mRNA vaccine showed a slight decline in NTAb activity in BA.3 and a marked reduction against Deltacron, which improved considerably after a booster dose (44.7% less to 13.3% less). Patients who had been admitted to the ICU with Delta had very little neutralizing activity against Deltacron, paralleling that of the BA.1 and BA.2 variants. Takeaway: BA.3 appears to be relatively sensitive to vaccination or previous infection, while Deltacron appears to be much less sensitive to those vaccinated with a primary series only or those with previous Delta infection.

Treatment

NIH Treatment Guidelines Webpage Updated for Paxlovid
The COVID-19 Treatment Guidelines Panel has revised the Ritonavir-Boosted Nirmatrelvir (Paxlovid) section of the COVID-19 Treatment Guidelines. The guidance on identifying and managing drug-drug interactions has moved to a new section of the guidelines, entitled Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications. This section also includes two quick reference lists for clinicians: Box 1 lists examples of commonly prescribed medications that can be safely coadministered with ritonavir-boosted nirmatrelvir. Box 2 lists medications with clinically significant interactions with ritonavir-boosted nirmatrelvir.
 
White House COVID-19 Response Team Concerned About Potential EVUSHELD Underutilization
The AAAAI and other specialty societies met by phone with Dr. Ashish Jha, the White House coronavirus response coordinator, on May 20 and discussed the apparent underutilization of EVUSHELD and barriers to its use. Several participants on the call shared problems with clearing use through hospital systems administration and confusion regarding low spike antibody levels as proof of need. The point was made during discussion that there are no correlates of protection with respect to spike antibody levels, and that EVUSHELD was likely to benefit anyone who has moderate-to-severe immunodeficiency and antibody levels should not be measured as a criteria for use. There was also concern about the impact of underutilization on the development of future innovative treatments and funding for COVID-19 therapeutics.

Testing

FDA Authorizes COVID-19 Test That Also Identifies Flu and RSV
On May 16, the FDA authorized the Labcorp Seasonal Respiratory Virus RT-PCR DTC Test for use without a prescription by individuals with symptoms of respiratory viral infection consistent with COVID-19. This product is the first direct-to-consumer (non-prescription) multi-analyte COVID-19 test authorized by FDA and allows an individual to self-collect a nasal swab sample at home and then send that sample to Labcorp for testing. The test can identify and differentiate multiple respiratory viruses at the same time, detecting influenza A and B, commonly known as the flu, respiratory syncytial virus, commonly known as RSV, along with SARS-CoV-2, the virus that causes COVID-19. Results are delivered through an online portal, with follow-up from a healthcare provider for positive or invalid test results. This home sample collection kit can be purchased online or in a store without a prescription.
 
More Antigen Tests Recalled

Woodside Acquisitions is recalling their TOPIC Oral Rapid SARS-CoV-2 Antigen Rapid Test Kits and Joysbio SARS-CoV-2 Antigen Rapid test Kits (Colloidal Gold), which were distributed to customers in the United States without authorization, clearance or approval by the FDA. The company did not provide the FDA with adequate validation data to show that the performance of these tests is accurate. The AAAAI COVID-19 resources page now has a list of antigen test recalls.
 
More COVID-19 Tests Available for Free
The government recently announced that individuals can apply for an additional eight COVID-19 antigen tests (third round) through COVIDtest.gov.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, May 16, 2022

Vaccine

Moderna Data on Children Ages 6-11 Published
4,016 children were randomly assigned (3:1) to receive two 50mcg doses of mRNA-1273 28 days apart and followed for a median of 82 days past the first dose. Side effects were typical of those in other age groups. No myocarditis, pericarditis or MIS-C were reported. Neutralizing antibody titers were slightly higher than those achieved in young adults. Vaccine efficacy was 88.0% against COVID-19 occurring 14 or more days after the first dose. The study was performed at the time that the Delta variant was predominant. Moderna has completed submission of data for an EUA for three distinct age groups: 12-17-year-olds, 6-11-year-olds, and 6 months-6-year-olds as of May 9. The FDA Advisory Committee will be meeting in June to discuss these applications.
 
So What Is the Novavax Vaccine?
On June 8, the Vaccines and Related Biologic Products Advisory Committee (VRBPAC) will meet to discuss the Novavax application for an EUA for their vaccine (NVX-CoV2373). This vaccine is a recombinant nanoparticle vaccine that contains the full-length spike protein of the prototype strain plus an adjuvant. It is administered as two 5mcg doses 21 days apart. Vaccine efficacy (VE) from a U.K. trial was 86.3% against the Alpha variant and 96.4% against other variants (non-Alpha but not sequenced). Side effects were similar to the other vaccines, although there was one case of myocarditis in the vaccinated group. The study took place before the emergence of the Delta and Omicron variants. A study from South Africa found the VE to be 60% in their trial when the Beta variant was predominant. A trial conducted in the United States and Mexico in the first half of 2021 found a VE of 90.4% against infection, mostly due to the Alpha variant, and 100% against severe disease. Potential advantages of this vaccine: more conventional development, which may assuage those who object to the mRNA vaccines because of their “rapid development”, also the vaccine is stable for 6 months at refrigerator temperatures.
 
Types of Antibody Responses Differ Among Recipients of Different mRNA Vaccines
This small study from the MGH group at Harvard of 73 patients looked at the post-boost binding and functional capacity of humoral immune responses induced by the BNT-162b2 and mRNA-1273 vaccines in a cohort of hospital staff. According to the results, higher concentrations of receptor-binding and N-terminal domain-specific IgA were observed in recipients of mRNA-1273. Antibodies eliciting neutrophil phagocytosis and NK cell activation were also increased after mRNA-1273. Other “real world” studies have noted superior protection from the mRNA-1273 vaccine, which may be related to the higher dose and longer dosing interval. These results may explain why there is a difference. Implications for heterologous dosing remain unknown.
 
But What About T-Cells
An article in Nature Immunology provides evidence that vaccination or infection result in a repertoire of spike-specific CD8+ T-cells, and breakthrough infection leads to an increase in spike-specific response but also induces a non-spike-specific response. The authors state that their data suggest that the T-cell memory repertoire established by SARS-CoV-2 infection or vaccination has great cross-reactivity potential against novel viral variants, and further shows that not all of the viral mutations affecting T-cell epitopes result in immune escape, even from the most public TCR clones. In another study on CD4+ T-cells, the authors showed that a third dose of vaccine resulted in a rapid expansion of spike-specific CD4+ T-cells.
 
B-Cell Number Crucial for Predicting Vaccine Response in MS Patients on Rituximab
This study from Sweden looked at a cohort of 67 patients with MS who were being treated with rituximab and found that the B-cell count was the only factor associated with the serological response to BNT-162b2 vaccination, not the cellular response. These results are consistent with other studies looking at vaccine response in immunosuppressed patients.
 
ACIP Meeting To Be Held May 19 From 11:00 am-4:00 pm ET
The CDC posted the notice of the meeting, but the agenda is not currently available on the website. According to the notice in the Federal Register, the agenda will include discussions on the use of COVID–19 vaccines. A recommendation vote(s) is scheduled. The webcast link to watch the meeting can be found here.
 
Omicron Infection Promotes Delta Immunity in Vaccinated But Not Unvaccinated
This small study on 15 vaccinated and 24 unvaccinated patients who had been infected with Omicron BA.1 found that neutralization titers against Delta and other variants rose significantly after infection in vaccinated patients, but not in those unvaccinated.

Infection

More on Long COVID or Post-COVID Conditions (PCC)
The CDC updated the website page on PCC on May 5. PCC is more likely to occur in those unvaccinated compared to vaccinated (see this study), in those with more severe disease (although asymptomatic patients and those with mild illness can also develop PCC), in females more than males and in older patients. There are a wide range of symptoms, but fatigue, “brain fog”, post-exertional fatigue and breathlessness are common. Some symptoms remain 2 years after infection in 55% of those hospitalized. British researchers have developed a tool to assess symptoms of PCC, which may help evaluate treatment outcomes.
 
Increased Mortality in the Elderly May Be Related to T-Cell Lymphopenia and Inability to Expand T-Cell Clones
According to the authors of this study, severe COVID-19 T-cell lymphopenia is more common among older adults and entails poor prognosis. Offsetting the decline in T-cell count during COVID-19 demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent. Using a model of TL-dependent T-cell clonal expansion capacity with age, an individual with average hematopoietic cell TL (HCTL) at age 20 years maintains maximal T-cell clonal expansion capacity until the sixth decade of life when this capacity rapidly declines by more than 90% over the next 10 years. The collapse in the T-cell clonal expansion capacity coincides with the steep increase in COVID-19 mortality with age.

Testing

More Antigen Test Recalls
Mesa Biotech is recalling the Accula SARS-CoV-2 Test (PCR), which is authorized for use in “point of care” settings, because contamination of certain lots may cause false positive results. Recalled lot numbers can be found here. The FDA also warned people to not use the Skippack Medical Lab SARS-CoV-2 Antigen Rapid Test (Colloidal Gold) because it is not authorized, cleared or approved for distribution or use in the United States. More information can be found here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, May 9, 2022

Vaccine

FDA Limits Use of J&J Vaccine
On May 6, the FDA announced that it has limited the authorized use of the Janssen COVID-19 vaccine to individuals 18 years of age and older for whom other authorized or approved COVID-19 vaccines are not accessible or clinically appropriate, and to individuals 18 years of age and older who elect to receive the Janssen COVID-19 vaccine because they would otherwise not receive a COVID-19 vaccine. This limitation is due to the rare but potentially life-threatening complication of Thrombosis with Thrombocytopenia Syndrome that occurs 1-2 weeks following vaccination.
 
Delayed Local Reaction After Moderna Vaccine May Be Due to Trometamol Sensitization
Localized erythema, induration and pruritis at the injection site that occurs about 8 days after the first shot, 2 days after the second shot and within 24 hours of the third shot was felt to be due to trometamol in the vaccine, based on intradermal skin test response in this small study of seven patients. Interestingly the patch tests were negative to this chemical, and five of the seven tolerated an oral medication containing trometamol after the vaccine reaction. Trometamol is used as an excipient in the pharmaceutical industry and as a pH stabilizer for improving the solubility and stability of various substances (e.g., contrast media, vaccines, eye drops, cosmetics). The Moderna vaccine contains trometamol but Pfizer does not, which may explain the increased incidence of this delayed reaction following Moderna vaccination. Topical steroids are usually effective in the treatment.
 
Allergy Referral Recommended in JAMA Pediatrics Article
This editorial in JAMA Pediatrics recommended an allergist referral for children at risk for a reaction to a COVID-19 vaccine or with a history of an allergic reaction to the first dose. Our members should be aware of this recommendation, and read the succinct description of the current evidence on vaccine reactions and the useful citations to be prepared for questions and referrals.
 
Pfizer Plans to Submit Data on 6 Months to 5-Year-Olds By Late May, Early June
In AP news, Pfizer announced their plans to submit their three-dose trial data to the FDA in late May or early June. The FDA and its advisory bodies have scheduled three meetings in June to decide on Moderna and Pfizer applications. On June 8, 21 and 22, the FDA has held dates for the Vaccines and Related Biologics Products Advisory Committee (VRBPAC) to discuss the Moderna and Pfizer applications for 6 months to 5-year-olds. On June 28, VRBPAC will discuss whether COVID-19 vaccines should be modified, and if so, which strain(s) should be selected for this fall. Once the meeting dates are finalized, the FDA intends to make background materials available to the public, including the meeting agenda and committee roster, no later than two business days before each meeting. On June 7, VRBPAC will meet to discuss an EUA request for the Novavax COVID-19 vaccine (protein subunit plus adjuvant) for those 18 and over.
 
What Is Going to Happen in the Fall?
See this opinion piece by Peter Marks, MD, PHD, et al from the FDA. Hint: regular seasonal vaccination along with the flu vaccine, perhaps with modified (bi-valent) COVID-19 vaccine.

Infection

Long COVID AKA Post-COVID Conditions (PCC), Post-Acute COVID Sequelae (PASC) Pulmonary Symptom Treatments
A prospective observational cohort study on 64 patients admitted to an outpatient pulmonary rehab center noted significant improvements in exercise performance, pulmonary function, diffusion capacity and reduction of dyspnea. The shortcoming of the study was the lack of a control group. In a parallel group, single-blind study from the UK in adults with ongoing breathlessness after COVID-19 infection, participants were randomized to either the English National Opera (ENO) Breathe program (a 6-week online breathing and wellbeing program, developed for people with long COVID experiencing breathlessness, focusing on breathing retraining using singing techniques) or usual care. 150 patients completed the trial which showed that the mental component of the HRQoL and VAS score for breathlessness improved with the ENO treatment.
 
Cognitive Symptoms in Long COVID
The CDC had a COCA Call on May 5 on post-COVID cognitive disorders. Long COVID, as it is generally known by the public and used by the White House, is also known as PCC (CDC and WHO) or PASC (NIH). Cognitive symptoms are some of the most common complaints that persist beyond 4 weeks after COVID-19 infection, or so-called “brain fog.” Patients may complain of memory problems, but that is largely due to attention issues and poor executive function. Why is this important to know? Some of our patients may have trouble with adherence with their medication regimens or have problems with following instructions. Females, older aged patients and patients with co-morbidities are more likely to suffer, and PCC can occur in patients who had mild or asymptomatic infections. Written instructions and setting digital reminders can be helpful. Simplify medication regimens if possible and try to avoid medications that can affect cognition and sleep.
 
WHO Estimate of Global Mortality
New figures from the WHO suggest that 15 million people have died during the first 2 years of the pandemic, about 2.7 times the toll officially reported and in line with other US and UK estimates. The difference is based on the estimates of excess mortality and may include deaths due to other causes but were the result of healthcare disruptions caused by the pandemic.

Testing

Counterfeit At-Home COVID-19 Diagnostic Tests
The FDA has become aware of counterfeit versions of the following tests: Flowflex COVID-19 Test Kits and iHealth COVID-19 Rapid Test Kits. They have a new webpage that provides information on how to check for counterfeits.
 
Antigen Testing Over the Course of Infection
Many people will develop URI symptoms and test once for COVID-19, with negative results, and decide they don’t have COVID-19 so they don’t need to isolate or wear a mask. How true is this and how much does this contribute to the spread of infection? This prospective cohort study involved 225 adults and children with RT-PCR confirmed COVID-19 who performed antigen tests daily for 15 days. Antigen test sensitivity was 64% and 84% compared with same day RT-PCR and viral culture, respectively. Antigen test sensitivity peaked at 4 days after illness onset; a second test 1-2 days later showed improved sensitivity (81-85%). These results may only apply to the Quidel QuickVue antigen test and may not apply to the Omicron variant.
 
Pharmacy Participants in Free Tests for Medicare
This website provides a partial list of pharmacies that are participating in this program. Most of the major pharmacies (CVS, Albertsons, Kroger, Rite Aid, Costco) are part of the group.

Treatment

What You Need to Know About Paxlovid
Supply is no longer limited. There are 789,621 treatment courses available in the US. Common asthma controller medications including corticosteroids and long-acting beta agonists are listed as precautionary medications due to potential for increasing blood levels of these medications while taking Paxlovid. The exception is salmeterol, which is contraindicated with Paxlovid due to cardiac risks. It is important for clinicians to be aware of this listing and also understand how best to communicate with patients and pharmacists who may have concerns. In most situations, the benefit of a short course of Paxlovid for someone with acute SARS-CoV-2 infection will outweigh any potential risk from interactions with inhaled corticosteroids or other long-acting beta agonists. If this potential interaction does manifest as being clinically relevant, then a short-term systemic increase in either class of medication will not likely pose any medical risk and may even have some potential benefit for a patient with asthma who is also experiencing lower respiratory symptoms. It is advised that clinicians be aware of this list of medications and to interpret with appropriate clinical context for each individual patient. The list of drug-drug interactions with this medication is long, and if you are going to treat your patient with this medication, you will need to have an accurate list of all medications they are taking and know how to adjust the doses if needed. Some helpful websites can be found here, here and here.
 
Update on EVUSHELD
This monoclonal antibody, indicated for prophylaxis against COVID-19 in patients with moderate-to-severe immunocompromise, is not being utilized to the extent it should be. Only about 3% of eligible patients have been treated. There is adequate supply (212,092 current doses available). A May 7 update sponsored by the CDC/Infectious Diseases Society of America has some extremely useful information. Also consult the NIH Treatment Guidelines. Useful points for consideration: If your patient is not up to date on vaccinations, vaccinate first, then give EVUSHELD 2 weeks later; if very high community transmission or patient circumstances indicate a high likelihood of exposure, then give EVUSHELD first, and vaccinate 2 weeks later (per EUA); antibody titers are not useful for identifying patients who are candidates, tracking response or course since there are some breakthrough infections that have occurred despite high levels and anti-spike antibodies; a pre-print study from South Africa suggests that EVUSHELD efficacy is much lower with BA.4/5 subvariants. Patients must be observed for one hour after injection for anaphylaxis.
 
Eicosanoid Signalling Blockade – Potential Therapy?
This study found that murine SARS shows age-dependent severity, and elevated levels of PGD2 and phospholipase A2 group 2D (PLA2G2D) contribute to poor outcomes. Elderly mice infected with SARS-CoV-2 show increased production of these eicosanoids. Mice lacking expression of the PGD2 receptor are protected from severe disease. Treatment with an antagonist to the PGD2 receptor, asapiprant, protected aged mice from lethal infection.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, May 2, 2022

Vaccines/Prophylaxis

SARS-CoV-2 Antibody in Commercial Immunoglobulin Preparations
This study of a small number of samples of a particular brand of immunoglobulin preparation found increasing amounts of SARS-CoV-2 antibodies present starting with the lots with expiration dates of July 2023 to those expiring in December 2023. In one lot, the level of antibodies was over 2-fold greater than the SARS-CoV-2 convalescent plasma control.
 
Guillain-barre Syndrome (GBS) After Vaccination
A cohort study of surveillance data from the Vaccine Safety Datalink found that the incidence of GBS after the J&J vaccine was 32.4 per 100,000 doses, which is significantly greater than the background rate, while the incidence after mRNA vaccines was no greater than the background rate.
 
Effect of a Third Dose of MRNA Vaccine on Immunity
A pre-proof, peer-reviewed article to be published in Nature found that the third dose is accompanied by an increase in, and evolution of, anti-receptor binding domain-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared to antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells that differed from the persisting clones in targeting more conserved regions of the RBD. This could explain why boosted individuals have protection against newer variants compared to individuals after two doses. T-cell reactivity is also conserved with variants as noted in earlier messages and this study.
 
Vaccine Numbers
According to data from the CDC, over 100 million people over the age of 12 (45.7% of eligible total) have received the first booster, including 68.5% of those over age 65.
 
New Applications
Moderna is filing a request for an EUA for its low dose vaccine for ages six months to five years. Pfizer has requested an expansion of its EUA to allow for boosters for 5-11 year-olds. The FDA plans to meet in June to discuss the request, and if Pfizer can submit data showing their three dose regimen is effective in children under five, the FDA would prefer to approve both at the same time.

Infection

Seroprevalence Surveys
Data from the CDC’s National Commercial Seroprevalence Study (a repeated national survey that estimates the seroprevalence of infection-induced SARS-CoV-2 antibodies by measuring anti-nucleocapsid antibodies specifically which are not vaccine-induced) for February 2022 showed an overall seroprevalence of 57.7%. When broken down, the data showed 75.2% for children 0-11 years of age, 74.2% for children 12-17 years, 63% for 18-49 years, 49.8% for 50-64 years, and 33.2% for those 65 and older. Combined with the 65+% of fully vaccinated people, you would expect that most of the citizens of the U.S. would be immune. Despite this, infections are again on the rise showing the effect of variants and re-infection. The pre-existing immunity has slowed the rate of hospitalization and death.
 
Vaccination has also been helpful. In this study from Hong Kong, the rate of death in those over age 60 was 20 times greater in those who had not been vaccinated.
 
Support of Patients With Cognitive Symptoms of Long-COVID
The CDC is hosting a COCA (Clinician Outreach and Communication Activity) call on May 5 to review the symptoms of long COVID, also known as PACS and PCC, and specifically the cognitive symptoms, often described by patients as “brain fog”, that are frequently reported following SARS-CoV-2 infection. The American Academy of Physical Medicine and Rehabilitation (AAPM&R) has recently published a Multi-Disciplinary Collaborative Consensus Guidance Statement on the Assessment and Treatment of Cognitive Symptoms in PCC that provides practical guidance to clinicians in the assessment and treatment of individuals with cognitive symptoms and a history consistent with PCC.
 
Rise of BA.4 and BA.5 Subvariants
These subvariants are increasing in the South African population, although hospitalizations and deaths are not rising. There is some concern that a specific mutation, F486V, on the spike protein, might lead to evasion of the immune response. These subvariants have also been noted in several other countries.

Treatment

FDA Approves Remdesivir for Hospitalized Children
This approval only applies for hospitalized children between 28 days of age and 12 years of age.

Paxlovid Availability to Increase
The administration has announced an increase in the number of pharmacies that will carry the drug, an expansion of the test-to-treat pharmacies and the ability for pharmacies to order the medication directly from the manufacturer. Production of the drug remains the rate-limiting step, however.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, April 25, 2022

AAAAI Meets Again With White House COVID Response Team
Representatives from the AAAAI met for a second time with members of the White House COVID Response Team last week. The White House team requested the conversation to discuss physician access to EVUSHELD and second booster doses for immunocompromised patients. Kathleen E. Sullivan, MD, PhD, FAAAAI, Thomas A. Fleisher, MD, FAAAAI, myself and members of the AAAAI staff joined the call to provide an update on the ongoing efforts of our COVID-19 Response Task Force and discussed ways we can continue to update and expand our COVID-19 resources page. These calls provide a valuable opportunity for the AAAAI to showcase the collective expertise of our members and the A/I specialty, and to provide critical input to the White House COVID Response Team. We look forward to continued conversations with the group.

Vaccines

Booster Effective for Children Ages 5-11
Pfizer recently released data from their Phase 2/3 study on vaccine booster effectiveness in 5-11-year-olds. These data have not been peer-reviewed or published. A 10mcg booster dose given 6 months after the second dose increased the level of neutralizing antibodies to the wild-type virus 6-fold compared to the levels 1 month after the second dose in 140 children. In a subset of 30 children, the booster increased the level of neutralizing antibodies against the Omicron variant by 36-fold. The company plans to submit this data for extension of the EUA.
 
Review of Potential Mechanisms for Vaccine Reactions and Proposed Approach
The authors of this article present an excellent review of potential mechanisms for hypersensitivity reactions to mRNA vaccines with suggestions on identifying at-risk patients and approaches to reduce risk.
 
Surveillance of Safety of Three Doses of mRNA Vaccines
This cohort study of electronic health record data for 47,999 individuals receiving three doses of mRNA COVID-19 vaccines found no significant increase in the reporting of severe adverse events (i.e., anaphylaxis, cerebral venous sinus thrombosis, myocarditis, and pericarditis) after the third vaccine dose compared with before vaccination and after prior doses. Significantly increased reporting was found for low-severity adverse events (i.e., fatigue, lymphadenopathy, nausea, and headache).
 
Benefit of Vaccination in Previously Infected People
It has been well established that vaccination after infection provides high levels of protection against hospitalization due to Alpha and Delta variants, but it hasn’t been clear that this is the same case for Omicron. In this study, estimated vaccine effectiveness against reinfection leading to hospitalization during the Omicron-predominant period was approximately 35% after dose 2, and 68% after a booster dose.

Infection

New Omicron Subvariants
In a recent Task Force message, we talked about the recombinant variants of Omicron and Delta, so called XE, XF and XD. Now there are reports of new Omicron variants, BA.2.12 and BA.2.12.1, which contain mutations of BA.2, which first appeared in central New York state and may be responsible for the majority of new cases in that region. According to the CDC, for the week ending April 16, BA.2 made up 74.4% of the variants in the United States while BA.2.12.1 made up 19%. These variants appear to be 23-27% more transmissible than BA.2. BA.2.12 is very similar to BA.2, but BA.2.12.1 has a mutation that has been found on other variants of concern including Delta and has been associated with immune escape. Since these variants are “daughters” of BA.2, vaccines (including boosters) and previous Omicron infection should be as protective as they were for BA.1. In South Africa, two additional subvariants, BA.4 and BA.5, have been reported but so far have not caused a marked increase in cases there.
 
Removal of Mask Mandates on Travel
While there are data on the efficiency of filtration systems on airplanes, this does not apply at all times during travel. Exposure occurs in crowded departure lounges, baggage claim areas, and on the plane while boarding and deplaning, when the air filtration systems are not running. In addition, there are buses, subways, ferries and trains where crowding occurs and there is no efficient air filtration and distancing is not possible. Masking is the only mitigation that is left. While overall transmission in airplanes is low, it is not if you are sitting next to an infected passenger. Remember our immunocompromised patients and those unable to be vaccinated when counseling our patients.
 
Can We Trust Case Counts?
With the increased availability of at-home tests and the milder disease associated with Omicron, more people are testing at home and not reporting the results or not testing at all. It may be more helpful to look at cases and regional wastewater testing. More recent data on wastewater testing shows the largest increase in the Northeast, where the counts are also higher, followed by the Midwest, South and West.
 
Update on Pediatric Hospitalizations
According to this CDC report, nearly 400 children were hospitalized with COVID-19 during the first few months of Omicron. 30% had no underlying conditions, 90% were unvaccinated, and 20% required ICU care. Unvaccinated children were hospitalized with COVID-19 twice as often as vaccinated children.
 
Mechanism of COVID-19 Induced Inflammation
Exuberant inflammatory responses are known to contribute to COVID-19 severity, but the mechanism is not clear. This review suggests that findings from several studies taken together suggest that antibody-mediated SARS-CoV-2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus, but causes systemic inflammation that contributes to COVID-19 pathogenesis. Vaccine recipient plasma does not promote antibody-dependent monocyte infection.
 
Herpes Zoster More Likely to Occur in Older Patients After COVID-19
Using claims databases, these authors found that individuals diagnosed with COVID-19 had a 15% higher herpes zoster (HZ) risk than those without COVID-19 (aIRR, 1.15; 95% CI, 1.07–1.24; p< .001). The increased HZ risk was more pronounced (21%) following COVID-19 hospitalization (aIRR, 1.21; 95% CI, 1.03–1.41; p= .02).

Treatment

Remember Prophylactic Monoclonal Antibody for Patients With Immunosuppression or Inability to Be Vaccinated
This paper presents the primary analysis of the Phase 3 trial for effectiveness of EVUSHELD (AZD7442, tixagevimab plus cilgavimab). The Phase 3 trial was performed in adults with an increased risk of inadequate response to vaccination, or increased risk of exposure, or both, and showed that symptomatic COVID-19 occurred in 0.2% of the treated group (3,441 patients) versus 1.0% in the placebo group (1,731 patients) for a relative risk reduction of 76.7% (95% CI, 46.0-90.0, p<0.001). At 6 months of follow-up, the relative risk reduction was 82.8% (95% CI, 65.8-91.4). There were no cases of severe or critical COVID-19 in the treated group, while there were five cases of severe disease and two deaths in the placebo group. About 1/3 of patients had at least one adverse event, although most were mild or moderate in severity. Members should keep EVUSHELD in mind for patients with immunosuppression, even if you are unsure of vaccine response.
 
Treatment Locator
A reminder that this website will help you identify available treatments, including monoclonal antibodies and anti-virals in your area.

Testing

FDA Grants EUA For COVID-19 Breath Test
The InspectIR COVID-19 Breathalyzer Test detects chemical compounds in breath that are associated with SARS-CoV-2 infection. This test is authorized to be performed in environments where the patient specimen is both collected and analyzed, such as doctor’s offices, hospitals, and mobile testing sites, using an instrument about the size of a piece of carry-on luggage. It is authorized to be performed by a qualified, trained operator under the supervision of a healthcare provider licensed or authorized by state law to prescribe tests and can provide results in less than three minutes, and is for people ages 18 and older with or without symptoms or other epidemiological reasons to suspect COVID-19. Positive tests should be confirmed with a PCR test. Data submitted by the company showed correct identification of 92.1% of positive specimens and 99.3% of negative specimens. Cost of the equipment is not known, but may be a good source for screening patients before in-office procedures. The test is expected to cost the same as a rapid antigen test. For now, this test is usually covered by insurance, but that is likely to change, since home antigen tests are available for free for most people.

Practice

HRSA Announces $1.75 Billion in Provider Relief Funds
On April 13, the Department of Health and Human Services (HHS), through the Health Resources and Services Administration (HRSA), announced more than $1.75 billion in Provider Relief Fund payments to 3,680 providers across the country. With this disbursement, HRSA has distributed approximately $13.5 billion from the Provider Relief Fund to nearly 86,000 and nearly $7.5 billion in American Rescue Plan (ARP) rural payments to more than 44,000 providers since November 2021

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, April 18, 2022

Practice

Guidance from the ADT Interest Section for Office Procedures
A work group report from the AAAAI's Asthma Diagnosis and Treatment (ADT) Interest Section on pulmonary office procedures is now available from JACI: In Practice. This work group report has diligently reviewed all aspects of office, community and patient considerations in approaching such procedures. The report is available online here and a link will also be provided on the AAAAI COVID-19 resources page.

Vaccines

ACIP to Hold Meeting on Boosters for Children
The ACIP will be holding a meeting to discuss COVID-19 boosters in children, with a recommendation vote to be held. The meeting is available to watch virtually here and is scheduled for Wednesday, April 20 from 11:00 am to 4:00 pm ET.
 
Immunogenicity of the mRNA-1273 Vaccines in Patients With Immune Disorders
In this prospective controlled study of over 500 patients with inborn errors of immunity, including CVID, XLA, specific antibody deficiencies, CID and phagocytic defects, COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with CID and CVID. T-cell responses were similar to controls in all IEI cohorts, with the exception of CVID patients.
 
Potential Target for Pan-Sarbecovirus Vaccine
Scientists in China, using sera from patients who had received two or three doses of an inactivated SARS-CoV-2 vaccine isolated human monoclonal antibodies from memory B cells and were able to identify a subset that potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments using these monoclonal antibodies were protective against infection in mice.
 
Vaccination After Multisystem Inflammatory Syndrome in Children (MIS-C) May Be Safe
There has been concern that vaccination of children with previous MIS-C could trigger a recurrence of the hyperinflammation. A study done in Italy and Texas involving 15 adolescent patients who were vaccinated a mean of 180 days after the MIS-C presentation demonstrated tolerance to the vaccination.

Infection

Reinfection Rate in Children Low
A prospective national surveillance study in the UK found that during the Alpha and Delta waves the reinfection rate was 0.18% in children <5-years-old, 0.24% in those 5-11 years, and 0.49% in those 12-16 years compared to a rate of 0.73% in adults. Numbers are likely to be higher during the Omicron surge.
 
Home Monitoring of COVID-19 Patients
This trial involving over 2,000 patients (1,200 with confirmed infection) could find no difference between monitoring pulse oximetry at home versus monitoring for subjective dyspnea.
 
Seroconversion After Mild Infection Possibly Lower in Children
In a small cohort study involving 57 children and 51 adults with mild COVID-19, the proportion of children with seroconversion to SARS-CoV-2 was half that of adults despite a similar viral load. This would imply that serology may provide a less reliable marker of prior infection in children.
 
Administration Announces Strategy to Research and Treat Long COVID
The AMA Morning Rounds for April 6 noted a report in the Washington Post that, under directions from President Biden, "the Department of Health and Human Services will coordinate a government-wide action plan to address long COVID.” Also, the government “will issue a report in 120 days detailing available services and support for those who suffer from long COVID, accelerate efforts to enroll participants in a clinical research study and pursue federal protections for people with the condition.”
 
Asthma Is Not Associated With Severe COVID-19, Is This Why?
Using cultured human airway epithelial cells treated with IL-13 three days prior to infection with SARS-CoV-2, these investigators were able to demonstrate a reduction in viral titers, viral mRNA, cell shedding, number of infected cells, reduced ACE2 expression and cell-to-cell transmission.

Treatment

Overuse of Steroids in Mild-Moderate COVID-19
Early in the pandemic, the RECOVERY trial in the UK found a benefit from the use of dexamethasone in severe COVID-19, but potential harm and lack of benefit in those not requiring oxygen. Since then the NIH Treatment Panel recommended against use in mild-to-moderate disease. This retrospective study of Medicare and large health system databases found that up to 16.4% of patients were given oral steroids as outpatients. The use was highest in the southern states, increased with age and over time. Almost 50% were also given azithromycin, but only 7% of Medicare age patients were given monoclonal antibodies. The use of ivermectin varied between 3.5-3.9%.
 
TMPRSS2 Inhibitor as Potential Therapy
Type-II transmembrane serine proteases (TTSPs) such as TMPRSS2 are important in viral cell entry, cleaving the viral spike protein to expose the fusion peptide for cell entry. This group of researchers from Canada and the United States have identified a small-molecule compound that potently inhibits SARS-CoV-2 infection in human lung cells and was effective prophylactically and therapeutically in mouse models with most variants of concern except omicron. Some variants, such as Omicron, may not be as dependent on TMPRSS2.
 
Fluvoxamine for Outpatient Management of COVID-19
This complicated meta-analysis of three clinical trials showed that there was a “high probability” that fluvoxamine was associated with a reduced risk for hospitalization, in the range of 25%. Fluvoxamine is an SSRI anti-depressant that is inexpensive and widely available and if further trials support these results, may prove to be helpful in resource-limited areas.
 
Ivermectin as Early Treatment for COVID-19
Even though many clinical trials have failed to identify any benefit to the use of ivermectin in COVID-19, including a large trial in Brazil, many proponents point to a meta-analysis published in the American Journal of Therapeutics in June of 2021 that reported benefit. This newer comparison of trials using ivermectin found that those that showed favorable results were all in regions with a high incidence of Strongyloidiasis, whereas studies in regions with low prevalence of this parasite were uniformly negative. The authors point to evidence that Strongyloidiasis itself has an increased risk for mortality in COVID-19 with hyperinfection triggered by steroids used for treatment of COVID-19. Since people in the ivermectin trials essentially received preventive treatment for hyperinfection, whereas those without anti-parasitic infection were not protected, studies would show an apparent beneficial effect of ivermectin on COVID-19.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, April 11, 2022

NEW ONE-STOP SHOP FOR EVERYTHING COVID
The administration just announced the launch of COVID.gov as a source for information on vaccines, tests, treatments, masks, information on local virus spread, guidance on travel rules and restrictions, and a new tool to help locate places to receive immediate antiviral treatments if testing positive.

Vaccines

Vaccine Provided Lower Protection Against Omicron-associated Hospitalization Among Adolescents but Prevented Critical Illness
Using a case-control, test negative design, this study found vaccine effectiveness (VE) against hospitalization and critical COVID-19 in adolescents dropped from 92% during delta to 40% during omicron for hospitalization, 79% against critical disease and 20% against infection. VE against hospitalization in children 5-11 years old was 68%. Booster doses would likely increase this protection.

Neutralization of BA.2 Compared to BA.1
It has been assumed that vaccine effectiveness against BA.2 would mirror that against BA.1. This small NIH-funded study confirmed that neutralizing antibody titers against BA.2 were lower than those against BA.1 by a factor of 1.3-1.4, and a booster dose was necessary to consistently increase and maintain those titers. They also noted that people previously infected by BA.1 had a substantial degree of cross-reactivity immunity against BA.2. This may not be the case with people previously infected by the delta variant.

Vaccine Response in Patients With Predominant Antibody Deficiency (PAD)
A study of 62 patients with PAD due to a variety of causes noted that the levels of antibody to SARS-CoV-2 following a primary series of either J&J, Pfizer or Moderna vaccine was 4-fold lower than healthy controls and less than what is considered most likely protective. Thirty-one patients had an additional dose of mRNA vaccine with a 14-fold increase in titer. Patients with PAD secondary to B-cell depletion therapy, and those with common variable immunodeficiency (CVID) with autoinflammatory complications had the lowest response. Correlates of low response included low CD4+ T-cells, low CD19+ total B-cells and low class-switched memory (CD27+IgD/M) B-cells. In another study of CVID patients, the authors also found similar predictive immune correlates for poor response, but these patients did respond to a third dose.

Fourth Dose of Pfizer Increases Protection, but Effect Wanes
Using the Israeli Ministry of Health database, the authors of this study compared the rate of confirmed infection and severe COVID-19 starting at eight days post receipt of a fourth dose of Pfizer mRNA vaccine with those who had received only three doses and those who had received the fourth dose <8 days earlier (internal control group). The adjusted rate of severe disease in the fourth week after the fourth dose was 3.5-fold lower compared to the three-dose group and 2.3-fold lower than the internal control group. Protection against severe disease did not wane during the six weeks after receipt. The rate of confirmed infection in the four-dose group was 2.0 times lower compared to the 3-dose group and 1.8 times lower than the internal control group. However, the rate of infection in the four-dose group was the same as the three-dose group after eight weeks. The fourth booster was given to patients 60 years of age and older.

Good Summary Article on Vaccine Allergy
This article contains a good evidence-based discussion that includes some history on vaccine reactions, potential mechanisms, and approach to patients with a history of excipient allergy or first dose reactions.

Infection

Will Premature Removal of Non-pharmocologic Interventions (NPIs) Lead to More Disease and Death?
A simulation modeling study, using simulated populations in the 50 U.S. states, Washington DC and Puerto Rico found that with the high transmissibility of current variants, the lifting of NPIs in March of 2022 was associated with resurgences of COVID-19 deaths in nearly every state. Delaying by even one month was estimated to mitigate the amplitude of the surge but for most states no amount of delay was estimated to be sufficient to prevent a surge in deaths completely.
 
UK Reports New Omicron Subvariant Designated XE
There are many news releases commenting on this subvariant, but little scientific information. According to the UK Health Security Agency March 22 technical briefing, this is a recombinant variant. Currently the UK has classified three recombinant variants, XD, XF and XE. XD and XF are a combination of delta and BA.1, XD has an omicron incorporated into the delta genome, has been reported in several European countries but not the UK. XF did cause a small cluster of infections in the UK but has not been seen since February 15. XE, which was first noted in the UK on January 19, is a BA.1/BA.2 recombinant with the majority of the genome including the S gene belonging to BA.2. It has three mutations that are not present in all BA.1 or BA.2 sequences. This subvariant shows evidence of community transmission in the UK but as of this report was <1% of the total sequenced cases, with 637 cases identified. It may be 10% more transmissible than BA.2, but this needs to be confirmed. There is no information on the severity of disease caused by this subvariant. Because of its increased transmissibility, it may surpass BA.2 as the predominant strain.

Treatment

Sotrovimab Authorization Removed For All States
In our prior message we noted that the FDA had pulled authorization for this monoclonal in any state in which BA.2 was predominant. That is now the case in all states, so this removal of authorization affects all states now. The reason for removal of authorization is the lack of efficacy against BA.2, although the company that produces the drug, Vir, is preparing a package of data to support the use of a higher dose. Bebtelovimab, remdesivir and the oral anti-virals remain treatment options.

Testing

Medicare Part B and Medicare Advantage Members Can Get Free COVID-19 Tests
Beginning April 4, patients with Medicare Part B and Medicare Advantage plans can now obtain up to eight free OTC at home COVID-19 tests per month through participating pharmacies and health care providers for the duration of the public health emergency. National pharmacy chains are participating in this initiative, including: Albertsons Companies, Inc., Costco Pharmacy, CVS, Food Lion, Giant Food, The Giant Company, Hannaford Pharmacies, H-E-B Pharmacy, Hy-Vee Pharmacy, Kroger Family of Pharmacies, Rite Aid Corp., Shop & Stop, Walgreens, and Walmart. Providers and suppliers eligible to participate include certain types of pharmacies and other health care providers who are enrolled in Medicare and able to furnish ambulatory health care services such as preventive vaccines, COVID-19 testing, and regular medical visits. A list of eligible pharmacies and other health care providers that have committed publicly to participate in this initiative can be found here. Information for providers is here.

New COVID-19 Test to Treat Initiative and Locator Tool
From CMS: A new federal Test to Treat program gives people a fast and easy way to get lifesaving treatment for COVID-19. In this program, people can get tested at Test to Treat sites. If they test positive and treatments are appropriate for them, they can get a prescription from a healthcare provider and have the prescription filled all in one location. People can also bring test results obtained from a home testing kit to Test to Treat sites and get evaluated by a healthcare provider for treatment. These one-stop Test to Treat sites are available nationwide at hundreds of pharmacy-based clinics and Health Resources and Services Administration (HRSA)-supported federally qualified health centers (FQHCs). In addition, the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS) launched a new COVID-19 Test to Treat Locator. People can use this web-based tool to find Test to Treat sites near them.

Practice

Provider Relief Fund Late Reports
Provider Relief Fund recipients will be able to submit a Request to Report Late Due to Extenuating Circumstances for Reporting Period 1 from Monday, April 11 to Friday, April 22 at 11:59 pm ET. The Request Form will be available starting on Monday, April 11.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, April 4, 2022

Vaccine

Do the Immunocompetent Need a Second Booster?
The short answer is that this has not been determined with certainty. Israel has demonstrated that a second booster in those over 65 reduces infection (two times lower) and hospitalization (four times lower) in this pre-print study, but it has limited effect in younger people. In this U.K. report, vaccine effectiveness (VE) against infection declines to 40% 15+ weeks after a Pfizer booster (60% 10-14 weeks after Moderna), but VE against hospitalization is about 75% for Pfizer after 10-14 weeks (92% 5-9 weeks after Moderna). The same waning has been seen in the United States as reported in an earlier message. VE in those over 65 is more important to track since 69% of severe breakthrough infections occur in this age group according to the Kaiser Family Foundation. VE for hospitalization in those over 65 from the above U.K. report remains over 80% up to 105 days post-booster. Hopefully the allergist can use this information in shared decision making with their patients. The FDA and CDC have authorized a second booster, but are not making that a recommendation at this time.
 
Homologous and Heterologous Booster Doses, Real-World Data
Data from the CDC’s VISION Network showed that VE against COVID-19–associated emergency department/urgent care (ED/UC) visits was 24% after one Jansen dose, 54% after two Jansen doses, and 79% after one Janssen/one mRNA dose, compared to 83% after three mRNA doses. VE for the same strategies against COVID-19–associated hospitalization was 31%, 67%, 78%, and 90% respectively. The study examined 80,287 ED/UC visits and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant. Allergists can use this information to guide booster dose recommendations.
 
Cardiac Complications After COVID-19 Compared to Vaccination
We know that myocarditis and pericarditis are rare complications of mRNA vaccines, particularly after the second dose and more common after the Moderna vaccine. This study using electronic health record data from 40 U.S. healthcare systems during January 1, 2021-January 31, 2022, found that the incidence of cardiac outcomes after mRNA vaccination was highest in the 12–17-year-olds after the second dose, but within this demographic group the risk for cardiac outcomes was 1.8-5.6 times as high after infection.
 
NIH Begins Study on Booster Doses
The NIH announced a new clinical trial to evaluate booster doses of COVID-19 vaccine using currently licensed vaccines and variant-specific vaccines. The study will be conducted at 24 sites around the nation and is enrolling now. For details on sites and participation, please visit clinicaltrials.gov and search identifier NCT05289037.

Infection

CDC Upgrades Isolation and Quarantine Page
The CDC has added a COVID-19 Quarantine and Isolation Calculator to its guidance page, allowing the user to plug in their situation (contact, symptoms, positive test) and determine specific recommendations for their situation.
 
Infection Rates in Europe the United States
Inevitably this will change by the time the message comes to you, but in Europe there are differences by country in infection rates with France increasing, U.K. plateauing, and rates declining in the rest of central Europe. In the United States, BA.2 is now dominant, with some geographic variability, with predictions for case growth by mid-April. There are increasing case rates now in 15 states with New York leading the pack, driven by the younger age groups.
 
Wastewater Surveillance
The CDC added a wastewater surveillance tab to their COVID-19 Tracker page in February which tracks 600 U.S. sites. Rise in viral levels in wastewater usually precedes an increase in cases by 4-6 days. Currently the levels in over half of the sites are declining, although a few are showing a modest uptick. It is too early to tell if this presages an increase in cases across the country, but it is an interesting tool for planning. Another guide to future surges is the percent positive NAAT tests, which is currently at 2.2% nationally, although this may vary by location. Increasing test positivity indicates a future increase in case rates.
 
Herd Immunity – Fuhgetaboutit
In this perspective published in the Journal of Infectious Disease, Anthony Fauci, MD, FAAAAI, and his colleagues write that achieving classical herd immunity against SARS-CoV-2 is unlikely, due to a combination of factors that include features of the virus as well as current societal dynamics. These include the virus’ ability to continually mutate to new variants; asymptomatic virus transmission, which complicates public health control strategies; the inability of prior infection or vaccination to provide durable protection against reinfection; suboptimal vaccination coverage; and adherence to non-pharmacologic interventions.

Treatment

Early Treatment of High-Risk Patients
This multi-center, double-blind, randomized controlled trial treated over 1,000 adult patients with positive tests for SARS-CoV-2 regardless of risk factors with high-titer convalescent plasma within 8 days of the onset of symptoms and found a 54% relative risk reduction for hospitalization (80% if treated in the first 5 days). The study was performed from June 2020 to October 21, 2021, prior to Omicron and in the early stages of Delta predominance. The effect on patients infected with Omicron cannot be predicted, although the authors report a soon-to-be-published study on the effect of plasma on Delta and Omicron. This might be considered an alternative when monoclonal antibodies and antiviral therapies are not available. Use in high-risk ambulatory patients with mild-moderate disease is recommended by the Infectious Diseases Society of America as of February 2022 and an EUA was granted by the FDA for treatment of immunosuppressed patients. Unfortunately, the FDA is withdrawing authorization for sotrovimab in those states in which BA.2 prevalence is >50% because it lacks effectiveness against that variant.

Practice

Uninsured Patients No Longer Covered by HRSA Funding
Funding for COVID-19 testing and treatment has run out for uninsured patients and CMS has stopped processing payments for these services. Until Congress agrees to additional funding, vaccines and treatment may no longer be available for free.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, March 28, 2022

Vaccine

Vaccines and Related Biological Products Advisory Committee to Meet
From the Federal Register: The Food and Drug Administration (FDA) announces a forthcoming public advisory committee meeting of the Vaccines and Related Biological Products Advisory Committee (VRBPAC). This meeting will be held to discuss considerations for use of COVID-19 vaccine booster doses and the process for COVID-19 vaccine strain selection to address current and emerging variants. The meeting will be held virtually on April 6, 2022, from 8:30 am to 5 pm ET. According to Reuters and AMA Morning Rounds, “The FDA 'said no vote was planned at this meeting and there will not be any discussion of any of the COVID vaccine makers’ applications for additional boosters.' The agency’s Vaccines and Related Biological Products Advisory Committee’s discussion will focus particularly on factors that need to be looked at to update the strains that make up the vaccines as well as the timing and populations for booster doses." On the other hand, numerous press reports as yet unconfirmed indicate that the FDA is going to “allow” a second booster for those over age 50, but not recommend it, later this week.
 
Moderna to Submit for EUA for Children
On March 23, Moderna released the results of the KidCOVE Phase 2/3 trial indicating that two 25mcg doses 28 days apart in children 6 months to 6 years resulted in immunogenicity similar to that seen in adults. Side effects were also similar. Vaccine efficacy (VE) during the Omicron surge was similar to adults, 44% in those 6 months to 2 years and 38% in 6 to 12-year-olds against infection. There were no severe infections in any trial participants, so they weren’t able to calculate VE against severe disease. Moderna plans to submit for an EUA for the 6 month to 6-year-old ages and also has additional data on 6 to 11-year-olds and 12 to 17-year-olds for their earlier application.
 
Vaccine Protection During Omicron
There has been a lot of press about breakthrough infections among vaccinated patients during the Omicron surge, but most articles end with the caveat that the vaccines offer good protection against severe disease. This should be the leading point rather than an afterthought based on these studies. In this CDC report, receiving two or three doses of an mRNA vaccine was associated with a 90% reduction in mechanical ventilation or death compared to the unvaccinated during the Omicron surge, and the reduction was 94% in those who had received a booster. In this BMJ article, protection against hospitalization due to Omicron after three doses of mRNA vaccine was similar to protection against the Alpha and Delta variants, and vaccinated patients had less severe disease with all variants. In January 2022, unvaccinated adults and those vaccinated with a primary series, but no booster or additional dose, were 12 and three times as likely to be hospitalized, respectively, as were adults who received booster or additional doses. Hospitalization rates among non-Hispanic Black adults increased more than rates in other racial/ethnic groups, emphasizing the need for increased vaccination rates in that ethnic group.

Infection

More on BA.2
This subvariant is rapidly increasing now in the United States. It has increased from roughly 3% of sequenced samples a few weeks ago to now over 50% in the northeast United States, New York and New Jersey according to the CDC’s COVID Data Tracker. So far there doesn’t appear to be a significant increase in the number of cases, but the case rates in the northeastern states are worth watching. Previous infections from Omicron and up-to-date (all doses including boosters) vaccinations should be protective from severe disease, but increases could be seen in the unvaccinated and immunocompromised. Another predictor of increasing cases has been the test positivity rate. This website from Carnegie Mellon University has been tracking those numbers across the United States.
 
Is It Time to Slow Tracking of SARS-CoV-2?
This editorial from Nature makes a case for continued vigilance.
 
True Mortality From the Pandemic
The reported death toll from COVID-19 worldwide was recently reported as 6,000,000. Using global excess mortality figures and calculations, the Institute of Health Metrics (IHME) in Seattle, Washington states that the actual toll is more like 18,000,000. This is due to a combination of undercounts owing to delayed and incomplete reporting and the lack of data from several countries. It also includes deaths that were not directly caused by COVID-19, but those that resulted from lack of access to adequate care during the pandemic. Some experts are critical of the IHME figures for individual countries, but feel the overall results are reasonable.
 
Asthma Not a Risk for COVID-19 in Children
As noted in previous messages and on our website, there are many studies and systematic reviews that indicate that asthma is not a risk factor for severe COVID-19. This retrospective review to be published in Pediatrics looked at risk for infection among children with asthma. Among children who tested positive for COVID-19 in the Duke medical system from March 2020 to September 2021 in a propensity score-matched cohort of 12,648 children, 706 (5.6%) children tested positive for SARS-CoV-2 infection, including 350 (2.8%) children with asthma and 356 (2.8%) children without asthma [risk ratio: 0.98, 95% confidence interval: 0.85-1.13]. Only one child with asthma was hospitalized over that time period. Interestingly, children with asthma were more likely to be tested for COVID-19 than children without asthma.
 
Hospitalization of Children During the Omicron Surge
Even though Omicron reportedly causes less severe disease, hospitalization of children was five times greater during the Omicron surge than the Delta surge. As was the case with all variants, the 0-6 month age group had the highest hospitalization rate. Is this due to hospitalization “with” COVID-19 rather than “for” COVID-19? Nonetheless, even mild COVID-19 infection may be associated with the development of MIS-C, which is of greater concern and reason to continue to encourage vaccination in children.
 
Long COVID in Children
The incidence has been difficult to estimate for a variety of reasons, with ranges from 1-14% in various studies. It is increased in teens compared to younger children and lower than in adults and increased in females. Symptoms are slightly different, with more digestive complaints and less respiratory complaints, but fatigue is the most common symptom, followed by headache. Breathlessness may be a presentation in adolescent females. The prognosis is good, with 98% of symptoms resolved within 60 days in one U.K. study. Nonetheless, children do show an increase in school absences due to these symptoms. Thanks to Katelyn Jetelina, PhD, at the University of Texas, Austin for gathering this information.
 
Long COVID (PASC) in Adults, Watch Out for Those Offering Diagnostic Tests and Treatment
The NIH has invested in research and clinics are opening at academic centers across the United States, but we still don’t know much about Post-acute Sequelae of COVID-19 (PASC) or Long COVID. The underlying causes are not well defined, there are no markers for the disease and no specific treatment, but scores of researchers are looking. We know that younger females, older males, more severe acute disease and autoimmunity are associated factors. Common symptoms include fatigue, headaches, mental confusion, and breathlessness. The absence of markers and specific treatment has opened the door to private companies to market “diagnostic tests” and “treatments.” This NBC News article mentions one such company. For more conventional care, Long COVID clinics, also called Post-COVID Care Centers, are now present in 48 states and can found by searching this website. Patient support centers can also be found there. This editorial in Annals of Internal Medicine outlines the problems with this condition.
 
Post-COVID Diabetes
In an earlier message, we posted a study summary on diabetes in children following COVID-19. This retrospective study from Lancet looking at VA records found an increase in incident diabetes and use of anti-hyperglycemia drugs in the 12 months post-COVID with increased risk with increased severity of COVID-19. It should be noted that this complication has been seen with other viral diseases.

Testing

More Recalled Antigen Tests
ACON laboratories has recalled Flowflex SARS-C0V-2 Rapid Antigen Test (Self-Testing) because it has not received an EUA from the FDA and has identified the U.S. distribution of unauthorized, adulterated and misbranded counterfeit product having that trade name. ACON does have an EUA for Flowflex COVID-19 Antigen Home Test. Celltrion USA is recalling specific lots of the DiaTrust COVID-19 Ag Rapid Test due to a high number of false positive reports.

Treatment

Pfizer to Begin Pediatric Trials of Paxlovid
News outlets report that Pfizer has started to enroll high-risk children ages 6-17 in a trial to determine the effectiveness of Paxlovid in preventing progression of disease. They expect results by the end of the year. They are also developing a formulation for patients younger than 6 years and will start enrolling this age group in trials once that formulation is ready.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, March 21, 2022

Where Do We Go From Here?
(Most of this information is from news releases and non-peer reviewed literature)

Epidemiology
Cases and deaths are increasing in Europe while wastewater surveillance in the northeast U.S. shows an increase in viral detection. Both have been indicators for predictions of an increase in infections in the United States. Most of the increase has been attributed to the BA.2 subvariant of Omicron, which is causing the majority of new U.K. cases. BA.2 is now the predominant strain in Europe and now 23.1% of sequenced cases in the United States, which has doubled in the last week. This could certainly rise, particularly in the unvaccinated and unboosted population. Another interesting fact is that U.K. hospitalizations and cases are increasing simultaneously, rather than the usual 10-14 day lag. Since BA.2 does not appear to cause more severe disease, this may be due to hospitalization “with” COVID-19 rather than “for” COVID-19. This blog report offers some evidence and good graphics on the topic.
 
Vaccines
While boosters and recent infection continue to protect from severe disease and death from BA.2, they do not have a significant impact on infection and there is evidence that vaccine effectiveness of the booster dose does wane after 4 months. Pfizer/BioNTech have filed for a change in the EUA for their vaccine to allow for a second booster after 4 months in those over 65 years of age based on the experience from Israel where they have been giving a second booster to this population for some time now and have noted a decline in infections in the boosted population. Studies in younger healthcare workers in Israel noted a 9-10 fold increase in antibody titers, but vaccine efficacy was only 30% at best against infection after the fourth dose. Now Moderna has filed for an authorization for a second booster for those over 18 years of age, according to the Washington Post.
 
Preparedness
While there appears to be bipartisan support in Congress for restoring our public health system, funding for SARS-CoV-2 programs is about to expire, and efforts to renew or increase the funding lacks support in the Senate. This could mean the end of free vaccines, testing and treatments as well as research to support new treatments and vaccines. Read more.
 
Test and Treat Program and Antigen Testing Sensitivity
The current administration is proposing a test and treatment program where people who test positive at a pharmacy can be immediately treated with medication for COVID-19. This program would rely on availability of medications, which is currently a problem that could be further impacted by expiration of COVID-19 pandemic funding. It would also rely on antigen testing which has been reported to have lower sensitivity (see below).

Vaccines

Safety in Patients With a History of PEG/Polysorbate Allergy
This study done at UCSF looked at 202 patients with a documented history of PEG/polysorbate allergy, 50 patients referred to their A/I clinic for reported PEG/polysorbate reactions, and 44 patients who had an acute reaction after immunization with mRNA vaccine but no history of PEG/polysorbate reactions. Of the 252 patients in the first two groups, 235 received both doses of an mRNA vaccine, and 3 had mild rashes. Of the 44 with a history of an acute reaction to the first dose, 43 received a second dose, 3 had reactions (one requiring epinephrine), and PEG testing was negative in all three. Take home (again): Most people with a history of PEG/polysorbate reactions can tolerate an mRNA vaccine, and PEG/polysorbate testing is not helpful in predicting tolerance or reaction.
 
Response to a Third Dose of mRNA Vaccine in PID Patients With Functional B Cell Defects
This small study from Stanford looked at a functional antibody assay as a measure of vaccine efficacy and noted an increase from 2% to 94.5% efficacy after a third dose, although this was reduced to 79% in those with more severe B cell defects. Patients with agammaglobulinemia were excluded.

Infections

Immunity From Previous Infection
A study of 816 people who had confirmed COVID-19, unconfirmed COVID-19 and no COVID-19 infection noted that 99% of those with confirmed infection had titers of anti-RBD antibodies >250 U/ml a median of 8.7 months post-infection. 55% of those with unconfirmed COVID-19 infection had such levels of antibodies and only 11% of those with no history of infection. Lesson: Confirmed infection is associated with protection similar to vaccination, but a large proportion of those with unconfirmed infection may not be protected. This does not mean that those with previous infection should not be vaccinated, since Omicron and the subvariant BA.2 show the ability to evade these antibodies.

Treatment

Monoclonal Antibody Effectiveness Against BA.2
As we reported in a previous message, most of the monoclonal antibodies available are not effective against Omicron BA.1 with the exception of sotrovimab. This study shows that BA.2 evades even sotrovimab and only bebtelovimab is effective against BA.2. The FDA has granted an EUA for beptelovimub, but supply is likely still limited.

Testing

Accuracy of Antigen Testing Compared Directly With RT-PCR
In this study of simultaneous RT-PCR testing and antigen testing specifically with Abbott’s BinaxNOW rapid test, the sensitivity was 95.2% when the RT-PCR cycle threshold was <30 (higher viral load). They also compared throat and cheek swabs with nasal swabs and with this test, nasal swabs were clearly more sensitive. This study only used the BinaxNOW antigen test and cannot be generalized to include all antigen tests. In another study using direct comparison with RT-PCR in 170,000 asymptomatic workers in New York between November 2020 and October 2021, 62% of the positive antigen tests were false positives but when the antigen test was repeated within an hour of the first test, a concordant result was associated with a 94% agreement with RT-PCR, but if the second test was negative, the RT-PCR was negative 95% of the time. The overall positive rate for the tests were only 0.35%. Antigen tests from three different manufacturers were used including the Abbott BINAXNow. Bottom line: If the first test is positive, repeat the test within the hour and use the result of the second test to determine positivity.
 
More Antigen Tests Recalled
LUSYS Laboratories COVID-19 Antigen test saliva and nasal swab, and Standard Q COV Antigen test by SD Biosensor have been recalled by the FDA because they were never authorized. Celltrion USA is recalling specific lots of the DiaTrust COVID-19 Ag Rapid Test due to a high number of false positive reports.

Practice

Telehealth Waiver Extended
The Omnibus spending bill just signed by the President contains a proviso that extends the pandemic telehealth waivers for 151 days past the declared end to the pandemic.
 
Reminder: The Provider Relief Fund Reporting Portal for Period 2 Reporting Closes March 31
Access the Reporting Portal here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, March 14, 2022

Vaccines

Kinetics of Vaccine Effectiveness (VE) and Neutralizing Antibodies Against Omicron After Booster Doses
This study from England measured the VE after primary immunization and booster doses following ChAdOx1 (Astra-Zeneca, similar to J&J), BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccination. VE after mRNA boosters regardless of primary series increased into the 60-70% range 2-4 weeks after booster with decline to the 40-64% range after 10 weeks or more (5-9 weeks after Moderna booster). VE was greatest after a Moderna booster regardless of the primary series. The study used a test-negative case-control design and involved 886,774 persons infected with the Omicron variant. In a separate study from Germany, authors followed neutralizing antibody titers in a prospective cohort of patients with an an average age of 82 (n=37) who received BNT162b2 primary and booster vaccination and noted a robust increase in titer with a 3-fold decrease over 3-5 months.
 
Effectiveness of Pediatric Vaccines
The national press has recently been reporting on the lack of effectiveness of the Pfizer vaccine in children, which may have lead to one state’s governor and public health director to advise against vaccines in children. This study from the CDC using a prospective cohort study called PROTECT, involving weekly SARS-CoV-2 testing in 1,364 children ages 5-15 regardless of symptoms from July 2021-February 2022 contradicts those reports. Approximately one half of Omicron infections in unvaccinated children and adolescents were asymptomatic. Two doses of Pfizer-BioNTech COVID-19 vaccine reduced the risk of Omicron infection by 31% among children aged 5–11 years and by 59% among persons aged 12–15 years. While children may have less severe disease, they are just as likely to spread it to others, including those who are immunosuppressed or at high risk for severe disease.
 
NIH Launches Reaction Trial
NIAID is launching a single-site study to help understand allergic reactions to mRNA vaccines. They will enroll 100 people who had an allergic reaction to the first dose of an mRNA vaccine. Study participants will receive a second dose as inpatients. They are only enrolling patients who had a mild or moderate allergic reaction, excluding those who had a severe reaction. The study will take place at the NIH Clinical Center and involves a 4-day inpatient stay. Additional information about the trial is available at ClinicalTrials.gov using the identifier NCT04977479. Hopefully some information on the mechanisms of these reactions will be forthcoming, but we already know that these patients can usually tolerate a second dose. The NIAID is already supporting a multi-center trial on vaccine tolerance in highly allergic patients and those with mast cell disease.

Infection

Possible Mechanism for Loss of Smell
Researchers from NYU and Columbia University, in studies involving SARS-CoV-2 infection in animal models and studies of autopsied humans who had died from COVID-19 and control autopsies, determined that infection causes widespread downregulation of olfactory receptors and their signaling components. This is preceded by a reorganization of the neuronal nuclear architecture that is not due to infection of the cell, but rather a non-cell-autonomous effect that can be triggered by acute phase serum. In a longitudinal U.K. study of brain imaging, the investigators noted greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex.
 
Secondary Household Attack Rates in Norway
In our last message, we reported secondary attack rates for Omicron in the 40-60+% range based on a CDC study, with lower rates depending on vaccination of the index case, isolation and mask wearing. In this study from Norway during the Omicron surge in that country that involved 31,220 households (80,957 non-index persons), the secondary attack rate was 25.1%. It should be noted that 90% of the Norwegian population is fully vaccinated and many have also had boosters. For a comparison, this study looked at household attack rates from April 2020-April 2021 (Alpha, Beta surges) in Tennessee and Wisconsin and noted rates ranging from 36-53% with no difference by age.
 
Masks and Schools
There has been an increase in statements made by policy makers and some healthcare professionals that there is no good evidence that masks work, particularly in schools, but there have been many epidemiologic studies that indicate they do. Now that schools across the country are considering removing mask mandates, here is information that might help in your counseling of patients. This study out of Arkansas in the summer and fall of 2021 compared the incidence of COVID-19 in schools that had universal mask requirements compared to those that did not, and even in schools that changed from no masking to universal masking. Districts with mask requirements had a 23% lower incidence of COVID-19 compared to those without mask requirements. They also noted among districts that switched from no mask requirements to mask requirements had a significant reduction in incidence. Note that this study occurred prior to Omicron, and the vaccination coverage among students and staff ranged from 13.5-18.6%. These results may not apply to other areas with higher vaccination rates. This study, cited by the NIH and published in Pediatrics, noted that schools with mandatory masking during the Delta surge had 72% fewer cases of school transmission when compared to schools with optional or partial masking policies. Most of the cases were acquired from the community, but the point is that masking prevents spread within the school. There is no mention whether schools that required masks also had other mitigation measures compared to those without mandates. This study involved 61 school districts and over 1 million students and staff. Perhaps we need to think about children with immune defects in the same way we think of children with food allergy in schools. Schools ask parents to be thoughtful of children with food allergies, perhaps we should start asking them to be similarly thoughtful about children in class with immune issues.
 
BA.2 Variant
The CDC reports that 100% of the virus sequenced in the United States is now the Omicron variant, but the BA.2 subvariant is increasing, from 6.6% two weeks ago to 11.6% last week.
 
Seroprevalence Studies in Children
This study suggests that seroprevalence studies in children may be underestimating the prevalence of COVID-19 in children. Although a small study, it does pose an interesting question. In this cohort study of 57 children and 51 adults with mild SARS-CoV-2 infection, the proportion of children with seroconversion to SARS-CoV-2 was half that found in adults despite a similar viral load. Does this also suggest they may be more prone to reinfection?

Testing

Rapid Antigen Tests Versus RT-PCR for Screeing School-Aged Children
In this single county study in Florida, 603 asymptomatic quarantined school contacts of students with positive COVID-19 tests were tested by RT-PCR and rapid antigen tests simultaneously on day 5 after exposure. Compared to the RT-PCR tests, the rapid antigen test had a sensitivity of 80% (95% CI, 61.4-92.3%) and specificity of 99.8% (95% CI, 99.0%- 100.0%).

Practice

Congress Passes Bill to Support Mental Health for Health Professionals
The Dr. Lorna Breen Health Care Provider Protection Act is designed to bolster the mental health infrastructure supporting healthcare professionals by establishing: 1) grants to help create evidence-based strategies to reduce burnout and the associated secondary health conditions related to job stress, 2) a national campaign to encourage health professionals to prioritize their mental health and to use available services, 3) grants for employee education and peer-support programming, and 4) identifying and disseminating evidence-based best practices for reducing and preventing suicide and burnout among health professionals, training them in appropriate strategies and promoting their mental and behavioral health and job satisfaction. The bill was named after a young ER doctor who committed suicide after an intense period of caring for COVID-19 patients in a Manhattan hospital.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, March 7, 2022

Infection

CDC Offers New Guidance On Prevention Measures

Vaccination, masking, ventilation and distancing remain key to prevention of the spread of infection, particularly for our patients and members at risk because of underlying conditions. The CDC now offers a tool for predicting what precautions are needed in your county based on number of new cases, number of hospitalizations and hospital utilization in individual counties across the country. This does not apply to healthcare facilities or public transportation and does not change any local mandates.

Biden Administration Plans For COVID-19 Fight

The administration has already extended the FEMA emergency pandemic aid package to states and tribes until July 1, which means testing sites, vaccination sites and other such state costs will be reimbursed at 100%. Now there are plans, subject to additional funding, to establish a test and treat protocol in select pharmacies and clinics where people with positive tests can be treated immediately. Beginning next week, people can order another four free COVID-19 tests to be delivered to their home. In addition, there are plans to expand vaccinations.

What is the Correct Duration of Quarantine?

A retrospective study in four universities involved 3,641 students and staff who were close contacts of confirmed COVID-19 individuals. In this cohort study, of the 301 quarantined university students and staff who tested positive for COVID-19, 40 (13.3%) tested negative and were asymptomatic on day seven, implying an approximate 13% post-quarantine transmission risk for 7-day test-based quarantine. Conclusions: “To maintain the 5% transmission risk used as the basis for the 7-day guideline, our data suggest that quantitative polymerase chain reaction test–based, nonstrict quarantine should be 10 days, 8 days for strict quarantine.” This study was done in late 2020 and early 2021, before Omicron. The onset of infection and duration of infectiousness may be different for Omicron.

In another report, during the Omicron surge, 54% of those infected with COVID-19 still had positive antigen tests between five to nine days after onset of symptoms or a positive test. Negative tests were associated with being vaccinated, previous infection and asymptomatic infection. Testing five to seven days after entering quarantine is important.

Household Transmission With Omicron

CDC partnered with four U.S. jurisdictions to describe Omicron household transmission during November 2021–February 2022. Overall transmission occurred in 67.8% of 183 households. Among 431 household contacts the attack rate (AR) was 52.7%. The AR in households in which the index patient was fully vaccinated was about 10% lower, and 10% higher if unvaccinated. The AR in homes in which the index patient isolated was 41.2% vs. 67.5% when the index patient did not isolate. The AR if a mask was worn was 39.5% vs. 68.9% if no mask was worn by the index patient. Multicomponent COVID-19 prevention strategies, including up-to-date vaccination, isolation of infected persons, and mask use at home, are critical to reducing Omicron transmission in households.

Number of Infected Americans Almost Double Reports

The CDC announced that nationwide seroprevalence surveys using nucleocapsid antibody testing indicate as of January 22 that over 140 million people have been infected with SARS-CoV-2, nearly double the 74 million reported cases. The seroprevalence is highest in the 0-17 year old age group, approaching 60%.

Influenza and SARS-CoV-2 Coinfection Uncommon

In the Influenza- and COVID-19-Associated Hospital Surveillance Networks (called FluSurv-NET and COVID-NET), from October 1, 2021, to February 5, 2022, *2.8% of patients hospitalized with flu also tested positive for SARS-CoV-2. Since October 3, 2021, of the 6,744 influenza positive specimens reported this season by the public health labs that were also tested for SARS-CoV-2, 402 (5.9%) were also positive for SARS-CoV-2. The proportion is published weekly in the FluSurv-NET section of FluView (CDC) - Frequently Asked Influenza (Flu) Questions: 2021-2022 Season.

Characteristics of Asthma and More Severe COVID-19

While most studies have not indicated an increased risk of severe COVID-19 in patients with asthma, this retrospective study from Spain on 201 asthmatics with confirmed COVID-19 infection noted that those with T2 high asthma were less likely to be admitted, and those with poor control or AERD had a higher risk for hospitalization.

Vaccines

ACIP Revises Vaccine Recommendations

On a recent webinar, the Advisory Committee on Immunization Practices (ACIP) revised their recommendations based on data that immune response is increased and myocarditis risk is reduced with a longer interval between the first and second doses. The new recommendation is that for some people ages 12-64 years of age and particularly for males 12-39 years old (peak age for myocarditis risk) they may benefit from getting their second mRNA dose eight weeks after the first dose. The three or four week interval is still recommended for those who are at higher risk for a poor response to the first dose, for adults 65 years and older, in areas with rapid need for protection (high levels of community transmission), and in children 5-11 years old.

New York Issues Report on Effectiveness (VE) of Pfizer Vaccine in Children

The New York State Department of Health this week released an analysis of their data on the effectiveness of the Pfizer vaccine in 5-11 year-old children during the Omicron surge. This data analysis has not been peer-reviewed but we are showing this summary because it is being widely reported. According to this analysis, from December 13, 2021, to January 30, 2022, among 852,384 fully-vaccinated children 12-17 years and 365,502 children 5 -11 years, VE against cases declined from 66% (95% CI: 64%, 67%) to 51% (95% CI: 48%, 54%) for those 12-17 years and from 68% (95% CI: 63%, 72%) to 12% (95% CI: 6%, 16%) for those 5-11 years. During the January 24-30 week, VE for children 11 years was 11% (95%CI -3%, 23%) and for those age 12 was 67% (95% CI: 62%, 71%). VE against hospitalization declined from 85% (95% CI: 63%, 95%) to 73% (95% CI: 53%, 87%) for children 12-17 years, and from 100% (95% CI: -189%, 100%) to 48% (95% CI: -12%, 75%) for those 5-11 years. The marked difference between 11 and 12 year-olds suggest that this may be due to the dose in 5-11 year-olds. The wide confidence intervals for the 5-11 year old group with respect to hospitalization limits interpretation (very few were hospitalized). It is important to note that protection against severe disease was much better. Find the abstract here. This study is also discussed on the CDC website.  

Risk of Second Allergic Reaction

This systematic review and meta-analysis of 22 studies involving 1,366 patients with a prior history of an immediate reaction to the first dose who were revaccinated under the supervision of an allergist demonstrated a low incidence (6/1,366) (0.16%) of immediate severe allergic reactions (anaphylaxis) associated with receiving a second dose of mRNA vaccine. The data show 232/1,366 developed minor symptoms. Of the 78 patients who initially had a severe immediate allergic reaction, six (5%) had a severe immediate allergic reaction after their second dose and 15 (19%) had non-severe symptoms. Graded vaccine dosing, skin testing and premedication did not alter the findings. There were no deaths, 5/6 who had a severe immediate allergic reaction recovered rapidly after IM epinephrine, and the sixth patient did not seek or receive treatment. During a plenary session on anaphylaxis at the 2022 AAAAI Annual Meeting, Kimberly G. Blumenthal, MD, MSc, FAAAAI, presented data from their Mass General/Brigham experience. Risk factors for a severe allergic reaction to vaccine included female sex, younger age and a history of drug allergy. Patients with an allergic reaction to the first vaccine usually tolerated the second dose, suggesting that the original reaction may not have been IgE-mediated.

Testing

FDA Warning on COVID-19 Antigen Tests

The FDA issued warnings about brands of COVID-19 rapid antigen tests that have not been authorized or cleared by the FDA but may be available for sale to U.S. consumers: SD Biosensor STANDARD Q COVID-19 Ag Home Tests, Celltrion DiaTrust COVID-19 Tests and ACON Flowflex COVID-19 Tests.

Treatment

FDA Increases Recommended Dose of Evusheld

Based on evidence that this antibody combination is less effective against Omicron, the FDA announced a change in the Emergency Use Authorization. Previously, the authorized Evusheld dosage was 150 mg of tixagevimab and 150 mg of cilgavimab administered as two separate consecutive intramuscular injections, with repeat doses every six months while SARS-CoV-2 remains in circulation. With this EUA revision, FDA has increased the initial authorized dose to 300 mg of tixagevimab and 300 mg of cilgavimab. Patients who have already received the previously authorized dose (150 mg of tixagevimab and 150 mg of cilgavimab) should receive an additional dose of 150 mg of tixagevimab and 150 mg of cilgavimab as soon as possible to raise their monoclonal antibody levels to those expected for patients receiving the higher dose. A New York Times article on March 6 noted confusion on availability. Want to know where to find it in your state? Check here.

Practice

MIPS Waiver Application Deadline Extended

Practices now have until March 31 to apply for an extreme and uncontrollable circumstance waiver for 2021 quality payment data.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, February 21, 2022

Vaccines/Immunity

FDA Advisory Panel (VRBPAC) Postpones Meeting on Vaccine for Ages 6 Months to 4 Years
This meeting was scheduled for last week. The agency said it wanted to wait until the data on the third dose of the Pfizer vaccine is available, which is due in April.

Waning of mRNA Vaccine Effectiveness After Boosters
Data from the CDC's VISION Network, which includes 10 states, showed that vaccine effectiveness (VE) against COVID-19–associated emergency department/urgent care (ED/UC) visits and hospitalizations was higher after the third dose than after the second dose but waned with time since vaccination. During the Omicron-predominant period, VE against COVID-19–associated ED/UC visits and hospitalizations was 87% and 91%, respectively, during the 2 months after a third dose and decreased to 66% and 78% by the fourth month after a third dose. In another study from the CDC, investigators found that the waning of VE was more related to time since vaccination compared to variant-specific differences.

Protection Against Reinfection Increased With Vaccination
Previous studies on the increased immune response in those vaccinated after infection have been in smaller cohorts and relied on biological information such as neutralizing antibody response. This large study from Israel looked at reinfection rates in groups that had been infected and recovered but not vaccinated versus those who had been infected, recovered and then given one dose of Pfizer mRNA vaccine at least 90 days later (the protocol in Israel at the time). Using an interesting retrospective observational electronic health record study and “emulating” randomized clinical trials with the data, the study estimated the hazard ratio for reinfection in recovered and vaccinated individuals was 0.18 (95% CI 0.15-0.20) compared to those who had recovered but not vaccinated, an 82% reduction in risk. The study involved over 1 million individuals. It is important to note that the study took place prior to Omicron in Israel, and it did not involve regular screening of patients (so it likely underestimated the reinfection rate), but they only had 10 patients in the entire cohort that were hospitalized, so infection even without vaccination was very protective.

Protection After Breakthrough Infection
Multiple studies have documented the elevated levels of immune response after vaccination in those who had a prior infection, but what about those who were infected after vaccination. This small study looked at 104 patients who had been vaccinated after infection, before infection and vaccinated but uninfected and found that human immune serum following breakthrough infection and vaccination following natural infection broadly neutralize SARS-CoV-2 variants to a similar degree, and, in contrast with those who had been vaccinated but not infected, no correlation was found with age. Vaccination before or after SARS-CoV-2 infection leads to robust humoral response and antibodies that effectively neutralize variants. Another study showed similar results and also showed that boosted individuals had similar levels of serum-neutralizing activity compared to those vaccinated after infection.

Vaccines and Post-Acute COVID-19 Sequelae (PACS)
This “rapid evidence briefing” from the U.K. Health Security Agency identified 15 studies that looked at the effects of vaccination on prevention or amelioration of PACS. It found that vaccination before infection reduced the likelihood of PACS following infection and vaccination among people with PACS reduced symptoms in the majority of patients, but some did get worse.

Update on Adverse Reactions to Vaccines
The CDC reviewed adverse events and health impact assessments following receipt of a booster dose among persons aged 18 years and older during September 22-February 6, 2022, that were reported to v-safe. Among 721,562 v-safe registrants aged18 years and older who reported receiving a booster, 88.8% received homologous COVID-19 mRNA vaccination. Among registrants who reported a homologous COVID-19 mRNA booster dose, systemic reactions (including fever, fatigue) were less frequent following the booster (58.4% [Pfizer-BioNTech] and 64.4% [Moderna], respectively) than were those following dose two (66.7% and 78.4%, respectively).

Vaccines and Immune Response

This article presents an informal but well referenced viewpoint on immune responses to infection and vaccination.

More on Natural Immunity
A retrospective cohort study including 325,157 patients in the United States found that previous infection was associated with 85.4% protection against reinfection during the Delta surge (88.2% against symptomatic infection, 66.6% against asymptomatic infection) and that this protection lasted up to 13 months. Patients over 65 had slightly less protection. This study did not cover the Omicron predominant period. A recent study in Qatar, published as a letter to the editor in NEJM, that used a test-negative case-control study design in over 16,000 unvaccinated individuals, found that the effectiveness of previous infection in preventing reinfection was estimated to be 90.2% against the Alpha variant, 85.7% against the Beta variant, 92% against the Delta variant and 56% against the Omicron variant. The effectiveness against severe, critical disease (there were no fatalities) was estimated to be 69.4% against the Alpha variant, 88% against the Beta variant, 100% against the Delta variant, and 87.8% against the Omicron variant.

Infection

COVID-19 Infection in Children
Vaccines are not approved yet for children younger than 5 years old. The percentage of children 5-11 who have gotten the vaccine is low. Many parents, and some doctors feel that the severity of infection in children is low enough that the potential risks of the vaccine are greater. This article presents data on the characteristics, outcomes and severity risk factors associated with COVID-19 in children using data from a large collaborative that includes 56 sites. It also compares pre-Delta and Delta surges, but was completed prior to the Omicron surge. Among 167,262 children with positive tests for SARS-CoV-2 (15.6% of the 1,068,410 children tested in the database), 10,425 (6.1%) were hospitalized. Of those hospitalized, 13.9% met the criteria for severe disease and 1.3% died. Male sex, Black/African American race, obesity and several pediatric complex chronic condition (PCCC) subcategories were predictive of peak disease severity. The study also looked specifically at asthma as a predictor, which was not predictive of severe disease. Comparing children from the Delta versus pre-Delta eras, there was no significant change in hospitalization rate and lower odds for severe disease. In comparison between the Delta predominance (July 1-December 18, 2021) and the Omicron predominance (December 18, 2021-January 22, 2022), hospitalizations during the Omicron peak were four times that during the Delta peak with the largest increase among children 0-4 years (five times as high). During December, the hospitalization rate among unvaccinated adolescents was six times that of fully vaccinated. Peak ICU admissions were 1.4 times higher during the Omicron peak, but were lower overall during the Omicron predominant period. COVID-19 was the reason for admission in 81.6% of the patients in the subgroup with complete clinical data. Take-home: Omicron may be less severe than Delta, but not mild and seems to cause more moderate disease than Delta as reflected in the higher hospitalization rates but lower ICU rates.

Is Omicron Really Less Severe?
Initial data out of South Africa indicated that Omicron was less severe than Delta, which was also supported by data from England. Generalizing data from different countries with different population ages, extent of vaccination and previous infection can be confusing. This study from Ontario, Canada may be more applicable to the United States. They identified 9,087 Omicron cases, which were matched 1:1 with Delta cases. The median follow-up time was 24 days (IQR, 21.0-28.0). There were 53 hospitalizations (0.6%) and three deaths (0.03%) among matched Omicron cases compared with 129 hospitalizations (1.4%) and 26 deaths (0.3%) among matched Delta cases. The HR for hospitalization or death among Omicron cases compared with Delta cases was 0.41 (95% CI, 0.30-0.55; 0.33 [95% CI, 0.19-0.56] in sensitivity analysis), while the HR for intensive care unit admission or death was 0.19 (95% CI, 0.09-0.39), and the HR for death was 0.12 (95% CI, 0.04-0.37). Stratified estimates of Omicron severity by age, sex, and vaccination status all indicated reduced Omicron severity.

Post-Acute COVID-19 Sequelae (PACS)
A retrospective cohort study using the UnitedHealth Group Clinical Research Database looked at the risk of persistent and new clinical sequelae in adults age 65 years and older after acute COVID-19 infection. The study involved 87,337 patients diagnosed with COVID-19, matched to three comparison groups who did not have COVID-19. 32% of those who were infected sought medical care 30 or more days after the acute infection for persistent or new problems. Adjusting for problems associated with viral lower respiratory infections in this age, the most common problem was respiratory failure (risk difference 2.39, 95% CI 1.79-2.94), followed by dementia, and fatigue. In another study, 153,760 U.S. veterans who survived COVID-19 and were followed for 12 months showed an increased risk of several categories of incident cardiovascular disease compared to two cohorts of uninfected veterans. These included cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis/myocarditis, heart failure and thromboembolic disease. The allergist should be aware of these conditions in older patients presenting with dyspnea after recovering from acute COVID-19.

Treatment

FDA Authorizes New Monoclonal Antibody That Retains Activity Against Omicron 
The FDA has granted an EUA for Eli Lilly’s betelovimab for the treatment of mild-moderate COVID-19 in adults and pediatric patients (12 years and older and weighing at least 40kg) who are at high risk for progression to severe COVID-19 and for whom other treatment options approved or authorized by the FDA are not accessible or clinically appropriate. This treatment joins Paxlovid, sotrovimab, remdesivir and molnupiravir as treatments for mild-to-moderate COVID-19.

Feedback Requested

We would like to hear from our members. Is there any topic we haven’t covered? Do you have any recommended articles for us to review and summarize? Write to us at practicematters@aaaai.org.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, February 14, 2022

A Somber Milestone
This is message #100 since the start of the COVID-19 Response Task Force. It all began on March 24, 2020, with this message:

Message #1
Hi! We are the AAAAI COVID-19 Response Task Force. Our members are:

  • Paul V. Williams, MD, FAAAAI, Chair (Chair of Advocacy Committee, member of the Office of Practice Management, member of the Executive Committee and Board)
  • Andrew W. Murphy, MD, FAAAAI (Chair of the Office of Practice Management)
  • Sharon B. Markovics, MD, FAAAAI (Vice Chair of the Office of Practice Management, Board member)
  • James H. Sussman, DO, FAAAAI (Chair of the RSL Assembly, member of the Office of Practice Management)
  • Priya J. Bansal, MD, FAAAAI (Chair of the Practice Management Committee)
  • Frank S. Virant, MD, FAAAAI (Board member)
  • Mitchell H. Grayson, MD, FAAAAI (scientific guidance, academic institution representative)
  • David R. Stukus, MD, FAAAAI (Social Media Medical Editor)
  • Thomas A. Fleisher, MD, FAAAAI (Executive Vice President) – Ex Officio
  • Mary Beth Fasano, MD, MSPH, FAAAAI (President) – Ex Officio
  • Rebecca Brandt, CAE – Staff Liaison

Our charge:

  • Monitor the impact of COVID-19 on the practicing allergist/immunologist, academic divisions of allergy/immunology and fellows-in-training
  • Serve as a rapid response team to address and communicate urgent issues related to the practice of allergy/immunology in the context of the pandemic
  • Develop and disseminate information and resources critical to the practice of A/I in the face of the pandemic and its aftermath
  • Work with Hart Health Strategies to assure the voice of the A/I community is heard at the state and federal level to address issues related to expanding coverage for telehealth services nationwide, home infusion services, potential risk for shortages of critical medications/supplies, financial impact of the pandemic on practices, etc.

Expect to see messages from us on a regular basis in the next several weeks with information and resources for you. Questions can be sent to practicematters@aaaai.org.

Since that time we have added Karen Gregory, DNP, APRN-BC, RRT, AE-C, as an allied health member to the Task Force. As chair, I spend about two hours each day scanning the literature, news, and suggestions from other members of the Task Force as well as AAAAI staff to put together summaries that we think are important for allergists concerning COVID-19. Once the summary is complete, the Task Force reviews it and staff puts it in its final form to be emailed to members. Along with messaging, the Task Force has answered questions from members and helped guide the content of the AAAAI COVID-19 resources website. The staff has been invaluable in this process, and I must give a special shout-out to Megan Brown, who puts this all together, Lauri Sweetman and Laura Bzdawka-Plizka, who help keep the webpage current and fresh, Sheila Heitzig, for making important connections to share our resources, Lori Holly, who has helped craft special messages, and, of course, Becky Brandt who keeps us all in line.

We never thought this Task Force would still be working almost 2 years after it started. Leadership has offered to sunset the Task Force but our job is not done, and we have all become attached to it. However, we keep thinking it will end soon! We have learned so much about COVID-19 from doing this, and it has also been extremely rewarding to hear positive responses from AAAAI members. This keeps us going when we get frustrated at times with the low vaccination numbers and the effect on our healthcare system. Open rates, metrics that measure the percentage rate at which emails are opened, have ranged from the high 30s to low 50s. These numbers are much higher than average open rates and are a testament to their value to membership. In light of the continuing concerns with COVID-19, we want to remind everyone of the precautions being taken for the 2022 AAAAI Annual Meeting that will be coming up at the end of this month. For those attending in person in Phoenix, proof of vaccination is required and masks are to be worn at all times in the venue. For sessions with meals, meals will be provided, but attendees are required to eat before or after the session as masks must be worn during the session.

We hope that you have all found this information helpful. We plan to continue as long as we can be of use to our members, which hopefully won’t be much longer!

Vaccines

Novavax Submits Data to FDA for EUA for Its Vaccine
This is a recombinant nanoparticle protein-based COVID-19 vaccine with adjuvant. This vaccine has been engineered from the genetic sequence of the first strain of SARS-CoV-2 to generate antigen from the spike protein. Phase 2/3 trials involving 25,000 participants are being conducted in the United States and Mexico showing 90.4% efficacy overall. It was also tested in the United Kingdom, with an efficacy of 89.7%. The vaccine was generally well tolerated and was given as two 0.5ml doses 3 weeks apart. This study was conducted in the first half of 2021 so efficacy data may not apply to the Delta or Omicron variants.

More Evidence That Vaccination Saves Lives
This study using analytical models comparing the cases and deaths during the actual vaccine rollout from December 12, 2020, to June 30, 2021, with scenarios of no vaccinations or 50% of the actual vaccinations, estimated that the actual vaccination campaign saved 240,797 lives and prevented 1,133,617 hospitalizations. The number of cases averted was projected to exceed 14 million.

Updated Data on Myocarditis After mRNA Vaccines
Most of what has been reported so far has come from the Vaccine Adverse Events Reporting System (VAERS). This is data reported at the recent ACIP meeting from the Vaccine Safety Datalink (VSD), a partnership between the CDC and nine integrated health systems and another safety monitoring system, which provides real-time links to the electronic health records of patients. This data is through January 15, 2022. Over 2.3 million doses of mRNA vaccine have been delivered to patients ages 18-39 in their health systems. They have verified 79 cases in this age group (80% after the second dose) and note 22.4 excess cases per million doses after Pfizer, and 31.2 per million after Moderna. Most were hospitalized, with a median length of stay of 1 day, and no ICU admits or deaths. It should be noted that there were 134 additional cases outside of this age group that were not presented in the analysis, so the risk only applies to this age group. They also did not break down the data into other age groups. At the same meeting, the Canadians presented their data on vaccine response and myocarditis after prolonged intervals between the first and second dose, and found that serologic responses were greater and the reports of myocarditis were less when the dosing interval was longer. The ACIP discussed but did not decide on a recommendation to increase the dosing interval to 8 weeks. Here is the Canadian presentation.

J&J Temporarily Halts Production of COVID-19 Vaccine
According to several news sources, Johnson & Johnson has temporarily shut down their plant in the Netherlands, the only one currently making usable batches of the vaccine. The plant is expected to start making vaccine again after a few months.

Infection

Continued Evidence for Effectiveness of Mask Wearing Indoors
Mask mandates have been one of the most inflammatory issues during the pandemic, and most people who oppose mask mandates cite personal liberty as the reason for their opposition. This data may not influence their decision, but will reinforce those who do wear masks indoors. This study used a test-negative case-control design enrolling persons who received a positive (case-participants) or negative (control-participants) COVID-19 test during February 18-December 1, selected from all California residents. The findings: Compared to wearing no mask, those consistently wearing a N95/KN95 indoors had 83% lower odds of testing positive, those who wore a surgical mask had 66% lower odds, and those who wore a cloth mask had 56% lower odds (the odds for a cloth mask were not statistically significant). There were 652 case- and 1,176 control-participants enrolled.

More on Post-Acute Sequelae of COVID-19 (PASC)
In this cohort study of 338,024 persons younger than 20 years and 1,790,886 persons 20 years or older who were tested for SARS-CoV-2, new diagnoses of shortness of breath, nonspecific heart rate abnormalities, and type 2 diabetes were more common among those hospitalized after testing positive to SARS-CoV-2 compared to those with negative test results; fatigue was more common among those aged 20 years or older.

Short-Term Increase in Primary Care for Children After COVID
This study from Norway on 700,000 children and adolescents followed for 6 months after COVID-19 showed a 300-400% increase in primary care visits in the first month after infection which declined by 3 months. The most common reason for visits were respiratory complaints.

Immune Response to SARS-CoV-2
The latest issue of Nature Immunology has three review articles on the immune response to SARS-CoV-2 that are worth reading for more in-depth information. Read the articles herehere and here.

Protection Against Omicron From Previous Infection
This study from Qatar using a test-negative, case-control design found the protection from a prior infection on reinfection was 56% for Omicron. The protection against severe disease due to Omicron was 87.8%. The median age across study samples was 31-35 years. This protection is comparable to vaccination.

Treatment

Another Anti-Helminth Treatment Failure
In this small phase 2 study, 73 patients with confirmed mild-to-moderate COVID-19 infections were randomized to niclosamide (an oral anti-helminth with potent in vitro antiviral activity against SARS-CoV-2) or placebo. There was no difference in respiratory viral clearance, viral shedding or duration of symptoms between the groups. This needs to be confirmed with a larger group of patients, but I would anticipate that some groups will seize upon the in vitro effects and promote the drug for treatment. Allergists should be aware of this drug and the results of the study.

Testing

CMS Releases Guidance for Over-the-Counter COVID-19 Testing Requirement
Per AMA News: “CMS released guidance around the over-the-counter coronavirus testing requirement, providing greater clarity regarding what kinds of direct-to-consumer access mechanisms fall under compliance and answering questions related to testing shortages and fraud.” The new “guidance explained that the requirement to provide adequate access to over-the-counter coronavirus tests entails establishing an in-person method of receiving the tests and a direct-to-consumer shipping option.” The agency “also outlined what kinds of tests count as over-the-counter tests eligible for coverage.”

Practice

Funds for Uninsured COVID-19 Care Soon to Run Out
Modern Healthcare reports that the Provider Relief Fund, which pays for COVID-19 uninsured patients, has only $7.6 billion dollars left, which is expected to run out in the coming months. According to the Department of Health and Human Services, Congress is not considering making more funding available.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, February 7, 2022

Here are today's important updates:

Vaccines

Vaccines for Children Under 5-Years-Old
With some urging from the FDA, Pfizer has applied for an EUA for the two-dose regimen for vaccination of children 6 months through 4 years of age, which will be reviewed at the Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting on February 15. The reason behind FDA’s encouragement is that if the vaccine is safe, it can be started now and then when the third dose study is done, a potential change in the EUA could occur. This is good news for the 6 months to 2-year-old group because the two-dose regimen was effective at reducing infection in that age group. It is a bit of a risk for the 2-5-year-old group, however, if the third dose does not improve the effectiveness and they may have received two doses of an ineffective regimen. Information on the VRBPAC meeting can be found here.
 
CDC to Revise Guidelines on Immunocompromised
The CDC plans to or has already revised the vaccination schedule for immunocompromised people after the ACIP meeting on February 4. Current schedule for mRNA vaccines is a three-dose primary series with the third dose at least 28 days after the second dose and a booster dose 5 months later. For J&J, a booster dose 2 months after the first dose. Revised guidance: The booster interval for mRNA vaccines will now be 3 months after the third dose in the primary series (rather than 5 months). For J&J, an additional dose can be given at least 28 days after the first dose and a booster dose given at least 2 months after the second dose. So now three doses for J&J. Additional guidance for certain subgroups: Recipients of HCT, CAR-T-cell or other B-cell depleting therapies who received doses of COVID-19 vaccine prior to or during treatment should be revaccinated for doses received before or during treatment. Based on clinical judgement, revaccination may also be considered once immune competence is regained for people who received COVID-19 vaccine doses during chemotherapy of radiation treatment. On a case-by-case basis, providers who care for moderately or severely immunocompromised patients may administer mRNA vaccines outside of the FDA and CDC dosing intervals based on clinical judgment when the benefits of vaccination are deemed to outweigh the potential and unknown risks.
 
CDC to Revise Vaccine Guidelines for Patients Who Have Received Passive Antibody Products
Following the ACIP meeting on February 4, the CDC also plans to revise (or has already revised) guidance on vaccination schedules for people who have received passive antibody products. Current guidance was to defer vaccination for 30 days if the product was used for post-exposure prophylaxis or 90 days if the product was used for treatment, and no guidance if product was used for pre-exposure prophylaxis. Revised guidance: No recommended deferral period except for EVUSHELD, which should be deferred for at least 2 weeks after vaccination. The rationale for this change is based on studies of nursing home residents and staff showing a robust immune response to mRNA vaccine in recipients of bamlanivimab and no correlation between interval to COVID-19 vaccination and neutralizing titers in recent monoclonal antibody recipients. Getting vaccinated is a priority.
 
Cellular Immunity to Omicron
This study shows that cellular immunity induced by current SARS-CoV-2 vaccines is highly conserved to the SARS-CoV-2 Omicron spike. Individuals who received Ad26.COV2.S or BNT162b2 vaccines demonstrated durable spike-specific CD8+ and CD4+ T cell responses, which showed extensive cross-reactivity against both the Delta and Omicron variants, including in central and effector memory cellular subpopulations. Median Omicron spike-specific CD8+ T cell responses were 82-84% of WA1/2020 spike-specific CD8+ T cell responses. This data was reinforced by another small study in the same journal, where researchers looked at the ability of T cells to react with the Omicron spike in participants who were vaccinated with Ad26.CoV2.S, BNT162b2, or unvaccinated convalescent COVID-19 patients (n=70). They found that 70-80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to Beta and Delta variants, despite Omicron harboring considerably more mutations. In Omicron-infected hospitalized patients (n=19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n=49).
 
Myocarditis After mRNA Vaccines
In this descriptive study of 1,626 cases of myocarditis in a national passive reporting system, the crude reporting rates within 7 days after vaccination exceeded the expected rates across multiple age and sex strata. The rates of myocarditis cases were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). Most of the cases are benign with hospital discharge within 2 days. Two deaths are being investigated by the CDC for a link to myocarditis. A good outline of the problem can be found here.
 
New Ways to Encourage Vaccination Needed
We have all felt the push-back from our patients when we encourage them to get vaccinated or boosted. This study may add to that frustration. In this randomized clinical trial of 133 skilled nursing facilities that included 7,496 residents and 17,963 staff, 81.1% of residents and 53.7% of staff were vaccinated. The 3-month-long campaign leveraged best practices for encouraging vaccination, such as identifying frontline champions and giving small gifts to vaccinated staff. There was no significant difference in resident or staff vaccination in facilities that received the vaccine campaign versus usual care.

Infection

U.S. Death Toll Leads All Comparable Nations
This article in the New York Times presents some concerning data on the U.S. death toll from the COVID-19 pandemic. Since December 1, the number of Americans who have died from COVID-19 is at least 63% higher than several large, comparably wealthy nations. The United States has also now surpassed these same nations in the cumulative death toll since the start of the pandemic. Despite the “less severe” Omicron variant, the death rate has surpassed the Delta peak and is more than two-thirds as high as the record tolls of last winter before the vaccines. The reason: We lag all these countries in percentage of elderly vaccinated and percentage of all eligible who have received a booster.
 
COVID-19 Antibodies Among Unvaccinated U.S. Adults
This cross-sectional study of anti-RBD (receptor-binding domain) and anti-nucleocapsid antibodies against SARS-CoV-2 in 816 unvaccinated adults between September and October of 2021 showed that 99% of those who had a history of confirmed COVID-19, 55% of those who thought they had had COVID-19 but not confirmed,and 11% of those who reported never having COVID-19 had antibodies. The median time from infection in the confirmed group was 8.7 months and there was no evidence of an association between time after infection and antibody titer. Take home message: Assumption of infection is only true half the time, and there isn’t a lot of asymptomatic immunity.

Testing

Need for Education on Use of Home Testing
A randomized clinical trial of 360 adults in the United States found that a substantial proportion misinterpreted the negative results of at-home tests by failing to consider the implications of high pre-test probability of infection and ignoring the CDC self-quarantine recommendations. Allergists should cover the correct approach with their patients or post the recommendations in their office, on their website and in any published materials.
 
Medicare to Cover Costs of COVID-19 Home Tests Starting This Spring
People in either Original Medicare or Medicare Advantage will be able to get over-the-counter COVID-19 tests at no cost starting in early spring. Under the new initiative, Medicare beneficiaries will be able to access up to eight over-the-counter COVID-19 tests per month for free. Tests will be available through eligible pharmacies and other participating entities. This new initiative will enable payment from Medicare directly to participating pharmacies and other participating entities to allow Medicare beneficiaries to pick up tests at no cost.
 
Do Not Use E25Bio COVID-19 Tests – FDA Safety Communication
The FDA is warning people not to use the E25Bio COVID-19 Direct Antigen Rapid Test (DART). This test has not been authorized, cleared, or approved by the FDA for distribution or use in the United States, and it may include false labeling representing that the test is authorized by the FDA. The E25Bio COVID-19 Direct Antigen Rapid Test (DART) may also be sold under the trade name E25Bio SARS-CoV-2 Antigen Test Kit.

Post-Acute COVID-19 Sequelae (PACS)

Review of PACS
This article in Nature Immunology reviews the pathological features of PASC by organ system. The most common manifestations of post-COVID-19 syndrome are systemic (fatigue and poor concentration), neuropsychiatric (sleep abnormalities, chronic headache, ‘brain fog’, defects in memory, mood impairment and pain syndromes), cardiac (palpitations, syncope, dysrhythmias and postural symptoms) and respiratory (dyspnea and cough). Of note to the allergist, pulmonary symptoms including breathlessness and cough are noted in a substantial proportion of patients with long COVID and may or may not correlate with prior COVID-19 severity. Other lung-related manifestations included prolonged oxygen requirement. Persistent radiological abnormalities include ground-glass opacities, signs of reticulation, including course fibrous bands either with or without obvious parenchymal distortion, bronchiectasis and pulmonary fibrosis, and appeared to be related to greater severity of acute COVID-19 syndrome. Abnormal lung function, including a reduction in DLCO, is the most commonly reported physiological impairment after acute COVID-19 and appears to be related to the severity of the acute illness.
 
Predicting PACS
As the number of worldwide cases of COVID-19 continue to mount, PACS is becoming a global health crisis. Identification of risk factors may improve treatment strategies. In an international multi-omic longitudinal investigation of 309 COVID-19 patients followed from diagnosis to convalescence 2-3 months later, these investigators found that the presence of pre-existing Type 2 DM, assessment of SARS-CoV-2 RNAemia, EBV viremia and autoantibodies can help predict PACS and even the subtype of PACS. In another study from Zurich, researchers discovered that an immunoglobulin signature, based on low total IgM and IgG3 levels which, when combined with age, history of asthma bronchiale and having five symptoms (fever, fatigue, cough, dyspnea and GI symptoms) during primary infection was able to predict the development of PACS.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, January 31, 2022

Here are today's important updates:

Vaccines

AAAAI COVID-19 Task Force Members, White House Team, CDC Discuss Need for Boosters for Immunocompromised
Members of the AAAAI COVID-19 Response Task Force met with representatives of the White House COVID Response Team and the CDC via Zoom this morning to discuss ongoing efforts to promote boosters, particularly for patients with moderate or severe immunodeficiency. The discussion underscored the importance of the need for allergists to open the conversation with their patients.  Those with moderate or severe immunodeficiency should receive an additional primary shot (third dose) if they received an mRNA vaccine as their initial series and a booster (fourth dose) 5 months after the additional primary shot (only Pfizer for 12-17-year-olds). If the patient received the J&J vaccine as their primary shot, no additional primary shot is recommended but a booster 2 months after the first dose is. Any patient with an immune deficiency who is a poor responder to immunizations should be considered for the third and fourth dose. They should also be considered for Evusheld, the prophylactic monoclonal antibody, perhaps after their third or fourth vaccine dose, whichever is applicable.
 
FDA Grants Full Authorization for the Moderna Vaccine
Read more about the full authorization. While it has been known as the Moderna COVID-19 vaccine, the approved vaccine will be marketed as Spikevax for the prevention of COVID-19 in individuals 18 years of age and older.
 
Durability of Natural Immunity
This study of four adult cohorts in California and New York before and after the predominance of the Delta variant noted a change in protection against hospitalization comparing the vaccinated but uninfected versus those unvaccinated and infected. Prior to Delta, participants who were vaccinated were 2-fold less likely to be hospitalized compared to those unvaccinated with previous infection. After Delta became predominant, that reversed with those who had survived a previous infection having a 2-4-fold reduction in hospitalization compared to those vaccinated without a previous infection. Since all participants had been vaccinated prior to May, this could reflect waning of vaccine immunity. The study was performed before many were eligible for booster vaccines and the results may not apply to Omicron.
 
Death Rates and Boosters - Real World
Only recently have countries posted data on death rates by vaccination and only a few have separated vaccinated and boosted from vaccinated. This report shows the mortality rate by vaccination and booster status in various countries around the world during the Omicron surge. In Switzerland, the mortality rate (per 100,000) is 13.06 for unvaccinated, 1.44 for fully vaccinated but no booster, and 0.27 for those fully vaccinated plus booster. In Chile, the rates are 3.26, 0.63 and 0.13 respectively. In the United States, data is available by vaccine type: the mortality rate is 3.47 for unvaccinated versus 0.72 for J&J, 0.6 for Moderna, and 0.48 for Pfizer; and by booster (November only): unvaccinated adults are 68 times more likely of dying compared to fully vaccinated adults with boosters. In England, the rates are 23.8 for unvaccinated and 5.2 for fully vaccinated. Take home message: Get your booster!
 
Hospitalizations in Vaccinated and Boosted Individuals in the US
This report from 25 U.S. jurisdictions compared care and death rates and incidence rate ratios among unvaccinated and fully vaccinated adults by receipt of booster doses during the pre-Delta, Delta and Omicron surges. Bottom line: Boosted adults over age 50 were five times less likely to be infected compared to the unvaccinated and three times less likely compared to vaccinated but not boosted. In another release, those who had been boosted were 94% and 82% less likely to need an ER or urgent care visit, respectively, compared to those who were eligible for a booster but had not received it. CDC data shows that the rates of COVID-19 associated hospitalizations were 44 times higher in unvaccinated adults 50-64 years, and 49 times higher in adults 65 and older compared to vaccinated adults. This week’s MMWR featured a study on vaccine booster effectiveness on hospitalization. In a study of hospitalized adults, compared with receipt of two mRNA COVID-19 vaccine doses, receipt of a third dose increased vaccine effectiveness against hospitalization among adults without and with immunocompromising conditions, from 82% to 97% and from 69% to 88%, respectively.
 
Are Vaccine Related Adverse Events (AEs) Mostly “Nocebo?”
In a systematic review and meta-analysis of 12 clinical trials involving SARS-CoV-2 vaccines which included AE reports for 45,380 participants, systemic AEs were experienced by 35% of placebo recipients after the first dose and 32% after the second dose. AEs in the placebo arms (“nocebo responses”) accounted for 76% of systemic AEs after the first dose and 52% after the second. Keep these numbers in mind when counseling patients who are vaccine hesitant.
 
Legal Hurdles for Administration's Vaccine Mandate for Healthcare Workers Resolved
Following dismissal of a challenge from Texas, the mandate that required vaccination for employees at Medicare and Medicaid-certified facilities can move forward in all states. The deadline for compliance is March 15. As noted before, this would not apply to most private allergists’ offices, but an individual may be affected through their hospital affiliations.

Infection/Transmission

U.S. Data Confirm Omicron's Lower Severity
CDC examined data from three surveillance systems and a large healthcare database to assess multiple indicators across three high COVID-19 transmission periods: winter 2020-2021, summer/fall 2021 (Delta wave) and this winter. Although the absolute number of cases and healthcare utilization was highest during the Omicron surge, the use of ICU beds and deaths were lower.
 
BA.2 – The New Omicron Subvariant
This subvariant first made an appearance in August of 2021. It has more mutations than Omicron (~85 compared to ~60), but lacks the one mutation that allows identification by PCR so sequencing is necessary. Considered a “Variant Under Investigation” by the United Kingdom, it has already taken hold in India, the Philippines, and Europe, and has also appeared now in the United States. It is slightly more transmissible than BA.1, and causes about the same severity of disease as BA.1 based on early data. Vaccine effectiveness is not known, but should be the same as for BA.1. A BA.3 variant has also been discovered.
 
Medicare Is Not Required to Cover At-Home COVID-19 Test Costs
According to CNN, the administration's requirement that health insurers cover the cost of home tests does not apply to Medicare. Enrollees in Medicare Advantage plans will need to check with their carriers.
 
There Is No Deltacron!
Not sure you heard this, but news spread rapidly about a “super variant” combining mutations of both Delta and Omicron. Turns out this may have been a sequencing error, and there is no evidence for the existence of this variant.
 
Cross-Reactivity and Infection in Children
The last Task Force message contained some information supporting the concept of cross-reactive immunity to other coronaviruses and possible impact on COVID-19 disease severity. This study of approximately 90 children with recent COVID-19 infection compared to 150 adults with recent infection noted that children produced a greater antibody and cellular immune response to infection and also develop cross-reactive responses to seasonal coronaviruses. Infections in participants were asymptomatic or mild. The study also noted cellular responses in 60% of seronegative children, which were markedly spike-specific. SARS-CoV-2 specific immune responses were maintained for 12 months.

Treatment

FDA Actions
The FDA expanded approval of remdesivir to patients with mild-to-moderate COVID-19 infection with high risk of hospitalization. The dose is 200mg IV on the first day, and 100mg per day for 2 more days. This should be started as soon as possible after confirmation of infection. On January 25, the FDA revoked the EUAs for two monoclonal antibodies, casirivimab + imdevimab made by Regeneron, and bamlanivimab + etesevimab made by Lilly, because they are ineffective against Omicron, which causes 99.5% of cases of COVID-19 in the United States. The FDA stated that they would reinstate the EUA if another variant arises that is responsive to these antibodies. On January 28, the FDA issued a warning to stop using Empowered Diagnostics COVID-19 Antigen Test and ImmunoPass COVID-19 Neutralizing Antibody Rapid Test because they have not been authorized, cleared or approved by the FDA.

Practice

Blood Specimen Collection Tubes in Short Supply
On January 19, the FDA updated the medical device shortage list to include all blood specimen collection tubes. Recommendations: limit testing at routine visits and testing only to target specific disease states or where it will change patient treatment.
 
HHS Distributing Another $2 Billion in PRF Payments
The U.S. Department of Health and Human Services (HHS), through the Health Resources and Services Administration (HRSA), is making more than $2 billion in Provider Relief Fund (PRF) Phase 4 General Distribution payments to more than 7,600 providers across the country this week.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, January 17, 2022

Here are today's important updates:

Vaccines

Effectiveness of Pfizer Vaccine Against Critical COVID-19 in Adolescents
This case-control, test-negative design study involved 445 patients and 777 controls at 31 hospitals in 23 states. In hospitalized adolescent patients, vaccine efficacy against hospitalization was 94% (95% CI, 90-96), 98% against ICU admission and 98% against COVID-19 resulting in the receipt of life support. There were no deaths in the vaccinated. Of note, 40% of the case patients were admitted to the ICU (only two had been vaccinated) and 29% required life support. This study took place during the Delta peak. Take home message: While the need for hospitalization may be low in adolescents, nearly half of those hospitalized need ICU care and almost one-third require life support. The Pfizer vaccine is highly effective against these outcomes.
 
Booster Benefit Among Younger Healthcare Workers in Israel
Like an earlier study on immunocompetent healthcare workers over the age of 60, administration of a third dose of the Pfizer vaccine to younger healthcare workers was associated with a lower rate of infection compared to those without a booster in this study. The adjusted hazard ratio was 0.07.
 
Antibody Titers as Correlates of Protection
This NIH-funded study analyzed blood samples from more than 1,000 people who had received the Moderna vaccine as part of the Coronavirus Efficacy (COVE) trial. Antibodies measured included spike protein binding antibodies and neutralizing antibodies. Data showed that for those with the highest antibody levels, the vaccine offered an estimated 98% protection. Those with levels about 1,000 times lower had 78% protection. Based on any of the antibodies tested, the estimated COVID-19 risk was about 10 times lower for vaccine recipients with antibodies in the top 10 percent of values compared to those with antibodies that weren’t detectable. This ability to correlate antibody levels with protection will help predict vaccine efficacy in groups in a much shorter time period than a conventional trial (2 months versus 7 months). Antibody levels are not precise enough to predict when someone would need a booster.

Immunity

Cross-Reactive Memory T Cells Protective?
A study from the National Heart and Lung Institute in the United Kingdom on 52 COVID-19 household contacts found higher frequencies of human endemic coronaviruses cross-reactive nucleocapsid-specific memory T-cells in contacts who remained PCR-negative after household contacts, compared to those who converted to PCR-positive. There was no difference in the frequency of spike-specific T-cells.

Infection

CDC Updates Guidelines for Isolation and Quarantine
On January 9, the CDC updated their guidelines for those in the general community, clarifying the guidelines that were updated on December 31 and covered in our last Task Force message. There were no changes in the duration as outlined in the earlier guidelines, but on a Clinician Outreach and Communication Activity (COCA) call on January 13 the CDC gave their reasons for the shortened duration: societal issues related to prolonged isolation, staffing issues for essential services, supply shortages and the fact that Omicron has a shorter incubation period, and the peak infectious period is from 1 day before to 1 week after symptom onset. Most of the public has focused on the 5-day duration for isolation (confirmed infection or likely infected), but key points that are often forgotten: These shortened guidelines apply to mild or asymptomatic disease only, and those over the age of 2 (<2 can’t wear a mask). Additional recommendations as part of the guidelines are often not stated but crucial: Wear a tight-fitting mask including indoors at home, avoid travel, stay away from immunocompromised or high-risk people, and avoid places where you can’t wear a mask for the next 5 days. They also clarified the difference between “fully vaccinated” and “up-to-date vaccination”. Fully vaccinated refers to those who have completed a two-dose mRNA vaccine series or a one-dose J&J vaccine, but have not been boosted if eligible. Up-to-date vaccination refers to those who are fully vaccinated and have received a booster if eligible. There are differences in the quarantine guidelines for fully vaccinated versus up-to-date. Those who are up-to-date on their vaccines and those within 90 days of a confirmed COVID-19 infection do not need to quarantine after close contact with a person with a confirmed COVID-19 infection, but should wear a mask around others for 10 days and get tested at least 5 days after contact, sooner if symptomatic. For those who are fully vaccinated but not up-to-date, with close contact to a person with a confirmed COVID-19 infection, stay at home for 5 days, wear a well-fitting mask when around others at home as well as elsewhere, if possible, for 10 days, monitor symptoms for 10 days, and get tested at 5 days. Slides from the call can be found here.
 
Choosing a Proper Mask and Avoiding Counterfeit Masks
The CDC updated their recommendations and guidance on masks on January 14. N95, KN95 and KF94 masks are recommended. If you wear a cloth mask, make sure it has at least two layers of cloth and fits tightly. If you can’t tolerate or find an N95 or equivalent, then consider wearing two masks, a procedure mask with a cloth mask over the top. “Surgical N95s” are a specific type of N95 and should be reserved for healthcare settings. Share this link with your staff and patients. Counterfeit masks are of special concern. 60% of KN95s are counterfeit, and many of the N95s. This article from NBC News offers helpful tips on spotting the counterfeit masks. The biggest tip when shopping for KN95s is: If it has the “NIOSH” markings, it is counterfeit because NIOSH does not certify KN95 masks. You can find which masks are certified by NIOSH here. Additional tips are also available at this CDC website.
 
Concurrent Influenza and SARS-CoV-2 Infection
Labeled “flurona” by the press, patients who have simultaneous infection with both influenza and SARS-CoV-2 are being increasingly reported in the United States and around the world. There are not enough cases to know if this combination will cause more severe disease, but some have been mild, particularly those who have been vaccinated for both and boosted for SARS-CoV-2. With increasing cases of influenza being reported in the United States and the Omicron surges, it is likely to see more of these cases. Since there are potential therapies for both, it makes sense to test for both in patients presenting with lower respiratory symptoms. Take home messages: Encourage vaccination for influenza and SARS-CoV-2, which can be given simultaneously. Encourage masking and think of the potential for both infections in sick patients.
 
HAE Attacks Increase But No Increased Risk for COVID-19 Severity
This small study conducted at 10 HAE reference centers in Latin America noted an increase in the frequency of attacks in HAE patients with confirmed SARS-CoV-2 infection, but no evidence for increased severity of infection in this patient population.

Testing

Insurers to Cover At-Home Testing
According to news sources, private health insurers are now required to cover up to eight home COVID-19 tests per month for people on their plans. People will be able to purchase home testing kits for free under their insurance or submit receipts for reimbursement (up to $12 per test). The program will allow insurers to set up networks of preferred suppliers to make tests available with no up-front costs.
 
Stop Using LuSys Laboratories COVID-19 Tests
An FDA safety communication was released on January 11 warning people to stop using LuSys Laboratories COVID-19 Antigen Test (Nasal/Saliva) and the LuSys Laboratories COVID-19 IgG/IgM Antibody Test. These may also be sold under the company names Luscient Diagnostics or Vivera Pharmaceuticals, or with the trade name EagleDx. Performance of these tests have not been adequately established, may produce false results and neither test has been authorized, cleared or approved by the FDA for distribution or use in the United States.
 
Free Antigen Tests for Families
Beginning on January 19, individuals may order free antigen tests for COVID-19 from the federal government through the website COVIDTests.gov. The limit is four tests per family. You can expect them to be shipped 7-12 days after ordering and to be delivered by the U.S. Postal Service. Delivery may take 2-3 days after shipping. Several news agencies carried this report, including AP, CNN, and the New York Times.

Misinformation

First Masks, Then Vaccines, Now Antigen Tests
The purveyors of misinformation and disinformation never rest. This New York Times article points out several social media sources trying to discredit at-home COVID-19 antigen tests. Allergists need to be aware of these claims and be ready to comment on them to their patients. For those without a subscription, the claims include that the tests are not accurate because tap water, soft drinks and juices can cause a positive test (may be true but doesn’t affect the results of the test when used correctly) and other distortions about PCR testing.

Treatment

Racial and Ethnic Disparities in Use of Monoclonal Antibodies
Analysis of data from 41 healthcare systems participating in the National Patient-Centered Clinical Research Network found lower use of monoclonal antibody treatment among Black, Asian, and other race and Hispanic patients with positive SARS-CoV-2 test results, relative to White and non-Hispanic patients. Racial and ethnic differences were smaller for inpatient administration of remdesivir and dexamethasone.

Practice

Provider Relief Fund (PRF) Reporting Portal Open
This portal is open for providers required to report on PRF payments during Reporting Period 2. The portal will remain open until March 31. Learn more here.
 
HHS Extends Public Health Emergency
The Secretary of the Department of Heath and Human Services (HHS) announced his intent to extend the public health emergency (PHE) for another 90 days, until April 16, 2022. This means that all waivers instituted by CMS and HHS for the PHE will also be extended.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, January 10, 2022

Here are today's important updates:

Vaccines

ACIP and CDC Concur With FDA Authorization
Shortly after the FDA expanded the EUA for the Pfizer vaccine, the CDC approved the indications: boosters for 12-years-old and above 5 months or more after their second dose, and a third dose 28 days after their second dose for 5-11-year-olds who are immunocompromised. On January 7, the FDA also amended the EUA for Moderna to allow a booster after 5 months. See here and here for more details.
 
Adverse Events Reported After Pfizer Vaccine in 5-11-Year-Olds
After nearly 8.7 million doses, serious adverse events were rarely reported to VAERS and V-safe. Fever, headache and fatigue were the most common systemic symptoms, usually mild to moderate. Of the 4,149 VAERS reports, 100 (2.4%) were for serious events, the most common were fever (29), vomiting (21) and increased troponin (15). There were 12 reports of seizures: two were febrile seizures and 5 were new onset seizures. Eleven of 15 of the preliminary reports of myocarditis were verified, all mild.
 
Vaccine Effectiveness in Adolescents
A prospective cohort of 243 adolescents aged 12-17 years in Arizona completed weekly SARS-CoV-2 testing by nasal swab for 19 consecutive weeks. Under real-world conditions, vaccine effectiveness of full immunization (completion of the second in a two-dose series at least 14 days earlier) was 92% against SARS-CoV-2 infections irrespective of symptom status.
 
Vaccine May Reduce MIS-C in Adolescents
In a study involving all pediatric patients in France admitted or diagnosed with Multisystem Inflammatory Condition – Children (MIS-C) from September 1 – October 31, 2021, the HR for MIS-C was 0.09 (95% CI, 0.04-0.21) after the first vaccine dose compared with unvaccinated adolescents. In a U.S. study, the CDC in collaboration with 70 pediatric hospitals found an estimated effectiveness of the Pfizer vaccine against MIS-C occurrence in 12-18-year-olds was 91%.
 
Neutralizing Antibody Titers After Infection, Vaccination and Both
This study looked at serum neutralizing antibody titers against USA-WA/2020-spike pseudotype virus in 497 participants, 170 after previous infection, 327 after vaccination, and 50 after infection and then vaccination. Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed neutralizing antibodies (nAb) with a GMT of 1,003 (95% CI=766-1,315). Among 139 previously uninfected participants, 138 (99%) developed nAb after mRNA vaccine dose two with a GMT of 3,257 (95% CI=2,596-4,052). GMT was higher among those receiving mRNA-1273 vaccine (GMT=4,698, 95%CI=3,186-6,926) compared to BNT162b2 vaccine (GMT=2,309, 95%CI=1,825-2,919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21,655 (95% CI=14,766-31,756) after mRNA vaccine dose one, without further increase after dose two. Take-home message: Vaccination provides greater protection than infection, and vaccination after infection provides the greatest protection.
 
Impact of Omicron Spike Protein Mutations
Fifteen of the 37 amino acid substitutions in the Omicron variant are in the receptor-binding domain (RBD), which leads to the question of these substitutions on binding and response to therapeutics and vaccines. Until now, most of the information has been in pre-print form. This peer-reviewed and accepted study employed a pseudovirus assay to study receptor usage and neutralization mediated by monoclonal and polyclonal antibodies, as well as surface plasmon resonance to measure binding of the RBD to human and mouse ACE2 receptor. Findings: Omicron RBD binds with increased affinity (2.4-fold) to human ACE2 receptors and also gains binding to mouse ACE2, suggesting the possibility of human-animal-human transmission, although passage through an animal species could also attenuate the virus; mRNA vaccines had some neutralizing activity but was reduced 37-39-fold; reduction in vaccinated and previously infected patients was 5-fold, and reduction in renal dialysis patients after a booster dose was 4-fold; only one of the currently approved monoclonal antibodies (sotrovimub, which targets non-RBD epitopes) had neutralizing activity against Omicron with only a 2-fold reduction. The authors did identify a few broadly neutralizing antibodies that were effective against the Omicron variant and many other non-SARS-CoV-2 sarbecoviruses. Similar findings of increased neutralizing response in boosted as well as previously infected and vaccinated individuals were noted in this study.

Infection

Antigen Test Sensitivity and Omicron
You may have read about this in the news. Here is the information directly from the FDA: “The FDA is collaborating with the National Institutes of Health’s (NIH) RADx program to study the performance of antigen tests with patient samples that have the Omicron variant. RADx recently performed preliminary studies evaluating the performance of some antigen tests using patient samples containing live virus, which represents the best way to evaluate true test performance in the short-term. Early data suggests that antigen tests do detect the Omicron variant but may have reduced sensitivity.” Prior testing by RADx on heat-treated patient samples suggested that these tests had similar performance when detecting other variants.
 
Increasing Hospitalization Rate in Children
Over the last two weeks, the rate of hospitalization in children (0-17-year-olds) has almost quadrupled, from 0.26/100,000 on December 15, 2021, to 0.92/100,000 on January 2, 2022, according to the CDC. Reasons behind this increase are not clear. Part of the explanation could be that many children may be hospitalized for another reason, but test positive for SARS-CoV-2 on admission. Since the start of the COVID-19 pandemic, 209 children have died from this disease. Since August of 2020, there have been over 80,000 admissions. Only 24% of children 5-11 have received one vaccination, and only slightly more than 15% are fully vaccinated. Most admissions now are preventable. (CDC Data Tracker as noted).
 
Increased Risk for Diabetes Post-COVID in Those <18-Years-Old
Data from two claims databases found that new diabetes diagnoses were 166% (IQVIA) and 31% (HealthVerity) more likely to occur among patients <18-years-old with COVID-19 than among those without COVID-19 during the pandemic, and 116% more likely to occur among those with COVID-19 than among those with an acute respiratory infection during the prepandemic period. Non-SARS-CoV-2 respiratory infection was not associated with diabetes. These findings are consistent with previous research demonstrating an association between SARS-CoV-2 infection and diabetes in adults. Bottom line is that providers should be on the lookout for diabetes >30 days post COVID in patients <18-years-old (and probably in all patients, given the references listed at the end). An interesting hypothesis on the mechanism underlying this risk can be found in this paper.
 
Risk for Severe Disease Among Hospitalized Adults With Asthma or COPD
A group of authors from the CDC, using data from 877 U.S. hospitals from the Premier Healthcare Database, assessed the risk of severe clinical outcomes during hospitalization of adults with asthma and/or COPD and COVID-19, and compared those risks with those during hospitalizations of adults with asthma and/or COPD without COVID-19. They found that among patients with asthma, the percentage requiring ICU admission, invasive mechanical ventilation (IMV) and death were 46.9%, 14.0% and 8.0% respectively. The risks were higher compared to those without COVID-19, with adjusted risk ratios of 1.17 (95% CI, 1.14-1.21), 1.61 (95% CI, 1.50-1.73), and 5.56 (95% CI, 4.89-6.32) respectively. Risks were also higher among adults with COPD.

Practice

CMS Announces Changes for Vaccination and Monoclonal Antibody Treatment
If you vaccinate or administer monoclonal antibody to patients enrolled in MA plans on or after January 1, 2022, you should submit claims to the MA plan. Original Medicare won’t pay those claims. Read more here.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Tuesday, January 4, 2022

Here are today's important updates:

Vaccine

FDA Announces Extension of EUA for Pfizer Vaccine Boosters
On a media call on January 3, the FDA announced several changes. First, they extended the EUA for the Pfizer vaccine to include 12-15-year-olds. They reviewed the Israeli data on myocarditis after the third dose in this age group and found that it was about one-third the risk compared to after the second dose. The peak age range for myocarditis was in the 16-17-year-old age range, about 1 in 10,000 and was mild in 98% of cases. They also announced a change in the booster timing, now authorized at 5 months after the second dose for Pfizer (Moderna remains at 6 months). Finally, they authorized a third dose in 5-11-year-olds who may be immunocompromised. Remember, these are authorizations for the vaccine. The ACIP and CDC have to weigh in on this and give their recommendations for using the vaccines as authorized in these age groups.
 
Boosters Markedly Reduce Infection
Data published in early December by the Massachusetts Department of Health showed that unvaccinated individuals were five times more likely to be infected compared to those fully vaccinated but not boosted, and 31 times as likely compared to those fully vaccinated and boosted. These numbers likely preceded the Omicron wave.
 
Pfizer Vaccine Efficacy Against Hospitalization Caused By the Omicron Variant
This has been widely covered in the press, but here is a published report. Using data from a South African managed care organization involving over 30,000 individuals, the effectiveness of the vaccine was 70% against hospitalization for those fully vaccinated (two doses) compared to an effectiveness of 93% during their period of Delta predominance.
 
Pfizer/BioNTech Announce Modification of 6-Month-Old to 5-Year-Old Vaccine Clinical Trial
In a December 17 press release, the companies announced that following a routine review by the Data Monitoring Committee, they will amend the clinical study to include evaluating a third 3 microgram dose at least 2 months after the second dose of the two-dose series. In a pre-specified immunogenicity analysis, compared to the 16-25-year-old population, non-inferiority was met for the 6-24-month-old age group but not the 2-5-year-old group. No safety concerns were noted. If the three-dose study is successful, the companies expect to submit for an EUA in the first half of 2022.
 
Neutralization of Omicron After Pfizer Booster Dose
Using microneutralization assays against the wild-type virus, Beta, Delta and Omicron variants, these authors from Israel found that the third dose efficiently neutralized infection with the Omicron variant, increasing the neutralization efficiency by 100-fold, but it was four-fold lower than the efficiency against the Delta variant.
 
Factors Associated With Vaccine Reactions
In this online cohort study in 19,586 participants, anaphylaxis or allergic reactions occurred in 0.3% after one dose and 0.2% after two doses. Factors associated with adverse reactions in general were number of doses of vaccine, mRNA vaccine, with Moderna more than Pfizer, younger age, female sex and previous COVID-19 infection. Major limitation of this study is the self-report of allergic or anaphylactic reactions. Overall, these reactions were very uncommon. Another study from the Kaiser Permanente Southern California system analyzing data on 391,123 vaccine recipients, noted a rate of treated first dose hypersensitivity reaction of 0.028%, and a second dose treated reaction rate of 0.014%. Only 0.00033% resulted in anaphylaxis. Nearly 80% of first dose reactors were able to get the second dose. 7.8% of those with first dose reactions who had a second dose had a subsequent reaction. Recipients with preexisting drug “allergies” were more likely to have a reaction. The figures from this study are more likely to represent the real incidence of reactions because they only looked at treated reactions, not reported reactions.
 
Tolerance of mRNA Vaccines in PEG Allergic Individuals
This study from Canada found that in 12 patients with either confirmed or highly likely PEG allergies, all were able to be safely vaccinated, 10 with mRNA vaccines. This included two individuals with positive ID tests to the vaccine. Some of the patients were given the vaccine in divided doses, the others as a single dose.
 
CMS Omnibus COVID-19 Healthcare Staff Vaccination
On December 29, the Centers for Medicare & Medicaid Services (CMS) released guidance on the Omnibus COVID-19 Healthcare Staff Vaccination Interim Final Rule that was published on November 5. This guidance provides important information on implementation, as well as guidelines to assess and maintain compliance with the COVID-19 vaccination requirements for healthcare workers at facilities participating in the Medicare and Medicaid programs. This guidance does not currently apply to the following states: Alabama, Alaska, Arizona, Arkansas, Georgia, Idaho, Indiana, Iowa, Kansas, Kentucky, Louisiana, Mississippi, Missouri, Montana, Nebraska, New Hampshire, North Dakota, Ohio, Oklahoma, South Carolina, South Dakota, Texas, Utah, West Virginia and Wyoming. Even though the guidance uses the term “facilities participating in Medicare and Medicaid programs”, it does not apply to private offices unless you are practicing in a Rural Health Clinic or Federally Qualified Health Center. You may have requirements based on your capacity as staff in a hospital if you provide care to patients in that facility.

Infection

Omicron and Severe Disease
In one of the first peer-reviewed studies from South Africa, this group compared the characteristics and outcomes of hospitalized patients during the Omicron wave with previous waves in a large hospital system. The number of patients treated in the hospitals was about one-third those in previous waves, 41.3% of patients presenting to the ER were admitted compared to 69%, median age of patients was 36 years compared to 59, significantly fewer had co-morbidities, those presenting with an acute respiratory condition was 31.6% compared to 91%, oxygen therapy was required in 17.6% versus 74%, and ICU admission in 18.5% compared to 30%. Mortality rate was 2.7% compared to 18.5-29.1% in previous waves. Two-thirds were unvaccinated. Some of these differences could be explained by the younger age of the patients, but it appears the variant causes less lower respiratory disease. Another study from Scotland, not yet peer-reviewed, showed that Omicron was associated with a two-thirds reduction in the risk of COVID-19 hospitalization when compared to Delta and the booster dose offered substantial additional protection against the risk of symptomatic COVID-19. Important note: These cases in Scotland were predominantly in the age group of 20-39 years. The jury is still out on risk for those over 65 years. An analysis by the U.K. Health Security Agency found that someone infected with the Omicron variant is estimated to be between 31% and 45% less likely to attend emergency care and 50-70% less likely to be admitted to the hospital. The Agency stated that the findings are preliminary and highly uncertain because of the small numbers of hospitalized patients with Omicron (132) and the limited spread into older age groups.
 
CDC Changes Quarantine/Isolation Recommendations for the General Population
Based on current knowledge of COVID-19 and the Omicron variant, on December 27 the CDC changed their recommendations concerning quarantine and isolation. They shortened the recommended time for isolation from 10 days for people with COVID-19 to 5 days, if asymptomatic, followed by 5 days of wearing a mask when around others. They also updated the recommended quarantine period for those exposed to COVID-19. For people who are unvaccinated or are more than 6 months out from their second mRNA dose (or more than 2 months after the J&J) and not yet boosted, quarantine for 5 days followed by followed by strict mask use for an additional 5 days. Alternatively, if a 5-day quarantine is not feasible, it is imperative that an exposed person wear a well-fitting mask at all times when around others for 10 days after exposure. Individuals who have received their booster shot do not need to quarantine following an exposure but should wear a mask when around others for 10 days after exposure. For all those exposed, best practice would also include a test for SARS-CoV-2 at day 5 after exposure. If symptoms occur, individuals should immediately quarantine until a negative test result. These new guidelines do not apply to healthcare workers, those remain unchanged from the December 23 update.
 
40.5% of Those With Confirmed COVID-19 Are Asymptomatic
Numerous studies have reported percentages of asymptomatic patients with COVID-19 that have varied from 20-50%. To a large extent, it varies depending on the population studied and perhaps the variant involved. This systematic review and meta-analysis on 29,776,306 individuals undergoing testing from 95 unique studies showed that the pooled percentage of asymptomatic infections was 40.5% among the population with confirmed COVID-19. These studies were done prior to Omicron, so we don’t know if this percentage will hold for that variant.

Treatment

Remdesivir Found Effective At Prevention of Hospitalization
This randomized, double-blind, placebo-controlled trial in 562 non-hospitalized patients with symptomatic COVID-19 infection within the previous 7 days and having at least one risk factor for severe disease was able to demonstrate that a 3-day course of remdesivir resulted in an 87% lower risk of hospitalization or death (HR 0.13 ;95% CI, 0.03-0.59). Adverse events were comparable to placebo, most common was nausea. These results are comparable to those achieved with Paxlovid, and almost three times better than molnupiravir. Important note: This study was performed before the Omicron variant was circulating. Data on effectiveness for that variant is limited, but should be effective based on in vitro data.
 
CDC Health Alert on Therapeutics to Prevent and Treat COVID-19
This alert was just released on December 31. In a given infected patient, you are most likely not going to know which variant is responsible, and timing is of the essence. You will have to rely on data on the most likely variant in your area. Monoclonal antibodies (bamlanivimab plus etesevimab, casirivimab plus imdevimab) are not effective against Omicron. Sotrovimab is effective but in short supply and use should be limited to nonhospitalized high-risk individuals including those who are unvaccinated or have not received a booster, older age (>65) or immunosuppressed. If Delta is still prominent in your area, you could use bamlanivimab plus etesevimab or casirivimab plus imdevimab, but should counsel your patient on potential lack of effectiveness. Some PCR tests that can identify SGTF (s-gene transcription failure) variants may be helpful in suggesting Omicron. Antivirals: remdesivir (see study above). Paxlovid and molnupiravir must be started within 5 days of symptoms onset, and is indicated for mild-moderate disease in nonhospitalized patients. There is marked difference in effectiveness (Paxlovid 88%, molnupiravir 30%). Paxlovid supplies are very limited so use should be limited to higher risk patients and those who are not limited due to the severe drug-drug interactions associated with the ritonavir component. CDC strongly recommends that healthcare providers who are not familiar with these potential interactions should refer to the NIH Statement on Paxlovid Drug-Drug Interactions/COVID-19 Treatment Guidelines. Molnupiravir is not recommended in pregnancy, people who are breast-feeding, or pediatric patients. Paxlovid is authorized (EUA) for pediatric patients 12 years and older who weigh at least 40kg. Pre-exposure therapeutics for high-risk groups: EVUSHELD, which contains two long-acting monoclonal antibodies, is the only EUA pre-exposure prophylactic product available, should be effective against Omicron, and is intended for the highest risk immunocompromised patients who are not expected to have an effective response to vaccination. This product is not indicated for treatment, only prophylaxis. This document provides a tiered approach to prioritization.
 
Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.
 
Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Thursday, December 23, 2021

Many of our patients consider their allergist to be their primary physician, and may call us with symptoms or a confirmed case of COVID-19. It is important for us to be aware of all possible treatments that need to be given early in the course of the disease.

On Wednesday, 12/22/21, the FDA granted an EUA for a new anti-viral medication for treatment of COVID-19 called Paxlovid (nirmatrelvir/ritonavir). This drug is indicated for the treatment of outpatients 12 years of age and older (weighing at least 40kg) with mild-moderate symptoms of confirmed COVID-19 within five days of symptom onset and who are at high risk for severe disease.

It should be started within three days of the onset of symptoms, but studies suggest that it might still be effective within five days. The pivotal clinical trial in high-risk patients showed that this drug was 89% effective in preventing hospitalization or death. There was a 94% reduction in people over age 65. A second trial is being conducted in standard-risk patients but hasn’t been completed yet.

Nirmatrelvir was derived from a precursor that was active against SARS and designed specifically for SARS-CoV-2. It binds to the virus’s main protease to inhibit replication. Paxlovid combines nirmatrelvir with ritonavir, a viral protease used for HIV, which has no effect against SARS-CoV-2 but works to increase the blood levels of nirmatrelvir.

The dose is two 150mg tablets of nirmatrelvir and one 100mg tablet of ritonavir twice daily for five days.

Possible side effects include an impaired sense of taste, diarrhea, high blood pressure and muscle aches. Be aware of potentially significant drug interactions, and use with caution in patients with HIV or liver disease.

This drug only treats acute disease and the patient will remain potentially susceptible to repeat infection. Paxlovid is not a preventative medication and is not a substitution for vaccination.

Initial supplies will be limited with only enough medication for 180,000 patients by the end of the year and an additional 30 million by the middle of 2022. It takes six to eight months to manufacture the drug.

The Fact Sheet for healthcare providers can be found here.

Today, 12/23/21, the FDA also granted an EUA to molnupiravir for people 18 years of age and older who are at high risk of severe COVID-19. Clinical trials of this drug show a reduction in hospitalization of 30%. This drug has fewer interactions with other medications compared to nirmatrelvir and fewer issues with liver disease. You can read the FDA’s press release on this medication here.


Monday, December 20, 2021

Here are today's important updates:

Omicron

The material on Omicron is not from peer-reviewed published papers (too soon for that) but relies on press releases, NIH newsletters and pre-print results of studies. Please take this into account, information will most likely change over time. Best advice at this time: If you have been vaccinated, get a booster. If not vaccinated, start. If you have been previously infected, vaccination will markedly increase your protection. Wear a mask indoors, continue social distancing and frequent hand washing. Remember, Delta continues to be the main variant circulating in the United States at this time.

Current EpidemiologyOmicron has been confirmed in 45 states, but probably is present in all 50. It appears to be rapidly increasing with 40% or more of new U.K. cases due to this variant. This MMWR article explains the enhanced surveillance currently undertaken to track it. In Washington state, which started with three cases in early December, researchers at the University of Washington found that the number of positive samples rose from 3% to 13% in just 3 days. Omicron now accounts for 40% of positive tests in the state based on S protein deletion picked up on PCR testing. The CDC predicts that Omicron could peak in a massive wave of infections as soon as January. In the New York/New Jersey area, the percentage of Omicron infections had reached 13.1% in the week ending December 11.

TransmissionU.K. data from 260 confirmed cases of Omicron indicate that the Omicron variant has about 3.2 times the risk of household transmission compared to Delta, and the household secondary attack rate is about twice that of Delta. Preliminary analyses indicate approximately 3-8-fold increased risk of reinfection with the Omicron variant. Commentary on the South African data indicate a doubling time for cases of 1.2 days, compared to 1.5 days for Delta.

Does It Cause Milder Disease?According to a report in the Washington Post on December 8, Botswana, one of the first countries to detect Omicron, had not seen a rise in hospitalizations. 71% of its 1.3 million eligible population is fully vaccinated. The WHO also stated that preliminary data presents a rapid increase in transmission but causes milder cases than Delta, although it is too early to be sure. The reassuring data from Botswana could be due to vaccination or mild disease from this variant. Details from 43 cases in the United States attributed to the variant from the above mentioned MMWR article include:

  • 58% of cases were in the 18-39-year-old age range (important when considering morbidity and mortality), only 33% reported international travel
  • 79% were fully vaccinated, 33% had received a booster dose, although one-third of these <14 days before symptom onset
  • 14% had a documented previous SARS-CoV-2 infection
  • Most common symptoms: cough, fatigue and runny nose/congestion
  • One person hospitalized for 2 days, no deaths reported as of December 8 among this group

The U.K. data on the 260 confirmed cases also mentioned above had no deaths or hospitalization.

Are Vaccines Protective?Early data out of South Africa, in a study involving a small number of patients (12) and not yet peer reviewed, found that neutralizing antibodies were 40 times less effective after two doses in six of the patients, but still showed protection in another six who had been infected previously and had two doses of vaccine (surrogate for a booster dose). Pfizer confirmed this with their own laboratory research. Preliminary laboratory studies demonstrate that three doses of the Pfizer-BioNTech COVID-19 vaccine neutralize the Omicron variant (B.1.1.529 lineage), while two doses show significantly reduced neutralization titers. Data indicate that a third dose of BNT162b2 increases the neutralizing antibody titers by 25-fold compared to two doses against the Omicron variant; titers after the booster dose are comparable to titers observed after two doses against the wild-type virus, which are associated with high levels of protection. As 80% of epitopes in the spike protein recognized by CD8+ T cells are not affected by the mutations in the Omicron variant, two doses may still induce protection against severe disease.

Much of the data reported so far relates to anti-spike and neutralizing antibodies. Alessandro Sette, PhD, of the La Jolla Institute for Immunology, reports that his lab shows high conservation of T cell epitopes in Omicron. A pre-print on real-world U.K. data showed vaccine effectiveness about 4 months after two doses of the Pfizer vaccine was about 40% against Omicron, but a booster dose increased the vaccine effectiveness to about 80%.

Is Previous Infection Protective?pre-print study from Austria using sera from people previously infected with Alpha, Beta or Delta antibodies failed to neutralize Omicron, but antibodies from patients with previous infection from other variants who were also vaccinated showed some neutralization.

And the Misinformation Beats the Real InformationThis article in the Washington Post notes that anti-vaccine influencers at the end of November reposted a fake slide deck with the logos of the WHO and World Economic Forum purporting to show a schedule for when coronavirus variants would be “released” that was originally posted last July. Other false claims: the vaccines caused the Omicron variant (reposted millions of times on Telegram messaging app), the variant is being pushed by the government and pharmaceutical companies to undermine ivermectin, and that the timing of the variant suggests that government officials are trying to distract people from following the trial of Ghislaine Maxwell.

Vaccines

Efficacy of Booster Doses Across Age RangesData from Israel on 4,696,865 persons ages 16 years or older who had received two doses of Pfizer vaccine at least 5 months earlier indicated that the rate of confirmed infection was lower in the booster group compared to the non-booster group by a factor of 10. The rates of severe illness were lower by a factor of 17.9 among those 60 years and older, and by a factor of 21.7 in those ages 40-59. Mortality among those 60 and older was lower by a factor of 14.7.

FDA Expands Pfizer EUAThe FDA has granted an extension to the EUA for the Pfizer vaccine to include booster doses for 16- and 17-year olds.

FDA and CDC Modify Recommendations for the J&J VaccineEarlier this month, the FDA announced people who have a history of thrombosis with thrombocytopenia (TTS) should not get the J&J vaccine. The CDC’s Advisory Committee for Immunization Practices (ACIP) met on December 16 and voted in favor of expressing a preference for the mRNA vaccines, but stopped short of saying that use of the J&J vaccine should be discontinued. There have been 54 cases of TTS after the J&J vaccine as of August 31, a rate of 3.83 cases per million doses. Males and females ages 18-70 have been affected with the highest rate among females ages 30-49 (about 10 per million doses). Just over half the cases have a cerebral venous sinus thrombosis, and there have been 9 deaths as of December 9. In the risk/benefit analysis, vaccination with the J&J vaccine will prevent 3,700-64,000 hospitalizations due to COVID-10 depending on age, so the risk/benefit still favors vaccination. Since the J&J vaccine has been the go-to recommendation from allergists for those who have had a severe allergic reaction to one of the mRNA vaccines, this information will be important to present to our patients in shared-decision making about vaccine choices. Slides from the ACIP meeting and the COCA call on December 17 are available here and here.

Myocarditis After Vaccination Mild, Resolves QuicklyThis retrospective analysis of 139 adolescents and young adults <21 years-old with 140 episodes of suspected myocarditis within 30 days of COVID-19 vaccination found that most had mild symptoms that resolved quickly. 96.8% followed an mRNA vaccine, with 91.4% after the second dose, a median of two days later. Chest pain was the presenting symptom in 99.3%, less than one-third with dyspnea or fever, and all had elevated troponin. Median hospital stay was two days. Information from the ACIP meeting on December 17 noted that there have been eight confirmed cases of myocarditis in the 5-11-year-old patients, out of 7 million doses. All cases have been mild.

Appeals Court Revives Administration's COVID-19 Vaccine Mandate For Healthcare Workers in 26 StatesReuters reported on December 15 that the U.S. Court of Appeals for the Fifth Circuit “on Wednesday revived in 26 U.S. states a COVID-19 mandate issued by President Joe Biden’s administration requiring millions of healthcare workers to get vaccinated if they work in facilities that receive federal dollars.” The three-judge panel “ruled that a lower court had the authority to block the mandate in only the 14 states that had sued and was wrong to impose a nationwide injunction.”

Treatment

FDA Grants EUA for AstraZeneca Monoclonal Antibody TreatmentOn December 8, the FDA granted an EUA for Evusheld (tixagevimab + cilgavimab) for pre-exposure prophylaxis of COVID-19 in persons 12 years of age (weighing at least 88 pounds) and older who are moderately to severely immunocompromised or have a history of severe adverse reactions to a COVID-19 vaccine or its components. This is a long-lasting monoclonal antibody administered as two IM injections in immediate succession and may be effective for prevention for 6 months.

Remember Monoclonal Antibody TherapyIt is often forgotten in patients with mild-moderate COVID-19 and at high risk for severe disease, and also for post-exposure prophylaxis. Find out more on the COVID-19 resources page on the AAAAI website. Pre-print studies here and here indicate that the monoclonal antibodies from Lilly, Regeneron and AstraZeneca may not be effective against Omicron, but that the GSK product, Sotrovimab, remains effective. On the other hand, the Washington Post mentioned in an article on December 16 that an independent study by scientists at the FDA found that the Astra Zeneca product, Evusheld, retained activity against Omicron. It is important to remember, with all the news about Omicron, that 95% or more of current infections in the United States are due to Delta, which does respond to the current licensed monoclonal antibodies.

Infection

Asthma Control and Hospitalization for COVID-19 in ChildrenThere have been over 100 articles including meta-analyses indicating that asthma is not a risk factor for severe COVID-19 and this has certainly been the case in the United States. Things may be different in the United Kingdom, however, with two studies suggesting that asthma may be a risk factor. A national incident cohort study of 63,463 children with asthma in Scotland looked specifically at asthma patients who were controlled versus uncontrolled based on a previous hospital admission, or two or more courses of oral steroids in the previous year. The HR for hospitalization for those with a previous asthma admission was 6.40 (95% CI 3.27-12.53), compared to those with controlled asthma whose HR was 1.36 (95% CI 1.02-1.80), compared to those with no asthma. In those with two previous courses of oral steroids, the HR for uncontrolled asthma was 3.38 (95% CI 1.84-6.21). Why are things different in the United Kingdom? Patients more readily admitted because of universal health care, and bias toward admission in someone with cough and shortness of breath with a history of exacerbations? As always, do your best to be sure that your pediatric asthma patients are well controlled.

Practice

Financial Relief May Be on Your WayHHS announced on December 14 that $9 billion is being distributed to practitioners as part of the Phase 4 Provider Relief Fund payments. The average amount for small providers is $58,000, for medium providers $289,000, and for large providers $1.7 million. HRSA is currently reviewing the remaining Phase 4 applications and will make the remainder of Phase 4 payments in 2022.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAIChair of the AAAAI COVID-19 Response Task Force


Monday, December 6, 2021

Here are today's important updates:

Omicron (B.1.1.529)

Limited Solid Information At This Time, But What We Do KnowAll of the data is in preprint form without peer review. Thanks to Katelyn Jetelina, PhD, our friendly local epidemiologist from University of Texas, Austin, for sharing this info. The rate of reinfection with Omicron is three times higher than with Delta, so people with previous infection are not as safe from reinfection with Omicron. Disease is exploding in South Africa now, but we don’t yet know if this is just because of Omicron. We still don’t know if it is more transmissible or more severe, but expect more information in the upcoming weeks. Although South Africa is experiencing exponential growth in cases and case positivity rates as high as 24%, cases had been low in South Africa before this, and they had little impact from Delta before Omicron. Symptoms appear to be the same with this variant, although details are still lacking.

Current Status in the United StatesCases of Omicron have now been detected at least 17 states. Not all of these have been directly linked to travel to South Africa and surrounding effected countries, suggesting community spread.

Vaccines

Will Vaccines Help Against Omicron?Vaccination or boosters are recommended now, and although we can’t be sure this will protect us from Omicron, waiting for the development and approval of a modified vaccine is not a wise choice. Delta is causing >99% of all infections in the United States now, and cases are rising again. This graph from The Economist shows how poorly we are doing with boosters in all. Data on primary vaccination for those <18 are not accurate in this graph. According to the AAP, 60% of 12-17 year-olds have received at least one dose and 51% have been fully vaccinated. 15% of 5-11 year-olds have received one dose.

Benefit of Boosters in IsraelA preliminary retrospective case-control study done in 306,710 subjects 40 years and older compared those who received a booster and those who received two doses. There was an estimated OR of 0.14 (95% CI, 0.13-0.15) of testing positive for SARS-CoV-2 28-65 days following receipt of the booster (86% reduction in odds).

Current State of Vaccine MandatesBoth CMS and OSHA mandates for healthcare workers and employees of companies with over 100 employees respectively have been temporarily halted by the courts. As of mid-September, 46 states proposed or enacted 148 legal interventions to impede or facilitate vaccine mandates. 88.5% were undertaken to impede mandates, with 11.5% to facilitate. Despite the majority of interventions to impede mandates, interventions to facilitate were more likely to be enacted (70.6% vs. 32.8%). Read more here.

Pfizer to Seek Full Authorization For Ages 12-15In a recent press release, Pfizer announced that its mRNA vaccine was 100% effective against COVID-19 measured 7 days through over 4 months after the second dose. They are also applying for an adjustment to the EUA to include boosters for 16-17 year-olds.

Treatment

Inhaled Steroids For Mild COVID-19 InfectionIn July, a previous COVID-19 Response Task Force message reported on a U.K. study of an open-labelled, parallel group randomized trial involving 146 patients of inhaled budesonide (Turbohaler) 800mcg twice daily in adults within 7 days of onset of mild COVID-19 symptoms. The result was a significant reduction in the need for ER care or hospitalization, and a more rapid reduction in symptoms. In this study published online November 22, which was a randomized, placebo controlled trial involving 400 patients treated with inhaled ciclesonide 320mcg twice daily or placebo, there was also a reduction in the need for ER care or hospitalization in the treated group, although no difference in resolution of symptoms.

FDA Advisory Panel Narrowly Recommends Approval of MolnupiravirIn a vote of 13-10, the panel recommended an EUA for Merck’s treatment, even though updated data on their ongoing clinical trial indicated a 30% reduction in severe illness compared to initial findings of 50%. There is no information yet on Pfizer’s drug.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAIChair of the AAAAI COVID-19 Response Task Force


Tuesday, November 23, 2021

Here are today's important updates:

On Behalf of the Task Force, Have a Safe and Happy ThanksgivingConsider gatherings of vaccinated individuals only. If that is not possible, outdoors is better than indoors, or consider rapid antigen testing on Tuesday and again on Thursday for those that are not fully vaccinated. These can be done at home with tests purchased at your local pharmacy.

Vaccines

Boosters Approved for AllThe FDA and CDC have approved boosters of Pfizer, Moderna and J&J for all over 18. For those ages 18-49 that have no medical comorbidities and are not at high risk because of living or work environments, a booster may be obtained. For all others, especially those over 50, a booster should be obtained.

Joint Statement Supporting OSHA COVID Vaccination or Testing RequirementThe AAAAI has joined dozens of other medical organizations, including the AMA, ACP and AAP in a joint statement urging the nation’s business community to follow OSHA’s requirement that large employers ensure their workers are fully vaccinated or tested weekly for COVID-19. For our nation to return to “normal” we need to vaccinate roughly 80 million more people. OSHA’s requirements are an important step toward getting us to that goal.

Real Life Effectiveness of a Booster DoseIn this study from Israel involving over 1,400,000 patients, those who received a third mRNA vaccine dose between July 2020 and September 2021 were matched 1:1 to demographically and clinically similar controls who had only two doses of vaccine with the second dose 5 months or more before. Vaccine effectiveness for prevention of hospitalization or death evaluated at least 7 days after receipt of the third dose, compared with only receiving two doses at least 5 months previously, was estimated to be 93% (231 events for two doses vs. 29 for three doses) for admission, 92% for severe disease (157 vs. 17 events) and 81% for death (44 vs. seven events).

Breakthrough Infection Less in Those With Prior InfectionIn a matched cohort study in Qatar involving 157,000 mRNA vaccinated patients with prior COVID-19 infection (including asymptomatic and mild disease) and 460,000 vaccinated patients without prior infection, the cumulative infection incidence was significantly lower in those with prior infection.

Vaccination Reduces Long COVIDTwo studies have shown that vaccination can reduce the incidence of long COVID or post-acute sequelae of COVID-19 (PASC). In the first study in healthcare workers from Israel, 19% of those with breakthrough infections had symptoms lasting longer than 6 weeks. In the second study, which involved over 1.2 million adults, the rate of long COVID in fully vaccinated patients with breakthrough infections was half that of unvaccinated.

Utility of Skin Testing for Evaluation of Vaccine or Potential Vaccine ReactionsThis small retrospective study from three Mayo Clinic sites evaluated 129 patients with either an allergic reaction to a first vaccine dose (55 patients) or a history of an allergic reaction to an excipient of the vaccine (74 patients). Results indicate that skin testing to PEG, polysorbate or vaccine is uncommonly positive and most patients tolerate vaccination. Only small numbers of these patients had moderate to severe anaphylaxis. The authors suggest that excipient skin testing may be of minimal value.

Do Vaccinated Healthcare Workers (HCWs) Need to Quarantine for 14 Days If COVID Positive?In this study, 2,397 fully vaccinated HCWs received PCR tests every 2-4 weeks, then daily if positive, until two consecutive tests were negative. A total of 33 workers (1.3%) tested positive and were asymptomatic. Eight (0.4%) were positive and symptomatic. All 33 of the asymptomatic cases were negative on testing the next day and subsequent tests 1 day later. IgG levels were higher in the asymptomatic compared to symptomatic cases. Because of the rapid clearance in the positive patients, the study likely missed many asymptomatic patients. Without more frequent testing, the true frequency of breakthrough asymptomatic infections cannot be determined by this study, although based on the rapid clearance of virus the authors speculate that 14-day quarantines may not be necessary.

CDC Vaccine Rollout "Close to Perfect"There have been many who have criticized the vaccine rollout in this country, but this mathematical study using a supercomputer compared the CDC strategy with 17.5 million possible strategies that also staggered rollout in phases, found that the CDC plan performed within 4% of perfect in all four measures (total deaths, cases, infections and years of life lost). U.S. vaccine rollout was close to optimal at reducing deaths and infections, according to a model comparing 17.5 million alternative approaches.

Infection

What Makes the Delta Variant More TransmissibleAn in-vitro study by investigators at Boston Children’s showed that the spike protein of the Delta variant rapidly fuses with cells for entry, using low levels of ACE2 receptor. This may contribute to its infectiousness. In another study, NIH-funded investigators, using research involving virus-like particles, discovered that a specific mutation in the N protein coding region of the Delta genome enabled the virus to pack more of its RNA code into the infected host cell, leading to increased production of fully functional new viral particles. All of the other variants of concern contain a mutation in the same region of the genome. The authors comment that the N protein could be a promising target for therapeutics.

NIH to Begin Long-Term Study of Children With COVID-19This study, supported by the NIAID, will enroll 1,000 children and young adults who previously tested positive for COVID-19 and evaluate the impact on their mental and physical health over a 3-year period. The investigators will also be looking at long-term immune responses, immunological and genetic risk factors. Household members who were not infected will serve as a cohort control. The study will take place at the NIH Clinical Research Center and the Children’s National Hospital.

Treatment

More About Pfizer's Antiviral PaxlovidPfizer has announced that they are seeking an EUA for their 5-day COVID-19 drug treatment. In the clinical trial mentioned in the previous Task Force message, the drug was 89% effective in reducing hospitalization, so much so that the trial was stopped. This compares to the 50% effectiveness of Merck’s molnupiravir. Paxlovid contains a protease inhibitor that inhibits the viral proteases that are crucial for the virus life cycle. Thus mutations in the spike protein would not alter the effectiveness of the drug. The protease inhibitor is combined with a low dose of ritonavir, which slows the metabolism of the protease inhibitor.

Early Treatment With Monoclonal Antibody SotrovimabThis ongoing phase 3 trial involving 583 high-risk patients with symptomatic COVID-19 5 days or less after symptom onset, showed a relative risk reduction for hospitalization or death of 85% (97.24% CI, 44-96). Three patients in the treated group as compared with 21 patients in the placebo group had disease progression leading to hospitalization or death.

Practice

CMS Announces Automatic Exemption for MIPS 2021 Reporting YearThis only applies to individual eligible physicians. The individuals will receive an automatic neutral payment adjustment for the 2023 MIPS payment year. The automatic exemption notably does not apply to eligible clinicians participating in groups, virtual groups, or as an Alternative Payment Model (APM) entity. CMS noted that group and APM participation is optional and individually eligible MIPS eligible clinicians will qualify for the automatic exemption if they do not report data at the group level. You can read more here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAIChair of the AAAAI COVID-19 Response Task Force


Monday, November 15, 2021

Here are today's important updates:

Vaccines

Effectiveness of mRNA Vaccine Against Hospitalization in Immunocompromised - Data From Nine StatesTo evaluate vaccine effectiveness (VE) among immunocompromised adults, data from the VISION Network on hospitalizations among persons aged 18 years and older with COVID-19–like illness from 187 hospitals in nine states during January 17–September 5, 2021 were analyzed. Using a test-negative design comparing 20,101 immunocompromised adults (10,564 [53%] of whom were fully vaccinated) and 69,116 immunocompetent adults (29,456 [43%] of whom were fully vaccinated). VE of two doses of mRNA COVID-19 vaccine against COVID-19–associated hospitalization was lower among immunocompromised patients (77%; 95% confidence interval [CI] = 74%–80%) than among immunocompetent patients (90%; 95% CI = 89%–91%). VE varied across immunocompromising condition subgroups, ranging from 59% (organ or stem cell transplant recipients) to 81% (persons with a rheumatologic or inflammatory disorder). Immunocompromised persons receiving mRNA COVID-19 vaccines should receive three doses and a booster, consistent with CDC recommendations, practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes.

Summary of CMS and OSHA Federal Vaccine Mandates, Updated CDC Guidance on Pre-Vaccine Risks and Post-Vaccine Reactions Related to Administering mRNA Vaccines Added to AAAAI COVID-19 Resources PageThese CMS interim final rules recently released do not apply to physicians' practices if they are not directly regulated by CMS. Physicians may face other requirements if they are on the staff of an acute care hospital. The OSHA rules also do not apply, but physicians' offices may already be covered by the OSHA Emergency Temporary Standard (ETS) that went into effect in January of 2021. A summary of these rules has been posted to the AAAAI COVID-19 resources page.

The AAAAI COVID-19 resources page also describes how the CDC recently updated their guidance on administration of the SARS-CoV-2 mRNA vaccines with respect to pre-vaccine risks and post-vaccine reactions. You can read more on our Vaccine Reactions page.

Vaccine Boosters in Older PatientsThis study from Israel on 97 healthcare workers and/or family members aged 60 years and older found that a booster dose of Pfizer vaccine increased IgG anti-spike antibody titers from a mean of 440 AU/ml (AU = arbitrary units) to 25,468 AU/ml 10-19 days after the booster dose. No correlation was observed between age and IgG titers, but the mean age of patient was 70 years (so narrow age range). Age, sex, presence of comorbidities and days after first vaccination was not associated with higher IgG titers.

Counseling Parents of Our Pediatric Patients About VaccinationThis editorial from JAMA presents useful information about pediatric vaccination. “Severe illness has been uncommon among the more than 6 million children who have tested positive for SARS-CoV-2. Depending on the state, 0.1% to 2.0% and 0.00% to 0.03% of pediatric COVID-19 cases resulted in hospitalization and death, respectively. As of October 4, 2021, a total of 5,217 cases of multisystem inflammatory syndrome in children (MIS-C) and 46 MIS-C deaths have been reported. The risk of severe illness and death is greater for children older than 10 years. Although the percentage of severe illness among pediatric cases is small, as infections increase, so too will the number of children who become seriously ill. At least 1.9 million children aged 5 to 11 years have been infected with SARS-CoV-2 and more than 8,300 of them have been hospitalized, a third of whom needed intensive care. Nearly 100 children aged 5 to 11 years have died, making COVID-19 among the leading causes of death in this age group. Hospitalization rates among children aged 5 to 11 years are 3 times higher for Black, Hispanic, or Native American children than for White children, with rates of 45 to 50 per 100,000 children vs 15 per 100,000 children, respectively. Data from adolescents suggest that BNT162b2 vaccinations for children 5 to 11 years old will likely prevent most hospitalizations and deaths.”

Details concerning the CDC assessment of vaccines for children ages 5-11 can be found here.

Delayed Angioedema After mRNA VaccineThis group from Northwestern reports three patients with angioedema that presented a mean of 39 hours after the vaccine and involved the airway in all three. They were all treated with epinephrine and steroids, and resolved within 24 hours. Serum tryptase was normal. One of the three received a second dose of the same vaccine 6 months later without any reaction.

AAAAI Podcast on COVID-19 Vaccination During PregnancyThis podcast episode (#59), featuring Jennifer Namazy, MD, FAAAAI, is now available for free on the AAAAI websiteApple or Google Podcasts, and Spotify.

Infection

U.S. Cases Plateau But European Cases IncreasingAccording to data from Johns Hopkins, cases in Europe are increasing exponentially, a potential bellwether for the near future for the United States. Europe has a higher vaccination rate than the United States. Currently the wave in Europe is being driven by all age groups. Get those boosters!

NIH Tool to Help Individuals on When to TestOn November 3, the NIH announced a tool to help individuals determine if they are at risk of getting or transmitting COVID-19, and whether and when they should be tested. The calculator includes answers to frequently asked questions and links both to resources on testing strategies and on obtaining supplies, including home tests. The test is simple, has only a few prompts and can be found at whentotest.org.

Treatment

Regeron Announces Long-Lasting Effect of COVID-19 Monoclonal AntibodyOn November 8, Regeneron announced additional results from a Phase 3 study, done jointly with the NIAID, on 1,683 uninfected, high-risk patients treated pre- or post-exposure with monoclonal antibody or placebo during months 2-8 of follow-up. There was an 81.6% reduced risk of developing COVID-19 during this time, and zero treated patients were hospitalized, compared to six in the placebo group. Vaccination was allowed after the first month, but was balanced between the treatment and placebo group. These results have not been published or peer-reviewed, but details of the study are available in the press release.

Pfizer Announces a New Anti-Viral Oral Treatment for COVID-19On November 5, Pfizer announced that its antiviral drug Paxlovid when given to high-risk infected patients within 3 days of symptom onset was 89% effective in reducing the risk of hospitalization and death (three hospitalizations and zero deaths in treated group vs. 27 hospitalizations and seven deaths in the placebo group). The study involved a total of 774 patients. The results of the clinical trial have not been peer-reviewed or published.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAIChair of the AAAAI COVID-19 Response Task Force


Wednesday, November 3, 2021

The Centers for Disease Control and Prevention (CDC) Tuesday recommended giving the Pfizer-BioNTech COVID-19 vaccine to children ages 5- to 11-years-old beginning as early as today (Wednesday, November 3, 2021).  

The recommendation follows a unanimous vote earlier in the day by the CDC’s Advisory Committee on Immunization Practices (ACIP) to recommend the vaccine under the FDA’s Emergency Use Authorization. 

The vaccine will be administered as a primary series of 2 doses 3 weeks apart. The dose is one-third of that given to adults and adolescents (10mcg vs. 30mcg).

Allergists should encourage their patients in this age group to contact their primary care physicians now to get on the list for vaccination. Doses have already been delivered to many states, if not all.

During a daylong meeting Tuesday, the ACIP was presented with robust data on efficacy and safety of the vaccine in this age group. They also heard presentations on the rapid rise in cases among children, as well as data on vaccine-associated Myocarditis

To date, there have been at least 1.9 million COVID-19 cases in the 5-11 age group, including 8,300 hospitalizations and 84 deaths, according to CDC data. You can find all of the presentations from Tuesday’s meeting here

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page for regular updates and information that can help you advise parents and your patients about the vaccine.  


Monday, November 1, 2021

Here are today's important updates:

Public Health Emergency (PHE)

HHS Extends the PHE Until January 18This means that the telehealth waivers will remain in effect and many insurers are extending their coverage allowances, but not all. Be sure and check with the patient’s carrier before COVID-19 vaccination, viral testing, antibody testing or monoclonal antibody therapy.

Vaccines

CDC Recommendation for a "Booster Dose" for Moderate to Severe ImmunocompromisedWe know about the “additional dose” for this group of people, but the CDC just updated information on a booster dose for this group. Moderately and severely immunocompromised people aged 18 years and older who completed an mRNA COVID-19 vaccine primary series and received an additional mRNA vaccine dose may receive a single COVID-19 booster dose (Pfizer-BioNTech, Moderna, or Janssen) at least 6 months after completing their third mRNA vaccine dose. In such situations, people who are moderately and severely immunocompromised may receive a total of four COVID-19 vaccine doses. A person who is moderately or severely immunocompromised and has received two doses of an mRNA vaccine and at least 28 days has elapsed since the second dose, should receive an additional mRNA dose immediately* (if Moderna COVID-19 vaccine is used, administer 100µg in 0.5ml), followed at least 6 months later by a single COVID-19 vaccine booster dose (if Moderna vaccine booster is used, administer 50µg in 0.25ml). 

Vaccine Effectiveness Against Hospitalization in Adolescentscase-control study involving 464 patients 12-18 years in 19 pediatric hospitals from June-September 2021 found that vaccination reduced risk for hospitalization by 93%. Of adolescents that were hospitalized for COVID-19, 97% were unvaccinated, and no vaccinated adolescents hospitalized with COVID-19 were admitted to the ICU. Since adolescents are lagging behind other groups in vaccination, this information might be helpful in discussing it with them or their parents. 

Vaccines for ChildrenThe FDA’s Vaccines and Related Biologics Advisory Committee (VRBAC) voted unanimously with one abstention to recommend Pfizer’s mRNA vaccine for children ages 5-11 at 1/3 the normal dose. Moderna’s application for approval for children ages 12-18 is still pending. The FDA followed VRBAC’s recommendation and granted an emergency use authorization on October 29. The ACIP will be meeting November 2-3 to discuss children and adolescent vaccines for COVID-19. This meeting will be open to the public here. Interestingly, pediatric doses are already being delivered to states in anticipation of approval.

Vaccine ReactionsEvidence from a prospective vaccine registry study in a single large health system found that of 113 patients with a history of reactions to the first dose of an mRNA vaccine, 86.7% tolerated the second dose when given under allergy clinic observation with antihistamine pre-treatment, and that PEG testing and challenges were not helpful, with a large number of false positives. Testing to the vaccine was not performed because the FDA required an IND for this and the companies would not provide vaccine. This included 4/5 with a history of anaphylaxis. This is one of a number of small studies on patients with allergic reactions to mRNA vaccines who have gone on to have subsequent vaccination with the same vaccine with tolerance. Testing to PEG has also not been helpful in a number of studies. 

In a second study reported in the same journal, a group from Michigan reported a retrospective study of 66 patients with alleged allergic reactions to their first vaccine (only one with anaphylaxis) and 80% successfully received their second vaccine

In another cohort study of 52,998 healthcare workers at the Massachusetts General Brigham Health System, self-reported high-risk allergy history was associated with an increased risk of self-reported allergic reactions after mRNA COVID-19 vaccination (adjusted Relative Risk 2.46; 95% CI, 1.92-3.16) with risk being highest for hives and angioedema. “However, following the CDC guidelines, with allergist consultation, risk stratification, and shared decision-making, all employees were able to complete the 2-dose vaccine series.” 

COVID-19 Hospital Admissions and Deaths After Vaccination 
We are hearing a lot about breakthrough infections, hospitalizations and death in vaccinated individuals, often as an excuse to not get the vaccine. This prospective study from Scotland who followed 2,572,008 individuals who had received their first dose of vaccine between December 2020 and April 2021 (32.7% received Pfizer, 67.3% AstraZeneca). 694,915 received a second vaccine dose during the study period (59.4% Pfizer). 1,196 (<0.1%) were hospitalized or died (883 hospitalized, 228 of these died, and 313 died without being hospitalized). Factors associated with severe disease were older age (>79), comorbidities, high-risk occupations, care home residence, socioeconomic deprivation, being male and being an ex-smoker, in that order. It is important to note that only 1/3 of this group received an mRNA vaccine, and most had not received a second dose. The rate of severe outcomes was similar for the two vaccines, however. 

Vaccinated Less Likely to Be Hospitalized With Subsequent COVID-19 Compared to Previously Infected People Data from nine states showed that among COVID-19-like illness hospitalizations among adults aged 18 years and older whose previous infection or vaccination occurred 90 to 179 days earlier, the adjusted odds of laboratory-confirmed COVID-19 among unvaccinated adults with previous SARS-CoV-2 infection were 5.49-fold higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine who had no previous documented infection (95% CI = 2.75-10.99). 

Lower Risk of Non-COVID Death After VaccinationThere have been reports of death after COVID-19 vaccination on the VAERS website, and much disinformation on social media regarding the same. In a study of 11,000,000 patients enrolled in the Vaccine Safety Datalink (VSD) researchers found that the rate of non-COVID deaths were over 65% lower in those vaccinated compared to those who were not vaccinated. This reinforces the safety of the vaccinations and adds to an earlier study that showed a similar reduction in mortality in nursing home residents.

Booster Provides Higher Antibody Response Which Is Sustained Researchers from the Vaccine Research Center of the NIAID with collaborators from Emory, Hopkins, Moderna and Bioqual studied booster doses of Moderna vaccine in Rhesus macaques and found the antibody response to be higher than after the primary series, sustained for at least 8 weeks, and were protective against all variants of concern. This study was focused on the Beta variant, which is more resistant to neutralization than the current Delta variant. 

Vaccinated Less Likely to Be Infected With Household Contacts But Just As Likely to Spread Disease This study confirms earlier findings. Fully vaccinated individuals who are infected are equally likely to spread the infection among household contacts as unvaccinated household members, but are less likely to be infected by other household members. Fully vaccinated had a faster reduction in viral load. 

Infection

CDC Data Tracker Now Reporting Rates of COVID-19 Cases, Hospitalizations and Death By Vaccinations Status Visit this page.

Delta Plus: Is It Important?Cases of COVID-19 have been increasing in the United Kingdom lately, with the current peak higher than during the earlier Delta peak. Some have been blaming this on the AY.4.2 Delta mutant strain that is currently present in about 10% of U.K. sequenced samples. This mutation is only 10-15% more transmissible than the original Delta, and appears to be susceptible to the current vaccines. This mutation is present in the United States, but makes up <0.5% of variants

Does the Delta Variant Cause More Severe Disease?It is well established that the Delta variant is more transmissible, but there is some disagreement on disease severity. Analysis of COVID-NET data from 14 states during the period of Delta predominance did not indicate an increase in the proportion of hospitalized patients with severe outcomes. The proportion of hospitalized unvaccinated persons ages 18-49 did increase significantly during this period. 

No Increased Risk in EoE PatientsInformation from a global registry of EOE and EGID patients published online in JACI: In Practice suggests that these patients are at no more risk for severe disease than the general population. 

Residual Cognitive Effects CommonIn this case-control prospective cohort study in patients within the Mount Sinai Health System in patients with mild to severe disease, 18-25% had cognitive deficits at a mean of 7.6 months after infection. The most prominent deficits were in processing speed (18%, n=133), executive functioning (16%, n=118), phonemic fluency (15%, n=111) and category fluency (20%, n=148), memory encoding (24%, n=178), and memory recall (23%, n=170). Mean age of the population was 49 years

Treatment

Antidepressant Reduces Risk of Hospitalization for COVID-19In case your patients mention this: A multi-center randomized, placebo-controlled, adaptive platform blinded trial in Brazil involved almost 1,500 high-risk patients. Those treated with fluvoxamine, an SSRI anti-depressant, 100mg twice daily for 10 days were less likely to be hospitalized (11% vs. 16%, RR 0.68, 95% CI 0.52-0.88).

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAIChair of the AAAAI COVID-19 Response Task Force


Friday, October 22, 2021

The Centers for Disease Control and Prevention (CDC) Thursday night expanded its recommendations for COVID-19 vaccine booster shots for certain populations to include the Moderna and Janssen (Johnson & Johnson) vaccines. The recommendation followed the CDC’s Advisory Committee on Immunization Practices (ACIP) endorsement of the boosters earlier in the day. The FDA granted Emergency Use Authorization of the boosters Wednesday.

The CDC also said eligible people can “mix and match” and choose to receive a booster vaccine that is different from the one they received for their initial series.

The recommendations call for:

  • A single COVID-19 vaccine booster dose at least six months after completion of an mRNA primary series for certain populations. The dose for the Moderna booster would be half that given during the primary series. The booster is recommended for individuals in the same risk groups identified when the Pfizer-BiNTech vaccine was approved last month, including those who are:
  • The use of a single booster dose of the Janssen (Johnson and Johnson) COVID-19 Vaccine at least two months after completion of the single-dose primary regimen to anyone 18 years of age and older. The dose would be the same as the primary dose.

In making its recommendation, the advisory panel stressed that people who have received two mRNA vaccine doses or a single Johnson & Johnson dose should still consider themselves fully vaccinated. Federal health officials said they would continue to study whether those who had weak immune systems and had already received a third dose of a vaccine should go on to get a booster shot.

Clinician Outreach and Communication Activity (COCA) will host a webinar on Tuesday, October 26 intended to give clinicians an overview of the most recent recommendations for administering COVID-19 booster vaccines.

The AAAAI COVID Resources page continues to be updated to provide you with resources and advice to provide optimal care to your patients during this time.


Monday, October 18, 2021

Here are today's important updates:

Vaccines

COVID-19 Breakthrough Infections in Healthcare Workers (HCW)
This case-control study from Israel involving 1,497 fully vaccinated HCWs documented 39 COVID-19 breakthrough infections (2.6%). Neutralizing antibody titers were lower in case patients (case-control ratio 0.361; 95% CI, 0.165-0.787). Higher peri-infection titers were associated with lower infectivity as measured by RT/PCR Ct values. Most cases were mild or asymptomatic, but 19% had symptoms that persisted for more than 6 weeks. Alpha variant was found in 85% of sequenced samples. 

FDA Advisory Committee Meets to Review Authorization for Booster for Moderna, J&J and Pfizer Application for Ages 5-11
The Vaccines and Related Biologics Advisory Committee (VRBPAC) met on October 14 and 15 and unaniminously recommended that Moderna be granted an EUA for a booster dose after 6 months for those 65 years of age and older, as well as 18-64 year-olds with risk of severe infection or high exposure, so essentially the same as Pfizer’s criteria. The recommended dose is 1/2 the dose (50mcg or 2.5cc) used in the primary series. They also recommended a second dose of the J&J vaccine for all recipients at least 2 months after the first dose. The FDA will need to consider the Advisory Committee’s recommendation and rule on it. The CDC's ACIP will meet to discuss this on October 20 and 21 with possible approval shortly after. VRBPAC will meet again on October 26 from 8:30 am to 5:00 pm ET to discuss Pfizer’s application for vaccine for 5-11 year-olds.

Real World Data on Myocarditis After mRNA Vaccines
This retrospective study from a large healthcare system in California on 2,393,924 patients who had received at least one dose of an mRNA vaccine noted an observed incidence of 0.8 cases per million after the first dose and 5.8 cases per million after the second dose, all occurring in males with median age of 25. This compares to 1.8 cases per million in controls, 52% in men, with a median age of 52. Most cases were mild and resolved with conservative management. 

Mix and Match Vaccine Effect
Media reports have highlighted the initial press releases surrounding an NIH study evaluating the effect on antibody production following booster doses of J&J, Pfizer and Moderna vaccines after initial dosing with J&J. The study has not been peer-reviewed and there has not been any official review by the FDA as of yet, so recommendations surrounding mixing different vaccines for booster doses are still forthcoming. 

Review Our Ask the AAAAI About COVID-19 Section 

A reminder that the AAAAI COVID-19 resources page includes an Ask the AAAAI About COVID-19 section where answers to member questions on vaccinesimmunocompromised patients and more are being posted. Have a question that has not been answered? Email it to practicematters@aaaai.org.

Transmission

Previous Infection or Complete Vaccination Offer Protection Against Family Member Disease
This cohort study of 1,789,728 individuals from 814,806 families in Sweden showed that the presence of one family member with either previous COVID-19 infection or complete vaccination was associated with a 45-61% reduced risk of contracting COVID-19. Risk reduction increased to 75-86% in families with two immune members, and 91-94% with three immune family members. Take home message: For the protection of vulnerable family members, it is important to immunize as many members of the household that are eligible for vaccination. 

Infection Risk Similar Between Children and Adults
cohort study of 1,236 participants in 310 households in Utah and New York City found that the incidence rates for infection with COVID-19 were similar in children and adults. Children were much less likely to be symptomatic than adults (50% versus 88%), but household transmission was 44% in Utah and 80% in New York City. With approval for pediatric vaccines likely in the next few weeks, parents will be asking our advice on whether their children should be vaccinated. Pediatric hospitalization rates are increasing with the Delta variant, asymptomatic children can transmit disease, and even though children are less likely to have severe disease, infection is likely to increase the risk for the development of variants of concern. Two editorials (here and here) accompanied the publication of this study. 

Multicomponent Strategies to Prevent COVID-19
Although this study was done in summer camps, the implications apply to other congregate settings, such as schools. During June-August 2021, among 7,173 campers and staff in nine overnight camps that utilized high vaccination coverage (93% of those eligible vaccinated), prearrival and frequent screening testing, cohorting, masking and physical distancing, there were nine cases of COVID-19. In contrast, in Louisiana summer camps this past summer, where Delta was dominant and transmission was high, there were 321 camp-associated cases among 2,988 campers and staff. Most were not vaccinated and only one of 28 camps required indoor masking. 

Infection

Latest on Long-term Post-Acute Sequelae of COVID-19 Infection (PASC)
This systematic review of 57 studies comprising more than 250,000 survivors of COVID-19 provides evidence that PASC affects 55% of survivors 6 months or more after infection. The most common sequelae included mental health, pulmonary and neurological disorders. It should be noted that 79% of the patients in these studies had been hospitalized with COVID-19. 

Treatment

Merck Applies for Approval of Oral Therapy  
Merck has applied to the FDA for approval for the first oral antiviral treatment for COVID-19. The treatment, molnupiravir, is given as four capsules twice daily for 5 days in patients with symptoms of COVID-19 within the last 5 days and who are at high risk for severe disease. Clinical trials of this agent have shown a 50% reduction in hospitalizations and death from COVID-19.

Monoclonal Antibody Treatment Criteria 
The NIH COVID-19 Treatment Guidelines Panel updated their recommendation for monoclonal antibody treatment on October 7, to reflect current supply constraints. Unvaccinated patients with COVID-19 should be prioritized to receive monoclonal antibodies. Pre-exposure prophylaxis is a lower priority when supply of product is inadequate. 

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, October 4, 2021

Here are today's important updates:

Vaccines

Reaction to Booster Doses of Pfizer Vaccine Similar to Reactions After the Second Dose 
During August 12-September 19, 2021, among 12,591 v-safe registrants who completed a health check-in survey after all three doses of an mRNA COVID-19 vaccine, 79.4% and 74.1% reported local or systemic reactions, respectively, after the third dose; 77.6% and 76.5% reported local or systemic reactions after the second dose, respectively. So far there is no evidence for increased cases of myocarditis, but only 22,000+ responses have been logged to date.

Possible Mechanism of Allergic Reaction
In this small but interesting study, researchers from Stanford studied 22 patients with a suspected history of an allergic reaction to an mRNA vaccine with skin tests to PEG, polysorbate 80 (P80) and the vaccine which they were given, as well as basophil activation testing (BAT) to the same antigens, and IgG and IgE to PEG. Seventeen out of 22 patients fulfilled the Brighton Criteria for anaphylaxis. None had positive skin tests to PEG or P80, and one had a positive skin test to the vaccine. Ten out of 11 had a positive BAT to PEG, and 11 out of 11 had a positive BAT to their vaccine. None had anti-PEG IgE, but all had anti-PEG IgG. Only one of the patients had received a second dose of the same vaccine, with a subsequent more severe reaction. That patient’s skin tests were negative, but skin testing reproduced the symptoms. Clearly more data is needed, but this might suggest that the anaphylactic reactions that are occurring are mediated by IgG.

CDC Urges Vaccine for Pregnant and Women of Childbearing Age
Released on September 29 from the CDC Health Alert Network, “the Centers for Disease Control and Prevention (CDC) recommends urgent action to increase Coronavirus Disease 2019 (COVID-19) vaccination among people who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future.” As of September 27, 2021, more than 125,000 laboratory-confirmed COVID-19 cases have been reported in pregnant people, including more than 22,000 hospitalized cases and 161 deaths. This doesn’t directly apply to the practice of allergy, but we can add this as another reason to encourage vaccination in our female patients.

Immunology of COVID-19 Infection

Anti-Interferon (IFN) Antibodies Tied to Severity
Researchers from the international COVID Human Genetic Effort have found that 20% of people hospitalized with severe COVID-19 had high or intermediate levels of autoantibodies to Type 1 IFNs, whereas people with mild disease and uninfected controls had very low levels of these autoantibodies. The level was also associated with age. Most with high levels were over 40. The study involved 3,500 people with severe or fatal disease and 34,000 uninfected volunteers. Testing for these autoantibodies in the future could help identify uninfected people who need aggressive preventive measures or infected people who need early aggressive treatment.

Testing

Interpreting SARS-CoV-2 Test Results
This article presents a concise and brief case-based discussion on testing which is helpful for the clinician.

Test Frequency and Turnaround Time More Important Than Sensitivity
We know that antigen testing has a lower sensitivity than RT-PCR for the diagnosis of COVID-19, particularly in asymptomatic people. Using modeling, this paper found little difference in averting infectiousness between frequent antigen testing (daily to every third day) and RT-PCR, and that testing frequency was found to be the primary driver of population-level epidemic control with only a small margin of improvement by using a more sensitive test. Delays in result reporting was a major factor in their analysis.

Infection

1 Year Outcomes in Hospital Survivors
This study from China looked at 1,276 hospitalized COVID-19 survivors at 6 months and 12 months post-discharge. The proportion of patients with at least one symptom declined from 68% at 6 months to 49% at 12 months, but the proportion of patients with dyspnea increased from 26% to 30%. Women appeared to be more affected than men. Spirometry was normal in most, but diffusion capacity was reduced in 23% at 12 months. Of the small number with CT scans (28), 39% still has at least one abnormality.

Masking and Prevention of School Outbreaks
A study from the CDC showed that based on county level data, after controlling for covariates, school mask requirements remained associated with lower daily case rates of pediatric COVID-19 (ß = -1.31; 95% confidence interval = -1.51 to -1.11) (p<0.001). Another CDC study done in Maricopa and Pima counties in Arizona found that schools without mask requirements were 3.5 times more likely to have COVID-19 outbreaks compared to schools that started the year with mask requirements.

Treatment

Inhaled Budesonide Treatment in Early COVID-19
This open-label, parallel-group randomized controlled trial in 139 people with early COVID-19 symptoms found that inhaled budesonide 800mcg twice daily started within 7 days of symptom-onset and continued until symptoms were resolved, resulted in a marked reduction in the need for an urgent care visit, ER or hospitalization, and reduced symptoms and symptom duration compared to usual care.

Monoclonal Antibodies to Prevent COVID-19
randomized, placebo controlled trial in over 1,500 patients 12 years of age or older who were treated with 1200mg of REGEN-COV subcutaneously within 96 hours of exposure to a household contact, found a relative risk reduction of 81.4% for symptomatic infection, 92.6% in weeks 2-4 after exposure, and an overall risk reduction for asymptomatic and symptomatic infection of 66.4%. There was also a 2 week shorter duration of symptoms in the treated group among symptomatic infected group.

Merck Seeks Authorization for New Antiviral Against SARS-CoV-2
An article in the New York Times reported that Merck will seek authorization for molnupiravir, which was shown in a clinical trial to reduce the risk for hospitalization or death by half if given to high-risk people early in the infection.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, September 20, 2021

Here are today's important updates:

Vaccines

Pfizer: Low Dose of Vaccine Safe and Effective in Children Ages 5 to 11 
Pfizer-BioNTech announced today that their studies show a 10 mcg dose (1/3 the adult dose) of their coronavirus vaccine results in a similar immune response to the higher dose in teens and adults. The companies plan to apply to the FDA by the end of the month for authorization to use the vaccine in these children. The findings have not yet been peer-reviewed nor published in a scientific journal.

Booster Doses – Yes/No – For Whom
On July 30, Israel approved a third (booster) dose of the Pfizer vaccine for people 60 years of age or older whose last vaccine dose was at least five months earlier. At least 12 days after the third dose, the rate of confirmed infection in the booster group was lower than the non-booster group by a factor of 11.3 (95% CI, 10.4-12.3); and the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9-29.5). Rates of infection at least 12 days after vaccination was lower by a factor of 5.4 compared to the rate after four to six days. On the other hand, a Viewpoint article written by several international experts including two scientists from the FDA’s Office of Vaccine Research and Review pointed out that the data supporting a third dose is preliminary and not very robust, and suggested that the vaccine focus should be on increasing the global number of people who have had at least one dose of a vaccine. These experts point out that the current variants causing the most problems (Delta and Gamma) both arose in countries with low vaccination rates. On September 17, the FDA Vaccine and Biologics Advisory Committee rejected Pfizer’s request to authorize a booster dose to all patients 16 years of age or older based on insufficient data but did approve a recommendation to authorize the vaccine booster for those over 65 years of age six months after the second dose and those at risk for severe infection. The full FDA, as well as the CDC and ACIP have to weigh in, and will probably meet this week.

Vaccine Effectiveness (VE) During Delta Predominance
This study examined the VE against infection, hospitalization and death before and during the period of Delta predominance. Across 13 U.S. jurisdictions, incidence rate ratios for hospitalization and death changed relatively little after the SARS-CoV-2 B.1.617.2 (Delta) variant reached predominance, suggesting high, continued vaccine effectiveness against severe COVID-19. Case IRRs decreased, suggesting reduced vaccine effectiveness for prevention of SARS-CoV-2 infections. Fully vaccinated people had five times lower risk of infection, and over 10 times lower risk for hospitalization and death compared to those not fully vaccinated. 

Using a different cohort among nine states which included several large health systems, during June through August of this year, VE against hospitalization was 86% (89% 18-74 years old vs. 76% for 75 and older)( Moderna 95% VE vs. 80% for Pfizer and 60% for J&J). VE for ER/Urgent Care visits was 82% overall (92% for Moderna, 77% for Pfizer, 66% for J&J). Data from the same health systems from January to June showed a VE of 89% against hospitalization, 90% against ICU admission and 91% against ER or Urgent Care visits. Finally, data from five VA Medical Centers from February to August showed similar results. Vaccine effectiveness in preventing COVID-19–related hospitalization was 80% among adults aged 65 years and older compared with 95% among adults aged 18–64 years.

ER Visits and Hospitalizations in Pediatrics
While the general impression among the public is that COVID-19 infections are milder in children, a recent report indicated how significant these infections really are, and that vaccines are effective in reducing severe disease even in children. This study demonstrated that ER visits and hospitalizations are four times greater in areas with low vaccine coverage compared to those with high vaccine coverage.  

Vaccination Reduces Household Transmission in Health Care Workers
This study from Scotland involved a large number of health care workers and their household members. The rate of household transmission was significantly lower after vaccination compared to the time prior to vaccination, suggesting that the vaccine may reduce transmission.

Additional Safety Information
Most of the reports on safety issues with the mRNA vaccines come from the Vaccine Adverse Events Reporting System (VAERS) which has significant limitations as previously discussed. This study used data from the Vaccine Safety Datalink which uses data entered on a regular basis on patients of several large health systems. The analysis included surveillance data on 6.2 million people who had received 11.8 million doses of mRNA vaccines and found no significant increase in 23 serious health care outcomes that had been followed during the clinical trials on the vaccines in the first 21 days after a vaccine dose, compared to matched patients with vaccination 22-42 days prior. Incidence of confirmed anaphylaxis was 4.8 per 1,000,000 doses. In an accompanying editorial, Kimberly G. Blumenthal, MD, MSc, FAAAAI, current Secretary of the AAAAI's ADDA Interest Section, and others further emphasize the findings of the study and do note that the risk for myocarditis/pericarditis was not significant overall. It was elevated in the 12-39 year old age group with an estimated 6.3 (95% CI, 4.9 to 6.8) additional cases per million doses in days zero through seven after vaccination. 

Vaccine Response in Stem Cell Transplant Patients
Results from a single center study of 117 patients with a previous allogeneic hematopoietic stem cell transplant without previous COVID-19 infection and no active graft vs. host disease showed that 83% of patients had an antibody response after the second dose of the Pfizer vaccine, with 62% of the group having similar titers to healthy vaccine recipients. Factors associated with an absence of response included a haplotransplant, recent (<1yr) HSCT, lymphopenia (<1000 cells/microliter) and receipt of immunosuppressive treatment at the time of the vaccination. This study was limited to antibody response, and did not evaluate T cell response.    

SARS-CoV-2

What About The “MU” (B.1.621) Variant?
This is currently considered a Variant of Interest (VOI) by the WHO, but has not been classified as such by the CDC at this time. It is present in most states, reached its peak in June and is declining since then, now representing 0.1% of all isolates. It is increasing in South America, with 39% of isolates in Colombia. It is of interest because of three mutations (in addition to the usual suspects) that affect the binding sites for monoclonal antibodies, antivirals and, perhaps more importantly, one on a location that inhibits B- and T-cell recognition. This was first discovered in Colombia and is another example of the importance of global vaccinations. 


Practice

Does Mandatory Vaccination of All Staff Apply to Your Practice?
In short, we don’t know yet. The Biden Administration announced that it "will require COVID-19 vaccination of staff within all Medicare and Medicaid-certified facilities.” Whether the typical allergy office is a “facility” as defined by CMS is not clear, and will be further defined in the development of the regulatory process. If you practice in a Federally Qualified Health Center or Rural Health Clinic or provide services under an arrangement with such a facility, then it will likely apply. Check in later messaging or the AAAAI COVID-19 Resource page for future developments.

Provider Relief Fund (PRF) Updates
HHS announced on September 16 a final 60 day grace period to help providers if they fail to meet the September 30 deadline for the first PRF Reporting Time Period. No collection activities or enforcement activities will occur during this time. HHS has completely revamped the PRF website and updated the FAQsQuestions relate to returning payments, period of time in which providers must use the payments, details on reporting of expenditures, audit extensions, eligible capital facility expenditures, and calculation of lost revenues. HHS announced it will make another $25.5 billion available to providers. This includes $8.5B for health care providers (HCPs) who serve rural Medicaid, CHIP or Medicare patients and $17B for a PRF Phase 4. PRF Phase 4 will reimburse smaller providers for their lost revenues and COVID-19 expenses at a higher rate compared to larger providers and will also include bonuses for those who serve Medicaid, CHIP and/or Medicare patients. Providers can apply for both programs in a single application. The application portal will open on September 29. 

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Tuesday, September 7, 2021

Here are today's important updates:

Vaccines

AAAAI Primary Immunodeficiency Committee Offers Advice on Who Needs an Additional Dose of the mRNA Vaccines
The AAAAI Primary Immunodeficiency (PIDD) Committee has reviewed available evidence on SARS-CoV-2 vaccine responses in patients with inborn errors of immunity (IEI), and acknowledges that information regarding the types of IEI that represent higher risk of either severe COVID-19 and/or suboptimal response to current SARS-CoV-2 vaccinations is still emerging. The AAAAI PIDD Committee endorses the third dose for people with immune deficiencies as it believes most patients will benefit from the extra dose. However, the timing and specifics should be discussed with one’s own immunologist.

Vaccine Effectiveness (VE) in Frontline Workers Before and After Delta Predominance
During December 14, 2020-April 10, 2021, data from the HEROES-RECOVER Cohorts, a network of prospective cohorts among frontline workers, showed that the Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines were approximately 90% effective in preventing symptomatic and asymptomatic infection with SARS-CoV-2 in real-world conditions. This report updates the VE estimates through August 14. Adjusted VE during Delta variant predominance (>50% of strains sequenced) was 66% (95% CI 26-84%), with a trend (not significant) toward lower VE in those with >150 days since completion of full vaccination. During this period, of those infected, 75% of the vaccinated were symptomatic versus 94.7% of the unvaccinated.

ACIP Meeting on August 30 and FDA Advisory Committee Meeting on September 17
At its August 30 meeting, the ACIP reaffirmed the FDA’s full approval for the Pfizer vaccine after reviewing the safety and efficacy data, and reaffirmed that the benefits outweigh the risks for vaccination. Data reviewed indicate that the rate of anaphylaxis after vaccination remains extremely low (5.0 per 1,000,000 doses), and that myocarditis is increased after mRNA vaccination, but cases are mostly mild and much less than with COVID-19 infection. They did not vote on booster doses, but shared information on continued vaccine effectiveness against severe disease and death. The ACIP will meet again in mid-September to discuss additional data on boosters. View the slides from this meeting.

The FDA’s Vaccine and Biological Products Advisory Committee will meet on September 17 from 8:30 am to 3:35 pm ET to discuss the Pfizer application for a booster dose. Here is the link to attend.

Infections and Hospitalizations By Vaccination Status
During May-July 25, 2021, among 43,127 SARS-CoV-2 infections in residents of Los Angeles County, Calfornia, 25.3% were in fully vaccinated persons, 3.3% in partially vaccinated persons, and 71.4% in unvaccinated persons. On July 25, infection and hospitalization rates among unvaccinated persons were 4.9 and 29.2 times, respectively, those in fully vaccinated persons.

Safety of the Pfizer Vaccine in a Nationwide Setting
This study from Israel examined adverse events in 884,828 matched vaccinated and unvaccinated persons and found an increased risk of myocarditis [risk difference (RD) 2.7 events per 100,000], lymphadenopathy (RD 78.4 events per 100,000), appendicitis (RD 5.0 events per 100,000) and herpes zoster infection (RD 15.8 events per 100,000). The risk of myocarditis from SARS-CoV-2 infection was six times higher than from vaccination.

Allergic Reactions to the Pfizer Vaccine
This cohort study from Israel involves 8,102 individuals with an allergy history. Using a detailed questionnaire, those with a history of prior anaphylactic reaction to any drug or vaccine, multiple drug allergies, multiple allergies, or mast cell disorders were considered high risk and vaccinated under medical supervision by a dedicated allergy team. Of the 429 individuals who were considered highly allergic, 97.9% had no reaction after the first dose, 1.4% developed minor allergic reactions, and 0.7% had anaphylactic reactions. Among the 281 who had a second dose during the study, 98.2% had no reaction, 1.8% had minor reactions and there were no anaphylactic reactions. This study reaffirms the safety of this vaccine and brings into question whether any screening is needed before vaccination.

FDA and AAP Warn Against Off-Label Use of the Pfizer Vaccine
There have been a significant number of children in the United States younger than 12 years who have been given this vaccine. Both the FDA and the AAP strongly advise against this. Studies are currently ongoing to determine the proper dose and to evaluate the response. Giving this vaccine off-label could threaten your liability protection.

NIH Launches Study of Additional Vaccine Dose in Patients With Autoimmune Disease
The NIH has begun a clinical trial to assess the antibody response to an extra dose of an authorized or approved COVID-19 vaccine in people with autoimmune disease who did not respond to an original COVID-19 vaccine regimen. The trial also will investigate whether pausing immunosuppressive therapy for autoimmune disease improves the antibody response to an extra dose of a COVID-19 vaccine in this population. The Phase 2 trial is sponsored and funded by the NIAID, part of NIH, and is being conducted by the NIAID-funded Autoimmunity Centers of Excellence.

Transmission

Delta Variant May Cause More Severe Disease
This cohort study published in Lancet Infectious Diseases on August 27 showed that the risk for hospitalization was about 45% greater with the Delta variant compared to the Alpha variant. This supports evidence presented earlier from Scotland where risk was 85% greater, and also involved younger people. 70% of the admissions were not associated with a comorbid condition.

Hospitalization Among Children and Adolescents
Weekly COVID-19-associated hospitalization rates among children and adolescents rose nearly five-fold during late June to mid-August 2021, coinciding with increased circulation of the highly transmissible SARS-CoV-2 Delta variant. The proportions of hospitalized children and adolescents with severe disease were similar before and during the period of Delta predominance. Hospitalization rates were 10 times higher among unvaccinated than among fully vaccinated adolescents.

Importance of Vaccines and Masks in the School Setting
The CDC reported an outbreak in Marin County, California in May-June of 2021 associated with an unvaccinated, symptomatic elementary teacher who was periodically unmasked, where 55% of her students were subsequently infected. The secondary attack rate was 80% in the rows closest to the teacher. The school had high adherence to masks among the students, six foot separation of desks and increased ventilation.

Guides for Masks for Children
Now that it is back to school time, some of your patient’s parents may ask which mask is best for their child. There are good resources here and here.

Practice

Time to Review CDC Guidelines for Healthcare Workers
As the entire United States is now considered an area of high transmission of COVID-19, the chances of one of your staff being exposed to a patient with COVID-19 is much higher. This would be a good time to review the CDC's Interim U.S. Guidance for Risk Assessment and Work Restrictions for Healthcare Personnel with Potential Exposure to SARS-CoV-2.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, August 23, 2021

Here are today's important updates:

Vaccines

FDA Grants Full Approval for Pfizer COVID-19 Vaccine for 16 Years and Older
The vaccine remains available under an EUA for 12-15 year-olds. Full approval for the 12-15 year-old patients remains a few months away.

FDA and CDC Advise Additional Dose of mRNA Vaccine
On August 12, the FDA amended the EUA for the Pfizer (for 12 years of age and older) and Moderna (for 18 years of age and older) vaccines to allow an additional dose for patients with moderate to severe immunosuppression or deficiency. This past week, the AAAAI sent a blast email to membership outlining more specifics about who that includes. This dose is called an “additional” dose and not a “booster,” as the latter term is reserved for those who had an adequate initial response which is waning over time. Since most allergist offices are not administering COVID-19 vaccines, you can inform your patients that they can get this at the pharmacy by attesting that they have such an immune deficiency (no proof needed) or you can communicate this to their primary physician if they are administering the vaccines. The additional dose should be given at least 28 days after the second dose, and should match the vaccine used in the primary series. In the rare instance that this is not possible, heterologous dosing is allowed (but only with the other mRNA vaccine). So far the data is insufficient concerning the J & J vaccine. Effective August 12, CMS will pay to administer additional doses of COVID-19 vaccines consistent with the FDA EUAs, using CPT code 0003A for the Pfizer vaccine and CPT code 0013A for the Moderna vaccine. They will pay the same amount to administer this additional dose as they did for other doses of the COVID-19 vaccine (approximately $40 each).

Booster Doses of mRNA Vaccines for All Likely to Begin September 20
Several news agencies reported on August 18 that the White House will announce booster doses of the mRNA vaccines would be authorized for all patients who completed their primary vaccine series 8 or more months ago. Although booster doses have not been approved yet by the FDA or CDC, heads of both agencies signed onto the announcement. The initial doses would be directed to healthcare workers, those over age 65 and residents of skilled nursing facilities and nursing homes. Data from the CMS-approved care facilities over the time period before and after the Delta variant became predominant show a progressive decline in vaccine effectiveness (VE) from 74.7% to 53.1%. This analysis could not distinguish between asymptomatic and symptomatic infection. Data from New York state showed a similar decline in age-adjusted VE from May 3-July 25 from 91.7% to 79.8% for any infection. The rate of infection in unvaccinated people was approximately 10 times the rate in vaccinated. Protection against hospitalization, on the other hand, was stable, from 91.9% to 95.3%. Data from 21 hospitals in 18 states from March to mid-July also showed VE against hospitalization remained steady for 24 weeks after vaccination (90% in immunocompetent adults).

Study Adds to Evidence That Previously Infected Benefit From Vaccination
Among Kentucky residents infected with SARS-CoV-2 in 2020, vaccination status of those reinfected during May-June 2021 was compared with that of residents who were not reinfected. In this case-control study, being unvaccinated was associated with 2.34 times the odds of reinfection compared with being fully vaccinated.

Half of Americans Fully Vaccinated
As of August 6, 165,918,256 people, or 50% of the total U.S. population, was fully vaccinated, while 182,368,493 or 70.6% of the adult population of the country had received one dose, according to the CDC. (Please note that the first figure reflects the entire U.S. population, while the second only the adult population.)

Vaccine Safety and Efficacy in Adolescents
Despite the earlier approval for the mRNA vaccines in adolescents, only a minority have received the vaccine. This update from the ongoing phase 2-3 placebo-controlled trial of the mRNA-1273 (Moderna) shows that local reactions (primarily injection site pain, swelling and erythema) occurred in 93.1% and 92.4% after the first and second dose respectively. 95% of these reactions were mild to moderate. Systemic reactions (headache, fatigue, chills were the most common) occurred in 68.5% and 86.1% respectively, with 85% being mild to moderate. Efficacy was similar to that in young adults. You can use this information to help convince your adolescent patients and their parents to consent to the vaccine. In another study, cardiologists report that in a small study of adolescents with myocarditis following the mRNA vaccine most tended to have a mild course, similar to young adults.

Vaccination Effects on Death and Dollars
This study estimated that by May 9, 2021, the U.S. vaccination campaign was associated with a reduction of 139,393 COVID-19 deaths. As of May 9, 2021, reductions in COVID-19 deaths associated with vaccines had translated to value of statistical life benefit ranging between $625 billion and $1.4 trillion.

Transmission

Pediatric Household Transmission of SARS-CoV-2 Infection
This study is particularly relevant as school reopens across the United States. It did take place prior to the dominance of the Delta variant. The study was done in Ontario, Canada and involved 6,280 households with pediatric index cases. 1,717 households (27.3%) experienced secondary transmission. The age group with the highest odds of transmitting the infection to household contacts compared with children aged 14-17 was the 0-3 year age group (1.43, 95% CI 1.17-1.75). Children in the 4-8 year age group also had a higher odds ratio (1.40, 95% CI 1.18-1.67). Since these age groups cannot be vaccinated, it is important for parents to take other precautions and be sure that the school or daycare is doing the same. As allergists who care for pediatric patients or young adults with children, we need to be aware of the family dynamics, childcare and school status in order to counsel our patients about prevention and precaution.

Treatment

Update on Monoclonal Antibodies
Current products that are available include casirivimab plus imdevimab (REGEN-COV) and sotrovimab. Current indications are for ambulatory adolescents and adults with mild-to-moderate COVID-19 who are at high risk of progression to severe disease. Treatment should be started ASAP and within 10 days of symptom onset. Casirivimab plus imdevimab can be administered IV or subcutaneously and have an expanded indication for post-exposure prophylaxis in individuals who are not fully vaccinated or are not expected to mount an adequate response to vaccination AND have been exposed to an infected individual or are at high risk of exposure to an infected individual because of infection occurring in the same institutional setting. Providers can directly order these medications from the distributor, AmerisourceBergen, although most will go through administration sites like hospital outpatient clinics. Details on dosing can be found on the NIH COVID-19 Treatment Guidelines page, and infusion sites close to your location can be found on the NICA Infusion Center Locator.

High-Titer Convalescent Plasma Not Effective
A randomized multi-center, placebo controlled single blind trial in 511 patients who presented to the ER for COVID-19 symptoms found that use of high-titer convalescent plasma was no better than placebo in preventing disease progression.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, August 9, 2021

Here are today's important updates:

Vaccines

NIAID/NIH Looking for Individuals With First Dose Allergic Reactions for Trial
The NIAID is looking for patients between the ages of 18-69 who experienced a systemic allergic reaction to the first dose of an mRNA vaccine for a clinical trial to study the safety of administering the second dose. Patients will be admitted to the ICU at the NIH and receive the second dose in a placebo-controlled crossover design. Patients will be compensated for their time, and travel to the NIH is covered. Interested people who qualify can contact the NIH Clinical Center Office of Patient Recruitment at (800) 411-1222 and refer to study #000460.

COVID-19 Vaccine Recommended for All Pregnant Women 
The American College of Obstetrics and Gynecology (ACOG) and the Society for Maternal and Fetal Medicine (SFMF) are now recommending that pregnant individuals be vaccinated against COVID-19. Allergists can use this information to reinforce vaccination for their pregnant asthmatics and allergic patients.

Second Dose of Vaccine Usually Tolerated in Those With Allergic Reactions to First
In this retrospective study from several different institutions involving 189 patients with a history of an allergic reaction after the first dose of mRNA vaccine, including 32 who met criteria for anaphylaxis, 159 patients (84%) tolerated a second dose, including 19 with first-dose anaphylaxis with mild reactions occurring in 32 (20%).

United States Reaches Vaccine Milestone
The United States now has 70% of adults with at least one dose of COVID-19 vaccine, a month past the July 4 goal set by President Joe Biden in May. The 70% goal is seen by federal health officials as a crucial step toward controlling the virus.

Booster Doses?
Germany, Israel and France are giving booster doses of vaccines for COVID-19 to immunocompromised patients, and Anthony Fauci, MD, FAAAAI, in a Reuters report stated that the United States would be joining them. In an article in the Wall Street Journal, the FDA will reportedly have a plan for booster doses in September. On the other hand, the New York Times quotes Paul Offit, MD, a member of the FDA Vaccine Advisory Committee, stating that the data submitted by Moderna and Pfizer does not support the need for boosters currently. For boosters to move forward either formal vaccine(s) approval by the Advisory Committee on Immunization Practices or amendment of the EUAs is required.

FDA Redeploying People and Equipment to Facilitate Full Approval of Vaccines
According to an article in the Washington Post, Peter Marks, MD, PhD, Director of the Center for Biologics Evaluation and Research (CBER) the FDA is redeploying staff and added technical resources to accelerate the effort to grant full approval to the Pfizer vaccine. Later news items state that the FDA is aiming for early September to complete this task.

COVID-19 Infection

Vaccinated Patients Can Spread the Delta Variant
Based on an analysis of a large outbreak of COVID-19 associated with July 4 celebrations in Massachusetts, the CDC has determined that fully vaccinated patients can spread the virus as readily as unvaccinated patients. This formed the basis for the recent change in mask recommendations. The same analysis found that the vaccines provide significant protection, with only five out of 900 infected patients hospitalized in this state with high levels of vaccinated individuals.

Trends in Hospitalization in Children Younger Than 4 Years
COVID-NET, the CDC surveillance system, notes that compared to June 26, 2021, weekly rates for the week ending July 17 have tripled from 0.2 to 0.6 per 100,000 population. Rates of infection in older children have steadily increased since early July, and increased from 39,000 to over 72,000 in the last week of July. Allergists need to remember that children, who will be returning to school soon, may not be required to wear masks, are not eligible to be vaccinated if less than 12, and could be a risk to other children and immunocompromised adults. Be aware of your local school district requirements and be an advocate for your patients’ safety.

Treatment

CDC COCA Call on Options to Prevent Severe COVID-19 in Immunocompromised People
This Clinician Outreach and Communication Activity (COCA) call will occur on Thursday, August 12 from 2:00 to 3:00 pm ET. No need to register, but this is the Zoom link to join.

Expansion of Regeneron's EUA for Monoclonal Antibodies
Reuters has reported that the FDA expanded the EUA to allow use in individuals who have been exposed to an infected individual, or who are at high risk for exposure, particularly if those individuals are at high risk for severe infection.

Subcutaneous REGEN-COV Antibody Combination Effective at Preventing COVID-19
REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirimivab and imdevimab, previously had an EUA for IV administration for individuals at high risk for severe COVID-19. This study looked at using this combination subcutaneously in individuals with recent (within 96 hours) household contact and found a relative risk reduction of 81.4% of developing symptomatic SARS-CoV-2 infection in the next 28 days. Relative risk reduction was 66.4% for asymptomatic infection and those that did get infected had a two week shorter duration of symptoms.

FDA Grants EUA to New Biologic
The FDA has granted an EUA to GSK’s sotrovimab, a recombinant monoclonal antibody directed at a conserved epitope on the receptor binding domain of SARS-CoV-2, for the treatment of mild-to-moderate COVID-19.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, July 26, 2021

Here are today's important updates:

Vaccines

AAAAI Joins 50+ Health Care Professional Organizations in Support of Mandatory Vaccination Against COVID-19 for Health Care Workers
We’re proud to join 50+ major health care professional organizations & societies in calling for mandatory #COVID19 vaccination for all health care workers. Health care workers have a duty to protect their patients, and that means getting the #COVID19 vaccine. The vaccine is safe, effective, and our best tool for ending the pandemic. As the health care community leads the way in requiring vaccines for our employees, we hope all other employers across the country will follow our lead and implement effective policies to encourage vaccination. The health and safety of U.S. workers, families, communities, and the nation depends on it. Read the full statement.

Approaching the Vaccine Hesitant
Hopefully all of us are asking whether our patients have been vaccinated against SARS-CoV-2. These two resources (linked here and here) can help you understand what these individuals are thinking and perhaps how to approach them. Counseling can depend on age, race and political leanings. 

Get That Second Dose
Recent news reports note that millions of Americans are late for their second dose of vaccine. This article shows that efficacy against the delta variant is low after one dose, but markedly better after two. A mRNA vaccine was more effective against symptomatic disease compared to an adenovirus-vector vaccine but both are very effective against severe disease and death. 

Heterologous Vaccine Schedules
In this phase 2, open label randomized trial, 450 adults who had been vaccinated with the AstraZeneca vaccine 8-12 weeks prior were given a dose of Pfizer vaccine or continued observation. Compared to the control group, the boosted group showed an increase in receptor binding domain antibodies from 71.46 to 7756.68 BAU/ml and IgG against the trimeric spike protein increased from 98.40 to 3684.87 BAU/ml 14 days after dosing.

similar study published in the NEJM on July 14 indicated heterologous dosing resulted in a much larger booster response and improved efficacy against the beta variant. 

Very Rare Skin Reactions After Vaccination
In an article published online on July 15 in JACI, the authors report on a small number of cases (12) of subepidermal blistering eruptions following mRNA vaccination. It showed 3/5 of those who developed the reaction after the first dose of vaccine tolerated a second dose, but the second dose was withheld in the other two. 

In another paper published online in JACI: In Practice on July 19, authors from Spain report on 26 patients with a variety of other delayed skin reactions. Interestingly, almost half of these patients had evidence of prior COVID-19 infection. All but one of the patients tolerated a second dose of the vaccine, one refused the second dose. The paper lists the variety of skin manifestations that may occur. 

Guillain-barre Syndrome Increased After J&J Vaccine
The FDA, through the VAERS reporting system has identified 100 cases of Guillain-Barre (GBS) following 12.5 million doses of the J&J vaccine. This number represents a 3-5-fold increase over the baseline rate. These cases have not been fully investigated yet, and the Advisory Committee on Immunization Practices (ACIP) met on July 22 to discuss their recommendations, but the warning is listed on the updated vaccine information sheet. The slides from the ACIP meeting are available on their website. Analysis of the data from the Vaccine Safety Datalink system and the VA did not notice a statistical signal for GBS but cases were numerically greater after the J&J vaccine compared to the mRNA vaccines. The European Medicines Agency has also noted the same after the AstraZeneca vaccine and posted a similar warning on that vaccine. The conclusions of the CDC from this July 22 meeting is that benefits of the vaccine continue to outweigh the risks.

COVID-19 Infection/Transmission

SARS-CoV-2 Infection In the Immunodeficient Host
This article published online in JACI: In Practice on July 14 discusses the immune response to the virus, effects of infection in immunodeficient patients and potential therapies in immunodeficient patients, and may be of special interest to allergist/immunologists who care for patients with immunodeficiency. 

Long COVID
The CDC issued interim guidance on evaluating and caring for patients with Post-COVID conditions on June 14. A prospective study involving 410 symptomatic persons, mostly mild to moderate, who tested positive for COVID-19 seven to nine months previously and had been followed prospectively with virtual and telephone interviews found that 39% reported residual symptoms, with fatigue (20.7%) the most common symptom, followed by loss of taste or smell (16.8%), dyspnea (11.7%) and headache (10%).  

Practice

HHS Updates Provider Relief Fund FAQs
Health and Human Services added or modified questions/answers on July 1. Most of these relate to returning unused funds, reporting expenditures/loss of revenue, appeal process, time limits on utilization of funds and what to do if practices are bought or sold during this time. 

HHS Extends the Public Health Emergency
HHS announced a 90 day extension of the Public Health Emergency on July 20, extending it to October 20, 2021. All the CMS waivers and flexibilities will continue to be in effect.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, July 12, 2021

Here are today's important updates:

Vaccines

Vaccine Effectiveness Against the Delta Variant
Using samples from previously infected or vaccinated patients, this study found that while neutralizing activity was lower against the Delta variant, the majority of samples from infected patients and all samples from vaccinated patients still had detectable neutralizing activity above the threshold of detection. In a press release from the Israeli Ministry of Health, the Pfizer vaccine was only 64% effective in preventing infection, but 94% effective at preventing severe illness. In a pre-print, accepted manuscript, researchers from France examined the neutralization effectiveness in sera from patients vaccinated with either the Pfizer or AstraZeneca vaccines, and found that one dose of vaccine barely inhibited the variant, but two doses generated a neutralizing response in 95% of individuals, although less than that against the Alpha variant.

Addressing Vaccine Hesitancy
There are many reasons expressed by our patients for avoidance of the COVID-19 vaccines. Here are some studies that may speak to some of the hesitancies allergists may encounter:

Add “COVID Toes” to the Localized Skin Reactions to mRNA Vaccines
There have been a small number of cases of pernio/chilbain-like lesions on the toes of people vaccinated with the Moderna mRNA vaccine. Allergists should be aware of this in patients who are referred with lesions on the feet for possible allergy.

Pfizer to Seek Authorization for Third Dose
Pfizer and its partner BioNTech plan to seek FDA authorization for a third dose based on data to be submitted on an ongoing trial that shows an increase in the levels of neutralizing antibodies 5-10 times higher than baseline when administered 6 months after the second dose. They also plan to develop a vaccine that is targeted directly at the Delta variant. U.S. officials do not feel that a booster dose is indicated at this time.

COVID-19 Transmission/Infection

Pediatric Cases Now a Larger Share of Infections

In March of 2020, children made up 2% of new COVID-19 infections. By the end of May of 2021, the share increased to 24% of new weekly infections, even though children only make up 16% of the population. We need to remind parents of our pediatric patients to continue masking and avoiding crowded places.

HEPA Filtration Plus Masking for Exam Rooms
This study would suggest that adding a HEPA filter to an exam room would decrease aerosol exposure over masking alone.

Systemic Corticosteroid Use in Asthma Linked With Poor Outcomes, But Biologics Are Not
This study from Israel looked at all asthmatic patients in a large healthcare system who tested positive for SARS-CoV-2 between March and December, and compared risk of infection, severity or composite severity and all-cause morality. It found that biologics were not associated with any of these outcomes, but recent (within 120 days) use of systemic corticosteroids was significantly associated with increased risk of moderate to severe disease and composite of severity and mortality. Just an additional factor to use in attempting authorization for biologics in our severe asthma patients.

Practice

HHS Provider Relief Fund Reporting Portal Now Open
Providers who need to report in Reporting Period 1 have until Thursday, September 30 to submit their information as part of the post-payment reporting process. Hart Health Strategies, the AAAAI's legislative and regulatory consultants, has made several resources available for your assistance.

CMS Updates Its FAQs on Accelerated and Advance Payment
Review the updated COVID-19 Accelerated and Advance Payment (CAAP) Repayment & Recovery FAQs here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, June 28, 2021

Here are today's important updates:

Transmission

Spread of the Delta Variant of Concern (VOC)
The WHO announced recently that the Delta variant (B.1.617.2) first appearing in India, has now spread to 80 countries. In fact, 20% of recent U.S. cases are due to this virus and it has surpassed the Alpha variant (B.1.117) in the UK, where the Alpha variant originated. WHO is now tracking recent reports of a “Delta plus” variant. The Delta variant is more transmissible than the Alpha and may cause more severe disease. Current vaccines are effective against the Delta variant, although less so than against other variants. Keep encouraging your patients to get vaccinated to stop this parade of mutations and VOCs!
 
More on the Delta Variant
A study out of Scotland evaluated 19,543 confirmed cases of COVID-19 from April 1 to June 6, 2021. The adjusted hazard ratio for hospitalization with the Delta variant was 1.85 (95% CI 1.39-2.47) compared to the Alpha variant. 70% of Delta cases had not been vaccinated. Vaccine effect did not clearly manifest until at least 28 days after first vaccine dose. There was no difference in vaccine effect against Alpha or Delta variants with respect to hospitalizations, with a reduction in hospitalization hazard ratio of 0.28 for the Alpha variant and 0.38 for the Delta variant.
 
So Who Is Following the Guidelines?
This AP NORC poll conducted from June 10-14 indicates that vaccinated people are much more likely to be avoiding large groups, wearing a face mask and avoiding nonessential travel compared to unvaccinated people even as restrictions are loosened for the vaccinated.
 
Cold Viruses Are Coming Back Out of Season
This report from the Washington Post notes a resurgence of common respiratory viruses now occurring out of their typical season as the country re-emerges from COVID-19, with schools opening and reduced mask use. Note the CDC warning about RSV that was in our last message.

Vaccines
 
ACIP/CDC Update on Myocarditis/Pericarditis
The ACIP discussed this issue at their scheduled meeting on June 23. There have been 484 cases reported to VAERS, 323 of which have been confirmed. Rates are highest in males, with the highest incidence in those aged 18-24 where the rate is 219 per million doses, so very rare. Although most have been hospitalized, the overwhelming majority of cases have been mild, treated with NSAIDs or steroids with discharge within 2-4 days. The CDC, along with a number of other national medical societies including the AAP, ACOG, AAFP, ACP, and AHA have recommended the benefits of vaccination far outweigh the risks of vaccine complications and vaccines are strongly encouraged. The ACIP does plan to add a statement on myocarditis in the vaccine facts document. Check here for the slides from the meeting.
 
Booster Doses
At the same meeting mentioned above, the booster work group from the CDC stated: “No data to support recommendations for booster doses currently, but will continue to monitor.” There are several studies ongoing in special populations and with vaccine effectiveness with variants that are anticipated this fall.
 
CDC Updates Considerations for Vaccines
Last updated on June 1, information of interest to the allergist includes clarification on contraindications and precautions and an updated Appendix B on guidance for people with a history of an immediate allergic reaction to a vaccine or injectable therapy that contains a component also contained in a COVID-19 vaccine. It’s important to remember: “Allergic reactions (including severe allergic reactions) not related to vaccines (COVID-19 or other vaccines) or injectable therapies, such as allergic reactions related to food, pet, venom, or environmental allergies, or allergies to oral medications (including the oral equivalents of injectable medications), are not a contraindication or precaution to COVID-19 vaccination.”
 
Self-Reported Allergic Reactions and Subsequent Vaccine Dose
Self-reported allergic symptoms following the first dose of mRNA vaccine was associated with a 5-fold (3% vs. 0.6%) increase in odds of not completing the second dose in a prospective cohort of healthcare workers in Boston. We know that most of these people can get the second dose, so allergists need to be consulted in anyone who might be reluctant to get the second dose.
 
Cutaneous Reactions After mRNA Vaccines
This study from the Mass General Brigham group involved 40,197 employees who completed symptom questionnaires after their first dose. Cutaneous reactions were reported by 776 (1.9%), with rash and itching (other than at the injection site) most common. Reactions were much more common in women (85% vs. 15%). Of these patients, 741 (95%) went on to receive a second dose, and 508 out of 609 who completed the symptom survey (85%) reported no recurrent cutaneous reactions.
 
Role for Excipient Skin Testing After First Dose Reactions to mRNA Vaccines
In this small study of 80 individuals who reported allergic reactions after the first dose of mRNA vaccines, excipient skin testing to PEG and/or polysorbate 80 did not impact tolerance of the second dose in those with positive skin tests. 70 out of the 80 received their second dose, 62 had either no reaction or a mild reaction managed by antihistamines, although two did require epinephrine.
 
Immunity From Infection Versus Vaccine - Is It Different?
A recent NIH-funded study adds to the evidence base that patients with acquired immunity may have different levels of protection by showing that antibodies generated following vaccination are more focused on the receptor binding domain (RBD) of the spike protein compared to the antibodies generated after acquired infection. Findings from this study suggest the vaccine-generated immunity may be more likely to target new SARS-CoV-2 variants potently even when the variants contain new mutations in the RBD.
 
Immunity After Infection Long-Lasting But Enhanced by Vaccination
This paper reports that 82% of 68 individuals recovered from COVID-19 showed continued IgG antibody titers and B cell memory 6-12 months after infection. In the participants who were vaccinated after infection (41%) IgG responses increased 30-fold, neutralizing activity by 50-fold and circulating number of memory B-cells by 9-fold.

Practice
 
HHS Modifies PRF FAQs
New or modified questions relate to set periods of time in which providers must use funds (e.g., funds received between April 10 and June 30, 2020, must be used by June 30, 2021, and so on),if providers can use payments for expenses prior to receipt of PRF funds, what to do with remaining PRF money, and auditing and reporting requirements.
 
AMA Announces That 96% of Practicing Physicians Have Been Fully Vaccinated
It's important to note that this data comes from a survey done from June 3-8 with a response from 300 physicians, half of whom were primary care

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, June 14, 2021

Here are today's important updates:

Vaccines
 
Allergic Reactions After COVID-19 Vaccine and Incomplete Vaccination
This prospective study of Mass General Brigham employees (50,167) was done following their first dose of mRNA vaccine. A total of 1,261 (2.5%) self-reported allergic symptoms, and 576 (46%) received an A/I consultation. While the adjusted odds ratio for incomplete vaccination was 5.15, 95% CI 3.75,7.06 for any self-reported allergic reaction and 23.19, 95% CI 9.74, 55.22 for severe allergic reactions, 1,218 of the 1,261 received the second dose and 17% had recurrent allergic symptoms. None were severe.
 
Update on Myocarditis/Pericarditis After mRNA Vaccines
Increased cases have been noted since April predominately in male adolescents and young adults 16 years of age and older, with onset within several days of vaccination, more after the second dose. Most cases have been mild and responded well to medications and rest. Allergists take note: patients present with acute chest pain and shortness of breath and may occur in your asthma patients. Consider an ECG, troponin level, EST, C-reactive protein, and consider acute or previous COVID-19 as etiology as well.
 
Efficacy of Single Dose of Pfizer Vaccine
This study from Israel involving 351,897 individuals found that the overall single-dose vaccine effectiveness of the Pfizer vaccine against symptomatic COVID-19 was 54.4% when measured 13-24 days after the dose. Results were similar across ages, genders and in individuals with comorbidities. Protection against severe disease is presumed to be higher, but this was not measured in the study.
 
Immunogenicity of J&J Vaccine (Ad26.COV2.S) Against Variants May Be  Better Than We Thought
While neutralizing antibody titers may be three to five fold less against the variants B.1.1.7, CAL.20C, P.1 and B.1.351 compared to the Wuhan strain (WA1/2020), this small study showed that non-neutralizing antibody responses and T cell responses were largely preserved against these variants.
 
Moderna to Apply for EUA for 12-17 Year Olds
The New York Times reported that Moderna filed for the EUA on 6/10. Their study in 3,732 children showed a vaccine efficacy of 100%. FDA approval of the EUA is expected in early July.
 
Vaccine Misinformation
The CDC has a resource page that may be useful to allergists who are talking to their patients about getting a vaccine against COVID-19. Refer your patients to this page: Myths and Facts about COVID-19 Vaccines. Facebook is becoming one of the leading sources of misinformation on COVID-19 vaccines.
 
Most Unvaccinated Adults Plan to Stay That Way
Allergists need to ask each and every patient if they are vaccinated and if not, why not. A recent Gallup poll found that 78% of U.S. adults who have not yet received a vaccine say they are unlikely to ever get it. On the positive side, 76% of adults have received at least one dose or “plan to get one.”
 
Treatment
 
Early Monoclonal Antibody Treatment
Treatment with casirivimab/imdevimab (83% of patients) and bamlanivimab (17% of patients) within five days of diagnosis in high risk patients was noted to decrease hospitalization and mortality. This was a retrospective study on 617 patients of a COVID-19 clinic at University of California, San Diego.
 
FDA Approves Injection Form of Monoclonal Antibodies
The FDA just approved REGEN-COV by means of injection, rather than IV infusion and also approved a lower dose.
 
Transmission

Are Americans Still Social Distancing?
Another recent Gallup poll found that less than 25% of Americans continue to practice safe social distancing, though 44% are avoiding crowded places.
 
SARS-CoV-2
 
Variants of Interest
Information has changed on distribution and nomenclature of the variants of interest (VOI) and variants of concern (VOC). WHO just agreed to use a new, simpler naming system. B.1.1.7 (UK variant) now called Alpha variant, B.1.351 (South African variant) now Beta, P.1 (Brazil) now Gamma, and B.1617.2 (India) now Delta. Consult the CDC website which was updated June 8 or visit the AAAAI COVID-19 resources page and check under Virus Variants.
 
Increased RSV Activity in Parts of the Southern U.S.
The CDC has issued a health advisory about increased interseasonal RSV in the southern U.S. and recommends testing for that infection in patients with acute respiratory illness who test negative for SARS-CoV-2.
 
ICS Therapy for COPD Safe
A large retrospective study involving 27,810 patients showed that ICS treatment for COPD did not increase the risk for hospitalization, ICU admission, mechanical ventilation or mortality from COVID-19.
 
CDC Adds Health Equity Data Page to Their COVID Data Tracker
Find it at: Health Equity Data. Other pages concerning the CDC and health equity related to COVID-19 can be found here: Health Equity, Promoting Fair Access to Health and Health Equity in Action.
 
Practice
 
HHS Revises Reporting Requirements and Timeline for PRF Recipients
This announcement includes expanding the amount of time providers will have to report information, aims to reduce burdens on smaller providers, and extends key deadlines for expending PRF payments for recipients who received payments after June 30, 2020. The revised reporting requirements will be applicable to providers who received one or more payments exceeding, in the aggregate, $10,000 during a single Payment Received Period from the PRF General Distributions and/or Targeted Distributions.
 
OSHA Announces a COVID-19 Safety Rule
It seems a little late in the game, but OSHA issued an emergency temporary standard (ETS) on 6/10 which applies to healthcare workers in healthcare settings where suspected or confirmed COVID-19 patients are treated. This may not apply to most allergist offices, but you need to be aware of the standard. Interestingly, the ETS exempts fully vaccinated workers from masking, distancing, and barrier requirements when in well-defined areas where there is no reasonable expectation that any person with suspected or confirmed COVID-19 will be present. The ETS becomes effective on the day it is published in the Federal Register, and healthcare facilities have 14 days to comply. Most practices are already doing these things, but you need to check and be sure. Practices with more than 10 employees that don’t meet the exceptions will need a written COVID-19 plan.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Tuesday, June 1, 2021

Here are today's important updates:

Our COVID-19 messages will be transitioning to every two weeks after this issue. Be sure to check the AAAAI COVID-19 resources page for continuous updates.

Vaccines

Talking to Your Patients About Getting Their COVID-19 Vaccine

The CDC has produced a comprehensive resource for providers on counseling patients about getting a vaccine, including communication points and ideas about proactive patient outreach. This is also linked on the AAAAI COVID-19 resources page.
 
Anaphylaxis to mRNA Vaccines

In our last message, we posted about a patient with anaphylaxis to the mRNA vaccine who was allergic to PEG. In a letter to the editor soon to be published in Allergy, researchers from Vanderbilt and Denmark report on eight healthcare workers referred for evaluation after a first dose anaphylactic reaction based on the Brighton Collaborative, NIAID/FAAN or Ring and Messmer validated scales. Serum tryptase levels were normal in the five who had that done, allergy to PEG (by skin testing to PEG 3350 and/or challenge and negative tolerance history) was ruled out (in the opinion of the authors), and the eight patients went on to tolerate the second dose of the vaccine as a single dose with antihistamine pre-treatment with lesser or no symptoms. The authors propose that this may indicate a non-IgE-mediated reaction and posit that pre-treatment with antihistamines can reduce some of the symptoms due to mast cell mediator release in the absence of an IgE-mediated reaction.
 
Breakthrough Infections After Vaccination

The CDC is working with state and territorial health departments to investigate SARS-CoV-2 infections among persons who are fully vaccinated. A total of 10,262 breakthrough infections had been reported as of April 30. Based on preliminary data, 27% were asymptomatic, 10% were known to be hospitalized (29% of these were asymptomatic or hospitalized for a reason unrelated to COVID-19), and 2% died (18% asymptomatic or died from another cause). The median breakthrough infection age was 58 (interquartile range 40-74), and the median age of those who died was 82 (interquartile range 71-89). Sequence data was only available from 5% of the cases, 64% of which were identified as variants of concern, with 56% of those B.1.1.7 and 25% B.1.429. Following release of this study, the CDC announced that they would be investigating only those breakthrough infections that result in hospitalization or death.

A study from Italy on reinfections 10-15 months after initial infection revealed a incidence density of 1.0 per 100,000 person days for reinfections compared to 15.1 for new infections, indicating prolonged protection against reinfection from natural infection.
 
Moderna to Submit an EUA for Ages 12-17 in June

Studies have shown similar immune response and vaccine efficacy as in older patients, as well as a similar safety profile.
 
Novavax Plans to Apply for an EUA for Their Vaccine in July

According to another article in the Washington Post, this nanoparticle vaccine has been shown to be 90% effective in UK trials. It is being studied in a 30,000 person trial in North America and the company expects to have the data from that trial complete by the end of the month.
 
Inactivated Virus Vaccines Show Efficacy

Two inactivated SARS-CoV-2 vaccines, using different strains of the virus, were 72-78% effective in preventing symptomatic infection in an interim analysis of data from a trial in 38,206 subjects. The vaccines were 100% effective against severe disease.
 
Myocarditis and Pericarditis After mRNA Vaccines

The CDC has added resources for the public to their website.

Transmission

Prevalence of Pediatric Infection in UK

A surveillance study of pediatric patients admitted to a hospital for any reason in the UK from March 2020 to February 2021 noted that 5.6% tested positive for SARS-CoV-2, 20% of whom were asymptomatic. The prevalence of new asymptomatic infections increased 1.65-fold during times when schools were open.
 
COVID-19 in Daycares

In this study among 469 child care facilities in Washington, DC, 23.9% reported at least one COVID-19 case, and 5.8% reported outbreak-associated cases during July 1-December 31, 2020. Outbreak-associated cases accounted for almost half of reported cases. Among 319 cases, approximately one-half were among teachers or staff members. Outbreak risk was increased in facilities operating <3 years, with symptomatic persons who sought testing 3 days or more after symptom onset, or with asymptomatic cases.

Immunity
 
Immunity to SARS-CoV-2 Infection May Last A Year

This study in 77 patients with a history of mild infection demonstrated long-lived SARS-CoV-2 specific bone marrow plasma cells, which correlated with serum anti-SARS-CoV-2 spike antibodies detectable at least 11 months after infection.

Infection
 
Persistent Symptoms After Infection

In this systematic review of 45 studies including 9,751 participants with COVID-19, the median proportion of individuals who experienced at least one persistent symptom was 73%. Symptoms occurring most frequently included shortness of breath or dyspnea, fatigue or exhaustion, and sleep disorders or insomnia.
 
Treatment
 
Study Suggests That Home Monitoring of Oxygen Saturation and Respiratory Rate Are Important

This study examined mortality in hospitalized patients with COVID-19 and noted that while many had hypoxemia and tachypnea on admission, few reported shortness of breath or cough. Patients with hypoxemia (O2 sat <92%) had a 1.8 to 4.0-fold increased mortality risk. The authors suggest that patients with other risk factors monitor respiratory rate and oxygen saturation at home and seek medical care if O2 sat is <92% and/or respiratory rate is >23 breaths/minute, when early treatment might be most helpful.
 
New Monoclonal Antibody

The FDA has granted an EUA for sotrovimab to GSK for the treatment of mild-to-moderate COVID-19 in patients at risk for progression. Sotrovimab is a recombinant human IgG1 kappa monoclonal antibody that binds to a conserved epitope on the spike protein receptor binding domain. Laboratory testing showed that sotrovimab retains activity against the current circulating variants first reported in the UK, South Africa, Brazil, California, New York and India.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, May 24, 2021

Here are today's important updates:

Vaccines

Anaphylaxis After Vaccination Linked to PEG Allergy in One Patient

Researchers in the UK have linked anaphylaxis after the Pfizer vaccine in one patient to her allergy to PEG. She had a history of anaphylaxis to azithromycin, which contained PEG with less severe reactions to shampoo, toothpaste and mouthwash also containing PEG. She had a systemic reaction while undergoing skin testing to a 1% concentration of PEG 4000.

Update on TTS After J&J Vaccine

Updates on TTS were given at the ACIP meeting on May 12. Cases now number 28 out of 8.7 million doses of J&J vaccine given. The median age is 40 (up from previous data). Median time to onset is nine days (range 3-15). It was reported in 22 females and six males, and 19 of the 28 had CVST (cerebral venous sinus thrombosis).

Myocarditis/Pericarditis After Vaccination

The Seattle/King County Public Health Department recently sent out a health advisory concerning 12 reported cases of myocarditis or pericarditis within two weeks following a mRNA vaccine. Ages range from 16-66 years, mostly males. Symptoms include chest pain or pressure, shortness of breath, EKG abnormalities, and abnormal cardiac enzymes. The ACIP COVID-19 Vaccine Safety Technical (VaST) Work Group session on May 17 heard several presentations on this from the Department of Defense, VAERS, and Vaccine Safety Data Link (VSD). VaST concluded that there are relatively few reports of this, they were predominately occurring in adolescent and young adult males following mRNA vaccine, more often after dose two, occurring four days to two weeks after vaccination and most were mild. Within the CDC monitoring systems, rates of myocarditis have not differed from expected baseline rates, but these reports should be communicated to providers. This is important to allergists because the presentation of chest pain/pressure and shortness of breath would not be unusual in a practice. If myocarditis is confirmed, be sure to report this to VAERS.

Mixing Vaccines – Reactogenicity Data

This UK multi-center randomized heterologous prime-boost COVID-19 vaccination study compared the AstraZeneca and Pfizer vaccines in various prime-boost permutations in 830 patients 50 years of age and older. Results showed that systemic reactogenicity was greater following the boost dose in heterologous schedules compared with homologous dosing. Symptoms were similar to those well known after receipt of the vaccines, but about twice as common when the prime dose and the boost dose were from different vaccines. The efficacy data is expected in June.

Why Are Vaccine Hesitant Americans “Hesitant”?

Results of a recent Harris poll taken from over 1,000 Americans who identify as unlikely to get a vaccine show that 60% cite blood clots, 57% cite systemic reactions to the vaccine, 45% cite death, 37% cited migraines and about 1/4 cited high blood pressure, DNA alterations, birth defects, infertility and cancer as reasons to not be vaccinated. It helps allergists to be familiar with the common reasons for avoidance so we can properly advise our patients.

CDC Updates Guidance on Coverage & Reimbursement of Vaccines for State Policymakers

On May 5, the CDC released an update of their vaccine toolkit for policymakers at the state level, concerning vaccine coverage, administration and cost-sharing under Medicaid, CHIP and Basic Health programs.

Immunity

Antibody Response Targets Many Parts of The Spike Protein

Recent research sponsored by the NIH and recently published in Science evaluated the array of antibodies against SARS-CoV-2 in a small number of patients who had recovered from natural infection. Most studies to date have focused on the antibody response to the receptor-binding domain (RBD), but these researchers found that about 84% of the antibody response targeted other portions of the spike protein. Among these are antibodies that target the N-terminal Domain (NTD) and these antibodies can neutralize the virus. The NTD is one part of the spike protein that has mutated frequently, especially in the variants of concern, allowing these viral variants to escape the effects of these antibodies. Fortunately, about 40% of the antibody response is directed toward the S2 subunit which is not as mutable as the NTD. The study can be found here. A nice summary with a helpful cartoon of the spike protein can be found in the NIH directors blog: Human Antibodies Target Many Parts of Coronavirus Spike Protein.

Transmission

Possible Explanation For Prolonged Shedding of SARS-CoV-2

Patients with COVID-19 are known to have continued positive RT/PCRs for SARS-CoV-2 for 30 days or more after infection. Data available indicate that these patients are not infectious, but why do some continue to have positive RT/PCR? This study found that SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of the infected cell and be expressed as chimeric transcripts fusing viral with cellular sequences. Such chimerics are detected in patient-derived tissues and may explain the prolonged presence of viral RNA. This could also be pointed out to vaccine hesitant patients who are concerned about genetic effects of the vaccine.

COVID-19 Infection

Risk of Reinfection

A study of 16,101 college students in South Carolina found that the risk of reinfection was 2.2% while estimated protection from previous infection was 84%. The median time to reinfection was 129 days.

Levels of Co-infection And Super-infection Found in Infected Patients

A meta-analysis of 118 studies found that up to 19% of patients had co-infection (other pathogens identified at the time of COVID-19 diagnosis) and 24% had super-infection (other pathogens detected during COVID-19 care). Such patients had an increased risk of mortality (OR 3.3). Co-infecting pathogens most common were influenza A and B and RSV.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, May 17, 2021

Here are today's important updates:
 
Vaccines
 
CDC Revises Guidance for Fully Vaccinated

Updated on May 13, the new guidelines state that fully vaccinated people can resume activities without wearing a mask or physically distancing, except where required by federal, state or local laws, rules and regulations. These recommendations are NOT intended for healthcare settings. You will still need to be tested when returning from international travel, and you will still need to wear a mask on planes, buses, trains and other forms of public transportation.
 
More Data on Real World Effectiveness of mRNA Vaccines

Interim data analysis from a test-negative design case-control study involving healthcare professionals ongoing at 33 sites across the United States showed vaccine efficacy of 82% after one dose and 94% after two.
 
FDA Authorizes Pfizer Vaccine for Emergency Use in Adolescents, CDC's ACIP Adds Interim Recommendation

Announced on May 10, the ACIP met on May 12 to decide how it is to be used. The ACIP analysis of the data from the clinical trial involving 2,200 adolescents noted efficacy of 100% against symptomatic infection. Immune responses were at least as high as those found in ages 16-25. There were 16 cases of COVID-19 in the trial, all in the placebo group. As noted in an earlier message, Pfizer also plans to seek full authorization by the end of May, which would allow their vaccine to be used after the pandemic emergency is over. Currently, EUAs expire at the end of the public health emergency. Full authorization should help convince some people who have been concerned about the speed of development and “emergency authorization” to go ahead with vaccination and would allow schools, etc. to mandate immunization.
 
Survey on Parental Attitudes Toward Vaccination of Children

This report from the COVID States Project: A 50-State COVID-19 Survey found that 11% of fathers are resistant to vaccination compared to 27% of mothers. Educational, income and partisan divides have become more pronounced, with college-educated, higher income and Democratic parents showing less resistance compared to those of low income, non-college educated or Republican parents who have increased their resistance. Parents of teenagers are less resistant and 58% support school vaccination requirements.
 
Moderna Vaccine Updates

In a press release from May 6, Moderna announced that in an updated review of the initial trial data, vaccine efficacy remained at 90% against all cases and 95% against severe disease 6 months after the second dose. Initial data from their Phase 2 study on booster doses against variants of concern showed that both the 50 mcg booster directed at the B.1.351 variant (mRNA-1273.351) and the 50 mcg booster of the original vaccine (mRNA-1273) increased neutralizing titer responses against B.1.351 and P.1, with the strain-matched booster showing better effect. Safety and tolerability was similar to the second dose of mRNA-1273. The Phase 2/3 study of mRNA-1273 in adolescents aged 12-17 has completed enrollment and initial results indicate 96% efficacy. Tolerability was comparable to that in adults.
 
Pfizer Vaccine Effects Against New Variants

In a small study on viral neutralization in vaccinated patients, these authors found that neutralization following vaccination was essentially equivalent against the new strains, including the new California and New York strains, as well as the recently identified B.1.1.7 variant.

COVID-19 Infection
 
Updated Guide to SARS-CoV-2 Variants

If you are having trouble keeping track of all the variants and the mutations that are present, this CDC resource will help spell it all out for you. The link is also listed on the Virus Variants and Vaccine Information section of the AAAAI COVID-19 resources page.
 
Viral Attack Rates

Among 2.5 million contacts of 1 million index cases of COVID-19 in the UK, researchers found that the B.1.1.7 variant had 55% attack rates. Attack rates were highest for household contacts (9%), followed by household visitors (7%), and lower among work/education contacts (5%) and outdoor contacts (3%). Contacts of children were least likely to test positive, particularly following contact outdoors or at work/educational settings.
 
Airborne Transmission

The CDC added back the notion that SARS-CoV-2 can spread via airborne transmission on May 7, which they admitted in earlier guidance but removed. Although this has been a source of controversy, there is a moderate degree of scientific evidence to support the notion that infectious material can spread beyond six feet in the form of aerosol particles. This article outlines methods and targets for improvement of indoor ventilation and filtration to reduce the risk of infection.
 
Duration of Immunity Updates

In this small study (32 patients) from Canada, 13 patients who were 8 months post-infection continued to show stable numbers of IgG-positive B cells and ADCC.

Another study from China assessed humoral, T and B cell responses in 59 asymptomatic to moderate COVID-19 patients a median of 317 days from symptom onset (range 257-343 days), and found that 90% still had detectable IgG antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus. Sixty percent of patients had detectable IgG antibodies against the receptor binding domain and surrogate virus-neutralizing antibodies, and SARS-CoV-2 specific IgG memory B cells and IFN-gamma secreting T cells were detectable in over 70% of patients. Interestingly, the immune response was greater in those who had asymptomatic/mild infection compared to those with moderate disease.

Future Research
 
NIAID Announces Updated COVID-19 Research Plan

The 2021 research plan update focuses on four priorities: 1) advance basic research, 2) identify and test promising COVID-19 therapeutics, 3) develop and test next-generation COVID-19 and pan-coronavirus vaccines, and 4) characterize, prevent and treat post-acute sequela of SARS-CoV-2 infection (PASC).

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, May 10, 2021

Here are today's important updates:

Vaccines
 
ACIP Meeting on Pfizer EUA Application for Ages 12-15

This virtual meeting will take place May 12 from 11:00 am to 3:30 pm ET. Following the Pfizer discussion and vote, there will be a session that will provide updates on TTS after the Janssen vaccine, COVID-19 vaccine effectiveness and virus variants. The agenda and webcast link can be found here.
 
Skin Reactions to mRNA Vaccines

Utilizing data from the international COVID-19 Dermatology Registry, this presentation at the American Academy of Dermatology (AAD) Virtual Meeting last month detailed reactions from 414 unique individuals who developed cutaneous reactions following the Moderna (83% of cases) or Pfizer vaccine (17%). The most common reactions were delayed large local reactions, urticaria and morbilliform eruptions. Delayed large local reactions occurred around day 7. The urticaria started around day 3 and occurred on the arms, trunk or legs, and the morbilliform rash also started around day 3 with similar distribution to the urticaria. These reactions occurred mainly in females and only 43% recurred after the second dose.
 
Symptomatic and Asymptomatic Infection After Pfizer Vaccine

A retrospective cohort study from Israel looked at COVID-19 infections in 5,517 fully vaccinated healthcare workers. The adjusted incidence rate ratio (IRR) (incidence rate in vaccinated/incidence in unvaccinated) was 0.03 (95% CI, 0.01-0.06) for symptomatic infection and 0.14 (95% CI, 0.07-0.13) for asymptomatic infection.
 
In a U.S. study performed on 2,776 healthcare workers, the IRR for asymptomatic infection 7 or more days after a second dose was 0.10 (95% CI, 0.04-0.22). There were no symptomatic infections in this group 7 or more days after the second dose.
 
Pfizer Vaccine and Variants

In a letter to the editor, researchers in Qatar using data from their COVID-19 national database noted vaccine efficacy against any documented infection with the B.1.1.7 variant was 89.5% and vaccine efficacy against any documented infection with the B.1.351 variant was 75%. Efficacy against severe, critical or fatal disease at a time when 50% of the cases were due to the B.1.351 variants and 45% due to B.1.1.7 variants was 97.4%. These numbers were confirmed using a cohort study design as well.
 
Vaccine Penetration and Infection Scenarios - Hope Lies Ahead!

Modeling of future cases, hospitalizations and deaths by vaccination rates and nonpharmaceutical intervention (NPI) was done across four scenarios of vaccination rates and NPI adherence. The most optimistic scenario indicates that with high vaccination coverage and moderate NPI adherence, hospitalizations and deaths will likely remain low nationally, with a sharp decline in cases projected by July 2021. On the other hand, a sharp decline in NPI adherence was shown to undermine vaccination-related gains, especially with low vaccination rates. There is likely to be state-wide variation in the scenarios due to differences in NPI adherence and vaccination rates.

Another modeling study demonstrated that every 1% increase in vaccination coverage could avert an average of 876,800 cases depending on the number of persons already vaccinated, with the greatest gains achieved when increasing vaccination coverage in the population from 0% to 50%. The study also demonstrated that increasing vaccination coverage may avert more cases than increases to the vaccine efficacy.
 
Novavax Vaccine Effectiveness Against B.1.351

In this study, the Novavax nanoparticle vaccine showed 51% efficacy against the virus variant B.1.351.
 
Extended Shelf Life Possible for Moderna Vaccine

In a press release on April 29, Moderna announced that ongoing development data related to the current formulation of the Moderna COVID-19 vaccine (mRNA-1273) could support a 3-month refrigerated (2-8°C) shelf life for the vaccine in alternative formats to facilitate easier distribution to doctor’s offices and other smaller settings if authorized. This change is not yet FDA approved. Currently, the Moderna COVID-19 vaccine is approved for storage up to 1 month at refrigerated temperatures (2-8°C) and up to 7 months in a standard freezer (-20°C).

COVID-19 Infection
 
Update on Children

The cumulative number of child cases (3,782,274) represents 13.8% of all cases, but for the week of April 22-29, 2021, children represented 22.4% of the new weekly cases. Also, 0.1-1.9% of all cases resulted in hospitalization, with up to 0.03% of cases resulting in death.
 
Impact on Children

COVID-19 certainly has a direct disease impact on children, but can also affect them in other ways without infection. This modeling study suggests that as of February 2021, 37,300 children ages 0 to 17 years had lost at least one parent due to COVID-19. If you include excess deaths, that number increases to 43,000.
 
Lawmakers Pressing Major Insurers Who Announced Resumption of Cost-Sharing for COVID-19 Treatments

AMA Morning Rounds reported that 10 Democratic members of Congress have sent letters to the CEOs of Anthem, UnitedHealthcare and Aetna urging the insurers to waive cost-sharing for COVID-19 treatment.

Practice
 
CMS Increases Payment for Monoclonal Antibody Infusions

Effective May 6, the national payment rate for administration of monoclonal antibodies for COVID-19 will increase from $310 to $450 for most healthcare settings, with a rate of $750 when administered in the beneficiary’s home. Beneficiaries pay nothing out of pocket.
 
COVID-19 Coverage Assistance Fund (CAF)

A webinar May 12 at 2:00 pm ET will present an overview of the enrollment, claims submission and payment processes. Register here. See also the fact sheet on the program.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Thursday, May 6, 2021

Here are today's important updates:

Vaccines
 
New Resource for Vaccine Availability

The CDC and HHS have announced a service, available now, allowing people to find COVID-19 vaccines nearby via text message. Anyone can text their ZIP code to GETVAX in English, or VACUNA in Spanish, to get information on three locations near them with available vaccines. Also announced was the conversion of VaccineFinder.org to a new site, Vaccines.gov, which will report information for all states. The website is currently available in English and Spanish. The National COVID-19 Vaccination Assistance Hotline, a 1-800 number to be announced, will be available for people who prefer to use the phone. Assistance will be provided in English, Spanish and more than 150 other languages and will also include a teletype line for the hearing impaired.
 
Canada Announces Emergency Authorization for Pfizer Vaccine in Ages 12-15
 
The FDA is expected to consider an EUA for the same age range in meetings this next week, according to an article in the New York Times. In another article from the New York Times, Pfizer will seek full authorization for its vaccine for ages 16-85 in the next month and will hope to apply for an EUA for ages 2-11 by September.
 
B and T Cell Responses After One Dose of Pfizer Vaccine in Those With Prior Infection

A study in a cohort of UK healthcare workers who had been followed serially since March of 2020 noted that after one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. Those without prior infection showed reduced immunity against the variants. Remember that this is after one dose.
 
CDC Reports Clusters of Anxiety-Related Events After Janssen Vaccination

The CDC received reports of clusters of anxiety-related events over a 3-day period of time (April 7-9) after administration of the Janssen vaccine at five mass-vaccination sites, all in different states. Overall there were 64 events, including 17 with syncope among 8,624 recipients. As follow-up, the CDC analyzed reports of syncope shortly after Janssen vaccine to VAERS for the period March 2-April 22, and compared them to reports of syncope after administration of the influenza vaccine during the 2019-2020 season. The rate of syncope after the Janssen vaccine was calculated at 8.2 per 100,000 doses compared to 0.05 per 100,000 doses after influenza vaccine.
 
CVST and the Janssen (J&J) Vaccine

In addition to the CDC COCA call mentioned in our last message, JAMA has published an article and editorial on this serious adverse event.
 
HHS Launches New Reimbursement Program for COVID-19 Vaccine Administrative Fees Not Covered by Insurance
 
Called the COVID-19 Coverage Assistance Fund (CAF) funded through the Provider Relief Fund, this program will cover the costs of administering COVID-19 vaccines to patients enrolled in health plans that either do not cover vaccination fees or cover them with patient cost-sharing. Since providers cannot bill patients for COVID-19 vaccine fees, this will fulfill a compensation need for providers. The CDC issued guidance in February that all organizations and providers participating in the CDC COVID-19 Vaccination Program (which currently includes any provider administering the vaccine): 1) must administer the vaccine regardless of the recipients ability to pay administration fees or coverage status, 2) must administer COVID-19 vaccine at no out-of-pocket cost to the recipient, and 3) may seek appropriate reimbursement from a program or plan that covers COVID-19 vaccine administration fees for the recipient.
 
Reminder: NIH Study on Vaccine in Highly Allergic/Mast Cell Disorder Patients to Complete Enrollment in June

The NIH is currently enrolling highly allergic or mast cell disorder patients in a multicenter study to determine risks for allergic reactions to the mRNA vaccines. Twenty-nine sites around the United States are currently enrolling patients with a history of severe allergic reactions to foods, immunotherapy or insects with use of epinephrine in the last 5 years, history of documented allergic reactions to two or more unrelated drugs within the last 5 years, convincing history (with/without positive skin test) of an immediate reaction to a drug or vaccine within the last 5 years, or physician-diagnosed mast cell disorder. Details can be found at Clinical Trials.gov. The AAAAI podcast series also has a new episode discussing the study.

COVID-19 Infection
 
Cytokine Profiles May Be Predictive of Mortality
 
This study looked at the level of certain cytokines on hospital admission and compared the results in patients who did not require invasive ventilation, those who did require invasive ventilation and those who required ECMO, and found that high levels of TNF-alpha, IL-6, IL-8 and IL-10 were characteristic of ECMO patients, whereas high interferon levels characterized non-ventilated patients.
 
COVID-19 Infection in Patients With Inborn Errors of Immunity

In this paper from Italy, patients with inborn errors of immunity (IEI) were no more likely to be infected or die from COVID-19 infection, although death occurred at a younger age and was not associated with the co-morbidities seen in those without IEI.

Therapeutics
 
IVIG

Several small studies (cohort, randomized double blind or retrospective) have shown benefit from early use of IVIG. This study, a randomized, parallel group controlled trial in 100 patients with moderate pneumonia due to COVID-19 in India, studied IVIG 0.4g/kg daily for 5 days at hospital admission. The primary outcome, days of hospitalization, was 7.72 in the treated group and 17.50 in the control group (p <.0001). Significant effects were also noted for clinical severity and days on mechanical ventilation. The NIH treatment guidelines currently state that IVIG should not be used outside of a clinical trial, but they have not been updated since July of 2020.
 
NIH To Start Clinical Trials for Mild-to-Moderate and Severe COVID-19

The ACTIV-6 trial will explore a pool of up to seven drugs that can be self administered that have already been FDA approved for other purposes.

The ACTIV-3 trial will test Zyesami, a formulation of aviptadil acetate, a synthetic version of vasoactive intestinal peptide (VIP), with or without remdesivir in severely ill patients with acute respiratory failure.

The ACTIV-2 trial, a Phase 2/3 trial to evaluate a new fully-human polyclonal antibody targeted to SARS-CoV-2, called SAB-185, has begun enrollment in non-hospitalized patients with mild or moderate cases of COVID-19. Other therapeutics being studies in ACTIV-2 include two other experimental antibodies, inhalable beta interferon (SNG001), a long-acting monoclonal antibody (AZD7442), and Camostat medilate, an orally administered serine protease inhibitor.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, May 3, 2021

Here are today's important updates:

Vaccines
 
Systemic Side Effects Uncommon in Real World Study

In a prospective app-based observational study in the UK involving over 600,000 vaccinated individuals (partial and complete), systemic side effects were reported in 13.5% after the first dose of the Pfizer vaccine, 22% after the second dose and 33.7% after the AstraZeneca vaccine. This rate is much lower than occurred in the trials. Local reactions were in the range of 60-70%. Many patients express reluctance to get the vaccine because of fear of systemic effects. You can use this information to reassure them. Systemic effects were 2.9 times higher after the first dose in those previously infected, but that is still less than 40% of patients who have systemic side effects. In a subset of vaccinated subjects, 3,106 of 103,622 vaccinated subjects subsequently tested positive for COVID-19 compared to 50,340 of 464,356 unvaccinated individuals.
 
CDC COCA Webinar on Janssen (J&J) Vaccine and Thrombosis with Thrombocytopenia Syndrome (TTS)

Through April 21, data from VAERS shows 15 cases of TTS out of 8 million doses of vaccine. All are females, with 13 out of 15 patients between the ages of 18-49. Of the 3.99 million doses given to women, the incidence of this complication was 5.2/1,000,000 for ages 18-29 and 11.8/1,000,000 for ages 30-39. Twelve had cerebral venous sinus thrombosis (CVST), 10/15 had platelet count <50,000 and there have been three deaths. The CDC is investigating an additional two cases reported since then. VAERS is a passive surveillance system. The active surveillance system, Vaccine Safety Datalink, found 11 cases of venous thrombosis/pulmonary embolus out of 142,222 vaccine doses, but none of these had thrombocytopenia. Background incidence of CVST is 14.5-28.5/million people and higher in females ages 18-49, but rarely associated with thrombocytopenia, and only occurring in <0.1% of hospitalized COVID-19 patients. TTS after the AstraZeneca vaccine has occurred in 169 cases (10/1,000,000) in the EU and 168 cases (7.9/1,000,000) in the UK. Take-home message: This complication is rare. Avoid Janssen vaccine if history of TTS [e.g., heparin-induced thrombocytopenia (HIT)]. Risk factors for VTE unlikely to be associated with an increased risk of TTS, including pregnancy and oral contraceptive use. Do not stop ASA or anticoagulants before vaccination.
 
Have a high index of suspicion in someone who presents with severe headache, visual changes, abdominal pain, nausea/vomiting, backache, shortness of breath, chest pain, leg pain or swelling 6-13 days after vaccination. Work-up should include CBC with platelet count, imaging as indicated and a PF-4 HIT ELISA. Do not treat with heparin unless HIT testing negative.

The CDC's Clinician Outreach and Communication Activity (COCA) webinar from April 27 can be viewed here.
 
Vaccine Efficacy in Those >65 Years of Age

In a multi-state network of U.S. hospitals during January-March 2021, receipt of Pfizer-BioNTech or Moderna COVID-19 vaccines was 94% effective against COVID-19 hospitalization among fully vaccinated adults and 64% effective among partially vaccinated adults aged 65 years and older.
 
Vaccine Response in Pregnancy

This small study looked at vaccine response in pregnant compared to non-pregnant women and those with previous infection, and found that the response to the mRNA vaccine was equal in pregnant women compared to non-pregnant women and greater than the response following infection. In a very small number of patients who had delivered, antibodies were also found in umbilical cord blood and breast milk.
 
Vaccine Response in Those With Immune Deficits

A prospective observational study in a small group of cancer patients noted that after one dose of the Pfizer vaccine, 38% of patients with solid cancers (21/56) had positive antibody titers and 18% (8/44) with hematologic cancer, compared to 94% (32/34) without cancer. These numbers did go up in the even smaller number of patients who had samples 2 weeks after a second dose of vaccine: 95% (18/19) with solid cancer and 60% (3/5) with hematologic cancer, compared to 100% without cancer.

The NIH just announced a study assessing how people with immune system deficiencies or dysregulations respond to COVID-19 vaccination. The study will enroll participants 16 years of age and older, and potential participants can be referred by healthcare providers. All study visits will be conducted in person at the NIH Clinical Center or remotely. Participants can be enrolled before or after vaccination, and can have received any of the approved vaccines.
 
Updated CDC Guidelines for the Fully Vaccinated

This guidance was updated on April 27. The most recent change was that fully vaccinated people can gather or conduct activities outdoors without wearing a mask except in certain crowded settings and venues. If you travel in the United States, you do not need to get tested before or after travel or quarantine after travel. There are still restrictions on returning to the United States after international travel.
 
Facial Paralysis After Vaccination

During the pivotal trials of mRNA vaccines, there appeared to be a preponderance of cases of facial paralysis in the vaccine group compared to the placebo group, although the rate of such reactions did not exceed the expected background rate. This disproportionality analysis using the WHO Pharmacovigilance Database found that mRNA vaccines did not display a signal for facial paralysis, after analyzing 320 million doses.

COVID-19 Infection

New Review on COVID-19

This article in press in the American Journal of Respiratory and Critical Care Medicine is a good update on COVID-19, and covers pathophysiology, clinical treatment and societal impact.
 
Re-infection

A retrospective chart review based on coded diagnoses noted that re-infection was identified in 0.7% (95% CI 0.5-0.9%) of 9,119 patients who underwent serial tests in healthcare facilities in the United States between December 2019 and November 2020. Mean period between initial and re-infection was 116 +/- 21 days. Asthma (OR 1.9, 95% CI 1.1-3.2) and nicotine dependence/tobacco use (OR 2.7, 95% CI 1.6-4.5) were associated with re-infection. COPD was also associated with re-infection to a similar degree as asthma, but not mentioned by the authors.
 
Persistent Problems After Acute COVID-19 in Patients With Mild-Moderate Disease

This study in Georgia on non-hospitalized patients 1-6 months after diagnosis noted that 69% had one or more outpatient visits during this time period. Two-thirds had a visit for a new primary diagnosis. Symptoms potentially related to COVID-19 were common new visit diagnoses.
 
An excellent review in a large VA population on COVID-19 sequelae can be found here.

Disparity Research
 
NIH Will Use American Rescue Plan Funds to Research Disparities

To bolster research to help communities disproportionately affected by COVID-19, the NIH is funding $29 million in additional grants for the NIH Community Engagement Alliance (CEAL) Against COVID-19 Disparities. This funding was supported by the American Rescue Plan. The awards will provide $15 million to 11 teams already conducting research and outreach to help strengthen COVID-19 vaccine confidence and access, as well as testing and treatment, in communities of color. An additional $14 million will fund 10 new research teams to extend the reach of COVID-19 community-engaged research and outreach.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, April 26, 2021

Here are today's important updates:

Vaccines

ACIP and CDC Lift Pause on J&J Vaccine

  • After a thorough safety review the ACIP, CDC and FDA agree that the known and potential benefits from the J&J vaccine outweigh the rare risk of the thrombotic complications that have been reported. Use of the vaccine will resume for all people 18 years of age or over, but there is now a warning about this complication in the provider and patient information accompanying the vaccine. The European Medicines Agency (EMA) announced on April 20 that there may be a link between the J&J/Janssen vaccine and this complication, but that the risk/benefit ratio favors immunization. They are going to ask for a change in the warnings for the vaccine. As of April 23, there have been 15 cases reported in the United States, all of which occurred in women between the ages of 18-59, with symptom onset between 6-15 days following vaccination.

Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) Or Thrombosis with Thrombocytopenia Syndrome (TTS)

  • With all the press surrounding this complication, it is hard to remember that this is a very rare event, but clinicians need to be aware of possible presenting symptoms, since treatment differs from the usual approach.
  • VITT is the new term coined by hematology researchers who are investigating the unusual blood clots and thrombocytopenia that has occurred rarely after the use of adenoviral vector COVID-19 vaccines. The CDC is calling it TTS. The American Society of Hematology offers key takeaway points from their webinar on this topic. Urgent medical evaluation for VITT is indicated if any of the following develop 4-30 days after vaccination: severe headache, visual changes, abdominal pain, nausea/vomiting, backache, shortness of breath, leg pain or swelling, petechiae or purpura. Initial work-up should include CBC with platelet count and imaging for thrombosis based on symptoms, PF-4 HIT ELISA, fibrinogen, followed by emergent hematology consult.
  • Information from the ACIP meetings: Incidence of cerebral venous sinus thrombosis (CVST) in the general population is higher than after vaccination, but this is not the case for TTS. The key difference is the association with thrombocytopenia. Pathogenesis and management of TTS slides are available. TTS has not been observed after mRNA vaccination, although there were 3 cases of CVST with normal platelet counts following the Moderna vaccine. Learn more about TTS following Janssen COVID-19 vaccine.
  • This analysis of 23 patients following vaccination with the AstraZeneca vaccine reviewed the proposed pathogenesis and offers an algorithm for diagnosis and treatment. They also state that the risk after vaccination does not appear to be higher than the background risks in the general population. This issue also contained an editorial on VITT induced by all of the SARS-CoV-2 vaccines, and a response from Johnson & Johnson pointing out the results of their clinical trials and ongoing safety assessment and the differences between the two adenoviral vector vaccines. For more discussion on pathogenesis, see also pathogenesis and management of TTS.
  • The CDC will host a COCA call on the J&J vaccine and TTS on Tuesday, April 27 at 10:00 am EDT titled Johnson & Johnson/Janssen COVID-19 Vaccine and Thrombosis with Thrombocytopenia Syndrome (TTS): Update for Clinicians.

Safety in Pregnant Patients

  • Using data from the V-safe program, the CDC reviewed preliminary data on over 35,000 women who identified as pregnant after their vaccine. Injection site pain was more common in pregnant persons, but other symptoms of reactogenicity were less. Data on almost 4,000 who participated in the pregnancy registry did not show any safety signals of concern, and outcomes were similar to studies on pregnant women before the pandemic. The CDC now recommends that all pregnant women be vaccinated.

More on the Israeli Experience

  • Two months after initiation of their vaccine program, there was a 77% decline in the number of cases, 45% decline in the number of positive tests, 68% decline in the number of hospitalizations, and 67% decline in severe cases compared to peak values. Declines in the clinical measures occurred only after >50% of the population of a given age group had been vaccinated.

Update on COVID-19 mRNA Vaccine Allergic Reactions

  • The Mass General-Brigham group has published a report on 16 patients who they evaluated pre-vaccine for a history of a severe allergic reaction to a vaccine or injectable with PEG/polysorbate (8), oral PEG (4), other vaccine or injectable (3), and food, drug, venom or latex (1). Only one (oral PEG allergy) had a positive skin test to PEG and that patient tolerated the Janssen vaccine. The other 15 were ST negative and tolerated the first dose of a mRNA vaccine.

Vaccine Response in Variants of Concern

  • Most studies on vaccine response to variants have measured antibody serology. This study looked at antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered patients. A single dose of a mRNA vaccine produced neutralizing activity against the D614G variant in 50% of naïve recipients and against the B1.351 variant in 16%. This improved to 100% against the D614G variant and 96% against the B.1.351 variant after the second dose. Two doses of the vaccine were required to achieve levels of SARS-CoV-2 receptor binding domain (RBD)-specific B cells comparable to those after infection. In previously infected patients, both antibody and antigen-specific B cell levels were significantly boosted after one dose, with negligible changes after the second dose. These results are encouraging and would argue against delaying the second dose in infection-naïve individuals.

Vaccine Response in Previously Infected Patients

  • Several studies involving small numbers of patients have indicated that immune responses after a single dose of mRNA vaccine produces levels comparable to those in infection-naïve patients after two doses. This study confirmed that finding in more than 1,000 people.

Vaccine Response in Immunosuppressed

  • A previous message noted an absence of immune response to vaccination in kidney transplant patients. This study notes that chronic lymphocytic leukemia patients overall had a 39.5% antibody response rate two weeks after the second vaccine dose. The response was 79.2% in patients in remission after treatment, 55.2% in treatment naïve, and 16% in those undergoing treatment.

 Breakthrough Infections

  • Of the more than 75 million people in the United States who have been fully vaccinated, the CDC has received 5,814 reports of breakthrough infections after completion of vaccination (0.008%). 45% were over the age of 60, 29% were asymptomatic, 7% hospitalized and 1% died. Of those that died, 12% were asymptomatic or the patient died from another cause.
  • The current system for collecting this data is passive, so the numbers are very likely to be higher, but estimates for reinfection from the pivotal trials is in the range of 4-6%. Bottom-line: More evidence of vaccine effectiveness.

Clinical Practice
 
HHS Extends the PHE

  • HHS extended the Public Health Emergency (PHE) from April 20 until July 19, so all payer waivers that are in effect for the duration of the PHE will remain in effect through July 19.

2021 COVID-19 MIPS Relief Now Available

  • For the 2021 Merit-based Incentive Payment System (MIPS) performance year, CMS will once again use its Extreme and Uncontrollable Circumstances Policy to allow clinicians, groups and APM Entities to submit an application requesting reweighting of MIPS performance categories due to the current COVID-19 PHE. CMS recently posted instructions for submitting this application on the QPP website. The Extreme and Uncontrollable Circumstances Exception Application deadline for PY 2021 is December 31, 2021.

Thought For the Week
 
Years of Life Lost

  • We are all aware of the number of deaths due to COVID-19 last year. Consideration of this number makes it easier to discount some of the deaths as occurring in people who would have died anyway, and doesn’t reflect deaths in younger people. These researchers framed the pandemic in a different way, looking at “Years of Life Lost (YLL)” and determined that in 2020 mortality from COVID-19 in the United States was responsible for 4,000,000 years of life lost, years that could have been spent with friends, family, attending school or providing service to society.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, April 19, 2021

Here are today's important updates:
 
SARS-CoV-2 Infection

Reinfection

  • A large multi-center prospective study in the UK from June to December 2020 notes a reinfection rate of 7.6/100,000 person-days whereas the new infection rate was 57.3/100,000 person-days. The B.1.1.7 variant was causing roughly 50% of the infections in the latter part of the study period, but no evidence for increased reinfection rates were noted during that time.

Oral Infection

  • Researchers at the NIH have discovered that the SARS-CoV-2 virus does infect epithelial cells in the oral cavity, which may explain some of the oral manifestations of the disease (ageusia, oral blistering, and dry mouth), the accuracy of salivary samples for diagnosis and also that saliva may be infectious.

Children and Severe Disease

  • CDC researchers conducted a cohort study to estimate adjusted associations between demographic and clinical characteristics and severe COVID-19 among hospitalized pediatric patients during 2020. Increased association of severe COVID-19 was seen most with one or more underlying conditions, but also in those aged 2-11 and males. There was no statistically significant association between race/ethnicity or insurance type.

Long-Term Outcomes in Mild Disease

  • This Swedish cohort study examined outcomes in 1,400 healthcare workers (HCWs) with asymptomatic or mild disease compared to uninfected, seronegative HCWs. 26% of the infected HCWs reported at least one moderate to severe symptom lasting for at least two months, and 15% reported at least one moderate to severe symptom lasting eight months. Marked disruption of work life was noted in 8% and social life in 15%.

Vaccines

Thrombotic Events and Thrombocytopenia Noted After Adenoviral Vector COVID-19 Vaccines

  • Last week the FDA and CDC recommended a pause in the use of the Johnson & Johnson vaccine because of this extremely rare condition (<1/1,000,000 doses) and all 50 states have complied. Cases so far have been limited to women aged 18-48. Symptoms typically start six to 13 days after vaccination and consist of headaches, with occasional abdominal and focal CNS complaints.
  • Treatment is different for this complication compared to other thrombotic events. Pathogenesis may include platelet-activating antibodies against platelet factor-4 (PF4). The ACIP met on April 14 to review the data and determined more information is needed before a decision on the pause will be made. They will meet again on April 23 in emergency session.
  • The AMA hosted a webinar on this topic on April 13, which can be viewed here. The CDC also held a Clinician Outreach and Communication Activity (COCA) webinar on April 15, which can be viewed here.

Antibodies in Breast Milk After Maternal Vaccination

  • An Israeli study involving 84 breastfeeding women who were vaccinated for COVID-19 found “robust secretion of SARS-CoV-2 specific IgA and IgG antibodies in breast milk for 6 weeks after vaccination.” IgA appeared as early as two weeks, and IgG after four weeks. These antibodies had strong neutralizing effects. Limitations of the study: Mothers did not have serology or RT/PCR testing for COVID-19 at the time of vaccination.

Reduction in Asymptomatic Infection

  • A study of healthcare workers (N=9,000) in the UK noted that one dose of the Pfizer vaccine was associated with a four-fold reduction in asymptomatic COVID-19 infection >/= 12 days post-vaccination, from 0.8% to 0.2%.

More Real World Data

  • A report out of Israel on 596,618 vaccinated (Pfizer) people matched 1:1 with unvaccinated controls shows vaccine effectiveness to prevent documented infection at 46% for 14 through 20 days after the first dose, and 92% for seven or more days after the second dose; 57% and 94%, respectively, in preventing symptomatic COVID-19; 74% and 87% for preventing hospitalization; and 62% and 92% for preventing severe disease.

Poor Response to Pfizer Vaccine in Kidney Transplant Patients

  • A study of 101 kidney transplant patients on belatacept noted poor humoral and T-cell response to the Pfizer vaccine after two doses. This may have implications for other solid-organ transplant patients.

Therapeutics
 
Baricitinib Plus Remdesivir

  • A double-blind, randomized placebo-controlled trial evaluated the antiviral remdesivir in combination with the Janus Kinase inhibitor baricitinib in hospitalized adults with COVID-19 and found that the combination was more effective than remdesivir alone, particularly for patients receiving high-flow O2 or noninvasive ventilation.
  • An accompanying editorial points out that the randomized trials for therapeutics have now helped clinicians identify the clinical parameters for which individual treatments may be most effective, based on the clinical score (based on respiratory support). Remdesivir seems to work best in individuals with a score of 4 (not receiving oxygen) to 5 (low-flow O2), dexamethasone works best in those with a score of 7 (invasive ventilation) and perhaps those with scores of 5 or 6 (high-flow O2), and the combination of remdesivir and baricitinib was most effective in those with a score of 6.

Remdesivir Plus Baricitinib Compared to Remdesivir Plus Dexamethasone

  • The NIH closed enrollment of this study after interim analysis indicated that neither treatment is significantly better than the other in preventing the need for invasive ventilation in hospitalized patients.

Bamlanivimab Effective in Preventing Hospitalization

  • A retrospective case control study looked at adults with documented COVID-19 and risk factors for severe disease who received bamlanivimab (218 patients) versus those who were referred for the drug but did not receive it (185 patients). Thirty-day hospitalization rate was significantly lower among patients who received the drug (7.3% v 20.0%, RR 0.37, 95% CI 0.21-0.64, p<0.001).

Inhaled Corticosteroids

  • A randomized open-label study in 146 participants in the UK found that treatment with inhaled budesonide, 1600mcg BID, within seven days of onset of mild COVID-19 symptoms was associated with reduced likelihood of needing urgent medical care and reduced time to recovery compared to regular care.

Anti-CD14 Antibody Trial

  • The NIH announced the start of a clinical trial of a monoclonal antibody to CD14 in people hospitalized with respiratory disease and low oxygen levels due to COVID-19. This is a Phase 2 trial, called the COVID-19 anti-CD14 Treatment Trial (CaTT), and will enroll 300-350 hospitalized patients 18 years of age and older. The primary outcome measure is recovery time. CD14 has been implicated in the overamplification of the immune response to the virus.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, April 12, 2021

Here are today's important updates:
 
SARS-CoV-2 Infection
 
Children & COVID-19 – An Update

  • AAP and Children’s Hospital Association data as of March 25: 3,405,638 cases of COVID-19 have been reported, 13.4% of all cases. There were 64,029 new cases from March 18-March 25, children represented 19.2% of all new cases. Hospitalization in 1.3-3.1%, mortality 0.00-0.03% of cases. In Michigan, during the last two weeks of March this year, the majority of new cases occurred in 10-19 year-olds.

Post-acute COVID-19 Syndrome

  • This term coined by Dr. Fauci is the new name for COVID-long-haulers. There is a new review covering any organ system that can be involved and the Annals of Internal Medicine just published the results of an NIH workshop on the topic.

Rheumatalogic Disease Treatment and COVID-19

  • A retrospective single center study examined the risk of COVID-19 in patients with connective tissue disease and on different therapies for treatment. In the study of 2,315 patients in Madrid of which 41 had inflammatory rheumatic diseases, there was a higher risk of hospitalization and death in those treated with rituximab. Conversely, there was no increased risk of severe infection in those treated with anti-TNF medications.

Reinfection Risk Post-COVID-19

  • In a population-level observational study, individual-level data was collected from the Danish Microbiology Database for all persons who had a PCR test for SARS-CoV-2 between February 26 and December 31, 2020. Over 500,000 tests were done during that time period. 80% protection against re-infection was seen in those under 65 years of age, in contrast to 47% in those 65 and older. Healthcare workers had a two-times higher risk of reinfection.

Diagnostics
 
Home Testing Initiative

  • The CDC and NIH have partnered to launch a “Say Yes! COVID Test” campaign. It will be launched in two communities in North Carolina and Tennessee where there will be access to free home rapid antigen COVID-19 testing kits that can be used at home three times per week for one month. This pilot will attempt to determine if frequent home testing can reduce viral transmission of disease in communities.

Therapeutics
 
Remdesivir Treatment

  • Final results of the double-blind, randomized, placebo-controlled trial of remdesivir in hospitalized adults with COVID-19 showed that remdesivir was superior to placebo in shortening the time to recovery.

Vitamin D and COVID-19

  • A JAMA Network study published online in February showed that a single high dose of vitamin D had no beneficial effect on hospital length of stay in patients with moderate to severe COVID-19. Another study in JAMA Network Open that was published online in March noted that the risk of acquiring COVID-19 infection was 2.64-fold higher in Black individuals with vitamin D levels in the 30-40ng/ml compared to White individuals with similar vitamin D levels. The authors suggest that randomized clinical trials are needed to determine if supplementation of vitamin D for Black individuals might reduce infection risk.

Vaccines
 
Moderna Vaccine Six-Month Data

  • In an ongoing Phase I trial of 33 healthy adults, binding and neutralizing antibodies elicited after the second dose of mRNA1273 persist at least six months as assessed by three distinct serologic assays.

Pfizer Vaccine Antibody Response in Those Previously Infected With SARS-CoV-2

  • In a cohort study of 1,090 patients, "spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228)." Post-vaccination symptoms were higher with the first dose of the vaccine in those that had previously had COVID-19, but were similar with the second dose of the vaccine in both groups.

AstraZeneca Vaccine and Thrombotic Thrombocytopenia

  • One to two weeks post vaccination with ChAdOx1 several cases of moderate to severe thrombocytopenia and thrombosis emerged. These patients were seen to have platelet factor 4 (PF4)–heparin antibodies WITHOUT previously receiving heparin. This clinically appears similar to autoimmune heparin induced thrombocytopenia. Complications of the thrombosis can be seen in the brain or abdomen five to 20 days after vaccination. ELISA to detect PF4–heparin antibodies should be performed in cases suspected of this disease. High dose IVIG can be used to raise the platelet count and reduce hypercoagulability. Read the paper.

Vaccine Hesitancy

  • The Kaiser Family Foundation (KFF) continues to follow public opinion on COVID-19 vaccination. Their March 30, 2021, release demonstrates an increase in enthusiasm for the vaccine across all ethnicities. The latest data show 61% of adults being vaccinated or intending to do so, while only 13% say they definitely will not get the vaccine (the "definitely will not" percent is unchanged since December). Importantly for practitioners, the KFF tested a number of statements to see which led participants in the "wait and see" group to most likely say they would get vaccinated. "Vaccines are nearly 100% effective at preventing hospitalization and death from COVID-19" was the "most impactful" statement, followed by "scientists have been working on the technology used in the new COVID-19 vaccines for 20 years", "more than 100,000 people from diverse backgrounds took part in the vaccine trials", "vast majority of doctors who have been offered the vaccine have taken it", and "there is no cost to get the vaccine". Notably these statements only swayed those in the "wait and see" category, but had no impact on the "definitely not" group. The complete report can be found here.

Clinical Practice
 
CMS Resources for Telehealth

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, April 5, 2021

Here are today's important updates:

More on Real World Effectiveness of Pfizer and Moderna Vaccines 

  • The MMWR from March 29 reports on prospective cohorts of patients who completed weekly SARS-CoV-2 testing for 13 weeks starting on the first day of vaccine administration. There was also weekly surveillance of symptoms. The majority of the 3,950 subjects were White, female and between the ages of 18-49. 87.3% of PCR-confirmed infections were symptomatic. The incidence rate of PCR-confirmed infections = 1.38/1,000 person-days before vaccination, 0.19/1,000 person-days between first and second dose, and 0.04/1,000 person-days after being fully vaccinated. Estimated adjusted vaccine effectiveness of full immunization was 90% (95% CI 68-97%), and 80% after partial vaccination (95% CI 59-90%). Since all subjects were routinely tested, these effectiveness numbers also apply to asymptomatic infection.

CDC Updates Travel Recommendations for the Fully Vaccinated

  • Based largely on the data published in the above item, the CDC now states that fully vaccinated people can travel safely without needing testing before or after travel, and they also do not need to self-quarantine after travel. The testing applies to domestic travel. For international travel, no testing is needed before, but it may be required upon return.

Other Vaccine News

  • The Pfizer mRNA vaccine shows 100% efficacy in a trial in 12-18 year-old subjects. (Caution: press release, numbers could change.)
  • In a press release from April 1, the Pfizer vaccine was 91.3% effective after six months, 100% effective against severe disease, and 100% effective in preventing cases in South Africa where B.1.351 is prevalent. This data comes from additional analysis of their vaccine trial, with six months post-second dose data. This has not been peer-reviewed and the South African data represents a small sample of participants.
  • In post-hoc analysis, the AstraZeneca vaccine showed 70.4% efficacy against the B.1.1.7 variant.
  • Viral load was lower in those infected after receiving the first dose of the Pfizer vaccine in data from Israel.

Immune Response to Variants of Concern

  • In a press release issued on March 30, the NIH announced results of a small NIAID study in 30 previously infected individuals. Results of the study showed that SARS-CoV-2-specific CD8+ T cell responses remained largely intact and could recognize virtually all mutations in the variants studied [B.1.1.7 (UK), B.1.351 (South Africa) and B.1.1.248 (Brazil)]. It is important to remember that details about the exact levels and composition of antibody and T cell responses needed to achieve immunity is still unknown.
  • The published article can be found here.

Moderna Begins Variant Vaccine Trial

  • The NIH announced on March 31 that Moderna has developed a vaccine called mRNA-1273.351 and is going to start a Phase 1 trial to determine safety and immunogenicity in adult volunteers. The study is funded by the NIAID, and will study subjects who have already received the mRNA-1273 vaccine and also those who have not been vaccinated. Previously vaccinated volunteers will be randomized to receive either a single booster dose of mRNA-1273.351 or a combination of mRNA-1273 and mRNA-1273.351. Unvaccinated subjects will be randomized for a dose-ranging study in various regimens.

Should I Check Antibody Titers After Vaccination?

  • From the AAAAI's Ask the Expert: The current mRNA COVID-19 encodes for the spike protein. One needs to have an assay specifically designed to detect IgG directed against the spike protein to see a positive response to a vaccination. Please review the enclosed CDC guidance. Specifically the CDC states that “Antibody testing is not currently recommended to assess for immunity to COVID-19 following COVID-19 vaccination or to assess the need for vaccination in an unvaccinated person. Since vaccines induce antibodies to specific viral protein targets, post-vaccination serologic test results will be negative in persons without history of previous natural infection if the test used does not detect antibodies induced by the vaccine.”

Transmission

  • Schools: The CDC adjusted its guidelines for schools to allow physical distancing >/= three feet when six feet is not possible in the classroom setting, but continued to recommend six feet distancing in other situations. Of course, universal masking and handwashing is still recommended. Several other studies recently mentioned in our messaging plus these continue to show that the school environment is not a significant source of transmission of COVID-19. School sports are another story, however. Three studies the CDC used to make that change can be found herehere and here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, March 29, 2021

Here are today's important updates:

NIAID Statement on AstraZeneca Vaccine

  • In the latest interim analysis of data (after DSMB comments), AstraZeneca states that their vaccine was 76% effective against symptomatic disease and 100% effective against severe or critical disease. The revised analysis notes efficacy of 80% for those over 65 years old.
  • We should remind our patients that despite this widespread news, authorizations and guidelines for use of this vaccine in the United States will be determined by the FDA and CDC after thorough review of the entire data by independent advisory committees.

ACP/Annals Forum on COVID-19 Vaccine: Practical Clinical Considerations

  • The video can be viewed here. Several infectious disease and epidemiology experts discuss considerations for the future now that the vaccines are here.

Real World Effectiveness of Vaccines

  • We know the efficacy of the vaccines in the clinical trials, but what is the experience in the real world? In this study from Israel, a two-campus health center employing 6,680 people evaluated the rate of positive COVID-19 tests in healthcare workers (HCWs) from the start of vaccinations for seven weeks, and found a steady reduction in incidence after vaccination from 9.4/1000 at week one after vaccine to 0.4/1000 two weeks after the second dose. The numbers of HCWs who did not receive a second dose was low, so the only comparable time point was at four weeks, when the rate in those who received a second dose was 1.4/1000 compared to 13.3/1000 in those who did not. Importantly, 80% of the new cases at that time in Israel were due to the variant B.1.1.7.
  • In California in early December before they started vaccinations, the University of California, San Diego (UCSD) mandated testing of asymptomatic HCWs weekly and the University of California, Los Angeles (UCLA) instituted voluntary testing for asymptomatic HCWs on December 26. They both started vaccinations on December 16. There were 36,659 who received their first dose and 28,184 the second. The absolute risk for testing positive after vaccination was 1.19% at UCSD and 0.97% at UCLA. The majority (270/379) tested positive within two weeks after the first dose and only eight tested positive 14 days after the second dose.
  • Data from the University of Texas Southwestern show that 2.61% of unvaccinated employees became infected, 1.82% of partially vaccinated employees became infected and 0.05% of fully vaccinated employees became infected.
  • These results are certainly reassuring, but the effects of the variants remain to be determined. In addition, testing was not done for the entire population at all time points, and testing criteria varied among the institutions.

Vaccines Effective for Pregnant Women and Offspring

  • small study of the Pfizer and Moderna vaccines in pregnant women found that antibody titers were equivalent to those produced in non-pregnant women, higher than those produced by natural infection in pregnant women, and these antibodies were also present in umbilical cord blood and breast milk samples.

But Doc, I Heard That People Have Died After Vaccination 

  • This was the number one trending story on social media for a few weeks in January, with many sources posting about the same patients, thus amplifying the reports and potentially affecting people’s plans to get vaccinated.
  • Although facts are not often helpful in countering these beliefs, in reality among the 85 million people in the United States who have been vaccinated, less than 0.0018% have died sometime afterward. You are three times as likely to be struck by lightning. None of these deaths have been linked to the vaccines.

High Social Vulnerability Counties Have Lower COVID-19 Vaccination Coverage

  • This is compared to low social vulnerability counties, based on the CDC social vulnerability index.
  • Vaccination coverage estimates by county-level social vulnerability varied widely among states, and disparities were observed in the majority of states.

European Task Force on Atopic Dermatitis (ETFAD): Position on Vaccination in Patients on Immunosuppression or Biologics

  • This position paper was published in February of this year on vaccination of adults with atopic dermatitis being treated with systemic medication and biologics.
  • Atopic dermatitis is not a contraindication to vaccination. Systemic immunosuppressants and JAK inhibitors may attenuate the vaccination response, but none is expected for dupilumab.
  • Although there is no clear evidence to make a recommendation, based on studies with methotrexate and RA where a temporary two-week discontinuation slightly improved the immunogenicity of influenza vaccine, the ETFAD stated that clinicians may consider pausing JAK inhibitors and cyclosporine for one week after vaccination, or for two weeks with methotrexate and azathioprineAlternately, the lowest dose possible might be considered.

Remember the CDC Website Page on Vaccines

  • The CDC link for vaccines has daily updated data on the number of vaccinated individuals for both first dose and second dose, as well as a host of other useful additional information.
  • This site now allows individual physicians to sign up for administering the COVID-19 vaccines if you click on “For Healthcare Workers” and then click on “Become a COVID-19 vaccine provider”. Check with your state's Department of Health to see if they follow these guidelines.

PPE Tax Deductible

  • The IRS announced on March 26 that the purchase of PPE, hand sanitizer, and sanitizing wipes for the primary purpose of preventing infection by SARS-CoV-2 are deductible medical expenses for individuals—provided you otherwise qualify for medical deductions, and are also eligible to be paid or reimbursed under an FSA, Archer MSA, HRA or HSA. They remain a deductible expense for businesses.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Tuesday, March 23, 2021

Here are today's important updates:

Vaccine News

  • Asymptomatic transmission: A retrospective cohort study on 39,156 adults across multiple U.S. states who were undergoing pre-procedural SARS-CoV-2 testing found that virus was detected in 3% of unvaccinated patients compared to 1% of participants who had received at least one dose of vaccine prior to screening. Adjusting for age, sex, race/ethnicity and location, the adjusted risk ratio for those who had received their first dose >10 days earlier was 0.49 and for those who had received their second dose >0 days was 0.27. This reduction is in line with what was reported in a small number of patients in the Moderna Phase 3 trial.
  • AstraZeneca vaccine and thromboembolic events: More than a dozen European countries suspended administration of the vaccine this past week due to thromboembolic events. Reports of pulmonary and CNS (sinus and cerebral vein) thromboembolic events and thrombocytopenia have been reported in a small number of patients among the millions vaccinated with this vaccine. The EMA does not feel that the number of events is greater than expected for the population, and announced on March 18 that the vaccine is safe and effective, but they couldn’t rule out a link between these events and the vaccine. France, Germany, Italy and Spain, as well as most of the other countries, have removed the suspension, although the top French health regulator recommended it only for those over 55, since the blood disorders were found in people younger than that, and Sweden, Denmark and Norway were awaiting further investigation.
  • AstraZeneca efficacy: The company announced that interim trial data from the United States, Chile and Peru show 79% efficacy across all age groups against symptomatic COVID-19 and 100% efficacy against severe disease. The trial involved over 32,000 patients. The vaccine was given in two doses, 4 weeks apart. No thromboembolic events were noted among the trial participants. The company will apply to the FDA for an EUA in “the coming weeks.”
  • Vaccines and variants: Two doses of the AstraZeneca vaccine showed efficacy of 10.4% against mild-to-moderate COVID-19 caused by the B.1.351 variant in a South African multicenter randomized trial. There were not enough severe cases in the trial to conclusively determine efficacy against severe disease. In a very small study involving 56 infected or vaccinated patients, neutralizing antibody was effective against the B.1.1.7 variant.
  • Payment rate: From CMS: Effective for COVID-19 vaccines administered on or after March 15, 2021, the national average payment rate for physicians, hospitals, pharmacies, and many other immunizers will be $40 to administer each dose of a COVID-19 vaccine. This represents an increase from approximately $28 to $40 for the administration of single-dose vaccines and an increase from approximately $45 to $80 for the administration of COVID-19 vaccines requiring two doses. The exact payment rate for administration of each dose of a COVID-19 vaccine will depend on the type of entity that furnishes the service and will be geographically adjusted based on where the service is furnished.
  • Vaccines in children: Both Moderna and Pfizer have enrolled children down to age 12 in vaccine trials, and now Moderna has announced a Phase 2/3 trial in children ages 6 months to 12 years, beginning with a dose-ranging study then moving into a randomized, placebo controlled trial. The company plans to enroll 6,750 children.
  • Vaccines in immunosuppressed patients: In this study, only 17% of solid organ transplant recipients developed antibody responses 20 days after a single dose of mRNA vaccine.

AMA Resources to Boost Vaccine Confidence

  • Counseling patients about the COVID-19 vaccine is consuming a lot of our time lately. To help, the AMA has a list of resources for practitioners. Called the “It’s Up to You” COVID-19 vaccine education initiative, it includes websites for the public in English and Spanish on vaccine information, messaging guide for physicians, physician FAQs, COVID-19 vaccine script for patient inquiries, and a video series including healthcare leaders addressing questions about vaccines.

Reinfection Rate

  • This study from Denmark compared infection rates during the spring of last year to fall of this year. Out of 11,068 people who had tested positive during the spring surge, only 72 (0.65%) tested positive again during the second surgeProtection was calculated at 80.5%. In an alternative cohort analysis, among those 65 and older, observed protection was 47.1%. There was no evidence of waning protection. Results were similar for 3-6 months follow-up versus 7 or more months of follow-up.

Long-Haul COVID-19 Now Called PASC

  • Dr. Anthony Fauci coined this new term recently during a White House news conference. Post Acute Sequelae of COVID-19 (PASC) was studied in a prospective uncontrolled cohort of 478 survivors of COVID-19 4 months after hospitalization. 51% reported at least one new symptom. Most common new symptoms at 4 months included fatigue (31%), cognitive symptoms (21%) and new-onset dyspnea (16%).

Testing

  • Antigen tests: Previous studies have suggested that antigen tests had low sensitivity in asymptomatic patients, but others have noted good sensitivity compared to RT/PCR. Two studies using different assays (here and here) noted that the sensitivity does depend on the viral load as measured by RT/PCR cycle thresholds. The sensitivity of the assays can be up to 90% or more with high viral loads. The real-world problem is that while symptomatic patients are more likely to have higher viral loads, that isn’t something a clinician could know when the test results come back negative.
  • Serology: A new, excellent resource is the AHRQ Evidence-based Practice Center’s Antibody Response Following SARS-CoV-2 Infection and Implications for Immunity: A Living Rapid Review. There is much we don’t know and much to learn about COVID-19 serology, and how to use this tool in practice (key message: not ready for primetime). While the majority of adults produce IgM and IgG antibody after infection, about 6-10% do not. Reasons for the absence of response are not clear, but may relate to the severity of disease. IgG levels persist for at least 120 days, and neutralizing antibodies for at least 152 days. Studies to date have not established the relationship between the development of antibodies and the risk of reinfection, although studies suggest the presence of antibodies is associated with lower risk.

Treatment Update

  • A recent press release from Eli Lilly presented new data from the BLAZE-1 Phase 3 study comparing bamlanivimab (LY-CoV555) 700mg plus etesevimab (LY-CoV016) 1400mg in high-risk adolescents and adults with mild-to-moderate COVID-19 to placebo, demonstrating 87% reduction in hospitalizations and deaths. This treatment has received an EUA from the FDA for non-hospitalized COVID-19 patients at high risk for more severe disease. Prior results from another cohort in the same study showed that higher doses of both drugs reduced the risk of these events by 70%. So far this information is not yet available in a peer-reviewed journal.
  • In another press release, Vir Biotechnology and GSK announced that their Phase 3 trial on a monoclonal antibody treatment VIR-7831 was stopped early given an 85% reduction in hospitalization or death in adults at high risk for hospitalization. This was based on an interim analysis of data from 583 patients enrolled in the trial. These companies plan to submit an EUA application. The companies also announced the results of another study indicating that this monoclonal maintains activity against the virus variants of concern, which was submitted for publication in bioRxiv (pre-print, not peer-reviewed site).
  • Taking another approach to therapy, this study looked at mavrilimumab, a monoclonal antibody to the GM-CSF receptor, in hospitalized patients with COVID-19 pneumonia, hypoxemia and elevated c-reactive protein, and did not find any significant difference in the proportions of patients alive and off oxygen therapy at day 14.

Decontaminating N95 Masks - What Works Best

  • A review of 42 studies in JAMA reported that ultraviolet germicidal irradiation, moist heat, and microwave-generated steam processing of filtering facepiece respirators are effective means for decontamination and are simple to implement.

Signs Your N95 Masks May Be Counterfeit

  • From AMA News: According to NIOSH, here are seven signs of counterfeit respirators that physicians and staffers at medical groups and health systems should look for: 1) No markings at all on the filtering facepiece respirator. 2) No approval number on filtering facepiece respirator or headband. 3) No NIOSH markings. 4) NIOSH spelled incorrectly. 5) Presence of decorative fabric or other decorative add-ons. 6) Claims of approval for children—NIOSH does not approve any type of respiratory protection for children. 7) Filtering facepiece respirator has ear loops instead of headbands.

CMS Updates COVID-19 Provider Toolkit and FAQs

  • Toolkits for vaccine providers and FAQs on FFS billing were updated the first week of March and can be accessed here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, March 15, 2021

Here are today's important updates:

So Is Asthma A Risk Factor for Severe Disease?

  • We all continue to get questions about asthma and COVID-19 from our patients. Earlier in the pandemic, they were concerned about getting sick and now they are concerned about which vaccine tier they should be in.
  • By early October of this past year, there have been over 110 publications including 4 meta-analyses that clearly demonstrate that asthma is not a risk. Similar findings are noted in the 10 or so papers published since then, and at least a few have demonstrated protection for those with asthma.
  • At this point, the answer is no.

Vaccine Anaphylaxis - Real World Data

  • In a research letter published in JAMA Online First on March 8, the group from Mass General Brigham reported on their prospective study of 52,805 employees who received their first dose of an mRNA vaccine. Acute allergic reactions were reported by 1,365 employees (2.1%), and anaphylaxis was confirmed in 16 employees (0.025%)94% of these were female, 10 had a prior allergy history and five had an anaphylaxis history. One patient was admitted to the ICU, all recovered. The incidence rate of anaphylaxis in this study was 2.47/10,000 vaccinations, which is higher than that reported via passive reporting measures (VAERS, Vsafe) but still rare.

B.1.1.7 Variant More Deadly

  • This variant was associated with an overall 1.6-fold increase in risk of death compared to previously circulating variants, with the increase noted from days 15-28 after infection. This corresponds to an increase in deaths from 2.5-4.1 per 1,000 cases. Read more.

Inpatient Treatment Updates

  • Baricitinib plus remdesivir in hospitalized adults was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with COVID-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. The study can be found here.
  • Anti-IL6 monoclonal antibodies: Two separate randomized trials using tocilizumab and sarilumab in patients with moderate-to-severe hospitalized COVID-19 patients showed no significant difference compared to standard care or placebo in improvement in the course of the disease. The studies can be found here and here.

NIH Highlights Comorbidities Associated With COVID-19 Hospitalization

  • A study published in late February in the Journal of the American Heart Association estimated that in the 900,000 hospitalizations that occurred in November 2020, 30% were attributable to obesity, 26% to hypertension, 21% to diabetes and 12% to heart failureObesity affected hospitalization similarly across age groups, whereas the other three were more likely in older patients.
  • In another study looking specifically at the degree of obesity among 148,494 adults diagnosed with COVID-19 between March and December of 2020, individuals with a BMI near the threshold between healthy weight and overweight generally had the lowest risk for hospitalization, ICU admission and death. Obesity was a particular risk for hospitalization and risk in those <65 years old. Individuals in the highest BMI category (>/= 45 kg/m2) had a 2-fold greater risk of death and 1.6-fold greater risk of hospitalization. Underweight individuals had a 20% greater risk for hospitalization.

T Cell Immune Response to COVID-19

  • Functional responses were retained 6 months after initial infection in this study of 100 convalescent donors. Responses were characterized by predominate CD4+ T cells with strong IL-2 cytokine expression. Responses were higher if the initial infection was symptomatic and correlated with peak antibody levels.

Transmission

  • Schools: Testing of asymptomatic students and staff in New York City public schools in the fall of 2020 noted that the incidence of COVID-19 was about 60% lower compared to the city population. 0.4% of 234,132 persons were positive on testing, rates were highest in K-8 staff and elementary students. Secondary attack rate was 0.5%, likely from a staff person. Read more.
  • retrospective cohort study of 537,336 students and 99,390 staff among 351 school districts in Massachusetts this fall showed that increasing physical distancing requirements from >/= three feet to >/= six feet was not associated with a reduction in COVID-19 cases if other mitigation measures were implemented.

Small Business Administration Issues Interim Final Rule With Changes to Paycheck Protection Program (PPP)

  • On December 27, 2020, the Economic Aid to Hard-Hit Small Businesses, Nonprofits, and Venues Act (Economic Aid Act) was enacted, extending the authority to make PPP loans through March 31, 2021, revising certain PPP requirements, and permitting second draw PPP loans. This interim final rule allows individuals who file an IRS Form 1040, Schedule C to calculate their maximum loan amount using gross income, and removes the eligibility restriction that prevents businesses with owners who are delinquent or in default on their Federal student loans from obtaining PPP loans. Unless otherwise specified in this interim final rule, the provisions of this interim final rule are effective March 4, 2021. Details can be found here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, March 8, 2021

Here are today's important updates:

CDC Issues New Interim Guidelines for Fully Vaccinated Persons in Non-Healthcare Settings

  • Released on March 8, the CDC now states that fully vaccinated persons can: visit with other fully vaccinated people indoors without wearing masks or physical distancing, visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing, and refrain from quarantine and testing following a known exposure if asymptomatic. In all other circumstances, they should continue to follow current mitigation recommendations and avoid medium and large in-person gatherings.

Delayed Local Reactions After Moderna Vaccine

  • In this NEJM paper, Blumenthal and colleagues report on 12 patients with delayed large local reactions. Median onset was on day eight after the first dose and had a variable appearance, many of which were large indurated erythematous plaques. Some had concurrent systemic symptoms. Treatment varied from antihistamines to steroids (oral or topical) with resolution over a median of six days. Skin biopsy from another patient supported a delayed-type hypersensitivity reactionAll 12 went on to get their second dose of the vaccine, half had no reaction, while the other half had similar reactions of the same severity or less. Median onset of the reaction after the second dose was day two.
  • Data from the original clinical trials did note such a reaction in 0.8% of participants.

Patients With Mastocytosis Should Tolerate COVID-19 Vaccines

  • In correspondence to the JACI, authors from Portugal and Brigham and Women’s Hospital report on two patients with systemic mastocytosis and a history of anaphylaxis who tolerated the Pfizer mRNA vaccine with pretreatment, without any adverse effects. They go on to recommend pretreatment with H1 and H2 antihistamines one hour before, and montelukast one and 24 hours before vaccination, and that vaccination be given in a hospital setting.

Is One Dose of Vaccine Enough for People Who Had COVID-19?

  • In a Lancet study published on February 25, anti-S (spike) antibodies following the first dose of the Pfizer vaccine in participants who were seronegative were equivalent to those with natural infection, while the titers in seropositive participants were 140-fold higher than pre-vaccine titers. There were 51 participants in the study. Another study in the same issue involving 71 participants showed similar results. In this study, however, those with T-cell response indicating prior infection, but negative serology for anti-S antibodies, had titers post-vaccination that were less than those with positive serology, but greater than those with no prior infection.
  • third study was published online in JAMA on March 2. This study in 59 participants showed that the antibody and neutralization titers 14 days after the first vaccine dose were several fold higher in those that had previous infection, compared to those who did not. Problems with this study included a poor antibody response after vaccination in those without previous infection.
  • ACIP doesn’t currently recommend this approach based on conversations published in AAP News this week. Also, in a given individual who has survived COVID-19, the level of antibodies is unknown. It would not be practical to check serology before vaccination, and we don’t know what level of anti-S antibodies would warrant skipping the second dose.

Household Transmission Rate

  • There have been several studies looking at household transmission rate, but this large study done in a Boston healthcare system (Massachusetts General Brigham) that involved 7,262 individuals who were COVID-19 positive and 17,917 household contacts, found the overall infection risk was 10.1%. Independent factors significantly associated with higher transmission were age >18 years and multiple comorbid conditions. This was done in the spring of 2020, before the more transmissible variants were present.

Persistent Viral Shedding

  • In this study of 109 patients with mild-to-moderate COVID-19 who underwent serial RT/PCR testing, the majority were found to have continued viral RNA shedding for more than 10 days, but cultures performed in 35 of the patients did not reveal replication competent viruses. This provides some evidence that individuals with mild-to-moderate COVID-19 are less likely to be infectious beyond 10 days after onset.

Convalescent Plasma Ineffective

  • meta-analysis of randomized clinical trials comparing COVID-19 patients treated with convalescent plasma to controls, involving almost 12,000 patients, found no significant differences in all-cause mortality, length of stay or mechanical ventilation. Most of the participants were inpatients, not all of whom were requiring supplemental oxygen. Four of the trials used high-titer convalescent plasma. Limitations of the study are that only four of 11 studies were published in peer-reviewed journals, five were preprints and two were press releases. The largest study (RECOVERY trial) included 10,000 of the 12,000 participants and only had data from a press release.
  • On February 4, the FDA revised the EUA for convalescent plasma, authorizing only high-titer plasma for hospitalized patients early in the course of the disease, as well as those hospitalized with impaired humoral immunity.

New Guidance on Coverage of COVID-19 Testing, Vaccination

  • In guidance released late last week, CMS—along with the Departments of Labor and the Treasury—issued guidance clarifying that “private group health plans and issuers generally cannot use medical screening criteria to deny coverage for COVID-19 diagnostic tests for individuals with health coverage who are asymptomatic, and who have no known or suspected exposure to COVID-19” and that “testing must be covered without cost sharing, prior authorization, or other medical management requirements imposed by the plan or issuer.” The guidance also discusses how providers can be reimbursed for COVID-19 testing and vaccinations for the uninsured. Read more in the CMS press release.

HCPCS CPT Codes for Vaccines

  • Codes for all the vaccines themselves and administration codes can be found here. These also include codes for the yet-to-be-approved AstraZeneca vaccine.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Tuesday, March 2, 2021

Here are today's important updates:

Janssen (Johnson & Johnson) Vaccine Receives EUA

  • This vaccine, Ad26.COV2.S, is a replication-incompetent adenovirus type 26 vectored vaccine encoding a stabilized variant of the SARS-CoV-2 S protein (spike) for individuals 18 years of age or older. It is a single dose vaccine. The EUA application included data from 39,321 randomized participants.
  • This is information from the FDA briefing document. Vaccine efficacy (VE) against laboratory-confirmed moderate-to-severe/critical COVID-19 across all geographic areas in which the trial was conducted was 66.9% at least 14 days after the dose and 66.1% after 28 days. VE against severe/critical COVID-19 was 76.7% after 14 days (68.5% in those 60 and older) and 85.4% after 28 days (70.3% in those 60 or older). There were two cases in the vaccine group that required hospitalization after 14 days and zero after 28 days, and 29 in the placebo group (16 after 28 days). There were seven deaths in the placebo group and zero in the vaccine group. VE for symptomatic COVID-19 of any severity was 66.5%. In general, VE across subgroups (age, comorbidity, race and ethnicity) appears to be similar. There were no COVID-19 cases requiring medical intervention 28 days or more after vaccination among participants 60 years of age or older with medical comorbidities in the vaccine group. Trial participants included 45.1% Hispanic/Latino, 17.2% Black, 8.3% American Indian or Alaskan Native, 3.5% Asian.
  • There was country-to-country variation in VE estimates and the predominant strains varied in different countries (Wuhan-H1 variant in the United States, B.1.351 in South Africa and P.2 in Brazil). VE in the United States was 72% with 44.1% of the participants, 61% in Latin America (38% of participants) and 64% in South Africa (15% of participants).
  • Common adverse events included injection site pain (48.6%), headache (38.9%), fatigue (38.2%), and myalgia (33.2%), were predominately mild and moderate, and were less common in those 60 years of age and older. A numerical imbalance was seen in non-serious urticaria events (five in vaccine group, one in placebo) within seven days following vaccination, thromboembolic events (15 versus 10) and tinnitus (six versus zero). Non-fatal serious adverse events were infrequent and balanced between study groups. One serious event of a hypersensitivity reaction, not classified as anaphylaxis, beginning two days following vaccination was likely related to receipt of the vaccine.
  • VE against asymptomatic infection, defined as +PCR and/or serology without previous symptoms, was 20% from day one through 29, but 74.0% after day 29. The FDA urges caution in interpreting this data because only a limited number of participants had serology done by the data cut-off date.

Other Vaccine News

  • Real world effectiveness: In a cohort study of vaccinated versus unvaccinated controls in Israel, involving almost 600,000 individuals in each group, the Pfizer BioNTech vaccine’s estimated effectiveness at 14-20 days after the first dose was 46% for any infection, 57% for symptomatic infection, 74% for hospitalization, and 62% for severe disease. At 7 or more days after the second dose, the efficacy was 92%, 94%, 87%, and 92% respectively for the same outcomes. Effectiveness for preventing death after the first dose was 72%. In another report from Israel, the ratio of COVID-19 patients over the age of 70 requiring mechanical ventilation declined 67% compared to those under 50 from October-December 2020 to February 2021 after their national vaccination program had fully vaccinated 84% of those over 70.
  • Improved response after delayed second dose with AstraZeneca vaccine: In this study published online in Lancet on February 19, efficacy was greater when the interval between first and second dose was <12 weeks compared to <6 weeks.

Treatment

  • Monoclonal antibodies: The FDA granted an EUA for the combination of bamlanivimab 700mg and etesevimab 1400mg for the treatment of outpatients with mild-to moderate COVID-19 who are at high risk of clinical progression to severe disease and/or hospitalization. Treatment should be started as soon as possible after the diagnosis has been confirmed and within 10 days of symptom onset. The NIH COVID-19 Treatment Guidelines Panel has added this as a recommendation.

Viral Variants

  • The mutations of concern in the widely discussed SARS-CoV-2 viral variants occur in the receptor-binding domain (RBD) of the spike protein, which is also the site for binding of neutralizing antibodies. The mutations in the ACE2-interactive surface of the RBD are N501Y in B.1.1.7, K417N, E484K and N501Y in B.1.351 and K417T, E484K and N501Y in P.1.
  • In this study of convalescent plasma and monoclonal antibodies using a small number of samples of convalescent or post-vaccination serum, neutralization of the B.1.351 variant was 13-fold lower for the convalescent plasma and 7.6 to 9-fold lower for the vaccinated serum. A panel of potent single monoclonal antibodies showed a severe reduction to complete knockout of neutralization, but combinations of monoclonal antibodies were more effective. The E484K mutation appears to be the key mutation in driving this resistance to antibodies.

COVID-19 Sessions at the 2021 AAAAI Virtual Annual Meeting

The 2021 AAAAI Virtual Annual Meeting included a variety of sessions related to COVID-19:

  • Session 1705: Immune Profiling of COVID-19 Patients
  • Session 2301: The Biomedical Research Response to COVID-19: A View From the National Institute of Allergy and Infectious Disease (NIAID)
  • Session 2403: COVID-19 and Pulmonary Manifestations in Different Populations
  • Session 2705: Finding Unicorns Among Zebras: When and How to Test COVID-19 Patients for Underlying Immunodysregulatory Conditions
  • Session 3404: Immune Responses to Key Respiratory Viral Illnesses: COVID-19, Respiratory Syncytial Virus (RSV) and Rhinovirus
  • Session 3405 (Allied Health): COVID-19: The Clinical Impact on Patients with Asthma and Allergic Disease
  • Session 3406: Allergic Reactions to COVID-19 Vaccines: Separating Fact from Fiction
  • Session 3710: Turning Lemons into Lemonade: Lessons Learned from the COVID-19 Pandemic
  • Session 4512: Telemedicine During the COVID-19 Pandemic: What We Learned and Where We Go From Here

If you attended the meeting, you can access the recordings of these sessions in the meeting platform. As a reminder, attendees will have access to the platform and the ability to watch session recordings and claim credit until March 1, 2022.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


Monday, February 22, 2021

Here are today's important updates:

Vaccine News

  • Efficacy: Serum samples from 20 participants in the Pfizer trial showed a reduction of 2/3 in neutralizing activity against the B.1.351 variant (South African origin) compared to the early strains and those from the UK and Brazil. Samples from participants in the Moderna trial showed a 6.4 fold reduction in neutralizing activity against the B.1.351 variant.
  • Safety: Results of safety monitoring from VAERS and Vsafe after one month of vaccinations can be found in this issue of MMWROver 90% of reactions were non-seriousAnaphylaxis rates (4.5 per million doses) remain in range of other vaccinesFemale gender may be a risk factor for adverse reactions and anaphylaxis. 113 deaths have been reported (65% in long-term care facilities) and based on medical review do not suggest a causal relationship between vaccination and death, although not all deaths have been reviewed.
  • The WAO has just issued a statement on COVID-19 Vaccine-Associated Anaphylaxis, which is similar to CDC guidance, except they do point out that cross-reactivity between PEG and polysorbate 80 are rare, and the amount of polysorbate 80 in the AstraZeneca vaccine is the same as in influenza vaccines. They have also launched a global surveillance project and encourage providing de-identified information on patients with anaphylaxis to the vaccine at this website.
  • Pregnancy: Pfizer/BioNTech plan to start trials in pregnant women soon, with AstraZeneca and Johnson & Johnson planning similar trials in the near future.
  • Children: Trials in children 12 years and older have just recently started, expect the first data by early summer.
  • Variants: Another good viewpoint was published February 17 in JAMA Online First, written by the head of the CDC and NIAID, which reviews the 3 variants of concern (B.1.1.7, B.1.351 and P.1), current data on spread and risk for increasing cases of disease, concerns and steps to ensure that our current testing can detect disease caused by these variants, and steps to be taken to slow transmission. The authors feel strongly that current mitigation methods must be continued, including delaying travel.

Treatment

  • Interim results of the WHO Solidarity Trial published in NEJM this month showed no significant effect on mortality, reduced initiation of ventilation or hospitalization duration with treatment of COVID-19 hospitalized patients with remdesivir, hydroxychloroquine, lopinavir (with or without interferon) or interferon.
  • NIH announces enrollment in four new Phase 2/3 sub-studies under the ACTIV-2 trial for non-hospitalized adults with mild-to-moderate symptoms of COVID-19. The four agents to be studied include: SNG001, an inhalable beta-interferon (Synairgen), AZD7442, a long-acting monoclonal antibody combination that will be studied IV and IM (AstraZeneca), and Camostat mesilate, an orally administered serine protease inhibitor that may block SARS-CoV-2 cell entry (Sagent Pharmaceuticals). Read further details.
  • The NIH has a “living” website page on COVID-19 Treatment Guidelineswhich has been updated as of February 11. The updated guidelines cover prevention and prophylaxis of SARS-CoV-2 infection, therapeutic management of patients with COVID-19, ivermectin, anti-SARS-CoV-2 monoclonal antibodies, and the kinase inhibitors.
  • In this article published online February 12 in JAMA Network Open, the authors compared zinc, ascorbic acid, or both versus usual care in a randomized trial in 214 adults and found no effect on length or reduction of symptoms.

Persistent Disease

  • This report from the UK indicates that about 10% of patients with ongoing symptoms 6 weeks after discharge had evidence of interstitial lung disease that responded to treatment with oral steroids.
  • In another study from Spain, less than 10% of patients followed after 2 months showed a reduction in FVC or FEV1, but 25% had a reduction in DLCO.

CDC Issues Updated Operational Strategy for Schools

  • This strategy has been updated as of February 12.
  • While emphasizing the importance of reopening schools, the guidance also emphasizes that success in preventing the introduction and subsequent transmission of SARS-CoV-2 in schools is connected to and facilitated by preventing transmission in the broader community.
  • Essential elements include mitigation strategies, indicators of community transmission, phased mitigation, learning modes, and testing and vaccination of teachers and staff when supply allows.

School Studies Confirm CDC Quarantine and School Mitigation Recommendations 

  • The CDC stated that quarantining for 10 days without testing does have a risk for transmission after this time period between 1 and 10%, and continues to prefer 14 days of quarantining.
  • Data from school testing involving 839 students in a single county in Florida showed that 7.4% of the 388 high school students may return to school with COVID-19 infection if the recommendation for 10 days of quarantine without testing is followedThe rate of potential infectiousness in elementary and middle school students was only 1.8%. Only one of 799 students who were negative at 9-14 days became positive after returning to school, and that was an infection due to a different strain. Limitations of this study relates to the different timing of testing.
  • The CDC also recommends strict mask policies, physical distancing and minimizing in-person adult interactions at school.
  • In another study in school transmission in Georgia, officials identified nine clusters of epidemiologically linked COVID-19 cases involving 13 educators and 32 students in six of eight elementary schools between December 2, 2020, and January 22, 2021. Half of the cases involved probable educator-to-educator transmission and subsequent educator-to-student transmission. All nine clusters involved less than ideal physical distancing, and five involved inadequate mask use by children. Educators were central to in-school transmission networks. Precautions should include promotion of COVID-19 precautions outside of school.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


February 15, 2021

Here are today's important updates:

Vaccines and Viral Variants

  • Sera from 20 participants who had received both doses of the Pfizer vaccine showed equivalent neutralization titers (differences of 4-fold or less) between the wild type and engineered variants that contained spike proteins from recently emerged variants, including those first described in the UK and South Africa. Neutralization geometric mean titers suggest small impacts of these mutations on neutralization by sera from vaccinated individuals. (Disclaimer: These engineered viruses do not contain all of the mutations present in the variants). Details can be found here.
  • Here's a good article on viral variants that was published online by JAMA on February 11.

CDC Updates Clinical Considerations for mRNA Vaccines

  • In an update from February 10, the CDC made new recommendations for preventing, reporting and managing mRNA vaccine administration errors, clarified contraindications and precautions, updated information on delayed local reactions, and updated quarantine recommendations for vaccinated persons.
  • Persons with a known (diagnosed) allergy to PEG or polysorbate have a contraindication to vaccination. Persons with a reaction to a vaccine or injectable therapy that contains multiple components, one of which is PEG, another mRNA vaccine component or polysorbate, but in whom it is unknown which component elicited the immediate allergic reaction have a precaution (counseling, 30-minute observation). Deferral of vaccination and/or consultation with an allergist may be considered.
  • Vaccinated persons with an exposure to someone with suspected or confirmed COVID-19 are not required to quarantine if they meet all of the following criteria: are fully vaccinated (two weeks or more after the final vaccine dose), are within 3 months following receipt of the final dose, and have remained asymptomatic since the current exposure. Such individuals should continue mitigation precautions and monitor for symptoms of infection.
  • Delayed local reactions beginning a few days through the second week have been reported and are not considered contraindications to receipt of the second dose. It is unknown whether such patients will experience a similar reaction after the second dose.

Update on Anaphylaxis Following Vaccination 

  • Updated information through January 18 indicates that rates continue to decline as more doses are given. Data are from VAERS and anaphylaxis is determined based on the Brighton Collaboration case definition. As of January 18, 17,524,676 doses have been administered of both the Pfizer and Moderna vaccines, with 66 cases that met the Brighton Collaborative case definition criteria of anaphylaxis, for a rate of 4.7 cases/million doses for Pfizer and 2.5 cases/million for Moderna. Interesting characteristics of these cases: 94-100% female (don’t know the percentage of females who have been vaccinated), 89% of reactions occurred within 30 minutes, 77-84% had a prior history of allergies or allergic reactions, and 32% a history of prior anaphylaxis. 48% were hospitalized, 27% in intensive care, and 11% required intubation. No deaths have been reported. These numbers remain reassuring that anaphylaxis after vaccination is rare, but reactions can be severe.

ARIA-EAACI Position Paper on Severe Allergic Reactions to the Vaccines

  • The authors of this paper stress that the recommendations will be fluid and reflect the knowledge at the time.
  • Key points: A better understanding of the mechanism of the reactions that have occurred is urgent, allergy patients should not be generally excluded from the vaccine, observation time of at least 15 minutes, and training of vaccine sites in the proper management of anaphylaxis. If PEG sensitization is confirmed as the cause, patients should be referred to an allergist for evaluation, current guidelines excluding patients with severe allergies from vaccination (British guidelines) should be re-evaluated, patients with a suspected allergic reaction should be referred to an allergist as the application of the second dose in a specialized setting or the applications of increments of the vaccine will be feasible for the majority.

National Forum on COVID-19 Vaccine

  • The CDC will be hosting this virtual forum for practitioners focused on vaccine implementation, and people and groups that can champion vaccine uptake in communities. The Forum will take place February 22-24, with registration closing February 16. Learn more here.

Russian Vaccine Efficacy 91.6%

  • In an interim analysis of Phase 3 data involving almost 20,000 people, the recombinant adenovirus-based vaccine Gam-COVID-Vac (Sputnik V) showed an efficacy OF 91.6% by 21 days after the first dose. Observed vaccine efficacy was >87% in all age and sex subgroups, and 91.8% for those over 60 years of age. 94% of adverse effects were mild, and serious adverse events were very low and similar to placebo.

CDC Posts Mask Guidance for Improved Protection 

  • This new guidance posted on February 10 suggests ways to improve the effectiveness of masking. Details on the evidence supporting these recommendations can be found here.

Transmission

  • systematic review and meta-analysis showed that secondary attack rates (SARs) were highest within households (21%) especially if duration of exposure was over 5 days. SARs for contacts with family and friends were higher than those for low-risk casual contacts (6% vs. 1%). Estimates of SARs for asymptomatic index cases were about 7-fold lower.

Burden of COVID-19 Disease in the United States as of November 20

  • Using a combination of data from public health surveillance of reported COVID-19 cases and seroprevalence surveys (to establish underreporting values), the authors report an estimated 46,910,006 infections, 28,122,752 symptomatic infections, 956,174 hospitalizations, and 304,915 deaths.
  • This suggests that 14% of the U.S. population was infected by SARS-CoV-2 by mid-November, that the number of actual infections is about 40% higher than the reported cases, and there is a long way to go to achieve herd immunity.
  • Details of the study can be found here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


February 8, 2021

Here are today's important updates:

Monoclonal Antibody Therapy for COVID-19

  • Bamlanivimab (LY-CoV555) from Eli Lilly initially reported successful reduction in viral load in non-hospitalized patients with mild to moderate COVID-19, but a later analysis of a larger number of patients in the same study, ironically published by JAMA on the same day as the first report, did not show a significant effect compared to placebo.
  • Combination therapy appears to be more effective. Bamlanivimab plus etesevimab did show a reduction in viral load in the same type of patient. Another monoclonal antibody cocktail (REGN-COV2) from Regeneron has also shown a reduction in viral load in a preliminary analysis.
  • These treatments have not shown effectiveness in patients already hospitalized with COVID-19.
  • There are ongoing studies on using these treatments for prophylaxis in nursing homes and in contacts of infected patients. In a press release dated January 21, Eli Lilly reported that bamlanivimab prevented symptomatic COVID-19 by 57% in nursing home residents and staff, and by 80% in residents. There were no COVID-19 deaths in the treated residents, compared to four deaths in the placebo group.
  • These treatments must be given in an infusion center, which has become somewhat of a barrier during the pandemic, but may offer an opportunity to reduce future COVID-19 morbidity and hospitalization. It is important to note that they do not have an EUA yet for prophylactic therapy. Medicare and most insurances have decided to cover these without co-pay or co-insurance.

High-Titer Convalescent Plasma for COVID-19

  • small study on the use of early high-titer plasma therapy in 160 adults age 65 or over with pre-existing conditions, or 75 and over without any pre-existing conditions, noted a 48% relative risk reduction for severe respiratory disease.
  • retrospective study that examined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat 3,082 hospitalized adults with COVID-19 found that treatment with high-titer convalescent plasma was associated with a lower rate of death at 30 days than low-titer convalescent plasma therapy, in patients who were not being mechanically ventilated.
  • The FDA has revised the EUA for convalescent plasma effective February 4. The EUA is now limited to high-titer convalescent plasma, for treatment of hospitalized patients early in the course of disease and those hospitalized with impaired humoral immunity. The EUA also lists those lab assays that are authorized for qualifying the plasma as high titer.
  • There are ongoing studies looking at the use of high-titer convalescent plasma as prophylaxis in people with predisposing conditions and COVID-19 contact.

More on Virus Variants

  • These points come from a summary on virus variants from the University of Washington Alliance for Pandemic Preparedness.
  • Naming Conventions: As the number of variants become more prevalent and widespread, it is important to move away from naming based on geographic origin. The problem is that there are multiple categorizations of these variants across research and public health organizations. Without going into a lot of detail on the naming conventions, here is a listing of the most referenced strains with their aliases:

- Lineage B.1.1.7 (aka variant 20I/501.Y.V1 or VOC 202012/01) first identified in the UK
- Lineage B.1.351 (aka variant 20H/501Y.V2) first identified in South Africa
- P.1 variant (aka variant 20J/501Y.V3, branch from B.1.1.28 lineage) first identified in Brazil
- CAL.20C variant first identified in southern California

  • Transmission: B.1.1.7 is found in 90% of samples across England, has a 25-40% higher attack rate, and 10-times higher affinity for the ACE2 receptor.
  • B.1.351 is the predominant strain now in South Africa, but has been found in the United States. It's estimated to be more transmissible, but less quantified than B.1.1.7.
  • P.1 variant is also estimated to be more transmissible and may lead to re-infection.
  • CAL.20C is showing increasing dominance in southern California, coinciding with the increased positivity in that region.
  • Implications for Re-Infection and Vaccine Efficacy: B.1.351 and P.1 mutations reduce neutralization by convalescent serum up to 10-fold, by most monoclonal antibodies and sera from vaccinated persons (6 to 8-fold). Cases of re-infection have been reported for all these variants. All vaccines approved or in Phase 3 trials have shown slight reduction in neutralization for the B.1.1.7 variant, and more so against the B.1.351 variant, although still over 50% efficacy.
  • Clinical Severity: Most of the data is on the B.1.1.7 variant out of the UK, which is conflicting, with some studies suggesting increased mortality, some finding no association and one showing equal likelihood of being asymptomatic.

AAAAI COVID-19 Response Task Force Vaccine Guidance Now Posted

Age Groups That Sustain Transmission: Are We Targeting the Right Population?

  • study published in Science on February 2 estimates that as of October 2020, individuals aged 20-49 are the only age groups sustaining resurgent SARS-CoV-2 transmission with reproduction numbers well above one, and that at least 65 of 100 COVID-19 infections originate from individuals aged 20-49 in the United States. The authors go on to speculate that perhaps vaccines should be focused on this age group earlier rather than later (assuming vaccines reduce transmission).
  • In a similar vein, a modeling study published in Science Advances on February 3 suggests that vaccines that are at least 50% effective in preventing infection could be sufficient to mitigate the pandemic, assuming roughly 70% vaccination coverage. For low vaccine effectiveness, vaccine allocation to high-risk and older age groups would optimally minimize deaths, regardless of coverage. In contrast, vaccines with higher effectiveness would optimally minimize deaths if allocated to high-transmission age groups.
  • As Dr. Fauci stated recently in an interview, if you stop transmission, then less people are infected and the virus has less chance to mutate.

HHS Provider Relief Fund FAQs Update

  • Important modifications relate to: fund allocation (first to unreimbursed expenses, then to losses), allowance for the use of 2020 budgeted revenues for reporting lost revenues with specific requirements, how you still have to report lost revenue even if you use all the funds for expenses, and modifications to the use of funds to support COVID-19 vaccine distribution.

Volunteering at a Vaccine Clinic

  • If you are considering helping out at a vaccine clinic, modifications were recently made to the PREP Act, stating that any healthcare professional who is licensed to prescribe, dispense or administer under the laws of any state, may prescribe, dispense or administer COVID-19 vaccine in any state, even in those in whom the professional is not licensed, although subject to completing the CDC Vaccine Training Modules, and is protected from any suit or liability under State or Federal Law. This also applies to healthcare professionals who are not currently licensed, but held a license in good standing in the last 5 years. Non-practicing healthcare professionals will require documentation of an observation period by a currently practicing healthcare professional adequately experienced in vaccination who confirms competency of the healthcare provider in preparation and administration of the particular COVID–19 vaccine(s) to be administered. Read more details.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


February 1, 2021

Here are today's important updates:

Vaccine News

  • Vaccine DistributionAnnals of Internal Medicine published a video on COVID-19 Vaccine Distribution and Allocation: What Physicians Need to Know.
  • Likelihood of Getting a Vaccine: Read this paper published by JAMA. The Understanding America Study (UAS) is a probability-based internet panel survey of approximately 9,000 noninstitutionalized U.S. adults. Beginning April 1-14 and continuing through November 25–December 8, over 8,000 adults responded to a biweekly survey asking how likely they were to get the vaccine. During November 25–December 8, the self-reported likelihood of getting COVID-19 vaccination was lower among women than men (51% vs 62%; aRR, 0.9 [95% CI, 0.8-0.9]) and Black versus White individuals (38% vs 59%; aRR, 0.7 [95% CI, 0.6-0.8]), and higher among adults aged 65 years and older versus those 18-49 years (69% vs 51%; aRR, 1.4 [95% CI, 1.3-1.5]) and those with at least a bachelor’s degree versus a high school education or less (70% vs 48%; aRR, 1.5 [95% CI, 1.3-1.6]). The surveys indicate an 18% decline in likelihood compared to April.
  • Allergists need to educate their patients about the safety, efficacy and need to receive the vaccine, especially in the underserved population. Top five messages for patients (from the FDA): FDA is publicly sharing information about the vaccines; only safe & effective vaccines tested on tens of thousands of volunteers will be approved; scientists and public health officials, not politicians or their appointees, will decide when a COVID-19 vaccine is safe & effective for public use; by getting the vaccine you protect yourself & family; the vaccine development is moving fast because the medical & scientific community has made it highest priority, not because steps have been skipped.
  • Vaccines and the Variants: In this excellent opinion article, the authors point out several issues related to this problem, including issues with suboptimal immunity limiting the number or increasing the interval between doses, ability of vaccine-induced neutralizing antibodies to attack the virus, the loss of effectiveness of monoclonal antibodies against the variants, and then they propose an approach to the problem.
  • A great video presentation can be found here.
  • Pre-print, not peer-reviewed articles are not usually presented in our messages, but in light of recent press, sera from patients who completed both doses of the Pfizer BioNTech vaccine had similar neutralizing geometric mean titers (GMTs) against SARS-CoV-2 engineered to contain the same mutations as the UK and South African variants, compared to the wild-type, although the GMTs against the South African variant were 19% lower. The authors note that the engineered viruses do not contain the full set of mutations present in the UK and South African variants. Read more.
  • Johnson & Johnson (Janssen) Vaccine: In a press release on January 29 but not published, the company announced preliminary data on their Phase 3 ENSEMBLE vaccine trial. Among all participants from different geographies and including those infected with an emerging viral variant, Janssen’s COVID-19 single shot vaccine candidate was 66% effective overall in preventing moderate to severe COVID-19, 28 days after vaccination. The onset of protection was observed as early as day 14. The level of protection against moderate to severe COVID-19 infection was 72% in the United States, 66% in Latin America and 57% in South Africa, 28 days post-vaccination. The vaccine candidate was 85% effective in preventing severe disease across all regions studied, 28 days after vaccination in all adults 18 years and older. The vaccine candidate demonstrated complete protection against COVID-related hospitalization and death, 28 days post-vaccination.
  • Novavax: Also announced in a press release, this adjuvated protein subunit vaccine, in preliminary results for Phase 2/3 trials showed up to 89.3% efficacy in the UK cohort and 85.6% efficacy against the UK variant, but results from the South African cohort showed an efficacy of 60% in the HIV-negative population where 93% had the South African variant.
  • Expansion of Vaccination Workforce: HHS issued an amendment to the Public Readiness and Emergency Preparedness Act (PREP Act) on January 28: “All licensed and certified healthcare professionals are now authorized to prescribe, dispense and administer COVID-19 vaccines in any state or U.S. territory after completing the CDC’s COVID-19 vaccine training, regardless of where they are licensed or certified.” The CDC training can be accessed here.
  • Vaccine Safety: According to an update from ACIP, there are now 50 cases of anaphylaxis following administration of the Pfizer BioNTech vaccine, after 10 million doses (5 per million) and 21 cases following administration of the Moderna vaccine (2.8 per million). As some experts have predicted, these rates will likely decline as more doses are administered and will likely not be significantly different from one another. There have now been reports of 196 deaths temporally associated with vaccination, 113 after Pfizer and 83 after Moderna. 66% were residents of long-term care facilities (LTCFs). Estimates of background mortality in LTCFs indicate an expected 11,440 deaths following vaccination. Mortality, then, was actually lower for vaccinated residents. Bottom line: This vaccine is very safe, and severe allergic reactions are very rare.
  • Remember the Second DoseVaxText is a free CDC program that will provide second dose reminders and let recipients know when a dose was missed. To sign up, patients should text ENROLL to 1-833-VaxText (829-8398).
  • Vaccine for Children: From AAP News on Call: Pfizer announced that its vaccine trial in 12-15 year-olds is fully enrolled and it could seek FDA EUA in the first half of 2021. Moderna is currently enrolling children 12-17 in trials.

Smoking and COVID-19 Outcomes

  • If you need another reason to counsel your patients about smoking cessation, JAMA Internal Medicine published a cohort study done at the Cleveland Clinic on patients who were COVID-19 positive and had a complete smoking history.
  • Key findings: The study included 172 current smokers and 910 former smokers. There was a dose response relationship between cumulative pack years of smoking and adverse COVID-19 outcomes. Patients who smoked more than 30 pack-years had 2.25 higher odds for hospitalization, and 1.89 higher odds for dying from COVID-19. This association is likely mediated in part by comorbidities.
  • The study can be found here.

Experience with In-School Learning in Wisconsin

  • As described in an MMWR from January 26, 17 K-12 schools in rural Wisconsin opened this fall and implemented measures to limit spread: masking, physical distancing, cohorts of 11-20 students, and quarantining after exposure.
  • During 13 weeks (August 31- November 29), seven of 4,876 students and zero of 654 staff are known to have gotten COVID-19 at school.
  • No spread is known to have occurred to or from staff in school.
  • >92% of students used masks.
  • The same issue contains a report on spread from a wrestling meet in Florida in December, where a single COVID-19 (+) individual spread the virus to multiple other attendees and teammates with subsequent spread to household contacts. Implications: Indoor sports, where masking and social distancing are not possible, may need to wait until community spread has declined. At the time of this meet, Florida had a community transmission rate of 363/100,000 residents.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


January 25, 2021

Here are today's important updates:

Allergic Reactions to Moderna Vaccine

  • An MMWR report published on January 22 on monitoring of the Vaccine Adverse Event Reporting System (VAERS) from December 21-January 10 detected 10 cases of anaphylaxis after administration of a reported 4,041,396 first doses of the Moderna COVID-19 vaccine, which equates to 2.5 cases per million doses. Nine of the 10 cases reported onset of symptoms within 15 minutes, no fatalities. Nine of the 10 cases had a documented history of allergies or allergic reactions, and five of the nine had a previous history of anaphylaxis. Six had a history of allergic reactions to drugs, two to contrast media and one to foods. All 10 were women.
  • Six patients were hospitalized, five in the ICU with four of those requiring intubation.
  • There were also 47 nonanaphylaxis allergic reactions reported.
  • This number is about 1/4 of the rate of anaphylaxis after the Pfizer vaccine (11.1 cases per million doses). Details of the patients with anaphylaxis to the Pfizer vaccine can be found in this JAMA paper published online on January 21.

CDC Updates Vaccine Recommendations

  • Intervals between first and second dose: “The second dose should be administered as close to the recommended interval as possible. However, if it is not feasible to adhere to the recommended interval, the second dose of Pfizer-BioNTech and Moderna COVID-19 vaccines may be scheduled for administration up to 6 weeks (42 days) after the first dose. There are currently limited data on efficacy of mRNA COVID-19 vaccines administered beyond this window. If the second dose is administered beyond these intervals, there is no need to restart the series.”
  • Interchangeability of vaccine products: “Every effort should be made to determine which vaccine product was received as the first dose, in order to ensure completion of the vaccine series with the same product. In exceptional situations in which the first-dose vaccine product cannot be determined or is no longer available, any available mRNA COVID-19 vaccine may be administered at a minimum interval of 28 days between doses to complete the mRNA COVID-19 vaccination series.”
  • Vaccination of persons with a SARS-CoV-2 infection or exposure: Vaccination of persons with known current SARS-CoV-2 infection should be deferred until the person has recovered from the acute illness (if the person had symptoms) and criteria have been met for them to discontinue isolation. This recommendation applies to persons who develop SARS-CoV-2 infection before receiving any vaccine doses as well as those who develop SARS-CoV-2 infection after the first dose but before receipt of the second dose. While there is no recommended minimum interval between infection and vaccination, current evidence suggests that the risk of SARS-CoV-2 reinfection is low in the months after initial infection but may increase with time due to waning immunity. Thus, while vaccine supply remains limited, persons with recent documented acute SARS-CoV-2 infection may choose to temporarily delay vaccination, if desired, recognizing that the risk of reinfection, and therefore the need for vaccination, may increase with time following initial infection.
  • Vaccinations in persons with a history of dermal filler use: Infrequently, persons who have received dermal fillers may develop swelling at or near the site of filler injection (usually face or lips) following administration of a dose of an mRNA COVID-19 vaccine. This appears to be temporary and can resolve with medical treatment, including corticosteroid therapy. mRNA COVID-19 vaccines may be administered to persons who have received injectable dermal fillers who have no contraindications to vaccination (see ‘contraindications’ section below). No additional precautions are needed. However, these persons should be advised to contact their healthcare provider for evaluation if they develop swelling at or near the site of dermal filler following vaccination.
  • Updated discussion on excipients in the vaccines related to PEG and polysorbate: This can be found in Appendix B at the bottom of the page on the CDC website.

Eosinophils Protective?

  • In a retrospective study published online in JACI: In Practice on January 22, the authors note that asthma patients who presented to the ED with COVID-19 symptoms and positive RT/PCR with an AEC >/= 150 cells/microliter were less likely to require admission for COVID-19, and development of eosinophilia during hospitalization was associated with decreased mortality.
  • The elevated AEC may just be a marker for T2-high asthma and not protective in and of themselves, since treatment with anti-IL5 biologics, which would lower the AEC, are not associated with increased admission or mortality.

Persistent Immunity

  • serological study of 104 patients who survived COVID-19 demonstrated persistence of neutralizing antibodies for at least 6 months, and despite lower amounts over time, these antibodies were still able to neutralize virus in 95% of patients.
  • In a separate serological analysis published in Nature of 87 SARS-CoV-2 recovered patients, neutralizing activity was found to decline by five-fold by 6 months but memory B cells remained largely unchanged. Antibodies expressed by the memory B cells at 6 months had increased potency and resistance to mutations.

Pediatric COVID-19

  • More than 211,000 COVID-19 cases were reported in the United States during the week of January 10-16, the most since the start of the pandemic. The total cases for children and adolescents in the United States is now just over 2.5 million (12.6% of all cases in the United States). Also, 10,182 children (0.8%) have been hospitalized and 191 (0.01%) have died. Read more.
  • An analysis of CDC data on 27,045 children with confirmed COVID-19 showed that African American (OR 2.28) or mixed race (OR 2.95) and an underlying medical condition (OR 3.55) are strong predictors for hospitalization. Death was rare (0.19%) in this population, but increased in children with a pre-existing medical condition (OR 8.88). Underlying medical conditions included asthma, autoimmune disease, cardiovascular disease, chronic lung disease, GI/liver disease, hypertension, immune suppression, metabolic disease, neurologic disease, obesity, and renal disease. Data were not available on the relative risk for specific underlying conditions. The study can be found here.

Food Insecurity Increasing in This Pandemic

  • Data from a predominantly Black cohort living in low-income, racially isolated neighborhoods in Pittsburgh showed an 80% increase in food insecurity as a result of the COVID-19 pandemic, in contrast to a nation-wide increase of 60%.
  • Allergists need to consider this in their food allergic patients.

Rapid Antigen Tests

  • This week’s issue of MMWR reports on the use of the Abbott BinaxNOW rapid antigen test for SARS-CoV-2 infection in 3,419 paired specimens collected from persons 10 years of age and older at two community testing sites in Pima County, Arizona, during November 3–17, 2020. Compared with real-time RT-PCR testing, the BinaxNOW antigen test had a sensitivity of 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons, with near 100% specificity in specimens from both groups.
  • Among specimens positive for viral culture, sensitivity was 92.6% for symptomatic and 78.6% for asymptomatic individuals. When the pre-test probability for receiving positive test results for SARS-CoV-2 is elevated (e.g., in symptomatic persons or in persons with a known COVID-19 exposure), a negative antigen test result should be confirmed by NAAT (nucleic acid amplification test).
  • Rapid antigen tests have shown low sensitivity in asymptomatic patients, but their high specificity and positive predictive value make them useful for testing of patients with a high pre-test probability, allowing for more rapid detection of infectious people for isolation.

So How Many SARS-CoV-2 (+) Patients Are Asymptomatic?

  • Percentages have varied depending on the study, reflecting different populations and different timing, with ranges of 25-40%. Annals of Internal Medicine published a systematic review on January 23, which stated that at least 1/3 of SARS-CoV-2 infections are asymptomatic. Longitudinal studies suggest that nearly 3/4 of persons who receive a positive PCR test who don’t have symptoms will remain asymptomatic.
  • The Asymptomatic novel CORonavirus iNfection (ACORN) study in Indianapolis studied the prevalence of asymptomatic infection in adults over a 6-week period in April and May. Ninety-one of 2,953 people (3.1%) initially presenting as asymptomatic tested (+). In a longitudinal follow-up of 86 of these, 19 (22.1%) developed at least one symptom a median of 6 days after testing (range 1-29 days).

Evidence for Pandemic Fatigue

  • An analysis of survey responses from 16 waves of the Coronavirus Tracking Survey (CTS) completed between April 1 and November 24 showed that adherence to most nonpharmaceutical interventions (NPIs) declined over that time period. The national NPI adherence index decreased from 70.0 in early April to the high 50s in June and increased again to 60.1 in November. The NPI adherence index declined in all regions, but was significantly greater in the Midwest. Of all the recommended NPIs, the only one to increase was mask wearing.

Vaccines: Immunology and the Pipeline

  • As we anticipate the arrival of additional vaccines for SARS-CoV-2, perhaps it is time to revisit this review on viral immunology and vaccines published this past October in Lancet and also this new article from Scientific American on novel vaccine approaches being studied now.

Billing and Administration Codes for Vaccines

  • Pfizer: billing: 91300, administration: 0001A (first dose), 0002A (second dose)
  • Moderna: billing: 91301, administration: 0011A (first dose), 0012A (second dose)
  • Astra-Zeneca: billing: 91302, administration: 0021A (first dose), 0022A (second dose)
  • Janssen (Johnson & Johnson): billing: 91303, administration: 0031A (single dose)

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


January 18, 2021

Here are today's important updates:

Ad26.COV2.S COVID-19 Vaccine

  • Interim results from the phase 1-2a trial of the Johnson & Johnson vaccine were reported in the NEJM on January 13. This vaccine is a recombinant, replication-incompetent adenovirus 26 vector encoding a full length and stabilized SARS-CoV-2 spike protein. Results from two of three cohorts (18 to 55-year-olds and >/=65-year-olds) were reported. This trial examined the effects of single versus double dose, and low dose versus high dose.
  • Neutralizing antibody titers were detected in 90% or more of all participants on day 29 after the first vaccine dose and reached 100% by day 57 in 18 to 55-year-olds with a further increase in titers, regardless of vaccine dose or age group. Titers remained stable until at least day 71 in the 18 to 55-year olds, the latest time period in this studyA second dose provided an increase in titer by a factor of 2.6-2.9Spike antibody titers were similarOn day 14, CD4+ T-cell responses were detected in 76 to 83% of the younger cohort, and 60 to 67% of the older cohortCD8+ T cell responses followed a similar pattern.
  • Adverse reactions were similar to current vaccines, and occurred in 65 to 85% of recipients. The most common were fatigue, headache and myalgia.
  • Further analysis of one versus two dose schedules, along with efficacy, are being assessed now in a phase 3 trial.

SARS-CoV-2 Variant

  • As of January 13, the SARS-CoV-2 B1.1.7 variant, which has been associated with increased transmissibility in Europe, has been identified in 76 cases across 10 states in the United States. Currently there is no known difference in clinical outcomes associated with the variant. Read more here.

Transmission of SARS-CoV-2 Low in Schools That Take Precautions

  • In this pre-print release of an article to be published in Pediatrics, researchers from Duke University and the University of North Carolina found that schools that employed mitigation strategies had a very low incidence of in-school transmission of SARS-CoV-2 in the first 9 weeks of this past fall. The effect of very high community transmission such as we are seeing now remains to be seen.
  • In a related study, the MMWR from January 13 reviewed data on testing results in large groups of patients in age categories comparable to school age differences. They noted similar trends in positive tests and percent positive compared to adults, and noted that rates were lowest in the age group 0-4 with an increase in each successive age group. Hospitalizations and ICU admissions were highest in the 0-4 age group, but all age groups 0-17 weekly incidence was lower than adults (>25) but the 18 to 24-year-old group was higher than adults for the entire study period. “Lower incidence among younger children and evidence from available studies (2–8) suggest that the risk for COVID-19 introduction and transmission among children associated with reopening child care centers and elementary schools might be lower than that for reopening high schools and institutions of higher education... CDC recommends that K–12 schools be the last settings to close after all other mitigation measures have been employed and the first to reopen when they can do so safely."
  • All this information may not be applicable if the more transmissible SARS-CoV-2 virus becomes widespread in the United States. A recent New York Times article may be reassuring. They cite recent research from Public Health England, based on detailed contract-tracing of about 20,000 people, including 3,000 children <10, showing young children were about half as likely as adults to transmit the virus to others.

Lockdowns Work

  • In this study published January 13 in the Journal of General Internal Medicine, the authors used WHO data from nine different countries (including the United States) and conducted a cross-country comparative evaluation using a susceptible-infected-recovered (SIR)-based model completed with pharmacokinetic approaches. In those countries that had an early lockdown period followed by a gradual deconfinement, it resulted in a rapid decline in infections and a reduced R0The countries that had no or inconsistent lockdowns followed by rapid deconfinement had a prolonged plateau of infections and an elevated R0 was noted during the study period from February 23 to June 14.

Saliva Versus NP Swab

  • systematic review and meta-analysis of 16 studies compared the salivary nucleic acid amplification test (NAAT) to an NP swab collection. The pooled sensitivity of the saliva NAAT was 83% compared to 85% for the NP swab NAAT, and both tests had a specificity of 99%. Limitations of the study: Eight peer-reviewed studies and eight pre-prints were included in the meta-analysis (5,922 unique patients). There was significant variability in patient selection, study design, and stage of illness at which patients were enrolled. Fifteen studies included ambulatory patients, and nine exclusively enrolled from an outpatient population with mild or no symptoms. Larger trials are needed to confirm this data, but it is good to see that the sensitivity was comparable in those with low-to-no symptoms, which is where many of the tests fail.

New HHS Provider Relief Fund FAQ Update

  • HHS has not yet made an announcement related to Phase 4 funding and the website still notes that the Reporting Portal is slated to be available as of Friday, January 15.
  • The latest questions modified or added relate to providers who purchased a TIN, an extension to submission date for audits, guidance for CPAs on audits, methodology for provider payment in Phase 3, and when Phase 3 payments will be made (through the first months of 2021).
  • Certain applicants may not receive these full amounts (88% of their reported losses) because HHS determined the revenues and operating expenses from patient care reported on their applications included figures that were not exclusively from patient care (as defined in the instructions), reported figures were not reflected in submitted financial documentation, or reported figures were extreme outliers in comparison to other applicants of the same provider type; instead, HHS capped the amount paid to these provider types based on industry estimates of revenue and operating expenses from patient care.

No, It's Not Just Another Flu!

  • Most people get it now, but you may still encounter patients who feel that COVID-19 is just another flu. This article may provide you some evidence for comparison in hospitalizations and mortality between the two diseases.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


January 12, 2021

Here are today's important updates:

Vaccine Reactions (Now What?)

  • The CDC has updated its guidance on the administration of the SARS-CoV-2 mRNA vaccines with respect to pre-vaccine risks and post-vaccine reactions. Contraindications to either of the mRNA vaccines now include immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components, including polyethylene glycol (PEG). The CDC goes on to state: These persons should not receive mRNA COVID-19 vaccination at this time unless they have been evaluated by an allergist/immunologist and it is determined that the person can safely receive the vaccine (e.g., under observation, in a setting with advanced medical care available). But then the CDC says: Persons with an immediate allergic reaction to the first dose of an mRNA vaccine should not receive additional doses of either of the mRNA COVID-19 vaccines.
  • Drs. Mariana Castells and Elizabeth Phillips have also written an article titled "Maintaining Safety with SARS-CoV-2 Vaccines" that was published in NEJM on December 30. It is worth reading for allergists who may encounter patients with reactions or potential reactions to the vaccines.
  • summary of allergic reactions following the Pfizer vaccine between December 14 and 23 was published in MMWR on January 6. There have been 104 cases of allergic reactions with 21 cases of anaphylaxis after administration of 1,893,360 first doses (11.1 cases per million), about 10 times the rate of anaphylaxis after the flu vaccine (1.3 cases per million). Seventeen of these cases occurred in persons with a documented history of allergies or allergic reactions, seven of whom had a history of anaphylaxis. Symptom onset after the vaccine was a median of 13 minutes (2-150 minutes), 71% onset within 15 minutes. Non-anaphylaxis symptoms included pruritis, rash, itchy and scratchy throat and mild respiratory symptoms. Case details are listed in the article.

Stick With Recommended Vaccine Dose Intervals

Delayed Face or Lip Swelling After Moderna Vaccine

  • There were three cases of lip or facial swelling that occurred 1-2 days after vaccination in the clinical trials, that are felt to be due to an inflammatory reaction occurring in dermal filler placement. These are not IgE-mediated reactions and can be treated with oral corticosteroids and are not contraindications for receipt of vaccines, according to the American Society for Dermatologic Surgery Guidance.

New Vaccine Resources

  • Hart Health Strategies, the AAAAI’s legislative and government consultants, have developed a handy PDF loaded with information and links about the COVID vaccines. A link to the PDF is posted on the AAAAI COVID-19 resources page. This PDF will be a “living” document and can also be accessed via this link.
  • The AAAAI has developed a patient article about vaccine safety and indications that is available in English and Spanish. Both versions of the article can also be found within the Patient Information section of the AAAAI COVID-19 resources page.

Transmission From Symptomatic Versus Asymptomatic COVID-19 Subjects

  • A modeling study published in JAMA Network Open on January 7 reports that 59% of all transmission came from asymptomatic transmission, with 35% from presymptomatic and 24% from asymptomatic patients.
  • On the other hand, an article published in Lancet on December 18 suggested that transmission from symptomatic patients was 3.85 times higher than asymptomatic (close contacts).

More on Herd Immunity and Vaccine Dosing

  • There has been extensive discussions on herd immunity in the lay and scientific press. This article in the American Journal of Clinical Pathology written by the Medical Director of the Immunopathology Lab at the Cleveland Clinic offers an interesting overview of herd immunity and the importance of vaccinating a large percentage of the population, and continued precautions such as mask wearing, physical distancing and handwashing.

Monoclonal Antibody Effect in COVID-19 Outpatients

  • In this NEJM article, Regeneron’s monoclonal antibody cocktail was noted to reduce viral load in outpatients with COVID-19. The effect was greatest in those with negative initial antibody titers and those with the highest initial viral load.

High-Titer Plasma Therapy May Be Effective If Given Early to Older Adults 

  • An article in NEJM that was published online January 6 reported the results of a trial of high-titer plasma therapy in 160 older adults (75 years of age and older) with mild disease, within 72 hours of onset of the disease. The relative risk reduction was 48% for the development of severe respiratory disease.

Latest Data Suggest Long-Term Immunity After Infection

  • In an article in Science, it was noted that B-cell and T-cell immunity were still robust 6 months or more after infection, although each immune component had different kinetics.

FDA Issues Alert for False Negative Results With Curative SARS-CoV-2 Test (RT/PCR)

  • In this alert, the FDA stresses the importance of performing the test in accordance with its authorization, that it is indicated only for symptomatic individuals within 14 days of symptom onset, samples must be collected by or under the direct supervision of a trained healthcare worker, and a negative result does not rule out COVID-19. Consider retesting with a different test if you suspect an inaccurate result. Find more details here.
  • In the MMWR from January 1, use of the Sofia antigen test to screen college students had an 80% sensitivity and 98.9% specificity in symptomatic students, but the sensitivity was only 41.2% in asymptomatic students.
  • On January 8, the FDA also issued an alert related to concerns over the effect of viral mutations on testing. Currently the impact is expected to be low, but this is going to be carefully followed.

HHS Renews Determination of a Public Health Emergency (PHE)

  • On January 7, HHS Secretary Azar renewed the determination of a PHE for another 90 days, thus extending the waivers and flexibilities granted for the earlier PHE.

AAP Updates Guidelines for Safe Schools 

ACIP Updates Allocation Recommendations

  • Read this MMWR.
  • It remains up to individual states, and sometimes individual counties, to determine the actual allocation guidelines for the SARS-CoV-2 vaccines.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


January 4, 2021

Here are today's important updates:

Factors Associated With Positive SARS-CoV-2 Test Results in Children and Adolescents

  • A study in Mississippi covering the time period from September through November found that among children and adolescents aged <18 years in Mississippi, close contact with persons with COVID-19 and gatherings with persons outside the household and lack of consistent mask use in school were associated with SARS-CoV-2 infection, whereas attending school or child care was not associated with receiving positive SARS-CoV-2 test results.

Reasons Behind Mask Wearing

  • In this narrative review titled "Masks and Face Coverings for the Lay Public" published in Annals of Internal Medicine on December 29, the authors do a good job of covering the latest findings on the dynamics of SARS-CoV-2 transmissions and the science behind masks as source control and personal protection.

Medicare FFS Claims: 2% Payment Adjustment (Sequestration) Suspended Through March

  • The Coronavirus Aid, Relief, and Economic Security (CARES) Act suspended the payment adjustment percentage of 2% applied to all Medicare Fee-For-Service (FFS) claims from May 1 through December 31. The Consolidated Appropriations Act, 2021, signed into law on December 27, extends the suspension period to March 31, 2021.

Latest Relief Funding Act Includes More Money for PPP

  • The bill includes $284 billion in funding for the Paycheck Protection Program (PPP).

Allergists Need to Encourage Vaccination

  • In a research letter published in JAMA on December 29 titled "National Trends in the US Public’s Likelihood of Getting a COVID-19 Vaccine—April 1 to December 8, 2020", the authors present the results of a nationally representative internet-based survey of U.S. adults that asked about the likelihood of an individual to get one of the vaccines. The results indicated that 74% of participants would be likely to get the vaccine in April, declining to 56% in early December. This decline was seen for both women and men and in all age, racial/ethnic and educational groups.

COVID-19 Risks in HIV

  • In a small international study published in HIV Medicine, a current CD4 T-cell count of <350 cells/microliter was independently associated with a 2.85-fold risk for severe COVID-19. A lower nadir CD4 T-cell count of <200 cells/microliter was associated with mortality.

HHS PRF Update

  • Most notably, HHS has clarified the funding methodology for the Phase 3 funding. What is the payment amount that an applicant should expect to receive from Phase 3 of the General Distribution? (Modified 12/28/2020) If an applicant has not yet received and kept a payment that is approximately 2% of annual revenue from patient care as part of either Phase 1 or 2 of the General Distribution, then they will receive at least that amount in Phase 3 payment. In addition to this amount, providers will be paid up to 88 percent of their reported losses and net change in their operating expenses from patient care from the first half of 2020. Some applicants will not receive an additional payment either because they experienced no change in revenues or net expenses attributable to COVID-19, or because they have already received funds that equal or exceed reimbursement of 88 percent of reported losses.
  • HHS has begun issuing payments in mid-December and will continue making payments through the first months of 2021.

COVID-19 Toll

  • According to figures from the Kaiser Health Foundation and the Guardian, over 2,900 healthcare workers have died from COVID-19, which is a much higher figure than what has been released by the federal government.
  • One million more children have been infected since mid-November, pushing the total children infected to over two million.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


December 24, 2020

Here are today's important updates:

Key Items in the Latest COVID-19 Relief Bill If Signed by the President 

  • Continued coverage of the temporary transitional home infusion therapy services for Medicare patients on biologics and IVIG/SCIG.
  • Labor/HHS Explanatory Statement encourages the NHLBI to develop a multidisciplinary project to examine inflammation in children with uncontrolled asthma.
  • The Medicare IVIG demonstration project has been extended through December 2023.
  • $22.4 billion for testing and contact tracing, with no less than $2.5 billion for high risk and underserved populations and $790 million for IHS to support tribes.
  • $19 billion dedicated for the nation’s supply of COVID-19 vaccines and therapeutics.
  • $8.75 billion for vaccine distribution, administration, planning, etc.
  • $3.25 billion for the Strategic National Stockpile.
  • Authorizes a national campaign for vaccine safety and effectiveness.
  • Expands, enhances and improves public health data systems at CDC.
  • Provider Relief Fund (PRF) impacts: $3 billion in new resources, additional flexibilities.
  • Provides for a three month delay of the Medicare sequester payment reductions through March 31, 2021.
  • Provides a one-time, 1 year increase in the Medicare Physician Fee Schedule of 3.75% (but puts a 3 year hold on the complex care add-on code).
  • Adds 1,000 new Medicare funded GME FTE residency positions, beginning in FY 2023 under certain circumstances.
  • Allows PAs to bill Medicare directly.
  • Protects against surprise medical bills by ensuring that the patient does not have to pay any more than the in-network cost sharing and provides for an independent resolution process for providers.
  • Requires Medicare Part D plans to use a “real time benefit tool” to inform providers how much a patient will have to pay for a drug, at the time of prescribing.

NIH Developing Study of Allergic Reactions to the Pfizer Vaccine

  • In a Washington Post article dated December 21, the NIH is “rushing” to develop a study protocol for people who have had anaphylactic reactions to the Pfizer vaccine. Daniel Rotrosen, MD, Director of the Division of Allergy, Immunology and Transplantation at the NIAID, will head up the study. Plans are to recruit volunteers who have had a history of severe allergic reactions who will receive the vaccine under close supervision. They considered enrolling volunteers with a history of allergy to PEG, but this condition is so rare, that they would not likely be able to recruit enough individuals. The group has been meeting with representatives from the FDA, Pfizer and Moderna, as well as scientists and researchers (including members of the AAAAI) with knowledge of allergic reactions to vaccines and vaccine components.
  • There have been 6 cases of anaphylaxis to the Pfizer vaccine out of 556,000 doses which are being evaluated.

NIH to Support Radical Approaches to Nationwide COVID-19 Testing and Surveillance

  • A variety of interesting approaches are being funded, some of which can be found here.

Long-Term Follow-up of COVID-19 Patients

  • A previous message reviewed information on the long-term outcomes in hospitalized patients with COVID-19. Here are two studies looking at the two extremes: non-hospitalized patients and ventilated patients.
  • In a study of 451 non-hospitalized COVID-19 patients in Norway, 53% of women and 67% of men were symptom-free at 1.5 to 6 months after the diagnosis, while 16% reported dyspnea, 12% loss/disturbance of smell, and 10% loss/disturbance of taste. In multivariable analysis, having persistent symptoms was associated with the number of comorbidities and number of symptoms during the acute COVID-19 phase. Median age of the participants was about 45 years.
  • A group from the Netherlands reported 3 month follow-up data on 94 patients who were mechanically ventilatedOnly 55% were still alive after 3 monthsOf those, 43 out of 48 had pulmonary function abnormalities, all restriction, and 47 out of 48 had abnormal CT scans. Half of the patients had an abnormal 6-MWT.

NIH Researchers Isolate Promising Mini Antibodies Against COVID-19

  • As described here, these are “nanobodies” which were produced by sensitizing a llama against COVID-19. Such tiny antibodies are naturally produced by camelids. Nanobodies isolated in the lab are essentially free-floating versions of the tips of the arms of the heavy chain proteins. They are more stable, less expensive to produce than typical antibodies and at least one of these appears to attach to the spike protein with greater affinity than other antibodies. These nanobodies are effective in an inhaled form as well.

Herd Immunity

  • recent study using modeled data from Japan, Italy, France and Switzerland that included asymptomatic infection suggests herd immunity could be achieved when active symptomatic patients are 10 to 25% of the population. The only problem is that would mean a total of 80 million cases in the United States and 1.6 million deaths.

Secondary Attack Rates in Households: The New Hot Spots

  • To quote the abstract from the article, which was published in JAMA Network Open on December 14: “In this meta-analysis of 54 studies with 77,758 participants, the estimated overall household secondary attack rate was 16.6%, higher than observed secondary attack rates for SARS-CoV and Middle East respiratory syndrome coronavirus. Controlling for differences across studies, secondary attack rates were higher in households from symptomatic index cases than asymptomatic index cases, to adult contacts than to child contacts, to spouses than to other family contacts, and in households with 1 contact than households with 3 or more contacts. These findings suggest that households are and will continue to be important venues for transmission, even in areas where community transmission is reduced.”

HHS Has Again Updated the PRF FAQs

  • New questions relate to receipt of form 1099’s and tax implications of the PRF.

Combat COVID Website

  • HHS in coordination with NIH and Operation Warp Speed has just launched a new website entitled Combat COVID to pull together the most current information for people of all groups, races, ethnicities and backgrounds who want to get involved in fighting the pandemic. You can find resources to join a prevention trial, locate treatment trials if you are infected, find places to donate plasma if you have recovered from an infection, or find treatment options or trials if you are a physician.

Another Home Test, Now Without a Prescription

  • FDA granted an EUA on December 15 for a SARS-CoV-2 antigen test—that was developed with support from the NIH RADx Initiative—from Ellume USA LLC (Valencia, CA) designed for use at home without a prescription. The test uses a self-collected mid-turbinate nasal swab, which is inserted into a single use cartridge with results in 15 minutes. The at-home analyzer connects to the user’s smart phone via Bluetooth and pairs with a downloadable app that provides step-by-step instructions and displays results. According to the approval letter, the sample can be self-collected by anyone 16 years of age or older, or by an adult for anyone 2 years of age or older. Sensitivity and specificity of the test is not listed on the FDA site. Allergists need to counsel their patients about the appropriate timing for the test, and that both negative and positive results may need to be confirmed with RT/PCR. Additional information can be found here.

NIOSH and ASTM International Writing Guidelines for Mask Ratings

  • In guidelines that may be released next month, these groups are working to develop minimum filter efficiency standards and labels.
  • The article can be found here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


December 21, 2020

Here are today's important updates:

CDC's ACIP Expands on Precautions and Contraindications for Pfizer Vaccine

  • "Severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech COVID-19 vaccine is a contraindication to vaccination listed in the prescribing information. Anaphylactic reactions in persons outside of clinical trials have been reported. While these reports are further investigated, CDC considers a history of severe allergic reaction (e.g., anaphylaxis) to any other vaccine or injectable therapy (e.g., intramuscular, intravenous, or subcutaneous) as a precaution but not a contraindication to vaccination. In persons who report a history of anaphylaxis to another vaccine (i.e., any other vaccine besides the Pfizer-BioNTech COVID-19 vaccine) or injectable therapy, a risk assessment should be conducted to determine type of reaction and certainty of information. For example, whether the medication was administered by injection or another route or whether the reaction constituted a severe allergic reaction (e.g., required use of epinephrine [EpiPen®, etc.], resulted in hospitalization). These persons may still receive vaccination, but they should be counseled about the unknown risks of developing a severe allergic reaction and balance these risks against the benefits of vaccination. A history of mild allergic reaction to a vaccine or injectable therapy, such as urticaria alone without signs or symptoms of anaphylaxis, is not a contraindication or precaution to Pfizer-BioNTech COVID-19 vaccination. In addition, allergic reactions (including severe allergic reactions) not related to vaccines or injectable therapies (e.g., food, pet, venom, environmental, or latex allergies; oral medications [including the oral equivalents of injectable medications]) are not a contraindication or precaution to vaccination with Pfizer-BioNTech COVID-19 vaccine.”
  • Additional discussion about clinical considerations for use of the vaccine can be found here.
  • Allergists need to know that the CDC/ACIP/FDA and NIAID are aware of the reactions that have occurred and are actively working, along with leadership of the AAAAI, to determine the cause for these reactions, and developing protocols to help you deal with them.
  • The CDC has also issued guidelines on precautions and management of anaphylaxis to sites that administer the vaccines.
  • Recommendations are to avoid any other vaccinations for 14 days before or after the SARS-CoV-2 vaccine, but if you have had another vaccine within that 14 day window, don’t wait to get this vaccine.
  • Recommendations are to defer vaccination for 90 days after receiving convalescent plasma or monoclonal antibody treatment for COVID-19.

Moderna Vaccine

  • This vaccine has been granted an EUA and approval from the CDC/ACIP.
  • Results from the clinical trials are very similar in efficacy and safety compared to the Pfizer vaccine. The FDA Briefing Document can be found here. This document presents both interim analysis using a data cutoff of November 7, with a median follow-up of 7 weeks post-dose one, and the final scheduled analysis from a data cutoff of November 21, with a median follow-up >2 months post-dose two. This summary covers the final scheduled analysis.
  • Efficacy: Vaccine efficacy was 94.1% (95% CI 89.3%, 96.8%) with 11 cases of COVID-19 in the vaccine group and 185 cases in the placebo group. Unlike the interim data, the vaccine efficacy when stratified by age group was 95.6% (95% CI 90.6%, 97.9%) for participants 18 to <65 years of age and 86.4% (95% CI 61.4%, 95.5%) for participants 65 years of age or older. Other than the age group difference, there were no vaccine efficacy differences based on race, ethnicity, gender or medical comorbidities associated with high risk for severe COVID-19. Vaccine efficacy against severe COVID-19: 30 cases in the placebo group, 0 in the vaccine group. Vaccine efficacy after the first dose was 80.2% (95% CI, 55.2%, 92.5%) in the 2,000+ patients who only received one dose, but these patients were only followed for 28 days.
  • Safety: The most common adverse reactions: injection site pain (91.6%), fatigue (68.5%), muscle pain (59.6%), joint pain (44.8%), chills (43.4%), fever (14.8%). Most of these were mild to moderate, began on day 1-2 and lasted 2 days. A small number of participants reported systemic reactions longer than 7 days, but there was no difference between vaccinated and placebo groups. Lymphadenopathy (axillary) was reported in 21.4% of vaccine recipients <65 years of age, and 12.4% in those >65 years of age, compared to 7.5% and 5.8% in placebo in those age groups respectively. Severe adverse reactions occurred in 0.2% to 9.7% of participants, and were more frequent after the second dose and less common in those 65 years of age and older. Hypersensitivity adverse events were slightly greater in the vaccine group (1.5%) compared to the placebo group (1.1%). There were no anaphylactic or severe hypersensitivity reactions. This vaccine also contains PEG in the lipid capsule. Serious adverse events were low (1.0%) without meaningful imbalances between study arms. Other than the differences in the age groups and reactogenic reactions, there were no safety differences with respect to race, ethnicity, gender or pre-existing conditions.
  • *Efficacy against asymptomatic infection: preliminary data only, NP swabs were collected pre-dose one and pre-dose two. Number of positive swabs pre-dose two in negative baseline participants was 14 in the vaccine group and 38 in the placebo group, suggesting that some asymptomatic infections may be prevented with just the first dose.

And the Disinformation Shifts to SARS-CoV-2 Vaccines

HHS Announces Increase in Provider Relief Funds

  • After review of Phase 3 applications, the Health Resources and Services Administration announced on December 16 that it would be distributing $24.5 billion to over 70,000 providers, up from the initial $20 billion. The $4.5 billion increase will allow reimbursement for up to 88% of reported losses. Over 35,000 applicants will not receive additional funding because they either had no losses or payments to date already equaled or exceeded the 88% threshold. Payments were to begin on December 16 and continue through January.
  • A state-by-state breakdown on the first batch of Phase 3 payments can be found here. The data will be updated through January as payments are completed.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


December 15, 2020

Here are today's important updates:

Additional Vaccine Information

  • Here is the Contraindications and Precautions section of the Pfizer-BioNTech vaccine PI:
    • Severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer BioNTech COVID-19 vaccine is a contraindication to vaccination.
    • Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of the vaccine.
    • Because of reports of anaphylactic reactions following vaccination outside of clinical trials, the additional following guidance is proposed: A severe allergic reaction to any vaccine or injectable therapy (IM, IV or SC) is a precaution to vaccination at this time; vaccine providers should observe patients after vaccination to monitor for the occurrence of immediate allergic reactions: persons with a history of anaphylaxis (not due to vaccines or injectable medications) 30 minutes, all other persons 15 minutes.
    • What does “precaution” mean: discussion with provider on risk assessment (evaluation of previous reaction), potential deferral of vaccination, 30 minute observation if vaccinated.
  • Here is a nice discussion of the data behind the ACIP decision to approve the Pfizer-BioNTech SARS-CoV-2 vaccine.
  • As far as monitoring for adverse reactions, there are four separate safety monitoring systems available for this vaccine: VAERS (adverse events requiring reporting listed under the EUA); V-Safe (a text- and web-based cell phone system requiring voluntary patient registration that should be encouraged by vaccine providers); VSD (Vaccine Safety Datalink, which is a passive system for patients enrolled in large healthcare systems); and CISA (Clinical Immunization Safety Assessment) Project. You can read more here.
  • ACOG and ACIP recommend that vaccination should not be withheld from pregnant or lactating women, but they should be informed that there are insufficient data on safety at this time.
  • The AAAAI COVID-19 resources page also has a new COVID-19 Vaccines, Monoclonal Antibodies and Other Treatments section that will be regularly updated. 

Coding for Vaccines

  • Pfizer vaccine: 91300 for vaccine, 0001A for administration (first dose) ($16.94), 0002A (second dose) ($28.39)
  • Moderna vaccine: 91301 for vaccine, 0011A and 0012A for first and second dose administration, respectively. Same reimbursement.
  • No payment allowance for vaccine at this time, since MD will receive at no cost.

Other COVID-19 Codes

  • Contact with and (suspected) exposure to COVID-19: Z20.822
  • Personal history of COVID-19: Z86.16
  • Multisystem inflammatory syndrome: M35.81

CDC Suggestions for Adverse Reactions in Healthcare Workers

  • Vaccine-related symptoms include fever, chills, myalgias, fatigue and headache. They typically start 1-3 days after vaccination and last 1-2 days. They DO NOT INCLUDE cough, shortness of breath, sore throat, rhinorrhea, loss of smell or taste.
  • If the healthcare worker has only vaccine-related symptoms with a consistent time course and has not been exposed to a known or probable case of COVID-19 in the previous 14 days, they do not need to be evaluated for other causes and can return to work when afebrile and feeling better.
  • If the time course is not consistent (e.g., fever lasting longer than 2 days) or additional symptoms are present, or they have had unprotected contact with a COVID-19 patient in the previous 14 days, they should be evaluated for other causes of the symptoms.

Treatment

  • Details on the EUA for bamlanivumab, Eli Lilly’s IgG1 neutralizing monoclonal antibody can be found here. This drug is indicated for patients 12 years of age or older with mild-moderate COVID-19 and high risk for severe disease. Overall markers for high risk: BMI greater or equal to 35, chronic kidney disease, DM, immunosuppression, being 65 years of age and older; in patients 55 years and older: cardiovascular disease, hypertension, COPD or other chronic respiratory disease; and in 12 to 17-year olds: sickle cell disease, congenital or acquired heart disease, neurodevelopmental disorders, a medical-related technological dependence (e.g., tracheostomy, gastrostomy) and asthma or other chronic respiratory disease that requires daily treatment. The drug is not authorized for use in patients who are hospitalized or require oxygen therapy because of COVID-19.

HHS Updates PRF FAQs Again

  • New or modified questions were posted on December 4. These relate to eligibility, provider overpayment and return of funds, eligible expenses, audit support and extensions, and reporting requirements.

Clarification on MIPS Exceptions

  • The deadline for hardship exceptions for MIPS reporting was extended to February 1, 2021, with one exception. If you are ONLY applying for a hardship exception to the interoperability measure, then that deadline remains December 31, 2020.

Clinical Status and Lung Function 10 Weeks After Severe Infection

  • An article in Respiratory Medicine that was published on November 29 evaluated 220 patients at a median of 10 weeks after discharge and noted that 54% had abnormal PFTs, mostly restriction. Lung function findings did not correlate with imaging results or symptoms, but did with hospital LOS, ICU and mechanical ventilation.

At-Home Testing

  • FDA has issued an EUA for the Lucira COVID-19 All-In-One Test Kit, the first COVID-19 diagnostic test for self-testing at home and that provides rapid results in individuals 14 years of age and older. This can also be used as a POC test for provider offices for all ages, but in offices the FDA requires that samples be collected by a healthcare provider for children less than 14 years of age. A patient, on advice of their healthcare provider, uses a self-collected swab that can be read directly from the test unit after 30 minutes.
  • In another study that may pave the way for more at-home testing, saliva sampling and oral rinses were found to be very comparable to NP and throat swabs in sensitivity for diagnosis.

Face Masks and Breathing

  • There continue to be myths and disinformation spread about the “risks” of face masks. Much of the published material to date has been limited to small groups of patients. In a review article published by Annals of the American Thoracic Society on November 16, the authors point out that there is a substantial body of literature on this question. Their review indicates little if any effect on work of breathing or other parameters during physical activity.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


December 11, 2020

Here are today's important updates:

Vaccine News

The FDA Briefing Document for the Vaccine and Related Biological Products Committee (VRBAC) meeting on December 10 concerning the Pfizer-BioNTech vaccine is available here and it has also been posted on the AAAAI COVID-19 resources page

Efficacy Summary: For participants without evidence of prior COVID-19, vaccine efficacy (VE) occurring at least 7 days after dose 2 was 95.0% (8 cases in the vaccine group and 162 in the placebo group). VE in patients with and without previous COVID-19 was 94.6% (9 and 169 cases respectively). Only 3% of participants had evidence of prior COVID-19 at the time of enrollment. The 95% credible interval for the vaccine efficacy was 90.3% to 97.6%. VE in patients >55 years of age was 93.8%. These results were consistent across gender, race and ethnicity. VE was also similar for those with co-morbidities, but the CI was wide due to small numbers of patients in any given category other than obesity or hypertension. Only one vaccine participant had severe disease, and that did not require hospitalization. Only 9 patients in the placebo group had severe disease, however. VE after dose 1 was 52.4% (75% for severe disease).

Safety Summary: The most common adverse systemic reactions were injection site reactions (84.7%), fatigue (62.8%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%). Most reactions were mild to moderate. The rate of severe adverse reactions was 0.0% to 4.6%, and were more frequent after dose 2 and less frequent in adults >55 years of age. Lymphadenopathy was reported in 0.3%. Bell’s Palsy occurred in 4 vaccine participants, but this is not greater than the expected background rate. Systemic adverse events generally occurred on the day after the dose and lasted 1-2 days.

Vaccine Reactions in the UK: Reports of two episodes of anaphylaxis and another of an allergic reaction have prompted Britain’s Medicine and Health Care Products Regulatory Agency (MHRA) to recommend that anyone with a history of anaphylaxis to a vaccine, food or drug not receive the vaccineHere is the British Society of Allergy & Clinical Immunology's statement concerning this recommendation. We do not have details on the reactions or the patients that reacted other than the two patients who had an anaphylactic reaction had a previous history of anaphylaxis. This topic was discussed at the AAAAI Board of Directors level on December 9 and the AAAAI Board and COVID-19 Response Task Force posted a statement on the VRBAC comment site for the FDA hearing on December 10 and will be following the development closely. If and when the FDA grants an EUA to the Pfizer vaccine, they will also list their recommendations about who should and should not receive the vaccine. The AAAAI will comment at that time.

Helpful References Concerning Anaphylaxis After Vaccination: JACI 2016; 137(3):868-78 and JACI 2019; 143:1465-73. Bottom line: anaphylaxis after vaccination is rare, and can occur in patients with no prior history of sensitization.

The Advisory Committee on Immunization Practices (ACIP) will meet today, December 11, from 12:00 to 5:00 pm EST and December 13 from 12:00 to 4:00 pm EST to discuss final recommendations on vaccine priorities. These hearings will be streamed live on the web here.

The CDC will host a COCA Call on COVID-19 Vaccine Safety on December 14 from 1:00 to 2:00 pm EST. Here is the Zoom link and the Webinar ID is: 161 126 4903

CMS Extends Deadline for MIPS Extreme and Uncontrollable Circumstances to February 1, 2021 

The previous deadline was December 31, 2020.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


December 7, 2020

Here are today's important updates:

Errata

  • Our last message stated that there were 100 million healthcare workers in the U.S., based on erroneous information from a source. According to the CDC there are 18 million healthcare workers, but according to the U.S. Census in 2018 there were 20.5 million people who self-identified as working in the healthcare field. There are also an additional three million nursing home residents and staff, so 48 million doses of vaccine will be required just to immunize the recommended initial groups.

CDC Revises Quarantine And Masking Guidelines

  • The CDC announced Options to Reduce Quarantine for Contacts of Persons with SARS-CoV-2 Infection Using Symptom Monitoring and Diagnostic Testing.
  • The CDC still recommends a quarantine period of 14 days, however, based on local circumstances and resources, the following options to shorten quarantine are acceptable alternatives.
  • Quarantine can end after day 10 without testing if there are no symptoms during daily monitoring (residual transmission risk estimates 1-10%).
  • When diagnostic testing resources are sufficient and available, then quarantine can end after day seven with individual testing negative within 48 hours before the time of planned quarantine discontinuation (residual transmission risk estimates 5-12%).
  • Continued symptom monitoring and masking must be done through day 14.
  • Background for the change and additional details can be found here.
  • On 12/4, the CDC announced new recommendations for universal mask wearing indoors except in your own home (unless non-household members are visiting).
  • A nice summary of Guidance for Public Health Strategies, with the rationale behind it, can be found here.

COVID-19 Is Not Always Mild In Younger People

  • From March-August 2020, data from the COVID-NET indicated that more than one in five younger adults (ages 18-49) without underlying conditions who were hospitalized with COVID-19 in the U.S. experienced severe illness requiring ICU-level care.

Vaccines

  • ACIP recommendations for vaccine allocation can be read here. These are interim recommendations for the initial vaccine distributionKey Message: health care workers and nursing home residents are at the top of the priority list. Expect states to approach the “health care workers” differently, depending on their vaccine allocation. They may subdivide HCWs into different risk categories for vaccination.
  • Studies of the current vaccine candidates have been focused on whether they protect a recipient from getting sick from the virus, but they haven’t looked at whether a vaccine recipient can still carry and transmit the virus. This is another reason why we should encourage our patients to get the vaccine and to continue other mitigation strategies. A good discussion on this issue can be found here.
  • Peer-reviewed publications: for the AstraZeneca/Oxford vaccine, Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial, and for the Moderna/NIAID vaccine Durability of Response after SARS-CoV-2 mRNA-12373 Vaccination. Key Message from the second study: levels of binding and neutralizing antibodies remain elevated three months after the second dose.
  • The public can attend the meeting of the Vaccine and Related Biologics Advisory Committee (VRBAC) virtually. VRBAC will meet from 9am to 6pm EST on 12/10 to review the application for an EUA from Pfizer and on 12/17 to review Moderna’s application. The entire dataset from the Pfizer vaccine trials will be available to the public on December 8 and for the Moderna vaccine on December 15.
  • In the Pfizer trials the rate of infection in the placebo groups was lower than expected, probably due to volunteer bias, and the efficacy of these vaccines may be a little lower when the general public receives them. On safety, two months of data in 40,000 people is reassuring that there are not common side effects that we need to worry about, but we won’t know about rare side effects until millions have been vaccinated. Good point to share with your patients. Watch this JAMA video interview with Dr. Paul Offit.
  • Additional talking points with patients can be found in this column in the New York Times which points out that immunity from the SARS-CoV-2 vaccine is at least equal to natural infection, but much safer.
  • You should also point out that patients (and staff) may miss a day of work due to the reaction to the vaccine. You might consider staggering immunization of your office staff for this reason.

Treatment

  • An interim analysis of the data on repurposed antiviral drugs for COVID-19 WHO Solidarity Trial was published in the NEJM on 12/2.
  • A randomized trial in 11,330 hospitalized adults with COVID-19 of four different drug regimens found that remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with COVID-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.
  • Nebulized interferon beta-1a was found to be safe and effective in a randomized phase II trial in 101 hospitalized COVID-19 patients in reducing the WHO Ordinal Scale for Clinical Improvement (OSCI) compared to placebo. The study was published in The Lancet on 11/12 and can be found here.

Telehealth

  • CMS announced on 12/1 that more than 60 services added to the Medicare telehealth list will continue to be covered beyond the end of the PHE, but also stated that *they did not have the statutory authority to pay for telehealth outside of rural areas or, with certain exceptions, allow beneficiaries to receive telehealth in their homes.
  • The AAAAI will continue to advocate to Congress to get this covered.
  • HHS announced that health care providers can provide telehealth across state lines during the PHE, regardless of state and local prohibitions.

Deadline For Applying For MIPS 2020 Hardship

  • The deadline to apply for a hardship exception for the 2020 performance year is December 31. Submit an application requesting reweighting of one or more MIPS performance categories. The application can be found here.
  • A reminder to our members: You must participate in MIPS (unless otherwise exempt) if, in both 12-month segments of the MIPS Determination Period, you: Bill more than $90,000 for Part B covered professional services, and; See more than 200 Part B patients, and; Provide more than 200 covered professional services to Part B patientsThus meaning if you do not meet those criteria, you do not exceed the low volume threshold. If you don’t exceed the low volume threshold, you may still voluntarily participate if you hope to qualify for increased Medicare reimbursement.

SARS-CoV-2 Mutations Do Not Appear To Increase Transmissibility

  • In this study published in Nature Communications published on 11/25 the authors studied 46,723 SARS-CoV-2 genomes isolated from patients worldwide. “We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent mutations currently in circulation appear to be evolutionary neutral and primarily induced by the human immune system via RNA editing, rather than being signatures of adaptation.”

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


December 1, 2020

Here are today's important updates:

Vaccine News

  • AstraZeneca has reported vaccine trial preliminary results. Several media outlets reported on November 23 that the vaccine maker released interim data analysis indicating that their vaccine was 62% effective in one trial involving two full doses one month apart, and 90% effective in another trial that offered a half-dose followed by a full dose one month apart, for an average efficacy of 70% over the two trials. It has been reported that there were mistakes made in dosing in the half-dose trial and that trial enrolled younger patients.
  • Moderna has applied for an EUA for their vaccine, joining Pfizer who has already applied. There could be two vaccines available by the end of December.
  • The FDA Vaccine Advisory Committee is slated to meet December 8-10 to review data for the Pfizer application and will reportedly meet the following week for the Moderna application.
  • Once the EUA has been granted, U.S. officials announced plans to immediately release 6.4 million doses nationwide as an initial distribution. States have already been informed of their estimated vaccine allocations.

ACIP Releases Statement on Ethical Principles for Allocating Vaccine

  • The Advisory Committee on Immunization Practices (ACIP) published their ethical principles for allocating initial supplies of COVID-19 vaccine in MMWR on November 23.
  • The four principles are: 1) maximize benefit and minimize harms, 2) promote justice, 3) mitigate health inequities, 4) promote transparency.
  • Four groups have been considered for initial vaccine allocation: healthcare workers, other essential workers, adults with high-risk conditions and adults >65. Initial allocations of vaccine will not be enough to vaccinate all these groups, since there are 100 million healthcare workers alone, and only 20 million doses of vaccine will be available.
  • Despite this, HHS announced that governors will have the final say on who receives the vaccine first.

AMA Passes Resolution on Combating Misinformation About COVID-19 Vaccines

  • At the AMA Special Meeting in November, the House of Delegates directed the AMA to institute a program to promote the integrity of a COVID-19 vaccination program by: educating physicians on speaking with patients about COVID-19 vaccination, educating the public about the safety and efficacy of the vaccines, forming a coalition of healthcare and public health organizations, inclusive of those respected in communities of color to develop and implement an education program, and supporting ongoing monitoring of COVID-19 vaccines.
  • Allergists need to prepare their patients for the side effect profile of the two vaccines, which include fever, malaise and myalgias, to encourage them to get the second dose.

NIAID Announces New Treatment Trial

  • This will be the fourth iteration of the Adaptive COVID-19 Treatment Trial (ACTT-4), which will be a randomized placebo controlled trial of remdesivir combined with either dexamethasone or baricitinib in hospitalized adults with supplemental oxygen requirements.

Convalescent Plasma Ineffective in COVID-19 Severe Pneumonia

  • As published in NEJM on November 24, a randomized, placebo-controlled trial in 228 patients with severe COVID-19 pneumonia demonstrated no significant differences in clinical status or overall mortality.

Predictors of Disease Severity in Hospitalized Children and Youth

  • A multicenter retrospective and prospective study on 281 hospitalized pediatric patients with acute COVID-19 and MIS-C published November 13 in The Journal of Pediatrics showed that patients with MIS-C were more likely to identify as non-Hispanic Black, and obesity and hypoxia on admission were predictive of severe respiratory disease. 41% of patients were admitted to the ICU, and 2% died. Lower absolute lymphocyte count and higher C-reactive protein were associated with more severe MIS-C.

Estimated Seroprevalence of SARS-CoV-2 in the United States

  • In this study published on November 24 in JAMA Internal Medicine, the authors collected serum samples used for screening labs from all 50 states, the District of Columbia and Puerto Rico and measured serology to SARS-CoV-2 every two weeks from July 27 to September 24. Seroprevalence varied from 0.0% to 23% over the time periods. In 42 of 49 jurisdictions with sufficient samples to estimate seroprevalence across all periods, fewer than 10% had detectable SARS-CoV-2 antibodies.
  • CDC model estimates that the actual number of COVID-19 cases is eight times the reported number.

FDA Approves Quantitative COVID-19 Serology Test

  • On November 23, the FDA granted an EUA to Kantaro Bioscience’s quantitative COVID-19 neutralizing antibody test. Most tests authorized to date are qualitative or semi-quantitative. This should allow for better epidemiologic studies and research on immune persistence post-infection and post-vaccine.

Prognostic Implications of Viral Load and Early Antibody Formation

  • SARS-CoV-2 viral load on admission (RT/PCR Ct <22) was associated with a significantly increased 30-day mortality (OR 4.20 [95% CI: 1.62-10.86]), and anti-SARS-CoV-2 nucleocapisid IgG seropositivity on admission trended toward a reduced 30-day mortality (OR 0.43 [95% CI: 0.15-1.26]). Reporting of quantitative SARS-CoV-2 viral load and serologic assays may offer prognostic clinical information.
  • The study was published online in Open Forum Infectious Diseases on November 3 and can be found here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


November 23, 2020

Here are today's important updates:

Travel, Gatherings and Masks

  • The November 20 issue of MMWR reviews 86 primary, secondary and tertiary cases in the state of Minnesota, that resulted from attendance at the Sturgis motorcycle rally in South Dakota this summerOne-third of the counties in Minnesota had at least one primary, secondary or tertiary case. These numbers are likely to be an underestimate, since the case reviews were voluntary. We also don’t know the number of Minnesota residents who attended. Use this information to inform your patients how holiday travel and lack of mitigation measures can affect their communities and state.
  • second article in the same issue reviewed the effect of mask mandates in Kansas this summer. The governor of Kansas issued an executive order requiring wearing masks in public spaces, effective July 3, 2020, which was subject to county authority to opt out. After July 3, COVID-19 incidence decreased 6% in 24 counties with mask mandates, but increased 100% in 81 counties without mask mandates. Another example to share with your patients.
  • In case you hear about it, an article in Annals of Internal Medicine on an individually randomized controlled trial in Denmark this past spring did not show additional benefit from positive messaging to support wearing masks compared to physical distancing alone. Limitations of this study are that only 46% adhered completely to mask wearing, and the study only looked at the risk of infection for the mask wearer, but not the effect on transmission to others. The study was not designed to demonstrate whether masks reduce transmission or infection, but rather the impact of messaging surrounding mask wearing.
  • To quote Dr. Vin Gupta’s Tweet (ICU doc and MSNBC consultant): “An ICU bed is only as good as the trained nurse, RT, and doc available to staff it. We do NOT have enough trained staff to contend with unplanned surges after holiday travel nationwide. This headline out of Switzerland will be ours post-Thanksgiving if we don’t act in unison.”

Vaccine News

  • You probably already know that Pfizer has applied to the FDA for an EUA for their vaccine. Moderna is expected to follow soon with the same request. The FDA will likely rule on this in early December, so vaccine may be available by the end of the year, if the pilot distribution testing goes well. There are still many questions about distribution, although several national pharmacy chains have signed on as participants.
  • An interesting article on the Ethical and Scientific Considerations Regarding the Early Approval and Deployment of a COVID-19 Vaccine that was published on November 20 in the Annals of Internal Medicine covers issues related to other vaccine trials and impact on long-term safety and efficacy data.

Treatment News

  • WHO recommends against using remdesivir as a treatment for hospitalized patients with COVID-19. The article is entitled A Living WHO Guideline on Drugs for COVID-19 and has a nice visual representation of treatments. The FDA, earlier this year, granted an EUA for remdesivir for patients with COVID-19.
  • Ah, the confusing shortcomings of clinical trials in a pandemic.
  • The FDA has granted an EUA for the combination of baricitinib with remdesivir for hospitalized patients with COVID-19. In a clinical trial of hospitalized patients with COVID-19, this combination was shown to reduce time to recovery within 29 days compared to remdesivir plus placebo.
  • The FDA has granted an EUA for casirivimab and imdevimab to be administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients 12 years of age or older weighing at least 40 kilograms (about 88 pounds) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progressing to severe COVID-19.

HHS Updates on PRF FAQs

  • Updates added on November 18 relate to qualifying expenses for capital equipment and facilities projects. Basically, expenses for capital facilities and equipment may be fully expensed only in cases where the purchase was directly related to prevent, prepare for and respond to the coronavirus.

Risk for COVID-19 Among Healthcare Workers

  • BMJ has published results from their nationwide linkage cohort study on hospital admission risk for healthcare workers. The study involved 158,445 healthcare workers and 229,905 household membersThey divided the healthcare workers into patient-facing and non-patient facing and also subdivided the patient-facing into “front door”, ICU and aerosol-generating settings.
  • Patient-facing healthcare workers were over three times as likely as non-patient facing healthcare workers to be hospitalized for COVID-19, and their household members almost twice as likely.
  • Non-patient facing healthcare workers were at no greater risk than the general population.
  • To put this into perspective, the estimated absolute risk of hospitalization for patient-facing workers was <0.5%.

COVID-19 Rates Higher in Small Cities and Rural Areas

  • MMWR from November 20 shows data indicating that the incidence of COVID-19 in September and October was higher in rural and medium/small counties compared to large urban areas.

Cases in Children Rising

  • According to state level data collected by the AAP and Children’s Hospital Association, the number of cases of COVID-19 in children now exceed 1 million. There has been a 22% increase in cases over the last 2 weeks, with 185,829 new cases.
  • In the 10 states reporting, 3.9%-18.8% of children tested were positive.
  • In 23 states and New York City, 0.5%-6.1% of cases resulted in hospitalization.
  • In 42 states and New York City, mortality varied from 0.00%-0.15%.

CDC COCA Call on Telehealth and Health Equity

NEJM Webinar on COVID-19 Comorbidities and Cutaneous Manifestations of Systemic Diseases in Adults and Children

  • This webinar takes place Wednesday, December 2 from 1:00 to 2:15 pm ET. Register here.

Please continue to regularly visit the AAAAI COVID-19 resources page and advocacy page. If you need to refer back to any of the previous Task Force messages, you can do so here.

Sincerely,

Paul V. Williams, MD, FAAAAI
Chair of the AAAAI COVID-19 Response Task Force


November 17, 2020

Here are today's important updates:

Here We Go Again

  • As case numbers rise to their highest since the pandemic began, it is time to refocus on patient and staff safety. Review your PPE supply and supply chain. Make early purchases while items are available. Begin networking with others to purchase supplies. Review and refine your telemedicine protocols and schedules. As the percentage of positive tests climb, the likelihood of asymptomatic patients in your offices will also climb. Re-evaluate in-office procedures with this in mind. The AMA is once more collaborating with Project N95, a not-for-profit organization, to reserve more quality-certified PPE exclusively for AMA members to purchase with no minimum. If you’d like to place an order, go here to begin the process.

Holiday Travel

  • As you consider visiting relatives for the holidays, note that the November 13 MMWR reported on the results of airport symptom-based screening of incoming passengers to prevent the spread of COVID-19. From mid-January to mid-September, 766,044 travelers were screened and 298 (0.04%) met criteria for public health assessment. Of those, 35 (0.005%) were tested for SARS-CoV-2 and 9 (0.001%) were positive. Overall this resulted in about one case for every 85,000 travelers screened.
  • While this study concerned the screening of passengers arriving at certain airports from certain countries, the point that was made and echoed by the study of Marine recruits published in NEJM last week, is that symptom screening is not effective. The fact that this is done by your airline is not that reassuring.
  • A better approach is to advise our patients, and heed the advice ourselves, to follow known mitigation strategies and consider pre-departure and/or post-arrival testing.
  • If you are thinking about family gatherings at home, the CDC has posted information on how to do that safely.
  • If you are curious about your risk in attending a gathering, the Georgia Institute of Technology, in collaboration with the Applied Bioinformatics Laboratory and Stanford University, has developed this handy assessment tool.

FDA Webinar Series on Respirators and Other PPE

  • The FDA will be hosting a webinar on this topic on December 8 from 12:00 to 1:00 pm EST. Information on this webinar and others that have been held with available transcripts can be found here.

Vaccine News

  • Moderna announced on Monday that its vaccine was showing 94.5% efficacy in preliminary results from their phase 3 trial. Unlike the Pfizer vaccine, this one will not require the same storage issues and can be safely stored at -25 degrees Fahrenheit.
  • This site has some great infographics on how vaccines and other treatments work that allergists can use with their patients.

Vaccine CPT Codes

  • The AMA, in cooperation with CMS, has released new codes specific for the vaccines to be released. A spreadsheet of all the COVID-19 testing, vaccine and vaccine administration codes can be downloaded here.
  • The vaccine codes currently available are 91300 for the 30 mcg/0.3mL dosage, diluent reconstituted and 91301 for the 100 mcg/0.5mL dosage.
  • According to CMS: If you intend to administer the COVID-19 vaccines when they become available, or the new monoclonal antibody bamlanivimab, especially if you intend to roster bill these codes, please download and install the new release of PC-ACE. This release includes the coding structure, currently comprised of both a HCPCS Level I CPT code structure issued by the American Medical Association (AMA) and a HCPCS Level II code structure issued by CMS. Together, these codes support the administration of the COVID-19 vaccines and the monoclonal antibody infusions, as they become available; this structure includes the codes for bamlanivimab.

Monoclonal Antibody Coverage and Access

  • CMS has announced that Medicare will cover these infusions without cost sharing. They anticipate initially giving the antibody product to healthcare providers at no cost and payment will be made for infusion. When healthcare providers begin to purchase monoclonal antibody products, Medicare anticipates setting the payment rate in the same way it set the payment rates for COVID-19 vaccines. CMS will issue billing and coding instructions for healthcare providers in the coming days.
  • HHS promised to fairly and swiftly distribute the treatment, but there are only 88,000 doses available now. Logistics will be an issue for receiving and administration.

Treatment Update

  • A small randomized study on inhaled interferon beta-1a in 98 hospitalized patients with COVID-19 was published in The Lancet Respiratory Medicine. The odds of improvement were more than two-fold greater in treated patients compared to placebo at day 15 or 16 (OR 2.32). Inhaled interferon beta-1a reduced the odds of developing severe disease by 79% (OR 0.21), and patients were more than twice as likely to recover (OR 2.19).

CDC Issues Scientific Brief on Community Mask Wearing

  • In an updated (November 11) resource, the CDC lays out the latest scientific basis for community use of cloth masks to control the spread of SARS-CoV-2. They provide experimental and epidemiologic data to support that masks reduce transmission and protect the wearer.
  • Details can be found here.

Long-Term Outcomes of Hospitalized Patients With COVID-19

  • Research was published in Annals of Internal Medicine on November 11. The observational cohort study of 1,250 patients discharged after hospitalization in Michigan from March 16 to July 1 describes 60 day post-discharge clinical, financial and mental health outcomes. Only 488 patients were available for the 60 day survey.
  • Key findings: Of the 1,250, 78% went home, 12.6% to a SNF or rehab facility, 6.7% died and 15.1% were re-hospitalized. Of those available for the survey after 60 days, 32.6% had persistent cardiopulmonary symptoms (over half of these had new or worsening symptoms), 12% had problems with activities of daily living, and nearly half reported emotional impact.
  • In another study using data from the Premier Healthcare Database, investigators were able to track re-admissions to the same hospital in 126,137 patients who had been hospitalized