September 25, 2023

It has been a long few years in our professional and personal lives as we navigate the coronavirus disease 2019 (COVID-19) pandemic. The presence of COVID-19 has forced allergists’ practices across the country to adapt to ever changing state-wide limitations in non-essential medical visits and testing, to the abrupt implementation of telemedicine and telehealth, to the mitigation of the risk of disease transmission to providers, staff and patients, and to issues concerning vaccination, not to mention a trying time for families and our personal wellbeing. The Centers for Disease Control and Prevention (CDC) has issued many guidelines for healthcare providers, which include the use of appropriate personal protective equipment (PPE) and the evaluation and testing of patients suspected of being infected with COVID-19. It has become more important than ever to recognize the differences between allergies, infection with COVID-19 and other common upper respiratory diseases. Educating staff and patients to recognize the differences is paramount in appropriately screening those who may otherwise need isolation or referral based on rapidly evolving state and federal guidelines.

COVID-19 is the name for the viral respiratory syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a coronavirus in a family of viruses causing diseases ranging from the common cold to more severe syndromes such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV).

COVID-19 was officially declared a pandemic by the World Health Organization (WHO) on March 11, 2020. The most common signs and symptoms occurring within two to 14 days after exposure include fever, cough and shortness of breath. The median length of time for presentation is five days. Older adults, male patients, and those with underlying chronic health conditions such as lung disease, heart disease, compromised immunity and diabetes appear to be at greater risk for developing severe complications. The disease also appears to affect many racial and ethnic minority groups disproportionately.

WHAT ARE THE KEY DIFFERENCES IN PRESENTATION BETWEEN ALLERGIES AND COVID-19 INFECTION?
Allergic symptoms typically include nasal congestion, runny nose and sneezing, itchy, swollen and watery eyes. Allergic asthma may present as coughing, wheezing and shortness of breath. Dry and itchy skin rashes are common. Headaches and fatigue are associated symptoms in some people. Fever is not a symptom of allergy.

According to early WHO reports symptoms of COVID-19 include fever (90%), a dry cough (68%), fatigue, sputum production (33%), shortness of breath (19%), sore throat (14%), myalgias, and rarely, diarrhea. Nasal congestion was present only in 5% of patients and conjunctival injection only in 0.8% of presenting cases. SARS-CoV-2 can cause a mild follicular conjunctivitis, and transmission via aerosol contact with conjunctiva is likely. The loss of taste or smell is an important early symptom of the disease, and as a sole symptom, may be a reason for testing for COVID-19. The CDC lists cough and shortness of breath as representative symptoms and has listed fever, chills, repeated shaking with chills, muscle pain, headache, and sore throat as potential symptoms of COVID-19. Additional skin symptoms, such as lesions on the feet and toes, resembling “chilblains”, may well be a manifestation of the disease.

It is still difficult to distinguish between influenza types A and B, the common cold and COVID-19 without formal testing. The common cold does not typically present with fevers, and symptoms are much milder, often involving nasal congestion and mucus production. Physical distancing measures also contributed to notable declines in true influenza activity last year, in addition to regular seasonal variation, and flu vaccination is strongly advised this fall to prevent winter disease outbreaks which may complicate the clinical and epidemiological picture of having the two diseases circulate widely.

A useful infographic that lists the differences in symptoms between COVID-19, allergies and other common infections may be found here.

Information from the WHO regarding symptom presentation and transmission can be found here.

WHAT ARE THE KEY CLINICAL CHARACTERISTICS OF COVID-19?
Person to person viral transmission is firmly entrenched within the United States although it appears to have been better controlled in states with lockdown measures and mask mandates. COVID-19 cases, hospitalizations, and deaths across the United States are declining significantly from earlier peaks with the introduction of widespread vaccination, including both Delta and Omicron peaks, which appeared more infectious. On January 22, 2020, the CDC reported one case of COVID-19 infection within the United States. As of this writing, the CDC is reporting more than 6 million hospitalizations and more than 1,000,000 deaths in this country. Fortunately more than 80% of the total population is now thought to have received the updated bivalent booster vaccine.

Most transmission is thought to be via droplet or aerosol spread and less likely through fomites, although some studies suggest that the virus may remain viable on surfaces for up to three days, possibly longer. This finding highlights the risk of spreading the disease in enclosed spaces with inadequate ventilation and over distances greater than six feet. The CDC recommends the use of appropriate PPE for any aerosol generating procedures, which includes testing patients (nasal swabs), the use of nebulizers, peak flow meters, and spirometry. Transmission also occurs unequivocally from both asymptomatic and pre-symptomatic individuals.

Up to 80% of cases of COVID-19 are considered mild to moderate, including both pneumonia and non-pneumonia subtypes, 13.8% have severe disease and 6.1% are critical, presenting with respiratory failure, septic shock, and/or multiple organ dysfunction/failure. The proportion of patients with truly asymptomatic presentation (who don’t otherwise ultimately present with symptoms) is not known. Disease in children is uncommon and mild, with only a very small proportion of those aged under 19 years developing severe (2.5%) or critical disease (0.2%). The new Omicron variant of COVID-19 tends to be more contagious and may be clinically milder than previous variants of the disease.

A new probable complication of COVID-19 infection in children known as multisystem inflammatory syndrome in children (MIS-C) is the occurrence of a severe inflammatory syndrome with Kawasaki disease-like features and/or shock in children with laboratory evidence of SARS-CoV-2 or known exposure to COVID-19. The CDC health advisory concerning MIS-C can be found here.

Long COVID refers to the presence of post-COVID-19 conditions four or more weeks after the initial SARS-CoV-2 infection and is being studied actively by researchers and clinicians.

Mortality rates from COVID-19 for those under 60 years of age are less than 1%, from 60 to 69 years of age - 3.5%, 70 to 79 years of age - 8%, and over 80 years of age - 15%. These figures are highly influenced by the presence of co-morbid disease in each age group and may as well be influenced by the burden of disease presenting to local centers or epicenters, with the potential for critical supply shortages. They are also influenced by the presence of variants of the disease itself. The Delta variant, a recent predominant COVID-19 strain in the United States, was more transmissible and was responsible for more serious disease in the unvaccinated than previous forms of the virus. The Omicron variant and subvariants cause less serious but more widespread disease, and have now taken the place of the Delta variant throughout the country.

HOW TO KEEP YOUR PATIENTS SAFE
Community efforts to minimize disease impact have focused on mitigation rather than containment, and public health efforts remain of paramount importance. Mitigation relies on reducing the caseload or slowing the infection rate on any given date so as not to overload the healthcare system and has been referred to as “flattening the curve”.

Steps to reduce disease burden include appropriate phone pre-screening of clinic patients to ask about symptoms such as fever, new onset cough, or recent exposure to COVID-19 infection. These patients may be referred to appropriate local screening centers in lieu of your office. It is important to remain up to date regarding any state or local requirements concerning testing and referral of suspected cases and to have strict procedures in place in your office for the management of patients, but also the necessary steps to be taken by your office staff, such as mask requirements and physical distancing.

Explanatory signage in your office should be readily visible before the patients check in, with means of isolation readily available and the staff trained to ask appropriate questions.

Patients and staff who are acutely ill should stay at home unless they are severely ill, and their condition warrants medical evaluation. Even in regions where “stay at home” orders are not in place, patients on regular allergy injections, especially the elderly and those from higher risk groups may be advised to forestall their office visits, especially if their risk for exposure (such as the use of public transit, exposure to crowds, lack of safe distancing) is greater.

In the office itself, coughing, sneezing, and medical procedures that increase the presence of aerosolized particles, especially in confined spaces, increase the risk for transmission. This includes intubation, extubation, bronchoscopy, nebulizer therapy, spirometry, sputum induction and rhinoscopy—all considered high-risk exposure.

Providers who wear a gown, gloves, eye protection and a face mask (instead of a respirator) during an aerosol-generating procedure are considered to have a medium-risk exposure. Additional resources regarding correct use of PPE can be found here.

HOW TO MANAGE PATIENTS WITH ASTHMA AND OTHER ALLERGIC AND IMMUNOLOGICAL DISEASES
There are no strong data at present regarding the management of asthma in association with COVD-19 co-infection. If an asthma or COPD exacerbation is likely, then typical treatment measures, such as use of corticosteroids, should be entertained. However, the routine use of corticosteroids in patients with mild to moderate COVID-19 without obstructive lung disease is not advised, since this may prolong viral replication. Dexamethasone has been found to reduce mortality in those with more severe disease who are receiving oxygen or ventilation therapy.

As always, patients with asthma should be well controlled and should not stop any of their medications. This also applies to the use of biologic therapies for asthma and associated diseases when used to maintain good asthma control. Many of these therapies are now available as self-injectable syringes and changing office-based injectables to home administration via self-administered syringe, will allow patients to stay at home and will further limit their exposure to potential viral transmission.

The CDC states that patients with moderate to severe asthma might be at increased risk for severe illness from COVID-19. Additional information for your patients on COVID-19 and asthma can be found here.

Patients with primary immunodeficiencies or who are taking immunosuppressant medication are likely at higher risk from infection, and consideration should also be given to rescheduling well patient visits and having them remain at home in self-isolation as much as possible.

A recent special article on Pandemic Contingency Planning for the Allergy and Immunology Clinic put forward by the AAAAI, in collaboration with the American College of Allergy, Asthma & Immunology (ACAAI) and the Canadian Society of Allergy and Clinical Immunology (CSACI), can be found here.

More specifically, information concerning the Administration of Subcutaneous Allergen Immunotherapy during the COVID-19 Outbreak can be found here.

Additional CDC clinical management guidelines for patients with COVID-19 may be found here.

Information for those patients at serious risk of disease, especially older adults and patients with comorbid disease, can be found here.

ARE THERE ANY SPECIFIC TREATMENTS FOR COVID-19?
Other than supportive care and the use of remdesivir, there have been no approved treatments for COVID-19 despite a flurry of coverage over false medical claims in the lay press and on social media. For example, most guidelines now recommend against the use of hydroxychloroquine, hydroxychloroquine plus azithromycin or ivermectin - therapies originally touted as beneficial. The Food and Drug Administration (FDA) has approved remdesivir (a direct acting antiviral drug that inhibits viral RNA synthesis), for the treatment of severe COVID-19. Convalescent plasma was approved early under an Emergency Use Authorization (EUA), but is now recommended only in the context of a clinical trial.

Additional recent EUA approvals include: bamlanivimab together with etesevimab, which are neutralizing monoclonal antibodies that bind to the receptor binding domain of the spike protein of SARS-CoV-2 and are used for post-exposure prophylaxis; and casirivimab and imdevimab, which are recombinant human IgG1 monoclonal antibodies that target the receptor binding domain of the spike protein of SARS-CoV-2 for select outpatients with COVID-19 that are at a high risk for severe disease and progression. Sotrovimab, another monoclonal antibody therapy, has been granted an EUA for mild to moderate COVID and with bebtelovimab has shown efficacy against the Omicron variant. Il-6 inhibitors tocilizumab and sarilumab have been used in select hospitalized patients. Baricitinib, a Janus kinase (JAK) inhibitor is also authorized for use with concomitant remdesivir in select hospital patients. The FDA has recently granted EUAs for the oral medications molnupiravir and paxlovid, which significantly reduce the risk of hospitalization and death in people with mild or moderate COVID-19 who are at high risk for severe COVID-19. Paxlovid is now an officially approved treatment. Evusheld (a combination of tixagevimab and cilgavimab) has an EUA for pre-exposure prophylaxis of COVID in certain high risk populations (eg, highly immunosuppressed or those unable to take COVID-19 vaccines).

The Infectious Diseases Society of America has issued recommendations regarding the treatment and management of patients with COVID-19, including the use of dexamethasone (for hospitalized patients with severe and/or critical disease) and remdesivir. Of note, many other therapeutic recommendations are currently only in the context of an ongoing clinical trial. The Journal of the American Medical Association has a page dedicated to updates in the diagnosis and treatment of COVID-19. Updated treatment guidelines from the National Institutes of Health (NIH) are also available.

COVID-19 VACCINES
Two vaccines (Comirnaty and Spikevax) have full FDA approval (in those 12 and older and 18 and older, respectively) and other candidates are seeking FDA authorization after completing large Phase 3 studies. These include mRNA vaccines, protein subunit vaccines, and viral vector vaccines. Issues related to optimal vaccination include storage requirements (for some, temperature storage requirements of -70 degrees C), optimal timing of two or three-dose regimens, mixing of vaccines, vaccine deployment logistics, and the vaccination of different demographic groups such as young children. Anti-vaccine sentiment is also an important roadblock in reducing the health impact of COVID-19.

The first of these to receive full FDA approval is an mRNA vaccine by Pfizer-BioNTech (Comirnaty) which was granted EUA status on December 11, 2020, for patients 16 years and older based on interim analysis of Phase 3 data and full approval in this population on August 23, 2021. It is now fully approved for those 12 years of age and older. The vaccine is also authorized under an EUA status for those 6 months to 11 years of age. Studies in adults have shown a greater than 90% efficacy in a diverse population of more than 40,000 participants (active and placebo) receiving two injections, 21 days apart. This is a lipid nanoparticle-formulated, modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2. Vaccination should be offered to persons regardless of history of prior symptomatic or asymptomatic SARS-CoV-2 infection. Additional study information including vaccine composition (ingredients) and storage information can be found in the FDA Briefing Document and the package insert.

The FDA also issued a formal approval on January 31, 2022, for a comparable mRNA vaccine by Moderna (Spikevax). This is indicated for active immunization for the prevention of COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older, with a dosing regimen of two doses, 100 μg each, administered one month apart. Moderna’s vaccine Phase 3 trial indicates 94.5% efficacy. The vaccine can be safely stored at -20 degrees Celsius (as opposed to Pfizer-BioNTech that requires storage at -70 degrees Celsius) and likely up to 30 days at standard refrigerator temperatures. The FDA briefing document is available for review here and the package insert here. The Moderna vaccine also now has EUA approval for those 6 months to 17 years of age.

The most common reported adverse events to these vaccines included injection site pain, fatigue, headache, muscle pain, joint pain, chills and fever.

Rare but severe allergies to these products are not only possible, but as with any vaccine, are to be expected. Possible cases of anaphylaxis have already been reported with the Pfizer-BioNTech vaccine. The CDC has put in place safety recommendations for those with allergies receiving Pfizer-BioNTech COVID-19 vaccination, which are true of the Moderna vaccine as well. These include:

•    Individuals with a history of food, pet, insect, venom, environmental or latex allergies are able to proceed with vaccination with a standard 15-minute observation period.
•    Those with a history of severe allergic reaction (e.g. anaphylaxis) to an injectable medication should use caution when receiving the vaccine and follow a 30-minute observation period if vaccinated with the Pfizer-BioNTech COVID-19 vaccine.
•    Those with a history of severe allergic reaction to any component of the Pfizer-BioNTech COVID-19 vaccine should not be vaccinated with the Pfizer-BioNTech COVID-19 vaccine.

The Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG), in line with recent CDC advisories, recommend that vaccination be given to all pregnant or lactating women. Contact MotherToBaby, a research partner of the AAAAI, for more information on the vaccine in pregnant and lactating women at mothertobaby.org.

Another vaccine receiving an EUA from the FDA in people aged 18 years and over, on February 27, 2021, is an adenoviral vector vaccine from Janssen (Johnson & Johnson). This vaccine uses a non-replicating viral vector to introduce DNA into cells to manufacture the COVID “spike protein” and lead to protective antibody production. Studies in roughly 40,000 participants have shown an efficacy of 66% in the prevention of moderate to severe/critical COVID-19, and 85% in the prevention of severe/critical COVID-19 at least 28 days after vaccination. This is a single-dose vaccine and requires only routine refrigeration for storage. Common side effects of the vaccine include injection site reactions and general side effects including headache, fatigue, muscle aches, nausea, and fever.

In mid-April, use of this vaccine was put on “pause” by the FDA and CDC because of six initial reports of a rare and severe type of blood clot combined with low blood platelet levels occurring in people after receiving this vaccine (known as thrombosis-thrombocytopenia syndrome, or TTS). Vaccine administration has now resumed, with the fact sheet having been revised to alert healthcare providers of the very rare chance of this syndrome post-vaccination. All other COVID-19 vaccines are now recommended over the Johnson & Johnson vaccine.

The newest vaccine to obtain an EUA from the FDA for those 12 years of age and older is the Novavax vaccine. This is a protein subunit, adjuvanted vaccine given in two doses, 3-8 weeks apart.

Updated mRNA vaccines were previously available as bivalent boosters, approved by the FDA for all patients 6 months and older for greater protection against the Omicron variants known as BA.4 and BA.5  - given 2 months after primary or booster doses of the original vaccines. Newer 2023-2034 formulations of the mRNA vaccines are now available, and are recommended as one dose in all patients 5 years and older, regardless of previous vaccination status. Children 6 months-4 years and those who are moderately to severely immunocompromised have their own dosing schedules.

Note that the Johnson & Johnson vaccine is not given as a booster. The Novavax vaccine can be given as a booster in those 18 years and older in certain circumstances.

Additional questions related to these, and forthcoming COVID-19 vaccines include the length or durability of immunity, whether vaccinated individuals can still transmit the virus, and how effective they may be against different variants of the COVID-19 virus. Very likely all approved vaccines induce a robust protective response to many different COVID-19 variants, and significantly limit viral transmission and carriage, as evidenced by a notable decline in COVID-19 infectivity and morbidity in regions with high vaccination rates.

ADDITIONAL MEASURES
Self-isolation, up to and including mandatory quarantine, has been recommended to limit the spread of the disease and is indicated for anyone who has tested positive for COVID-19, and for those with presumptive infection (cough, fever, fatigue) with mild symptoms. For patients and staff who have been exposed to COVID-19, or to those travelling and returning from a high-risk country or state, the recommendations are evolving, and the CDC has now proposed that in most circumstances, asymptomatic HCP with higher-risk exposures do not require work restriction in the context of a testing strategy. More precise information may be found at the federal, state and local levels.

There are updated guidelines in place for when infected persons can safely return to work. A symptom-based strategy for those on home isolation includes the following: at least one day has passed since recovery (resolution of fever without the use of fever-reducing medications and improvement in respiratory symptoms) in addition to 7 days having passed since symptoms first appeared. In patients with severe to critical illness or who are severely immunocompromised the recommendations recommend remaining isolated up to 20 days since the first appearance of symptoms.

A test-based strategy includes resolution of symptoms as above, in addition to negative results from at least two consecutive nasopharyngeal swabs collected ≥ 48 hours apart.

Healthcare personnel with laboratory-confirmed COVID-19 who have not had any symptoms should be excluded from work per evolving guidelines. This may include no restrictions in asymptomatic boosted healthcare personnel under both contingency and crisis situations. This evolution in guidelines has become necessary in the face of likely staff shortages due to the more widely spread Omicron variant of the disease.

More information may be found here.

COMMON SENSE MEASURES FOR EVERYONE
Measures to reduce risk of infection and transmission of COVID-19 include:
1.    Washing hands and using a sanitizing hand wash containing at least 60% alcohol.
2.    Refraining from touching your face.
3.    Avoiding close contact, such as staying six feet away from other people or self-isolating, especially if in a high-risk group.
4.    Staying home if you’re sick or staying at home in general and avoiding large crowds and indoor spaces. Pay attention to state and local directives.
5.    Covering your mouth and nose when coughing with your elbow or a tissue. Dispose of your tissue immediately afterward.
6.    Wearing a face mask if you’re sick. The CDC now recommends wearing cloth face coverings in public settings where other physical distancing measures are difficult to maintain (e.g., grocery stores and pharmacies), especially in areas of significant community-based transmission, reserving surgical and N95 masks for healthcare providers. These recommendations may now be required in certain jurisdictions.
7.    Cleaning and disinfecting surfaces regularly.
8.    Fully vaccinated people can resume activities without wearing a mask or physical distancing, except where required by federal or local laws, including local business and workplace guidance. For example, masks are generally required in all healthcare settings despite vaccination.

Additional resources

AAAAI’s Resources for A/I Clinicians during the COVID-19 Pandemic
https://education.aaaai.org/resources-for-a-i-clinicians/expert_covid-19

A Physician’s Guide to COVID-19
https://www.ama-assn.org/delivering-care/public-health/physicians-guide-covid-19

CDC COVID-19 Hub
https://www.cdc.gov/coronavirus/2019-ncov/index.html

FDA COVD-19 Website
https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/coronavirus-disease-2019-covid-19

WHO Coronavirus Information and Guidance
https://www.who.int/emergencies/diseases/novel-coronavirus-2019