Several SARS-CoV-2 virus variants are causing concern in the US and globally right now. These include:
- Omicron (B.1.1.529). There is limited information at this point, but it appears the rate of infection is three times higher than with Delta, so people with previous infection are not as safe from reinfection. Omicron has been confirmed in 30 states but probably is present in all 50 by now. This article explains the enhanced surveillance currently undertaken to track it. (MMWR, Dec 2021)
- Delta (B.1.617.2). This variant is now the most common COVID-19 variant in the U.S. and spreads more easily than other variants.
- Alpha. (B.1.1.7). This variant also appears to spread more easily, and might have an increased risk of hospitalization and death.
- Gamma (P.1)
- Beta (B.1.351)
- Lambda (C.37) is considered a variant of interest by WHO
- MU (B.1.621) is considered a variant of interest by WHO
- Delta plus (AY.4.2) - This mutant strain is only 10-15% more transmissible than the original and appears to be susceptible to the current vaccines. This mutation is present in the United States, but makes up <0.5% of variants.
- See the CDC's list of SARS-CoV-2 Variant Classifications and Definitions and the Variant Proportions Tracker for more detailed information on the variants currently in circulation.
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.
Vaccines and Virus Variants
- In this study from Israel involving over 1,400,000 patients, those who received a third mRNA vaccine dose 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. Findings suggest a third dose is effective in protecting against severe disease and death. (Lancet, Oct 29, 2021)
- This study examined the vaccine effectiveness against infection, hospitalization and death before and during the period of Delta predominance. 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. (MMWR, Sept 17, 2021)
- Similar results of vaccine effectiveness were found in studies that included data from a 9 state cohort (MMWR, Sept 17, 2021), several large health systems (NEJM, Sept 8, 2021), and five VA medical centers (MMWR, Sept 17, 2021).
- 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. (NEJM, July 21, 2021)
- 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. (NEJM, July 7, 2021)
- 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. (Nature, July 2021)
- In a press release from May 6, 2021, 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 Beta variant (mRNA-1273.351) and the 50 mcg booster of the original vaccine (mRNA-1273) increased neutralizing titer responses against Beta and Gamma, with the strain-matched booster showing better effect. Safety and tolerability were similar to the second dose of mRNA-1273.
- In a small study on viral neutralization in patients receiving the Pfizer vaccine, these authors found that neutralization following vaccination was equivalent against the new strains, including the new California and New York strains, as well as the recently identified Alpha variant. (NEJM, May 12, 2021)
- 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 an mRNA vaccine produced neutralizing activity against the D614G variant in 50% of naïve recipients and against the Beta variant in 16%. This improved to 100% against the D614G variant and 96% against the Beta variant after the second dose. These results are encouraging and would argue against delaying the second dose in infection-naïve individuals. (Nat Med; April 2021)
- Serum samples from 20 participants in the Pfizer trial showed a reduction of 2/3 in neutralizing activity against the Beta variant compared to the early strains and those from the UK and Brazil. (N Engl J Med, February 17, 2021)
- Samples from participants in the Moderna trial showed a 6.4-fold reduction in neutralizing activity against the Beta variant. (N Engl J Med, February 17, 2021)
- Another good viewpoint written by the head of the CDC and NIAID reviews the 3 variants of concern (Alpha, Beta and Gamma), 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. (JAMA Online First, February 17, 2021)
- 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 the mutations present in the variants). (Nature Medicine, February 8 ,2021)
- SARS-CoV2 viral variants: capturing a moving target (JAMA, February 11 ,2021)
- SARS-CoV2 vaccines and the growing threat of viral variants (JAMA, January 28 ,2021)—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.
- This pre-print article shows 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. (bioRxiv, January 27 ,2021)