SARS-CoV-2 Variants: implications for A post-covid society

MARCH 9, 2021 PRIYA NORI, MD MONTEFIORE HEALTH SYSTEM ALBERT EINSTEIN COLLEGE OF MEDICINE

SARS-COV-2 VARIANTS: IMPLICATIONS FOR A POST-COVID SOCIETY

GLOBAL TRACKING OF VARIANTS • B.117 (9/2020, UK) detected in >90 countries and >46 states in the US • 35% more deadly • Doubling every 10 days in U.S. • CDC predicts that B.1.17 could predominate in the US by spring

• B.1.351 (12/2020, South Africa) • Less protection vs. vaccines & reinfection • At least 48 countries, including the U.S • P.1 (11/2020, Brazil) • Detected in at least 4 countries and 7 states

https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html Galloway SE, Paul P, MacCannell DR, et al. Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021. MMWR Morb Mortal Wkly Rep 2021;70:95–99. DOI: http://dx.doi.org/10.15585/mmwr.mm7003e2external icon.

ESTABLISHED MUTATIONS OF CONCERN

https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html

VARIANTS TO WATCH

https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html

KEY POINTS ABOUT VARIANTS • Mutations found in B.1.1.7, B.1.351, P.1, B.1.526 lineages have a “selective advantage” • Share concerning mutations in spike protein receptor binding domain, N-terminal domain, and furin cleavage site, which increase ACE-2 receptor binding affinity and evade antibody responses • Considered more infectious/transmissible, with higher viral loads among infected individuals • B.117 may be up to 35% more deadly • B. 1.351 & P.1 may evade immunity from past infection (e.g. reinfection) • B.1.526 may account for 30% or more of circulating virus in NYC • Older, more frequently hospitalized

https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html

SARS-COV-2 THERAPEUTICS

https://www.pbs.org/newshour/health/6-covid-19-treatments-helping-patients-survive

Pfizer/BioNTech & Moderna

COVID-19 VACCINES

J&J

IMPLICATIONS FOR VACCINES • Extending interval between first and second vaccine doses could be riskier1 • mRNA vaccines induce a broad neutralizing antibody response against entire spike protein as well as virus-specific T & B-cell responses2 • Vaccines that induce lower levels of neutralizing antibodies (viral vector vaccines or protein subunit vaccines) may be less effective against mild to moderate illness • Efficacy of AZ vaccine dropped to 10% against mild-moderate illness from the B.1.351 • Efficacy of Novavax reduced from 89% to 60% against B.1.351 • Likely still >85% protective against severe illness • Expect need for booster shots to cover B.1.351 and other variants; FDA states large clinical trials not required • mRNA vaccine booster development already in early stages3 1. Moore JP, Offit PA. SARS-CoV-2 Vaccines and the Growing Threat of Viral Variants. JAMA. 2021;325(9):821–822. doi:10.1001/jama.2021.1114 2. Lauring AS, Hodcroft EB. Genetic Variants of SARS-CoV-2—What Do They Mean? JAMA. 2021;325(6):529–531.

• Manaus, Brazil - an estimated two-thirds of residents were infected by October 2020 (thought to be approaching herd immunity) • January 2021, rising cases and hospitalizations were linked to new variant identified as P.1 with 17 mutations, including spike protein changes linked to increased transmission and immune evasion

VARIANTS, REINFECTION & POST-VACCINE INFECTION

• Infections post vaccination – contribution from variants remains to be seen • Must be a focus of public health surveillance by CDC • FDA must lead effort quickly adapt vaccines to widely circulating variants

Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees Alison Tarke, John Sidney, Nils Methot, Yun Zhang, et al. bioRxiv 2021.02.27.433180; doi: https://doi.org/10.1101/2021.02.27.433180

• Variants can evade antibody therapies and antibodies generated in response to vaccines • Scientists at the La Jolla Institute for Immunology tested T cells from volunteers who had recovered from infection or received an mRNA vaccine against 4 emerging variants (B.1.1.7, B.1.351, P.1, and CAL.20C) • Volunteers’ CD4+ and CD8+ T cells were not impacted by mutations found in variants

A. Tarke et al. Preprint at bioRxiv https://doi.org/gh6tkp; 2021.

INTERVENTIONS THAT RESIST VARIANTS • Non-pharmacologic interventions remain highly effective!

• • • • • • •

Well-fitting masks with multiple layers Hand hygiene Social distancing of 6-feet Limitations on large gatherings Physical barriers in schools and other public spaces Outdoor air circulation HEPA filtration systems

• Testing!

• Must be frequent and widely available at multiple access points (home, schools, airports, restaurants, sporting events, entertainment venues) • Antigen and PCR tests must detect variants

Moore JP, Offit PA. SARS-CoV-2 Vaccines and the Growing Threat of Viral Variants. JAMA. 2021;325(9):821–822.

WHAT IS THE U.S. DOING ABOUT VARIANTS • SARS-CoV-2 interagency group (HHS, CDC, NIH, FDA, BARDA, USDA, DoD) • Rapid characterization of variants by genomic sequencing • Active monitoring of impact of variants on diagnostics, therapeutics, and vaccines • NIH-funded studies of in vitro neutralization assays of convalescent and post-vaccination sera and antibody therapies

• CDC partnership with state health departments and academic medical centers to conduct strain surveillance of 750 specimens/week • Partnership with private laboratories to increase capacity to 6000 specimens/week • Focus on “breakthrough” infections post-vaccination

Walensky RP, Walke HT, Fauci AS. SARS-CoV-2 Variants of Concern in the United States—Challenges and Opportunities. JAMA. Published online February 17, 2021. doi:10.1001/jama.2021.2294

https://www.nature.com/articles/d41586-021-00396-2#:~:text=A%20Nature%20survey%20shows %20many,pose%20less%20danger%20over%20time.

REFERENCES • https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html •https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html • https://www.pbs.org/newshour/health/6-covid-19-treatments-helping-patients-survive • Moore JP, Offit PA. SARS-CoV-2 Vaccines and the Growing Threat of Viral Variants. JAMA. 2021;325(9):821–822. doi:10.1001/jama.2021.1114 • Lauring AS, Hodcroft EB. Genetic Variants of SARS-CoV-2—What Do They Mean? JAMA. 2021;325(6):529–531. doi:10.1001/jama.2020.27124 • https://www.scientificamerican.com/article/booster-shots-against-scary-covid-virus-variants-are-in-the-works1/ • Negligible impact of SARS-CoV-2 variants on CD4 + and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees • Alison Tarke, John Sidney, Nils Methot, Yun Zhang, et al. bioRxiv 2021.02.27.433180; doi: https://doi.org/10.1101/2021.02.27.433180 • A. Tarke et al. Preprint at bioRxiv https://doi.org/gh6tkp; 2021 • Walensky RP, Walke HT, Fauci AS. SARS-CoV-2 Variants of Concern in the United States—Challenges and Opportunities. JAMA. Published online February 17, 2021. doi:10.1001/jama.2021.2294 • https://www.nature.com/articles/d41586-021-00396-2#:~:text=A%20Nature%20survey%20shows%20many,pose%20less%20danger%20over%20time