Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City

• Published in: The Journal of clinical investigation Vol. 131; no. 18; pp. 1 - 9
• Main Authors: Duerr, Ralf, Dimartino, Dacia, Marier, Christian, Zappile, Paul, Wang, Guiqing, Lighter, Jennifer, Elbel, Brian, Troxel, Andrea B, Heguy, Adriana
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15.09.2021
• Subjects: 2019-nCoV Vaccine mRNA-1273; Ad26COVS1; Adult; Aged; Aged, 80 and over; Biomedical research; BNT162 Vaccine; Coronaviruses; COVID-19; COVID-19 - genetics; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - adverse effects; COVID-19 Vaccines - immunology; Epidemics; Evolution, Molecular; Female; Genomic analysis; Humans; Immune Evasion - genetics; Immunization; Male; Middle Aged; mRNA; Mutation; New York; New York City; Phylogeny; Protein Domains; Risk factors; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Statistical analysis; Statistics; United States; Vaccine efficacy; Vaccines; New York City; New York; United States; United States > US; New York City New York; COVID-19; Molecular biology; Epidemiology
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/jci152702

The efficacy of COVID-19 mRNA vaccines is high, but breakthrough infections still occur. We compared the SARS-CoV-2 genomes of 76 breakthrough cases after full vaccination with BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Janssen) to unvaccinated controls (February-April 2021) in metropolitan New York, including their phylogenetic relationship, distribution of variants, and full spike mutation profiles. The median age of patients in the study was 48 years; 7 required hospitalization and 1 died. Most breakthrough infections (57/76) occurred with B.1.1.7 (Alpha) or B.1.526 (Iota). Among the 7 hospitalized cases, 4 were infected with B.1.1.7, including 1 death. Both unmatched and matched statistical analyses considering age, sex, vaccine type, and study month as covariates supported the null hypothesis of equal variant distributions between vaccinated and unvaccinated in χ2 and McNemar tests (P > 0.1), highlighting a high vaccine efficacy against B.1.1.7 and B.1.526. There was no clear association among breakthroughs between type of vaccine received and variant. In the vaccinated group, spike mutations in the N-terminal domain and receptor-binding domain that have been associated with immune evasion were overrepresented. The evolving dynamic of SARS-CoV-2 variants requires broad genomic analyses of breakthrough infections to provide real-life information on immune escape mediated by circulating variants and their spike mutations.