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Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City
Ralf Duerr, … , Andrea B. Troxel, Adriana Heguy
Ralf Duerr, … , Andrea B. Troxel, Adriana Heguy
Published August 10, 2021
Citation Information: J Clin Invest. 2021;131(18):e152702. https://doi.org/10.1172/JCI152702.
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Research Article

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

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Abstract

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.

Authors

Ralf Duerr, Dacia Dimartino, Christian Marier, Paul Zappile, Guiqing Wang, Jennifer Lighter, Brian Elbel, Andrea B. Troxel, Adriana Heguy

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Figure 2

Maximum likelihood tree of SARS-CoV-2 vaccine breakthrough, unvaccinated matched control, and global reference sequences.

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Maximum likelihood tree of SARS-CoV-2 vaccine breakthrough, unvaccinated...
IQ tree of 4923 SARS-CoV-2 full-genome sequences (base pairs 202–29,657 according to Wuhan-Hu-1 as reference), including 76 vaccine breakthrough (orange) and 1046 unvaccinated control SARS-CoV-2 sequences from our NYU cohort (greater NYC area) (purple) together with 1361 other US (cyan) and 2440 non-US global reference sequences (black). The tree was generated with a GTR+I+G substitution model and 1000 bootstrap replicates. The substitution scale of the tree is indicated at the bottom right. The branches of the tree are colored as indicated. Vaccine breakthrough sequences are highlighted by orange triangles as branch symbols and gray rays radiating from the root to the outer rim of the tree. Hospitalizations due to COVID-19 among the vaccine breakthrough infections are indicated by black triangles (h). The variants responsible for most vaccine breakthrough infections in our study cohort are labeled with respective Pango lineages (WHO classification in parenthesis).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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