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Severe Acute Respiratory Syndrome Coronavirus 2 Delta Variant Genomic Variation Associated With Breakthrough Infection in Northern California: A Retrospective Cohort Study.


ABSTRACT:

Background

The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic variation and breakthrough infection is not well defined among persons with Delta variant SARS-CoV-2 infection.

Methods

In a retrospective cohort, we assessed whether individual nonlineage defining mutations and overall genomic variation (including low-frequency alleles) were associated with breakthrough infection, defined as SARS-CoV-2 infection after coronavirus disease 2019 primary vaccine series. We identified all nonsynonymous single-nucleotide polymorphisms, insertions, and deletions in SARS-CoV-2 genomes with ≥5% allelic frequency and population frequency of ≥5% and ≤95%. Using Poisson regression, we assessed the association with breakthrough infection for each individual mutation and a viral genomic risk score.

Results

Thirty-six mutations met our inclusion criteria. Among 12 744 persons infected with Delta variant SARS-CoV-2, 5949 (47%) were vaccinated and 6795 (53%) were unvaccinated. Viruses with a viral genomic risk score in the highest quintile were 9% more likely to be associated with breakthrough infection than viruses in the lowest quintile, but including the risk score improved overall predictive model performance (measured by C statistic) by only +0.0006.

Conclusions

Genomic variation within SARS-CoV-2 Delta variant was weakly associated with breakthrough infection, but several potential nonlineage defining mutations were identified that might contribute to immune evasion by SARS-CoV-2.

SUBMITTER: Skarbinski J 

PROVIDER: S-EPMC11009495 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Severe Acute Respiratory Syndrome Coronavirus 2 Delta Variant Genomic Variation Associated With Breakthrough Infection in Northern California: A Retrospective Cohort Study.

Skarbinski Jacek J   Nugent Joshua R JR   Wood Mariah S MS   Liu Liyan L   Bullick Teal T   Schapiro Jeffrey M JM   Arunleung Phacharee P   Morales Christina C   Amsden Laura B LB   Hsiao Crystal A CA   Wadford Debra A DA   Chai Shua J SJ   Reingold Arthur A   Wyman Stacia K SK  

The Journal of infectious diseases 20231001 7


<h4>Background</h4>The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic variation and breakthrough infection is not well defined among persons with Delta variant SARS-CoV-2 infection.<h4>Methods</h4>In a retrospective cohort, we assessed whether individual nonlineage defining mutations and overall genomic variation (including low-frequency alleles) were associated with breakthrough infection, defined as SARS-CoV-2 infection after coronavirus disease 2019 p  ...[more]

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