SARS-CoV-2 Omicron subvariant genomic variation associations with immune evasion in Northern California: A retrospective cohort study.

Background: The possibility of association between SARS-CoV-2 genomic variation and immune evasion is not known among persons with Omicron variant SARS-CoV-2 infection. Methods: In a retrospective cohort, using Poisson regression adjusting for sociodemographic variables and month of infection, we examined associations between individual non-lineage defining mutations and SARS-CoV-2 immunity status, defined as a) no prior recorded infection, b) not vaccinated but with at least one prior recorded infection, c) complete primary series vaccination, and/or d) primary series vaccination and ≥ 1 booster. We identified all non-synonymous single nucleotide polymorphisms (SNPs), insertions and deletions in SARS-CoV-2 genomes with ≥5% allelic frequency and population frequency of ≥5% and ≤95%. We also examined correlations between the presence of SNPs with each other, with subvariants, and over time. Results: Seventy-nine mutations met inclusion criteria. Among 15,566 persons infected with Omicron SARS-CoV-2, 1,825 (12%) were unvaccinated with no prior recorded infection, 360 (2%) were unvaccinated with a recorded prior infection, 13,381 (86%) had a complete primary series vaccination, and 9,172 (58%) had at least one booster. After examining correlation between SNPs, 79 individual non-lineage defining mutations were organized into 38 groups. After correction for multiple testing, no individual SNPs or SNP groups were significantly associated with immunity status levels. Conclusions: Genomic variation identified within SARS-CoV-2 Omicron specimens was not significantly associated with immunity status, suggesting that contribution of non-lineage defining SNPs to immune evasion is minimal. Larger-scale surveillance of SARS-CoV-2 genomes linked with clinical data can help provide information to inform future vaccine development.