“Abstract: Associations between vaccine breakthrough cases and infection by SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analyzed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from February 1 to June 30, 2021, of which 125 (9.1%) were vaccine breakthrough infections. Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations associated with decreased antibody neutralization (L452R, L452Q, E484K, and/or F490S) (78% versus 48%, p = 1.96e-08), but not by those associated with increased infectivity (L452R and/or N501Y) (85% versus 77%, p = 0.092). Differences in viral loads were non-significant between unvaccinated and fully vaccinated persons overall (p = 0.99) and according to lineage (p = 0.09 – 0.78)… In 5 cases with available longitudinal samples for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to immunocompromised state or infection by an antibody-resistant lineage. These findings suggest that vaccine breakthrough cases are preferentially caused by circulating antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infections, regardless of the infecting lineage…
Discussion: … [W]e found that vaccine breakthrough infections are more likely to be caused by immunity-evading variants as compared to unvaccinated infections. Phylogenetic analyses revealed that the viruses in vaccine breakthrough and unvaccinated cases had similar genomes with assignment to subclades representing all major variants circulating in the community. The overrepresentation of infection from immunity-evading variants in vaccinated cases thus most likely arises from differential effectiveness of neutralizing antibodies against multiple circulating lineages. Notably, a decreased proportion of vaccine breakthrough infections from the Alpha variant was observed, despite its documented higher infectivity relative to all VOCs except Delta and Gamma10,30. Decreased Alpha infections are consistent with the higher effectiveness of available SARS-CoV-2 vaccines against Alpha relative to other VOCs2,11,13,21."
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