Impacts of vaccination on the variant selection of SARS-CoV-2 and the subsequent case hospitalization rate: insights from the first U.S. Omicron wave

BackgroundCOVID-19 vaccines, while providing protection against hospitalization, could inadvertently increase selection pressure on new immune-escape variants, impacting case hospitalization rate (CHR). MethodsUsing epidemiological and genomic sequence data, we calculated daily state-level CHR and the proportion of Omicron mutations in the United States during the first Omicron wave (between December 11, 2021, and March 22, 2022). We derived mathematical formulas to link evolution responses to an increasing population immunity with lagged regression models. Using mediation analysis, together with generalized linear mixed models and distributed lag nonlinear models, we assessed how natural selection, shaped by vaccine coverage, impacts CHR. ResultsThe model showed that increasing vaccination coverage from 45% to 70% contributed to a reduction in CHR from 5.8% to 4.4%. Part of the reduction resulted from direct vaccine protection (OR: 0.85, p-value=0.012). However, the higher vaccination coverage was correlated with a 20% increase in the proportion of BA.1/BA.1.1-associated mutations. As the Omicron variants were less severe than their predecessors (Delta), CHR further reduced (OR: 0.87, p-value<0.001). Marginally, this could reduce CHR from 5.8% to 5.1% via the adaptation of Omicron variants as marginal effect without accounting for direct vaccine protection. ConclusionsThe study offers new insight into vaccine strategies for reducing hospitalization risk by shortening [or maintaining] the circulation of more [or less] virulent variants among infectious diseases. Continuous monitoring of variant evolution, including their virulence, is critical.