Abstract
BACKGROUND: The purpose of this study was to evaluate whether a bivalent coronavirus disease 2019 (COVID-19) vaccine protects against COVID-19. METHODS: The study included employees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available. Cumulative incidence of COVID-19 over the following 26 weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred and the number of prior vaccine doses. RESULTS: Among 51 017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent-vaccinated state was associated with lower risk of COVID-19 during the BA.4/5-dominant (hazard ratio, 0.71 [95% confidence interval, .63-79]) and the BQ-dominant (0.80 [.69-.94]) phases, but decreased risk was not found during the XBB-dominant phase (0.96 [.82-.1.12]). The estimated vaccine effectiveness was 29% (95% confidence interval, 21%-37%), 20% (6%-31%), and 4% (-12% to 18%), during the BA.4/5-, BQ-, and XBB-dominant phases, respectively. The risk of COVID-19 also increased with time since the most recent prior COVID-19 episode and with the number of vaccine doses previously received. CONCLUSIONS: The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.