BACKGROUND: Data describing the effectiveness of COVID-19 vaccines during the 2023-2024 fall and winter viral respiratory season are lacking. We estimated BNT162b2 XBB.1.5 vaccine effectiveness (VE) against COVID-19-associated hospital admission and emergency department (ED) visits in two heterogenous U.S. States. METHODS: We conducted a retrospective cohort study among immunocompetent non-pregnant adults ≥18 years of age between September 25, 2023, and March 31, 2024 who were residents of California or Louisiana and enrolled in health insurance plans reporting to HealthVerity. Receipt of BNT162b2 XBB.1.5 vaccine was determined using State vaccine registry data (in addition to health insurance claims) and measured as a time-varying exposure. VE against COVID-19-associated hospital admission and ED visits was measured as 1- adjusted hazard ratio from Cox proportional hazards models. Models were adjusted for age, sex, State, insurance payor, presence of any condition(s) indicating CDC-defined high risk for severe COVID-19, wellness visit, influenza vaccination, outpatient visits, emergency department visits, and whether they had medically attended COVID-19 in the 91 to 365 days prior to index. RESULTS: Overall, 6,344,448 individuals met selection criteria. Median age was 40 years and 54% were female. By the end of follow-up (median 6.3 months), 254,068 (4%) had received a BNT162b2 XBB.1.5 vaccine
2346 (of whom 68 received BNT162b2 XBB.1.5 vaccine and 2278 did not) and 9327 (of whom 135 received BNT162b2 XBB.1.5 vaccine and 9192 did not) experienced a COVID-19-associated hospital admission and ED visit, respectively. VE was 36% (95% confidence interval [CI]: 18-50%) and 45% (95% CI: 34-54%) against COVID-19-associated hospital admission and ED visits, respectively. Prior formulations offered no significant residual protection. DISCUSSION: BNT162b2 XBB.1.5 vaccine provided significant additional protection for immunocompetent adults against COVID-19-associated hospital admission and emergency department visits during the 2023-2024 fall and winter respiratory virus season. This study is registered on clinicaltrials.gov as NCT06199934.