Abstract Background The continued evolution of SARS-CoV-2 has led to annual reformulations of COVID-19 vaccines to maintain protection against emerging variants. Updates to Moderna’s mRNA-1273 vaccine (Spikevax) have included a bivalent (Wuhan-Hu-1 + Omicron BA.4/5) formulation in 2022, a monovalent XBB.1.5 formulation in 2023, and a monovalent KP.2 formulation in 2024. Evaluating real-world vaccine effectiveness (VE) of COVID-19 vaccines across these seasons, interpreted as incremental effectiveness against a background of immunity from prior vaccination and infection, is critical to understanding their public health impact and guiding ongoing vaccination strategies.Vaccine effectiveness of Spikevax (mRNA-1273) against COVID-19-associated hospitalization and medically attended COVID-19, 2022–2025. Methods We share findings from five retrospective matched cohort studies with similar methodology in U.S. electronic health record and administrative claims databases that focused on the VE of mRNA-1273 specifically. Each study compared adults vaccinated with mRNA-1273 to controls had not received a COVID-19 vaccine during the same respiratory virus season. Exact match, and multivariable adjustment or propensity score weighting were used to account for measured confounding. Potential confounders with absolute standardized difference 0.1 were included in the adjusted models. VE was estimated as 1 minus the adjusted hazard ratio from Cox proportional hazards models, with outcomes including COVID-19-associated hospitalization and medically attended COVID-19. Results Across seasons and formulations, VE in adults aged ≥18 years ranged from 51% to 70% against COVID-19-associated hospitalization and from 24% to 39% against medically attended COVID-19 (See Figure). VE estimates were similar for adults aged ≥18 years, aged ≥65 years, and aged ≥18 years at high risk of severe outcomes. Conclusion The effectiveness of Moderna's updated mRNA-1273 vaccine formulations against severe COVID-19 outcomes remained stable across the most recent three respiratory virus seasons in the United States. These findings support the role of annual COVID-19 vaccination in reducing hospitalization and healthcare burden. Disclosures Amanda Wilson, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Chris Clarke, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Keya Joshi, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Gigi Zheng, MD, PhD, ModernaTX: Employee|ModernaTX: Stocks/Bonds (Public Company) Nevena Vicic, MSc, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company)
Wilson et al. (Thu,) studied this question.