Effectiveness of 2023–2024 mRNA-1273 XBB.1.5 vaccine against COVID-19 associated hospitalizations and medically attended COVID-19 in the United States

COVID-19 remains a public health concern, causing an estimated 50,000 deaths and 827,000 hospitalizations in the United States during the 2023–2024 season. As SARS-CoV-2 continues to evolve, assessing COVID-19 vaccine effectiveness (VE) remains essential. This study evaluated the effectiveness of Moderna's 2023–2024 mRNA-1273 vaccine formulation targeting the XBB.1.5 variant in preventing COVID-19 associated hospitalizations and medically attended COVID-19 in the US. This non-interventional, matched retrospective cohort study used US administrative claims data (September 2023–February 2024). Individuals vaccinated with mRNA-1273 XBB.1.5 were matched to individuals who did not receive an updated 2023–2024 COVID-19 vaccine. COVID-19 associated hospitalizations and medically attended COVID-19 outcomes were identified 7 days after the index date. Subpopulations of interest included age group, immunocompromised individuals, and those received a BA.4/BA.5 vaccine in the prior season. VE was estimated using 1 minus hazard ratios. Among 900,194 mRNA-1273 vaccinated and matched unexposed individuals, median follow-up for COVID-19 associated hospitalizations was 111 days (vaccinated) and 99 days (unexposed). Overall, VE against COVID-19 associated hospitalizations was 56 % (95 % CI: 52 %–60 %). VE ranged from 52 % (95 % CI: 43 %–59 %) in immunocompromised individuals to 62 % (95 % CI: 35 %–78 %) in those aged 50–64 years. For medically attended COVID-19, VE was 24 % (95 % CI: 22 %–25 %). mRNA-1273 XBB.1.5 demonstrates significant incremental protection against COVID-19 associated hospitalizations and medically attended COVID-19 relative to those who did not receive 2023–2024 COVID-19 vaccination. These findings reinforce the need for vaccination efforts to reduce the burden of COVID-19. • This large, real-world study evaluated the effectiveness of mRNA-1273 XBB.1.5 COVID-19 vaccination in over 900,000 individuals across all ages. • The mRNA-1273 XBB.1.5 vaccine was 56 % effective against COVID-19 associated hospitalization and 24 % effective against medically attended COVID-19. • Protection against hospitalization was consistent across age groups, high-risk, and immunocompromised populations. • Although formulated to target XBB.1.5, mRNA-1273 provided protection during a period when multiple variants co-circulated and JN.1 became the predominant lineage.