Association of 2024–2025 Covid-19 Vaccine with Covid-19 Outcomes in U.S. Veterans

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BACKGROUND: Amid the declining clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and diminishing public uptake of annual coronavirus disease 2019 (Covid-19) vaccines, contemporary evidence on vaccine effectiveness against clinically relevant outcomes is needed. METHODS: We conducted an observational study that used the electronic health records of the Department of Veterans Affairs to evaluate the effectiveness of the 2024-2025 Covid-19 vaccine among veterans who received the Covid-19 and influenza vaccines on the same day (164,132 participants) and in an active-comparator group of veterans who received the influenza vaccine only (131,839 participants), between September 3 and December 31, 2024. Participants were followed for 180 days or until the occurrence of an outcome, whichever came first. We used inverse-probability-weighted models to estimate vaccine effectiveness (calculated as 1 minus the risk ratio) against Covid-19-associated emergency department visits, hospitalizations, and deaths at 6 months. RESULTS: At 6 months of follow-up, the estimated vaccine effectiveness was 29.3% (95% confidence interval [CI], 19.1 to 39.2) against Covid-19-associated emergency department visits (risk difference per 10,000 persons, 18.3; 95% CI, 10.8 to 27.6), 39.2% (95% CI, 21.6 to 54.5) against Covid-19-associated hospitalizations (risk difference per 10,000 persons, 7.5; 95% CI, 3.4 to 13.0), and 64.0% (95% CI, 23.0 to 85.8) against Covid-19-associated deaths (risk difference per 10,000 persons, 2.2; 95% CI, 0.5 to 6.9). Vaccine effectiveness against a composite of these outcomes was 28.3% (95% CI, 18.2 to 38.2), with a risk difference per 10,000 persons of 18.2 (95% CI, 10.7 to 27.5). The Covid-19 vaccine was associated with decreased risks of these outcomes across prespecified subgroups defined according to age (<65 years, 65 to 75 years, and >75 years), the presence or absence of major coexisting conditions, and immunocompetence status. CONCLUSIONS: In this national cohort of U.S. veterans, the receipt of the 2024-2025 Covid-19 vaccine was associated with decreased risks of severe clinical outcomes. (Funded by the Department of Veterans Affairs.).

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