Association of 2024–2025 Covid-19 Vaccine with Covid-19 Outcomes in U.S. Veterans
Miao Cai, Yan Xie, Ziyad Al-Aly
N Engl J Med Published October 8, 2025
DOI: 10.1056/NEJMoa2510226
Abstract
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.)
