NEJM 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.
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.