04/04/2026
COVID-19 vaccination was associated with a lower risk of death in one of the largest long-term studies to date.
A nationwide French cohort study published in JAMA Network Open followed more than 28 million adults aged 18 to 59 from November 1, 2021, through January 31, 2025. Researchers found that people who received at least one mRNA COVID-19 vaccine dose had a 25% lower risk of death from any cause compared with unvaccinated adults. The protection was even stronger for severe COVID-19 outcomes, with vaccinated individuals showing a markedly lower risk of death linked to serious infection.
The authors also tested whether the result could simply reflect the “healthy user effect,” where people who choose vaccination may already be healthier than those who do not. Even after multiple sensitivity analyses, the study found no evidence that mRNA vaccination increased long-term all-cause mortality in this age group. The reduction in mortality was strongest during the first six months after vaccination, when deaths were about 29% lower, but the benefit remained statistically significant over the full follow-up period.
This does not prove the vaccine directly lowers every cause of death, because the study was observational rather than randomized. But it does provide large-scale real-world evidence that mRNA COVID-19 vaccination was associated with better long-term survival, while also showing no sign of increased mortality risk over nearly four years of follow-up.
Source: Semenzato, L., Le Vu, S., Botton, J., et al. COVID-19 mRNA Vaccination and 4-Year All-Cause Mortality Among Adults Aged 18 to 59 Years in France. JAMA Network Open. 2025;8(12):e2546822.