Huge Study Shows mRNA COVID Vaccines Associated with 25 Percent Lower Risk Of Death From Any Cause

In a national cohort study of 28 million individuals, researchers found no increased risk of four-year all-cause mortality in individuals aged 18 to 59 years vaccinated against COVID-19, further supporting the safety of the mRNA vaccines that are widely used worldwide.

The study used data from the French National Health Data System for all individuals in the French population aged 18 to 59 years who were alive on Nov. 1, 2021. Data analysis was conducted from June 2024 to September 2025. 

In the study, individuals were assigned either to an exposure cohort, defined as receiving a first mRNA dose between May 1 and Oct. 31, 2021, and an unvaccinated cohort, defined as not having received a first mRNA vaccine by Nov. 1, 2021. Individuals were assigned a random index date based on vaccinated individuals’ vaccination dates.

Cox models weighted for sociodemographic characteristics and 41 comorbidities were used to estimate four-year all-cause mortality. Time to event was censored at all-cause death, COVID-19 vaccination for unexposed individuals or study termination on March 31, 2025. Complementary analyses were performed, including a comparison of the main causes of death available up to Dec. 31, 2023. Follow-up began six months after the index date in both groups to address immortal time bias. Short-term mortality within six months after vaccination was assessed in a separate, independent study using adapted self-controlled case series models.

A total of 22,767,546 vaccinated and 5,932,443 unvaccinated individuals were followed up for a median of 45 (44-46) months. Vaccinated individuals were older than unvaccinated individuals (mean age, 38.0 [11.8] years vs. 37.1 [11.4] years), more frequently women (11 688,603 [51.3 percent] vs. 2 876,039 [48.5 percent]) and had more cardiometabolic comorbidities (2,126,250 [9.3 percent] vs. 464,596 [7.8 percent]). During follow-up, 98,429 (0.4 percent) and 32,662 (0.6 percent) all-cause deaths occurred in the vaccinated and unvaccinated groups, respectively. Vaccinated individuals had a 74 percent lower risk of death from severe COVID-19 (weighted hazard ratio [wHR], 0.26) and a 25 percent lower risk of all-cause mortality (wHR, 0.75), with a similar association observed when excluding severe COVID-19 death. Sensitivity analysis revealed that vaccinated individuals consistently had a lower risk of death, regardless of the cause. Mortality was 29 percent lower within six months following COVID-19 vaccination (relative incidence, 0.71).

While several studies have assessed the impact of COVID-19 vaccination on short-term mortality, this is the first that has compared long-term mortality by vaccination status, particularly in young individuals who are less likely to experience severe disease following SARS-CoV-2 infection.