A major new scientific study has found that adults who received mRNA COVID‑19 vaccines were significantly less likely to die from any cause over four years compared with those who remained unvaccinated. The study, published in the medical journal JAMA Network Open, followed almost 28 million adults in France and provides one of the most comprehensive looks yet at the long‑term effects of COVID‑19 vaccination.
Groundbreaking Long‑Term Research on COVID‑19 Vaccines
In a large national study using data from the French National Health Data System, researchers looked at mortality outcomes among adults aged 18 to 59 years who were either vaccinated with COVID‑19 mRNA vaccines or unvaccinated.
The vaccinated group included 22.7 million people who received their first mRNA dose between May and October 2021. The unvaccinated group included 5.9 million people who had not received any COVID‑19 vaccine by November 1, 2021. Both groups were tracked for nearly four years — through March 31, 2025 — giving researchers a rare chance to compare long‑term health outcomes in real‑world conditions.
Key Findings: Lower Mortality with Vaccination
The results were clear and striking:
Vaccinated individuals had a 25% lower risk of dying from any cause over the four‑year period compared with unvaccinated individuals.
When looking specifically at deaths from severe COVID‑19, vaccinated people had a 74% lower risk of death.
The lower risk of death was consistent even when excluding deaths directly caused by COVID‑19, which suggests broader health benefits.
In raw numbers, about 0.4% of vaccinated adults died from any cause during the study period, compared with 0.6% of unvaccinated adults. The statistical analysis controlled for age, sex, and 41 different health conditions, meaning the results were adjusted to reduce the influence of possible differences between the groups.
Why These Findings Matter
This study is one of the largest and longest to compare health outcomes between vaccinated and unvaccinated people. Most previous research focused only on short‑term vaccine effectiveness or on deaths directly caused by COVID‑19. This new study instead looked at all‑cause mortality — a broader measure that captures deaths from diseases, accidents, and other causes.
Because the dataset included nearly 28 million people and spanned almost four years, the findings carry strong weight and help answer one of the biggest public questions about COVID‑19 vaccines: Do they affect long‑term health outcomes beyond protecting against COVID infection?
Understanding What “All‑Cause Mortality” Means
All‑cause mortality refers to deaths from any cause — whether that’s COVID‑19, heart disease, accidents, cancer, or other health issues. When researchers find a difference in all‑cause mortality between two groups, it can indicate that one group has better overall health outcomes.
In this study, vaccinated individuals were found to have fewer deaths overall, which suggests that vaccination may offer broader protective effects. Some of this benefit likely comes from preventing severe COVID‑19 illness and related complications. But the results also raise possibilities that vaccinated individuals may engage more with healthcare services or adopt healthier behaviors, which can also improve survival over time.
Important Context and Limitations
While the study’s findings are important, it’s also essential to be clear about what they do and do not prove:
The study was observational, meaning it did not randomly assign people to be vaccinated or unvaccinated. Researchers used statistical methods to account for differences, but some unknown factors could still influence the results.
A lower risk of death from any cause does not mean the vaccine magically prevents all kinds of illnesses. The direct benefit is mainly linked to strong protection against dangerous COVID‑19 outcomes.
Other lifestyle and social factors (like access to healthcare, diet, and physical activity) may also affect mortality and are harder to fully measure.
Despite these considerations, the large size and length of follow‑up make this study a powerful piece of evidence supporting the long‑term safety and benefits of mRNA COVID‑19 vaccines.
Expert Reactions
Public health experts note that these findings add to a body of evidence showing that COVID‑19 vaccines are safe and effective over the long term. Observational studies like this one cannot demonstrate absolute causation, but they do reflect real‑world outcomes across very large populations.
Many scientists also highlight that vaccinated people may benefit from both direct protection against severe disease and indirect advantages, such as being more likely to seek regular medical care.
What This Means for You
If you’re considering COVID‑19 vaccination or updating your booster, these results provide additional reassurance about long‑term safety. While individual health decisions should always involve personal medical advice, the data suggests that mRNA vaccines are not only effective against COVID‑19 but also associated with better overall health outcomes over several years.
Source
COVID‑19 mRNA Vaccination and 4‑Year All‑Cause Mortality Among Adults Aged 18 to 59 Years in France JAMA Network Open (December 2025)