Massive four-year study finds no increase in deaths linked to COVID-19 mRNA vaccination
Data from 30 million French adults suggests Covid-19 vaccines did not lead to higher death rates. Instead, they reduced them.
- 12 December 2025
- 4 min read
- by Linda Geddes
At a glance
- Among 28 million French adults aged 18–59, those who received an mRNA-based COVID-19 vaccine were less likely to die in the subsequent four years than those who remained unvaccinated, corresponding to a 25% lower risk of death from all causes.
- Although vaccinated adults were 74% less likely to die from severe COVID-19, the reduced mortality risk persisted after COVID-19 deaths were excluded from the analysis.
- The study found no increase in the risk of deaths from cancer, heart disease, accidental injury or any other major category: in every case, vaccinated individuals had equal or lower rates of death.
For years, a lingering question has shadowed COVID-19 vaccination campaigns: are mRNA vaccines safe in the long run?
While many studies have established that COVID-19 vaccines prevent severe illness and death in the weeks and months after injection, sceptics have continued to ask whether any hidden harms might surface later on.
Now, one of the largest long-term vaccine safety studies ever undertaken – including data from more than 28 million adults aged 18 to 59 – offers the clearest answer yet.
It found those who were vaccinated against COVID-19 were no more likely to die over the subsequent four years than those who remained unvaccinated. In fact, they were less likely to.
“To our knowledge, this is the first national population-based study to examine differences in all-cause mortality between individuals who did and did not receive COVID-19 vaccines 4 years after their first dose of COVID-19 vaccination,” said Dr Laura Semenzato at the French National Agency for the Safety of Medicines and Health Products, who led the study.
Are mRNA-based COVID-19 vaccines safe in the longer term?
Although various studies have assessed the impact of COVID-19 vaccination on the short-term risk of death, “none have compared long-term mortality by vaccination status, particularly in young individuals who are less likely to experience severe disease following SARS-CoV-2 infection,” said Semenzato. Public concerns about long-term safety also persist, she added.
To investigate this issue, Semenzato and colleagues drew on data from the French National Health Data System, which enabled them to track the health of more than 28 million adults from late 2021 to March 2025. Of these people, some 22.8 million received at least one dose of COVID-19 mRNA vaccine during France’s mass roll-out from mid-2021, while 5.9 million did not.
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The study, published in JAMA Network Open, found that in the four years since then, 0.4% of vaccinated individuals died, compared with 0.6% of unvaccinated ones.
After adjusting for age, health conditions and socioeconomic factors, it concluded that vaccination was associated with a 25% lower risk of deaths from all causes.
Part of that difference is likely to stem from COVID-19 itself: vaccinated people were 74% less likely to die from severe COVID-19. However, the protective association remained even after COVID-19 deaths were removed from the analysis.
Did COVID-19 vaccines increase the risk of cancer or heart disease?
To address persistent concerns about potential delayed harms – including claims that vaccination might increase deaths from cancer, heart disease or other causes – the researchers also examined cause-of-death data, available up to December 2023.
Across almost every category, vaccinated adults had lower death rates. Cancer deaths were somewhat lower (769 vs. 853 per million individuals), as were deaths from circulatory diseases (282 vs. 367 per million) and external causes, such as accidents or suicides (493 vs. 597 per million).
Crucially, no category showed an increase in deaths among the vaccinated group.
Why might vaccinated people fare better?
One explanation is that avoiding severe COVID-19 prevents downstream illness.
The virus can cast a long shadow – lingering inflammation, cardiovascular issues or Long COVID – which may influence people’s risk of death years later.
Vaccinated people were 74% less likely to die from severe COVID-19. However, the protective association remained even after COVID-19 deaths were removed from the analysis.
However, the study also acknowledged that people who get vaccinated may differ from those who do not. They may have better access to healthcare, live in less deprived areas or be more health-conscious in the first place. These traits could also help protect against death in ways unrelated to the vaccine itself.
Even so, the authors note that some differences favoured the unvaccinated. For instance, vaccinated individuals tended to be slightly older and had cardiometabolic disease, which usually increases the risk of death. Yet their risk was still lower.
Reassuring data
Although this isn’t the first study to find that vaccinated people don’t die at higher rates, it is the first to follow such a large population of young to middle-aged adults for such a long period, incorporating the statistical tools to rule out biases.
Its message is clear: “A causal link between mRNA vaccination and excess long-term mortality appears highly unlikely,” the researchers said.
