Metadata

• Authors: Laura Semenzato, Stéphane Le Vu, Jérémie Botton, Marion Bertrand, Marie-Joelle Jabagi, Jérôme Drouin, François Cuenot, Valérie Olié, Rosemary Dray-Spira, Alain Weill, Mahmoud Zureik
• Publication Date: 2025
• Journal/Source: JAMA Network Open
• URL: 10.1001/jamanetworkopen.2025.46822

Abstract

Importance: While several studies have assessed the impact of COVID-19 vaccination on short-term mortality, 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.

Objective: To compare 4-year all-cause mortality in individuals aged 18 to 59 years vaccinated with the mRNA COVID-19 vaccine vs unvaccinated individuals.

Key Findings

• Vaccinated individuals had a 74% lower risk of death from severe COVID-19 (weighted hazard ratio [wHR], 0.26 [95% CI, 0.22-0.30]).
• Vaccinated individuals had a 25% lower risk of all-cause mortality (wHR, 0.75 [95% CI, 0.75-0.76]), 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% lower within 6 months following COVID-19 vaccination (relative incidence, 0.71 [95% CI, 0.69-0.73]).

Notes

• This study is a cohort study utilizing the French National Health Data System and focused on individuals aged 18 to 59 years as of November 1, 2021.
• Participants were categorized based on having received a first mRNA vaccine dose between May 1 and October 31, 2021, or being unvaccinated by November 1, 2021.
• The median follow-up period was 45 months, with vaccinated individuals commonly being older and having more cardiometabolic comorbidities.
• The study supports the long-term safety of COVID-19 mRNA vaccines, as there was no increased risk of 4-year all-cause mortality among vaccinated individuals compared to unvaccinated individuals.