By Terrence Rudd

In a French cohort, the incidence of all-cause mortality among those who received a first dose of an mRNA COVID vaccine was 0.4% after a median follow-up of 45 months, compared with 0.6% of those who were unvaccinated.

After standardizing characteristics between the two groups, all-cause mortality incidence was 25% lower in those who had received a COVID shot.

Vaccinated people were 74% less likely to die in a hospital because of COVID-19 compared with those who weren't vaccinated.

Young and middle-age adults who had at least one dose of a COVID-19 mRNA vaccine were less likely to die of any cause in the following 4 years compared with those who weren't vaccinated, a nationwide French cohort study found.

Among over 28 million adults under 60 years of age, the incidence of all-cause mortality among those who received a first dose of mRNA vaccine from May 1 to Oct. 31, 2021, was 0.4% after a median follow-up of 45 months, compared with 0.6% in those who were unvaccinated by Nov. 1, 2021.

After standardizing characteristics between the two groups, all-cause mortality incidence was 25% lower in those who had received an mRNA shot (weighted hazard ratio [wHR] 0.75, 95% CI 0.75-0.76), according to Mahmoud Zureik, MD, PhD, of the French National Agency for the Safety of Medicines and Health Products in Saint-Denis, and colleagues.

Vaccinated people were 74% less likely to die in a hospital because of COVID-19 compared with those who weren't vaccinated (wHR 0.26, 95% CI 0.21-0.32). Even when those COVID-related hospital deaths were excluded from the analysis, people who'd been vaccinated were still 24% less likely to die of any cause during the follow-up period (wHR 0.76, 95% CI 0.75-0.77), the researchers reported.

"Although vaccinated individuals in our study were generally older and tended to have more comorbidities -- factors that would typically bias the association toward higher mortality in the vaccinated group -- this was not observed in the crude hazard ratio," Zureik and colleagues wrote. People who were vaccinated were more socioeconomically advantaged and probably had better healthcare management, they added, factors that "may partly explain the observed negative association between vaccination and mortality, counterbalancing the effects of age and comorbidities."

The findings come as the Trump administration turns sharply against mRNA vaccines due to supposed concerns about effectiveness and safety.

Federal health authorities in August ended research funding on 22 mRNA vaccine-related projects -- a move critics called "reckless." In October, the CDC's Advisory Committee on Immunization Practices stopped recommending COVID-19 vaccination for anyone -- even for high-risk groups such as seniors -- instead saying the choice should be a personal one. And just last week, the FDA's top vaccine regulator, Vinay Prasad, MD, MPH, told staff in a memo that an FDA review determined that at least 10 children had died due to a COVID shot.

The study from Zureik and co-authors analyzed national health data covering all 68 million residents of France. The study cohort included all people ages 18 to 59 years in France as of Nov. 1, 2021, resulting in 22,767,546 people vaccinated with a first dose of mRNA vaccine between May 1 and Oct. 31, 2021, and 5,932,443 individuals still unvaccinated by Nov. 1. Follow-up began 6 months after one dose of COVID-19 mRNA vaccine or a randomly assigned index date for unvaccinated people within those time periods. Among those unvaccinated, 10.8% were vaccinated during follow-up.

The positive association between vaccination and lower all-cause mortality waned over time. The wHR favoring vaccination was 0.61 (95% CI 0.58-0.64) in the first 6 to 9 months of follow-up but slid to 0.79 (95% CI 0.75-0.82) at 39 to 42 months of follow-up.

Declining COVID-related mortality among the unvaccinated by the end of the follow-up period may have helped drive that decline, Zureik and colleagues noted, given increasing vaccine-induced protection and changes in circulating SARS-CoV-2 viruses. In the first 6 to 9 months of follow-up, 10.5% of deaths among the unvaccinated were related to COVID-19, compared with 1.9% in those who were vaccinated. By 24 to 27 months of follow-up, those percentages dropped to 0.5% and 0.3%, respectively.

The researchers were able to determine causes of death only for 59% of people in the study. However, the main causes of death among vaccinated and unvaccinated people were cancer (769 and 853 cases per million, respectively), external causes of mortality such as unintentional injuries or self-inflicted injuries (493 and 597), and circulatory system diseases (282 and 367).

To control for some risk behaviors linked to vaccination status, the researchers removed deaths involving hospitalization for traumatic injury or involuntary injury from the all-cause mortality calculations. Those deletions dropped the wHR favoring vaccination to 0.80 (95% CI 0.79-0.81) and 0.83 (95% CI 0.81-0.84), respectively.

Vaccinated people were older compared with those who were unvaccinated (mean age 38 vs 37.1 years) and more frequently women (51.3% vs 48.5%). Those vaccinated also were less likely to live in an area that was in the most disadvantaged quintile (19.1% vs 27%) and to be covered by complementary state health insurance (9.2% vs 20.9%). Vaccinated adults had more cardiac comorbidities than unvaccinated adults (9.3% vs 7.8%), more chronic respiratory diseases (3.3% vs 3.1%), and more cancer of any type (1.5% vs 1.4%).

Study limitations included the impact socioeconomic status has on vaccination and mortality, which the study's source data couldn't account for completely and may lead to unmeasured confounding. People who chose vaccination also may have other factors that differentiate them from those who remain unvaccinated, potentially creating more confounding bias in the results.