A new peer-reviewed study has challenged the U.S. Food and Drug Administration’s (FDA) 2022 benefit-risk assessment of Moderna’s mRNA COVID-19 vaccine, concluding that for males aged 18 to 25, the shot may have posed more risks than benefits during the Omicron wave.
The study, published last week in the journal Vaccines, found that among young adult males, Moderna’s mRNA-1273 COVID-19 vaccine was associated with between 8% and 52% more hospitalizations for vaccine-attributable myocarditis and pericarditis (VAM/P) than the number of COVID-19 hospitalizations it was projected to prevent over a five-month period.
The research was led by Paul S. Bourdon, Ph.D., a retired mathematics professor at the University of Virginia. Bourdon said the study aimed to reassess whether the vaccine provided net benefits to young men, “given the high level of natural immunity in the population at the time of the FDA benefit-risk assessment.”
The FDA completed its benefit-risk review of Moderna’s vaccine in January 2022, shortly before granting it full approval.
According to epidemiologist and public health research scientist M. Nathaniel Mead, the FDA’s “most likely scenario” estimated a benefit-risk ratio of approximately 43:1 in favor of vaccination.
However, Bourdon’s reanalysis—using what the authors describe as more realistic assumptions—yielded a benefit-risk ratio of 0.67, which Mead said was roughly 60 times lower than the FDA’s estimate.
“Over the assumed five-month protection window, the shots led to as much as 63% more myocarditis/pericarditis hospitalizations than COVID-19 hospitalizations prevented,” Mead said.
The new study relied on data that were publicly available to the FDA at the time of its original assessment but applied different assumptions.
Bourdon argued that the FDA’s analysis had a significant limitation: although males aged 18 to 25 were known to be at the highest risk of vaccine-associated myocarditis and pericarditis, the agency assumed uniform COVID-19 hospitalization rates for males aged 18 to 45.
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According to the authors, data from the Centers for Disease Control and Prevention (CDC) indicated that hospitalization rates for males aged 30 to 49 were roughly double those of males aged 18 to 29.
By combining all males aged 18 to 45 into one category, Mead said, the FDA likely overestimated COVID-19 hospitalization risk for the narrower 18–25 age group.
The new model also incorporated additional factors not fully accounted for in the FDA’s framework, including:
Bourdon said that at the time of the FDA’s review, approximately 70% of males aged 18 to 25 had already been infected with COVID-19, and multiple studies suggested that natural immunity offered protection comparable to vaccination. The FDA, he noted, did not factor prior infection benefits into its core analysis.
Mead also questioned the FDA’s estimate of 12.8 myocarditis/pericarditis cases per 100,000 people following the initial two-dose Moderna series, suggesting the rate may have been understated in the agency’s modeling.
Karl Jablonowski, Ph.D., senior research scientist at the advocacy group Children’s Health Defense (CHD), said the new findings challenge what he described as a “one-size-fits-all approach” to vaccination policy.
The authors argue that future benefit-risk assessments should allow for more granular stratification of vaccine recommendations based on age, sex, prior infection status and comorbidities.
Mead said that if the FDA had used the modified assumptions applied in Bourdon’s model, it would have been difficult to characterize the vaccine as “safe and effective” for this specific demographic group during the Omicron period.
The study adds to ongoing scientific debate about myocarditis risk following mRNA vaccination, particularly in young males. In 2024, a large-scale study of 9.3 million South Koreans published in Nature Communications reported a significantly elevated risk of myocarditis and pericarditis following mRNA COVID-19 vaccination.
That same year, a report by the National Academies of Sciences, Engineering, and Medicine confirmed a causal link between mRNA COVID-19 vaccines and myocarditis, while emphasizing that cases are generally rare.