Key result
SARS-CoV-2 infection is linked to ~4.9-fold higher myocarditis risk compared with no infection.
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Why the study?
Concerns about myocarditis and mortality after COVID-19 vaccination in adolescents and young adults persist despite limited direct comparisons with SARS-CoV-2 infection risks.
Does BNT162b2 vaccination, compared to SARS-CoV-2 infection, alter the risk of myocarditis, pericarditis, and mortality in adolescents and young adults?
Cohort (n=4,072,375)
Does BNT162b2 vaccination, compared to SARS-CoV-2 infection, alter the risk of myocarditis, pericarditis, and mortality in adolescents and young adults?
Relative Risk: 4.91 (95% CI 3.11–7.77)
In adolescents and young adults, SARS-CoV-2 infection is associated with significantly higher short-term risks of myocarditis, pericarditis, and mortality compared to BNT162b2 vaccination, supporting a favorable benefit-risk profile for vaccination.
BACKGROUND: Concerns about myocarditis and mortality after COVID-19 vaccination in pediatrics persist despite limited direct comparisons with SARS-CoV-2 infection risks. We compared risks of myocarditis, pericarditis, and mortality between infection and BNT162b2 vaccination in adolescents and young adults. METHODS: This retrospective cohort study used TriNetX data (December 2020-September 2025) for 4,072,375 individuals aged 16-25 years, categorized as uninfected/unvaccinated (n = 3,572,000), infected/unvaccinated (n = 248,546), vaccinated/uninfected (n = 241,152), or hybrid immunity (n = 10,677). We used competing risk analysis, propensity-score matching, and Cox regression, and sex-stratified analyses to assess 6-month outcomes. FINDINGS: The infected/unvaccinated group had the highest cumulative incidence of myocarditis (0.116%). After 1:1 propensity-score matching, SARS-CoV-2 infection was associated with significantly higher risks of myocarditis (relative risk [RR] = 4.91; 95%CI = 3.11-7.77), pericarditis (RR = 1.93; 95%CI = 1.39-2.67), and mortality (RR = 1.33; 95%CI = 1.04-1.71) versus no infection. In direct comparison, vaccination was associated with 85% lower myocarditis risk, 79% lower pericarditis risk, and 72% lower mortality versus infection. Protection was consistent across sexes. The absolute risk difference for myocarditis was 0.0354%, corresponding to one fewer recorded myocarditis event per 2827 individuals in the vaccinated/uninfected group compared with the infected/unvaccinated group. INTERPRETATION: Recorded SARS-CoV-2 infection was associated with higher short-term risks of myocarditis, pericarditis, and all-cause mortality than recorded BNT162b2 vaccination in adolescents and young adults. These findings support a favorable benefit-risk profile for BNT162b2 vaccination relative to documented infection, although the observational all-cause mortality comparison should be interpreted as descriptive rather than causal.
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Toraih et al. (2026) conducted a cohort in SARS-CoV-2 infection and BNT162b2 vaccination (n=4,072,375). SARS-CoV-2 infection vs. no infection was evaluated on myocarditis (RR 4.91, 95% CI 3.11-7.77). SARS-CoV-2 infection was associated with a significantly higher risk of myocarditis (RR 4.91; 95% CI 3.11-7.77) versus no infection, while vaccination had an 85% lower risk versus infection.
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