How does myocarditis risk after mRNA COVID-19 vaccination compare to risk after SARS-CoV-2 infection by age and sex?
Executive summary
Large, population-level studies and reviews consistently find that myocarditis risk is higher after SARS‑CoV‑2 infection than after mRNA COVID‑19 vaccination for most age‑sex groups, but young males (adolescents and men under ~40) show the clearest vaccine‑associated excess risk—especially after a second mRNA dose—while infection generally produces larger absolute excesses across most groups [1] [2] [3]. Estimates vary by study, vaccine product, dose number and time window: for example, males <40 had an excess ~97 myocarditis events per million after a second Moderna dose versus ~16 per million after infection in one England analysis [4]; other pooled analyses report infection-associated myocarditis risks more than sevenfold higher than vaccine‑associated risk overall [3].
1. What the big studies say: infection > vaccination for most people
Multiple large analyses conclude myocarditis is more common after SARS‑CoV‑2 infection than after COVID‑19 vaccination overall. A broadly cited England self‑controlled case‑series covering tens of millions found myocarditis was "more common following SARS‑CoV‑2 infection than following COVID‑19 vaccination" across age and sex strata, while noting stronger vaccine associations in younger males [1]. Systematic reviews and meta‑analyses similarly report substantially higher relative risks after infection than after vaccination — one meta‑analysis estimated infection risk to be >7× higher than vaccination [3].
2. Young males are the exception in nuance: vaccine risk concentrated after dose two
Data repeatedly identify adolescent and young adult males as the group with the clearest vaccine‑linked myocarditis signal and the highest vaccine‑associated incidence, predominantly within a week of the second mRNA dose [5] [6] [7]. Clinical and surveillance summaries report the highest observed incidence in males 12–24 years (FDA labeling cites ~27 cases per million doses for males 12–24 in a 1–7 day window for 2023–24 formulas) and other studies report higher per‑million excess after second doses, especially with Moderna [8] [6] [9].
3. Product and dose matter: Moderna vs Pfizer, dose spacing, boosters
Some analyses show Moderna's mRNA‑1273 is associated with larger myocarditis excess after the second dose than Pfizer's BNT162b2 in younger males; the England study reported ~97 excess events per million after second‑dose mRNA‑1273 in men <40 versus ~16 per million after infection [4]. Other reports note lower myocarditis signals with later‑generation or updated formulations and with additional doses/boosters in some datasets, though surveillance and biomarker studies vary [10] [11].
4. Absolute risk is rare; severity and prognosis differ by cause
Although relative risks can be notable in subsets, myocarditis after vaccination remains a rare event in absolute terms (single‑digit to low‑hundreds per million depending on age/sex/dose), and many cases reported after mRNA vaccines are described as clinically mild with recovery by hospital discharge in surveillance summaries [5] [12]. Several analyses also reported worse outcomes and higher mortality for myocarditis caused by viral infection compared with vaccine‑associated myocarditis [7].
5. Why estimates vary: methods, windows and background rates
Differences across studies stem from study design (self‑controlled case series, cohort, passive surveillance), choice of risk window (days vs weeks), case ascertainment (diagnostic codes vs adjudicated myocarditis), and background myocarditis incidence pre‑COVID. This produces a range of reported incidence ratios and excesses and explains why some subgroup findings (e.g., men <40 with Moderna) appear to deviate from the overall pattern [4] [13] [7].
6. Competing viewpoints and limitations in the literature
Authors and commentators have debated interpretations—some caution that certain subgroup findings require careful benefit‑risk assessment (especially adolescents and young males receiving Moderna) and critique specific study assumptions [14]. At the same time, regulatory bodies (FDA, CDC) and clinical societies emphasize that overall vaccination benefits outweigh myocarditis risks for most groups while updating labels and guidance to reflect highest‑risk demographics [8] [5] [12].
7. Practical takeaways for clinicians and the public
The evidence supports that SARS‑CoV‑2 infection poses a larger myocarditis risk for most people than mRNA vaccination, but clinicians should counsel young males that their vaccine‑associated myocarditis risk—especially after the second mRNA dose—is elevated relative to other demographics and may be influenced by product and dosing schedule [1] [4] [9]. Available sources do not mention long‑term comparative outcomes beyond the reports cited here in full detail; readers should consult up‑to‑date regulatory guidance and local public‑health analyses for policy decisions [8] [5].
Caveat: this summary is limited to the studies and reviews in the supplied set; estimates and guidance continue to evolve as surveillance and clinical follow‑up accrue [10] [11].