Abstract
Background: Myocarditis is an uncommon but recognized adverse event following mRNA COVID-19 vaccination, with risk varying by age, sex, dose number, and vaccine product. Clarifying the magnitude of risk, clinical course, and recovery-relative to myocarditis following SARS-CoV-2 infection-is essential for risk-benefit assessment and public health guidance. Methods: We performed a systematic PubMed and Embase search (January 2020-December 2024) and synthesized cohort, registry, and surveillance data on myocarditis incidence and outcomes following mRNA COVID-19 vaccination. Outcomes included incidence, observed-to-expected (OE) or incidence rate (IRRs) ratios, hospitalization, and short-term recovery. Study selection followed PRISMA 2020 systematic review guidelines. Results: Myocarditis following mRNA COVID-19 vaccination was identified as a rare adverse event, most commonly occurring after the second dose and in younger male individuals. Across multiple cohort and registry-based studies, cases were generally mild and self-limited, with most patients recovering without complication. In contrast, myocarditis following SARS-CoV-2 infection was consistently associated with more severe outcomes, including higher rates of hospitalization and mortality. Conclusions: Vaccine-associated myocarditis is rare, typically mild, and self-limited, with excellent short-term recovery; vaccinated individuals also exhibit lower odds of in-hospital death and intubation. In contrast, infection-associated myocarditis is more frequent and severe. Overall, the benefit-risk profile of mRNA vaccination remains strongly favorable.