Risk of Coronavirus Disease 2019 Messenger RNA Vaccination-Associated Myocarditis - A Systematic Review of Population-Based Data

Background: Early studies showed that the risks of mRNA vaccine-associated myocarditis are low and mainly occur in young male recipients following a second dose, but with substantial variation across studies.Methods: We comprehensively searched MEDLINE for relevant articles published before August 31, 2022. We also searched the websites of health authorities in several countries for unpublished surveillance data on myocarditis after mRNA vaccination. The outcome of interest was the cumulative incidence of vaccinees who developed myocarditis after mRNA vaccination for COVID-19. We included population-based studies that provided sex- and age-specific rates of myocarditis following the first and second doses of BNT162b2 or mRNA-1273 vaccine separately. Data was extracted from the studies by two physician reviewers independently for further comparison.Results: A total of 15 studies form 10 countries were included for review. We noted considerable heterogeneity in study characteristics, including surveillance method, case definition, and duration of observation. Active surveillance studies from Hong Kong China and Israel reported higher rates than countries using passive surveillance. Our comparison of sex-, age-, vaccine type-, and dose-specific rates of myocarditis across countries did not support the hypothesis that young Asian males and individuals without recent SARS-CoV-2 infection were at higher risk. We also could not find sufficient evidence to conclude whether extending the between-dose interval could reduce myocarditis incidence following mRNA vaccination. However, the comparative safety of the two types of mRNA vaccines may vary with different age and sex groups.Interpretation: Differences in the study characteristics must be fully considered when comparing the risks of mRNA vaccine-related myocarditis in different countries. International collaborative research under the same framework is needed to continuously monitor and reduce the risk of mRNA vaccine-associated myocarditis, especially in younger populations.Funding Information: None.Declaration of Interests: None reported.