Occurrence of Myocarditis in Patients Immunized with Different Types of COVID-19 Vaccines: A Systematic Review and Meta-Analysis.

backgroundMyocarditis has emerged as a rare but clinically relevant adverse event reported after COVID-19 vaccination, particularly following widespread use of vaccines based on novel molecular platforms. Given variability in vaccine technologies, population characteristics, and surveillance methodologies, a comprehensive quantitative synthesis is required to better characterize the occurrence of post-vaccination myocarditis. This study aimed to characterize the distribution of reported myocarditis cases among individuals receiving COVID-19 vaccines, including mRNA, viral vector, and protein-subunit platforms, and to synthesize available evidence on reported post-vaccination myocarditis across different demographic and geographic subgroups.

methodsThis systematic review and meta-analysis was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251118332). MEDLINE, Web of Science, Scopus, CINAHL, Google Scholar, and LILACS were searched from inception to January 2024 for observational studies reporting myocarditis following COVID-19 vaccination. Cohort, case-control, cross-sectional studies, and case series were eligible. Study quality was assessed using the ROBINS-I tool. Random-effects models were applied to estimate pooled proportions with 95% confidence intervals (CIs). Statistical heterogeneity was quantified using the I² statistic, and prespecified subgroup analyses were performed by sex, age, geographic region, and vaccine platform. Publication bias was explored using funnel plot analysis.

resultsFifty-nine studies comprising 196,478,861 vaccinated individuals and 13,348 reported myocarditis cases were included. Due to substantial heterogeneity in study designs and denominators, pooled estimates represent the proportion of myocarditis cases within reported samples rather than population-level incidence or risk. Across all included studies, the pooled proportion of myocarditis cases within reported study samples was 34% (95% CI: 19-50%), with considerable heterogeneity (I² = 100%). These estimates should not be interpreted as population-level incidence or risk. Reported myocarditis cases were more frequently observed among males (72%, 95% CI: 58-86%) than females (56%, 95% CI: 35-77%) and were predominantly identified in individuals younger than 40 years. Subgroup analyses by region and vaccine platform should be interpreted cautiously due to methodological variability and potential selection bias. Funnel plot asymmetry suggested possible small-study effects.

conclusionsThis systematic review and meta-analysis aimed to characterize the distribution of reported myocarditis cases following COVID-19 vaccination rather than to estimate population-level incidence or risk. Although pooled proportions within reported samples were substantial, these estimates do not reflect population-level incidence. Available evidence suggests that myocarditis following COVID-19 vaccination remains uncommon at the population level, predominantly affecting younger males and more commonly reported after mRNA-based vaccines. Most reported cases appear to follow a benign and self-limited clinical course. These findings support the overall favorable benefit-risk profile of COVID-19 vaccines while underscoring the need for continued pharmacovigilance and more robust epidemiological studies to better characterize the epidemiology of vaccine-associated myocarditis.