Systematic Review and Meta-Analysis of the Incidence of Myocarditis and Guillain-Barré Syndrome in Adolescents Receiving COVID-19 mRNA Vaccine

This study aimed to evaluate the incidence and risk of rare long-term adverse events, specifically myocarditis and Guillain-Barré syndrome (GBS), in adolescents (12-19 years) following COVID-19 mRNA vaccination. We systematically searched MEDLINE, Embase, Cochrane CENTRAL, and Scopus, supplemented by trial registries and reference lists (PROSPERO: CRD420251045173). Eligible studies included randomized controlled trials (RCTs), cohort studies, case-control studies, self-controlled case series, and pharmacovigilance database analyses reporting myocarditis or GBS outcomes in adolescents receiving BNT162b2 or mRNA-1273. The search was conducted in June 2025, and all published studies were included. Risk of bias was assessed using the Cochrane RoB-2 tool, Newcastle-Ottawa Scale, or adapted criteria for pharmacovigilance studies. Effect measures were expressed as incidence rate or incidence rate ratios (IRRs) with 95% confidence intervals (CIs). Meta-analyses were conducted using random-effects models. Ten studies met the inclusion criteria. Myocarditis incidence was elevated in adolescent and young adult males, particularly after the second dose. Pooled analyses indicated a higher risk with mRNA-1273 compared to BNT162b2 (pooled IRR ≈ 3.9), although heterogeneity was very high (I² > 95%). For GBS, global pharmacovigilance data suggested only a modest association with mRNA vaccines (ROR 9.66), substantially weaker than for adenoviral vector or influenza vaccines. COVID-19 mRNA vaccination in adolescents is associated with a small but measurable increased risk of myocarditis, particularly in males, after the second dose, with a higher incidence following mRNA-1273. No consistent evidence of increased GBS risk was observed. Absolute risks remain low, and outcomes are generally favorable compared to SARS-CoV-2 infection. Continued surveillance and long-term follow-up are warranted.