Relative Incidence and Attributable Risk of Myocarditis and Pericarditis following COVID-19 Vaccination: A Self-Controlled Case Series Study from Global Vaccine Data Network (GVDN)
Background: mRNA COVID-19 vaccines have been associated with myocarditis and pericarditis, with the highest risk among adolescent and young adult males after the second dose. However, risks following subsequent doses and across age- and sex-specific subgroups remain inadequately characterized, particularly for less common vaccine platforms and later doses.Methods: A self-controlled case series (SCCS) study was conducted through Global Vaccine Data Network™ (GVDN®) and included 15 sites across 18 countries and regions. This study evaluated the relative incidence and attributable risk of myocarditis and pericarditis following COVID-19 vaccination, stratified by vaccine platform and brand, dose number, and age and sex groups.Findings: The study identified 4,333 myocarditis cases and 7,875 pericarditis cases from an estimated population of 344 million people. An increased relative incidence of myocarditis was found following doses one, two, and three of mRNA vaccines in all age/sex groups and pericarditis in most age/sex groups, with the highest attributable risk of 1 in 20,000 for myocarditis after the second dose of mRNA vaccines among males 12–17 years. Non-replicating viral vector and inactivated vaccines were not associated with myocarditis or pericarditis.Interpretation: In this large multinational SCCS study of COVID-19 vaccination and myocarditis/pericarditis, mRNA vaccines were associated with an increased relative incidence of both myocarditis and pericarditis. While an increase in relative incidence was found across all age and sex groups, the magnitude of the increase and corresponding attributable risk varied widely between age and sex groups. This study provides precise attributable risk estimates for each age and sex group. Patient decision-making, provider recommendations, and vaccine recommendations must consider the risks of myocarditis and pericarditis in the context of vaccine benefits.