ABSTRACT
ImportanceThe SARS-CoV-2 mRNA vaccines are associated with an increased risk of myocarditis. This association appears to be strongest in male adolescents and younger males and after the second dose. Few studies have evaluated the association after booster doses. ObjectiveTo evaluate the risk of myocarditis following SARS-CoV-2 mRNA booster vaccination in 12-to-39-year-olds. DesignA multinational cohort study using nationwide register data. SettingDenmark, Finland, Norway, and Sweden. ParticipantsCohorts comprising all 8.9 million individuals residing in each of the four countries, born 1982-2009, and alive at start of study on December 27, 2020, without a previous diagnosis of myocarditis or pericarditis or laboratory-confirmed SARS-CoV-2 infection. ExposuresThe 28-day acute risk periods following the second and third dose of BNT162b2 and mRNA-1273, respectively, in a homologous schedule defines the exposures of interest. Main Outcomes and MeasuresCohort participants were followed until an inpatient diagnosis of myocarditis, loss to follow-up, or end of study (latest data availability in each country), whichever occurred first. In each of the four countries, Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) of myocarditis, with associated 95% confidence intervals (CIs), according to vaccination status. Country-specific results were combined in meta-analyses. ResultsA total of 8.9 million residents were followed for 12,271,861 person-years. We identified 1533 cases of myocarditis. In 12-to-39-year-old males, the 28-day acute risk period following the third dose of BNT162b2 or mRNA-1273 was associated with an increased incidence rate of myocarditis compared to the post-acute risk period 28 days or more after a second homologous dose (IRR, 2.08 [95% CI, 1.31 to 3.33] and 8.89 [95% CI, 2.26 to 35.03], respectively). The corresponding incidence rates following the third dose of BNT162b2 and mRNA-1273 were 0.86 and 1.95, respectively, within 28 days of follow-up among 100,000 individuals. Conclusions and RelevanceOur results suggest that a booster dose is associated with increased myocarditis risk in male adolescents and young male adults. KEY POINTSO_ST_ABSQuestionC_ST_ABSIs a first booster dose of SARS-CoV-2 messenger RNA (mRNA) vaccine associated with increased risk of myocarditis in male adolescents and young male adults? FindingsIn a cohort study of 8.9 million residents in Denmark, Finland, Norway, and Sweden, a booster dose of BNT162b2 or mRNA-1273 vaccine was associated with increased risk of myocarditis in 12-to-39-year-old males, with incidence rates 0.86 and 1.95, respectively, within 28 days of follow-up per 100,000 vaccinated individuals. MeaningA booster dose with a SARS-CoV-2 mRNA vaccine is associated with increased myocarditis risk in male adolescents and young male adults. Compared to after a primary course, the risk appears attenuated.
