Background: Myocarditis refers to inflammation of the myocardium. The most common etiology is viral infection, including SARS-CoV-2. Younger men are typically at higher risk. Although cases are rare, myocarditis is an identified risk of mRNA vaccines targeting SARS-CoV-2.
Objectives: To evaluate the risk of myocarditis following doses 1, 2, and 3 of Spikevax.
Methods: This observational study used US open and closed healthcare claims data from HealthVerity to identify individuals receiving ≥1 dose of Spikevax between December 2020 and July 2022. A cohort of adults was formed requiring valid age/gender and no past claims for myocarditis before vaccination. Myocarditis case characteristics were assessed. Primary self-controlled risk interval analyses (SCRI) calculated event rate ratios (ERR) and 95% CIs comparing rates in 7-day risk and 42-day control periods, stratified by age, sex and dose. Analyses also considered alternative risk windows (e.g., days 1-21) and heterologous vaccination.
Results: There were 23,684,727 adults who received at least one dose of Spikevax and met inclusion criteria. Among adults, 15,257,865 received a second dose and 3,900,615 received a third dose. Myocarditis was identified in 2,082 cases, with a large majority (91.6%) occurring more than 21 days after vaccination. Cases that occurred within days 1-7 following a vaccine dose were younger than across cases. There were 560 adults included in SCRI analyses, which showed an elevated overall ERR (2.00, 95%CI 1.66-2.40) driven by increases in younger adults. Estimates were highest in males ages 18-29, especially after the second dose of the primary series (12.00, 6.70-21.48). An increased risk of lesser magnitude was also observed in this group after dose 1 (3.48, 1.98-6.12) and dose 3 (4.41, 0.99-19.73). Results of sensitivity analyses were directionally consistent with the main analysis.
Conclusions: Results of this study were largely consistent with the known safety profile of Spikevax, with an increase in the risk of myocarditis in young adults. Stronger associations were seen in young men, especially within 7 days of the second dose.
