BACKGROUND: Myocarditis is more common following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than following COVID-19 vaccination but the risks in younger persons and following sequential vaccine doses are less certain.

METHODS: A self-controlled case series study of people aged 13 or older vaccinated for COVID-19 in England between 1 December 2020 and 15 December 2021 evaluated the association between vaccination and myocarditis, stratified by age and sex. The incidence rate ratio (IRR) and excess number of hospital admissions or deaths from myocarditis per million persons were estimated for the 1-28 days following sequential doses of adenovirus (ChAdOx1) or messenger RNA-based (BNT162b2, mRNA-1273) vaccines, or after a positive SARS-CoV-2 test.

RESULTS: In 42,842,345 people receiving at least one dose of vaccine, 21,242,629 received three doses and 5,934,153 had SARS-CoV-2 infection before or after vaccination. Myocarditis occurred in 2,861 (0.007%) persons, with 617 events 1-28 days following vaccination. Risk of myocarditis was increased in the 1-28 days following a first dose of ChAdOx1 (IRR: 1.33 [95% confidence interval 1.09, 1.62]) and a first, second, and booster dose of BNT162b2 (1.52 [1.24, 1.85], 1.57 [1.28, 1.92], and 1.72 [1.33, 2.22], respectively) but was lower than the risks following a positive SARS-CoV-2 test before or after vaccination (11.14 [8.64, 14.36] and 5.97 [4.54, 7.87], respectively). The risk of myocarditis was higher 1-28 days following a second dose of mRNA-1273 (11.76 [7.25, 19.08]) and persisted following a booster dose (2.64 [1.25, 5.58]). Associations were stronger in males younger than 40 years for all vaccines, where the number of excess myocarditis events per million persons was higher following a second dose of mRNA-1273 than following a positive SARS-CoV-2 test (97 [91, 99] versus 16 [12, 18]). In females younger than 40 years, the number of excess events per million was similar following a second dose of mRNA-1273 and a positive test (7 [1, 9] versus 8 [6, 8]).

CONCLUSIONS: Overall, the risk of myocarditis is greater following SARS-CoV-2 infection than following COVID-19 vaccination and remains modest following sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis following vaccination is higher in younger males, particularly following a second dose of the mRNA-1273 vaccine.

Cite as

Patone, M., Mei, X., Handunnetthi, L., Dixon, S., Zaccardi, F., Shankar-Hari, M., Watkinson, P., Khunti, K., Harnden, A., Coupland, C., Channon, K., Mills, N., Sheikh, A. & Hippisley-Cox, J. 2022, 'Risk of myocarditis following sequential doses of COVID-19 vaccine and SARS-CoV-2 infection by age and sex', Circulation. https://doi.org/10.1161/CIRCULATIONAHA.122.059970

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Last updated: 05 October 2022
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