We conducted a self-controlled case series analysis of hospital admissions for
myocarditis or
pericarditis in England between 22 February 2021 and 6 February 2022 in the 50 million individuals eligible to receive the adenovirus-vectored
vaccine (ChAdOx1-S) for priming or an
mRNA vaccine (
BNT162b2 or
mRNA-1273) for priming or boosting.
Myocarditis and
pericarditis admissions were extracted from the Secondary Uses Service (SUS) database in England and vaccination histories from the National Immunisation Management System (NIMS); prior
infections were obtained from the UK Health Security Agency's Second-Generation Surveillance Systems. The relative incidence (RI) of admission within 0 to 6 and 7 to 14 days of vaccination compared with periods outside these risk windows stratified by age, dose, and prior
SARS-CoV-2 infection for individuals aged 12 to 101 years was estimated. The RI within 27 days of an
infection was assessed in the same model. There were 2,284 admissions for
myocarditis and 1,651 for
pericarditis in the study period. Elevated RIs were only observed in 16- to 39-year-olds 0 to 6 days postvaccination, mainly in males for
myocarditis. Both
mRNA vaccines showed elevated RIs after first, second, and third doses with the highest RIs after a second dose 5.34 (95% confidence interval (CI) [3.81, 7.48]; p < 0.001) for
BNT162b2 and 56.48 (95% CI [33.95, 93.97]; p < 0.001) for
mRNA-1273 compared with 4.38 (95% CI [2.59, 7.38]; p < 0.001) and 7.88 (95% CI [4.02, 15.44]; p < 0.001), respectively, after a third dose. For ChAdOx1-S, an elevated RI was only observed after a first dose, RI 5.23 (95% CI [2.48, 11.01]; p < 0.001). An elevated risk of admission for
pericarditis was only observed 0 to 6 days after a second dose of
mRNA-1273 vaccine in 16 to 39 year olds, RI 4.84 (95% CI [1.62, 14.01]; p = 0.004). RIs were lower in those with a prior
SARS-CoV-2 infection than in those without, 2.47 (95% CI [1.32,4.63]; p = 0.005) versus 4.45 (95% [3.12, 6.34]; p = 0.001) after a second
BNT162b2 dose, and 19.07 (95% CI [8.62, 42.19]; p < 0.001) versus 37.2 (95% CI [22.18, 62.38]; p < 0.001) for
mRNA-1273 (
myocarditis and
pericarditis outcomes combined). RIs 1 to 27 days postinfection were elevated in all ages and were marginally lower for
breakthrough infections, 2.33 (95% CI [1.96, 2.76]; p < 0.001) compared with 3.32 (95% CI [2.54, 4.33]; p < 0.001) in
vaccine-naïve individuals respectively.
CONCLUSIONS: We observed an increased risk of
myocarditis within the first week after priming and booster doses of
mRNA vaccines, predominantly in males under 40 years with the highest risks after a second dose. The risk difference between the second and the third doses was particularly marked for the
mRNA-1273 vaccine that contains half the amount of
mRNA when used for boosting than priming. The lower risk in those with prior
SARS-CoV-2 infection, and lack of an enhanced effect post-booster, does not suggest a spike-directed immune mechanism. Research to understand the mechanism of
vaccine-associated
myocarditis and to document the risk with bivalent
mRNA vaccines is warranted.