Myopericarditis following COVID-19 vaccination and non-COVID-19 vaccination: a systematic review and meta-analysis

Abstract

Background: Myopericarditis is a rare complication of vaccination. However, there have been increasing reports of myopericarditis following COVID-19 vaccination, especially among adolescents and young adults. We aimed to characterise the incidence of myopericarditis following COVID-19 vaccination, and compare this with non-COVID-19 vaccination.

Methods: We did a systematic review and meta-analysis, searching four international databases from Jan 1, 1947, to Dec 31, 2021, for studies in English reporting on the incidence of myopericarditis following vaccination (the primary outcome). We included studies reporting on people in the general population who had myopericarditis in temporal relation to receiving vaccines, and excluded studies on a specific subpopulation of patients, non-human studies, and studies in which the number of doses was not reported. Random-effects meta-analyses (DerSimonian and Laird) were conducted, and the intra-study risk of bias (Joanna Briggs Institute checklist) and certainty of evidence (Grading of Recommendations, Assessment, Development and Evaluations approach) were assessed. We analysed the difference in incidence of myopericarditis among subpopulations, stratifying by the type of vaccine (COVID-19 vs non-COVID-19) and age group (adult vs paediatric). Among COVID-19 vaccinations, we examined the effect of the type of vaccine (mRNA or non-mRNA), sex, age, and dose on the incidence of myopericarditis. This study was registered with PROSPERO (CRD42021275477).

Findings: The overall incidence of myopericarditis from 22 studies (405 272 721 vaccine doses) was 33·3 cases (95% CI 15·3-72·6) per million vaccine doses, and did not differ significantly between people who received COVID-19 vaccines (18·2 [10·9-30·3], 11 studies [395 361 933 doses], high certainty) and those who received non-COVID-19 vaccines (56·0 [10·7-293·7], 11 studies [9 910 788 doses], moderate certainty, p=0·20). Compared with COVID-19 vaccination, the incidence of myopericarditis was significantly higher following smallpox vaccinations (132·1 [81·3-214·6], p<0·0001) but was not significantly different after influenza vaccinations (1·3 [0·0-884·1], p=0·43) or in studies reporting on various other non-smallpox vaccinations (57·0 [1·1-3036·6], p=0·58). Among people who received COVID-19 vaccines, the incidence of myopericarditis was significantly higher in males (vs females), in people younger than 30 years (vs 30 years or older), after receiving an mRNA vaccine (vs non-mRNA vaccine), and after a second dose of vaccine (vs a first or third dose).

Interpretation: The overall risk of myopericarditis after receiving a COVID-19 vaccine is low. However, younger males have an increased incidence of myopericarditis, particularly after receiving mRNA vaccines. Nevertheless, the risks of such rare adverse events should be balanced against the risks of COVID-19 infection (including myopericarditis).

Funding: None.

Figure 1

Flow diagram of study identification and inclusion

Figure 2

Incidence of myopericarditis following vaccination in studies investigating COVID-19 and non-COVID-19 vaccines The pooled incidence of myopericarditis following vaccination was 18·2 cases per million doses of COVID-19 vaccine and 56·0 cases per million doses of non-COVID-19 vaccine (p=0·20).

Figure 3

Incidence of myopericarditis following vaccination in studies investigating mRNA and non-mRNA COVID-19 vaccines The pooled incidence of myopericarditis following COVID-19 vaccination was 22·6 cases per million doses of mRNA vaccine and 7·9 cases per million doses of non-mRNA vaccine (p=0·0010).

Figure 4

Effect of age on incidence of myopericarditis following COVID-19 vaccination Strata-level meta-regression between age and logit-transformed robust-variance estimated incidence of myopericarditis following COVID-19 vaccination. Bubble sizes correspond to the weights of each study, which are computed as an inverse of the SE of the strata-level pooled estimate. Horizontal error bars correspond to the range of ages that each strata represents. Excluding people younger than 12 years, for whom few data were reported in the studies included, the incidence of myopericarditis increases as the mean age of each subgroup decreases.