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While elevated rates of myopericarditis after COVID vaccination have been observed in younger males, rates in the overall population are low and not significantly different from non-COVID vaccines, a systematic review and meta-analysis suggested.

In an analysis of 11 studies with over 400 million vaccine doses, there was no significant difference in incidence of myopericarditis after COVID vaccines versus non-COVID vaccines (18.2 vs 56.0 cases per million doses, P=0.20), reported Kollengode Ramanathan, MD, of National University Hospital in Singapore, and colleagues.

And compared with COVID vaccinations, there was no significant difference in incidence of myopericarditis after influenza vaccinations (1.3 per million doses, P=0.43), they wrote in .

"The occurrence of myopericarditis following non-COVID-19 vaccination could suggest that myopericarditis is a side effect of the inflammatory processes induced by any vaccination and is not unique to the SARS-CoV-2 spike proteins in COVID-19 vaccines or infection," said co-author Jyoti Somani, MD, also of National University Hospital, in a statement.

Indeed, Ramanathan's group noted that prior to COVID vaccines, the only vaccines with links to increased risk of myopericarditis were smallpox vaccines.

"Whether these findings reflect a true increase in incidence or merely improved reporting and recall bias remains inconclusive," they wrote.

They searched for studies from Jan. 1, 1947 to Dec. 31, 2021 with a primary outcome of incidence of myopericarditis in temporal relation to vaccination.

Overall, incidence of myopericarditis following vaccination in 22 studies was 33 cases per million doses (95% CI 15.3-72.6).

Myopericarditis was significantly higher following smallpox vaccination (132.1 cases per million) compared to COVID vaccination (P<0.001).

Among COVID vaccines, incidence of myopericarditis did not differ significantly between the adult and pediatric subgroups (26.0 vs 18.4 cases per million, P=0.58).

As other studies have confirmed, incidence of myopericarditis was significantly higher among those who received mRNA vaccines (22.6 cases per million doses), higher in people younger than age 30 (40.9 per million), and higher in males than females (23 vs 5.1 per million). The authors highlighted that "These findings are important additions to the conversation when weighing the risks and benefits of COVID-19 vaccination during this pandemic."

Ramanathan's group also found that pooled all-cause mortality was non-significant when comparing COVID vaccines (8.4 per million) and non-COVID vaccines (7.2 per million, P=0.93).

In an , Margaret Ryan, MD, and Jay Montgomery, MD, both of the Defense Health Agency in Falls Church, Virginia, characterized myopericarditis following vaccination as "unexpected, but not unprecedented."

They stated that there were "common demographic and clinical features" between myopericarditis cases associated with smallpox and mRNA COVID vaccines. Indeed, Ryan and Montgomery pointed out that U.S. military professionals ("a large number of young men," they noted), who were familiar with adverse events (AEs) following smallpox vaccination, "were among the first to observe myocarditis cases after mRNA COVID-19 vaccines," given that they likely received a two-dose vaccine series in early 2021.

The editorialists also discussed the paucity of information on myocarditis following immunizations other than smallpox or COVID, finding only five publications in a literature review spanning 75 years.

"Among the populations who received billions of vaccine doses after which myopericarditis was not observed or very rarely observed, published literature might not exist; reassuring data from background populations would not be captured in analyses of the literature," they wrote, adding that it is important to fully investigate these AEs, given their link to vaccine confidence.

"Alternative vaccine platforms, vaccine doses, or vaccine schedules could reduce the risk of rare adverse events and must be explored in the context of changing infection risk," Ryan and Montgomery added.

Study limitations included that the findings are not generalizable to children ages 12 years and younger who received the COVID vaccine, and that the vaccines were compared across different time periods, which could lead to potential confounders. Lastly, vaccines against hepatitis, Haemophilus influenzae, pneumococcus and diphtheria, pertussis and tetanus were underrepresented in the literature review.

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