Risk for Myopericarditis Minimal Following COVID-19 Vaccination

Close up view of an adult young man receiving a vaccine at a medical clinic. Female nurse or doctor injecting vaccine into african american male patient.
A study was conducted to determine the incidence of myopericarditis following COVID-19 vaccination compared with non-COVID-19 vaccination.

The risk of a COVID-19 vaccine resulting in myopericarditis is minimal. Although it is rare following mRNA vaccines, a subgroup of younger males shows a slightly increased occurrence of myopericarditis. These findings were published in The Lancet Respiratory Medicine.

Prior to the pandemic, myopericarditis, an uncommon complication of vaccination, was only related to smallpox vaccination. However, as of March 2022, with more than 10 billion doses of COVID-19 vaccines dispensed, reports of myopericarditis have increased significantly and studies have suggested a link to the COVID-19 vaccination, especially in men aged younger than 30 years.

Researchers sought to compare the incidence of myopericarditis following COVID-19 and non-COVID-19 vaccination to determine the risk for myopericarditis in subpopulations receiving COVID-19 vaccinations. They also sought to quantify the incidence of myocarditis, pericarditis, and mortality after receiving a vaccine. The primary outcome was myopericarditis following vaccination.

To accomplish this, they conducted a systematic review and meta-analysis of 22 studies from MEDLINE, Embase, Cochrane, and Scopus databases. The review and analysis was done on 405,272,721 vaccine doses from January 1947 through December 2021. This included 11 studies reporting on 395,361,933 COVID-19 vaccine doses. The balance reported on smallpox, influenza, and an assortment of non-COVID-19 vaccines.

The difference in incidence of myopericarditis among subpopulations was analyzed, stratifying for vaccine (COVID-19 vs non-COVID-19), age (adult vs pre-adult), sex, and sub-stratifying for mRNA vs non-mRNA in COVID-19 vaccines. The researchers also used the Grading of Recommendations, Assessment, Development and Evaluations approach to assess the certainty of their evidence (low-high).

Overall, myopericarditis occurred in 33.3 cases per million vaccine doses (95% CI, 15.3-72.6), with no significant difference between COVID-19 vaccines (18.2 cases per million vaccine doses; 95% CI, 10.9-30.3; high certainty) and non-COVID-19 vaccines (56.0 cases per million vaccine doses; 95% CI, 10.7-293.7; moderate certainty; P =.20). Myopericarditis incidence was significantly higher following smallpox vaccinations (132.1 cases per million doses; 95% CI, 81.3-214.6; P <.0001) compared with COVID-19 vaccination, but with no significant difference following influenza vaccinations (1.3 cases per million doses; 95% CI, 0.0-884.1; P =.43), and no significant difference compared with other non-smallpox vaccinations (57 cases per million doses; 95% CI, 1.1-3036.6; P =.58).

The incidence of myopericarditis was significantly higher in men and in people younger than 30 years, as well as in patients who had received an mRNA vaccine or a second dose of vaccine (vs a first or third dose).

Study limitations included lack of generalizability to children younger than 12 years of age and use of a heterogeneity confounding analysis. There was also underrepresentation of some important non-COVID-19 vaccines and statistical comparisons across a wide span of time for non-COVID-19 vaccines vs a short span for COVID-19 vaccines. Other limitations were lack of granular data and inability to confirm myopericarditis diagnosis induced by COVID-19 vaccine.

The researchers concluded that, “meta-analysis of more than 400 million doses of vaccines suggests that the overall incidence of myopericarditis following COVID-19 vaccination is similar to that in the published literature on its incidence after influenza vaccination, and is lower than the incidence after live smallpox vaccination.” They noted, “certain subpopulations—those of male sex or younger age and those receiving an mRNA vaccine, particularly the second dose—appear to be at increased risk of myopericarditis following COVID-19 vaccination.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Ling RR, Ramanathan K, Tan FL, et al. Myopericarditis following COVID-19 vaccination and non-COVID-19 vaccination: a systematic review and meta-analysis. Lancet Respir Med. Published online April 11, 2022. doi:10.1016/S2213-2600(22)00059-5