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Review
. 2021 Aug 10;144(6):471-484.
doi: 10.1161/CIRCULATIONAHA.121.056135. Epub 2021 Jul 20.

Myocarditis With COVID-19 mRNA Vaccines

Biykem Bozkurt  1 , Ishan Kamat  2 , Peter J Hotez  3
Affiliations
Review

Myocarditis With COVID-19 mRNA Vaccines

Biykem Bozkurt et al. Circulation. .

Abstract

Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males. According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age. In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels. ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients. There was no evidence of acute COVID-19 or other viral infections. In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased. Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed. The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women. Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment. Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.

Keywords: COVID-19; COVID-19 vaccines; SARS-CoV-2; mRNA vaccine; myocarditis; pericarditis; vaccination.

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Figures

Figure 1.
Figure 1.
Centers for Disease Control and Prevention working case definitions for acute myocarditis and acute pericarditis. Adapted from Centers for Disease Control and Prevention with permission. Copyright ©2021, Centers for Disease Control and Prevention.
Figure 2.
Figure 2.
Predicted benefits of reduction in COVID-19–related hospitalizations and death and risks of myocarditis after second dose of mRNA COVID-19 vaccination by age group. Adapted from Centers for Disease Control and Prevention with permission. Copyright ©2021, Centers for Disease Control and Prevention (“COVID-19 mRNA vaccines in adolescents and young adults: Benefit-risk presentation”). Predictions for hospitalization and myocarditis rates were calculated for every million doses of mRNA vaccine based on hospitalization rates from Coronavirus Disease 2019 (COVID-19)–Associated Hospitalization Surveillance Network (COVID-NET) as of May 22. Benefit/risk were calculated over 120 days. To meet the ECG or rhythm-monitoring criterion, at least 1 of the following must be included: ST-segment or T-wave abnormalities, paroxysmal or sustained atrial, supraventricular, or ventricular arrhythmias, atrioventricular nodal conduction delays or intraventricular conduction defects. COVID-19 indicates coronavirus disease 2019; ICU, intensive care unit; MIS-C, multisystem inflammatory syndrome in children; and SARS-CoV-2, severe acute respiratory syndrome coronavirus-2. †Using either the original or revised Lake Louise criteria. ‡Using the Dallas criteria. §Autopsy cases may be classified as pericarditis on the basis of meeting histopathologic criteria of the pericardium.
Figure 3.
Figure 3.
Potential risk of myocarditis with COVID-19 mRNA vaccination in the 120 days after vaccination and predicted prevention of COVID-19 cases, COVID-19–related hospitalizations, intensive care unit admissions, and deaths according to age groups and sex. Adapted from Centers for Disease Control and Prevention with permission. Copyright ©2021, Centers for Disease Control and Prevention (“COVID-19 mRNA vaccines in adolescents and young adults: Benefit-risk presentation”). Predictions for hospitalization and myocarditis rates were calculated for every million doses of mRNA vaccine based on hospitalization rates from Coronavirus Disease 2019 (COVID-19)–Associated Hospitalization Surveillance Network (COVID-NET) as of May 22, 2021. Benefit/risk was calculated over 120 days.
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