COVID-19 vaccine-associated myocarditis

Abstract

Myocarditis is now recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccination, particularly in adolescent and young adult males. Since the authorization of the Pfizer-BioNTech™ and Moderna™ mRNA vaccines targeting the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein, the Centers for Disease Control and Prevention (CDC) has reported 1175 confirmed cases of myocarditis after COVID-19 vaccination in individuals ages 30 years and younger as of January 2022. According to CDC data in June 2021, the incidence of vaccine-mediated myocarditis in males ages 12-29 years old was estimated to be 40.6 cases per million second doses of COVID-19 mRNA vaccination administered. Individuals with cases of COVID-19 vaccine-mediated myocarditis typically present with acute chest pain and elevated serum troponin levels, often within one week of receiving the second dose of mRNA COVID-19 vaccination. Most cases follow a benign clinical course with prompt resolution of symptoms. Proposed mechanisms of COVID-19 vaccine myocarditis include molecular mimicry between SARS-CoV-2 spike protein and self-antigens and the triggering of preexisting dysregulated immune pathways in predisposed individuals. The higher incidence of COVID-19 vaccine myocarditis in young males may be explained by testosterone and its role in modulating the immune response in myocarditis. There is limited data on long-term outcomes in these cases given the recency of their occurrence. The CDC continues to recommend COVID-19 vaccination for everyone 5 years of age and older given the greater risk of serious complications related to natural COVID-19 infection including hospitalization, multisystem organ dysfunction, and death. Further study is needed to better understand the immunopathology and long-term outcomes behind COVID-19 mRNA vaccine-mediated myocarditis.

Keywords: COVID-19; Myocarditis; Pericarditis; SARS-CoV-2; mRNA vaccine.

Figure 1

Coronavirus disease 2019 vaccine-mediated myocarditis and pericarditis cases reported to Vaccine Adverse Event Reporting System. A: Age. A total of 4317 events of myocarditis and pericarditis after receiving coronavirus disease 2019 (COVID-19) vaccine were reported to Vaccine Adverse Event Reporting System (VAERS) as of December 31, 2021. Age group 18-29 had the highest number of cases reported for myocarditis (763 cases) as well as pericarditis (404 cases). Adapted from centers for disease control and prevention (CDC) WONDER and VAERS which is updated weekly for continuous updates including revisions and new reports for preceding time periods[9]; B: Vaccine manufacturer. A total of 2512 cases of myocarditis and 1805 cases pericarditis after receiving COVID-19 vaccine were reported to VAERS as of December 31, 2021. Pfizer-BioNTech™ had the highest number of cases reported for myocarditis (1615 cases) as well as pericarditis (1063 cases). Adapted from CDC WONDER and VAERS which is updated weekly for continuous updates including revisions and new reports for preceding time periods[11]. COVID-19: Coronavirus disease 2019.

Figure 2

Cardiac magnetic resonance imaging of coronavirus disease 2019 vaccine-associated myocarditis. Cardiac magnetic resonance imaging slice of a 21-year-old male six days after receiving his second dose of the Moderna™ mRNA coronavirus disease 2019 vaccination showing evidence of significant diffuse late gadolinium enhancement and myocardial edema consistent with myocarditis.

Figure 3

Clinical decision-making algorithm for diagnosis and management of suspected coronavirus disease 2019 vaccine-associated myocarditis. ¹All cases should have monitoring with close cardiology follow up. Initial evaluation should include a basic workup in addition to ruling out other etiologies that can present similarly. Early cardiac consultation should occur for suspected coronavirus disease 2019 vaccine myocarditis along with close cardiac monitoring and follow-up. SOB: Shortness of breath; EKG: Electrocardiogram; Echo: Echocardiogram; CXR: Chest x-ray; CBC: Complete blood count; CRP: C-reactive protein; BNP: Brain natriuretic peptide; ESR: Erythrocyte sedimentation rate; CMRI: Cardiac magnetic resonance imaging; EBV: Epstein-barr virus; CMV: Cytomegalovirus; Parvo: Parvovirus; RSV: Respiratory syncytial virus.