Myocarditis With COVID-19 mRNA Vaccines

Bozkurt B, Kamat I, Hotez PJ, et al.
Myocarditis With COVID-19 mRNA Vaccines. Circulation 2021;144:471-484.

The following are key points to remember from this primer on myocarditis associated with the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines:

  1. The overall rates of myocarditis/pericarditis after the second dose of mRNA vaccines for COVID-19 are approximately 12.6 per million doses in individuals 12-39 years of age.
  2. The data in this manuscript are based on Centers for Disease Control and Prevention (CDC) data through June 11, 2021. Observed cases may include probable and confirmed cases by the CDC using the Vaccine Adverse Event Reporting System (VAERS).
  3. The rates of myocarditis are highest in young males. For males 12-17 years old, there were 128 observed cases in the setting of 2,039,871 second doses administered, with 0-4 cases expected. The rate in this group was therefore 62.7 per million doses or approximately 1 out of 16,000.
  4. For females aged 12-17, there were 19 observed cases in the setting of 2,189,726 doses, with 0-2 cases expected. The rate in this group was 8.7 per million or approximately 1 out of 115,000 doses.
  5. The mechanisms for the development of myocarditis after vaccination are not clear. Proposed mechanisms include molecular mimicry between the spike protein of the virus and self-antigens, trigger of pre-existing dysregulated immune pathways in certain individuals, immune response to mRNA and activation of immunologic pathways, and dysregulated cytokine expression.
  6. The reasons for male predominance in post-vaccine myocarditis remain unknown. Possible explanations relate to sex hormone differences in immune response and myocarditis, as well as the underdiagnosis of cardiac disease in women.
  7. The risk-benefit assessment appears to continue to favor vaccination, even for patients in the highest risk group for myocarditis. For example, in males aged 12-17, in which there have been 56-69 myocarditis cases per million doses, those vaccines would be expected to prevent 8,500 COVID-19 cases, 183 hospitalizations, 38 intensive care unit (ICU) admissions, and one death. For older males (24-29 years), the 15-18 myocarditis cases would be compared against 936 hospitalizations, 215 ICU admissions, and 13 deaths.
  8. Data from this study used to project vaccine efficacy and benefits of vaccination should be interpreted in the setting of the delta variant and potential for changes in vaccine efficacy in the current time period.
  9. Myocarditis after vaccination has generally been mild, with almost all patients having resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment.

Clinical Topics: COVID-19 Hub, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Pericardial Disease, Prevention, Acute Heart Failure

Keywords: Autoantigens, COVID-19, COVID-19 Vaccines, Cytokines, Diagnostic Imaging, Heart Failure, Immunity, Intensive Care Units, Molecular Mimicry, Myocarditis, Pericarditis, Primary Prevention, Risk Assessment, RNA, Messenger, Spike Glycoprotein, Coronavirus, Vaccination, Vaccines

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