Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination

PCORnet, United States, January 2021-January 2022

Jason P. Block, MD; Tegan K. Boehmer, PhD; Christopher B. Forrest, MD, PhD; Thomas W. Carton, PhD; Grace M. Lee, MD; Umed A. Ajani, MBBS; Dimitri A. Christakis, MD; Lindsay G. Cowell, PhD; Christine Draper; Nidhi Ghildayal, PhD; Aaron M. Harris, MD; Michael D. Kappelman, MD; Jean Y. Ko, PhD; Kenneth H. Mayer, MD; Kshema Nagavedu, MPH; Matthew E. Oster, MD; Anuradha Paranjape, MD; Jon Puro, MPA; Matthew D. Ritchey; David K. Shay, MD; Deepika Thacker, MD; Adi V. Gundlapalli, MD, PhD


Morbidity and Mortality Weekly Report. 2022;71(14):517-523. 

In This Article


Analysis of EHR data from 40 U.S. health care systems found that the incidences of cardiac complications after SARS-CoV-2 infection or mRNA COVID-19 vaccination were low overall but were higher after infection than after vaccination for both males and females in all age groups. Two studies from Israel[2] and the United Kingdom[3] have found similar higher risk for myocarditis after SARS-CoV-2 infection compared with that after mRNA COVID-19 vaccination.

Myocarditis or pericarditis incidence after mRNA COVID-19 vaccination in the current study (0–35.9 per 100,000 for males and 0–10.9 for females across age groups and vaccine cohorts) was similar to estimates found in a study from eight U.S. health systems in the Vaccine Safety Datalink.[10] Previous CDC estimates found the highest risk for post-vaccination myocarditis among males aged 16–17 years (10.6 per 100,000) during a 7-day risk window after receipt of a second mRNA COVID-19 vaccine dose.[5] Estimates from the current study (22.0 per 100,000 males aged 12–17 years) are higher, likely because outcomes were captured using ICD-10-CM codes alone rather than through passive reporting with subsequent verification through medical record review. Even among males aged 12–17 years, the group with the highest incidence of cardiac complications after receipt of a second mRNA COVID-19 vaccine dose, the risk was 1.8–5.6 times as high after SARS-CoV-2 infection than after vaccination.

The findings in this report are subject to at least six limitations. First, data were obtained using a query that returned aggregate data from sites, precluding adjustment for potential confounders. Stratification by age and sex was performed because of their clear prior association with cardiac outcomes. Second, outcomes were rare in some cohorts, leading to wide CIs around RR estimates. Third, only SARS-CoV-2 test results and mRNA COVID-19 vaccinations documented in EHRs were available for assessment. SARS-CoV-2 infections were not captured if testing occurred in homes, schools, community sites, or pharmacies. Similarly, EHR data in this study captured ≥1 dose of mRNA COVID-19 vaccine for 28% of persons aged ≥5 years. Nationally, 82% of persons aged ≥5 years were reported to have received any COVID-19 vaccination; 97% of all vaccinations administered were mRNA COVID-19 vaccines.§§ Underascertainment of SARS-CoV-2 infections and mRNA COVID-19 vaccinations reduced sample size and might have introduced bias if capture of infection or vaccination within the EHR occurred differentially for those with cardiac outcomes.¶¶ Fourth, case definitions for myocarditis, pericarditis, or MIS were ICD-10-CM code–based; diagnoses were not confirmed with chart review and are subject to misclassification. Fifth, cases of MIS among persons without documented SARS-CoV-2 infection were not included.[9] Finally, some overlap might have occurred in risk windows for persons who had a SARS-CoV-2 infection soon after vaccination or a vaccination soon after infection. Exclusions were made for persons who received COVID-19 vaccine doses ≤30 days before infection or who had infections ≤30 days before vaccination.

Cardiac complications were rare after SARS-CoV-2 infection or mRNA COVID-19 vaccination. However, the risks for these complications were higher after infection than after vaccination among males and females in all age groups. These findings provide important context for balancing risks and benefits of mRNA COVID-19 vaccination among eligible persons ≥5 years.

§§ (Accessed March 29, 2022).
¶¶If patients who received a SARS-CoV-2–positive test result at a health care system were more likely to return to the same health care system for myocarditis, pericarditis, or MIS treatment than were patients who had their mRNA COVID-19 vaccination documented at the health care system, then the underascertainment of outcomes might be higher in the vaccination cohorts, introducing bias away from the null. This scenario might occur if a person was more likely to visit a tertiary care referral center participating in this study if they were more severely ill with a cardiac complication after SARS-CoV-2 infection than a perhaps mild cardiac complication after COVID-19 vaccination. However, if the cardiac complications were more commonly linked to vaccination than infection in the EHR, bias would be toward the null. This scenario might occur if clinicians were more likely to document an mRNA COVID-19 vaccination in the EHR if a cardiac complication was noted after vaccination than if the cardiac complication occurred after SARS-CoV-2 infection.