By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

SYNOPSIS: Receipt of a COVID-19 mRNA vaccine is associated with a small but real risk of development of myocarditis, predominantly in young males. The vast majority of cases are mild, self-limited, and require no intervention.

SOURCES: Mevorach D, Anis E, Cedar N, et al. Myocarditis after BNT162b2 mRNA vaccine against Covid-19 in Israel. N Engl J Med 2021; Oct 6. doi: 10.1056/NEJMoa2109730. [Online ahead of print].

Witberg G, Barda N, Hoss S, et al. Myocarditis after Covid-19 vaccination in a large health care organization. N Engl J Med 2021; Oct 6. doi: 10.1056/NEJMoa2110737. [Online ahead of print].

Israel initiated an effective national program of immunization against COVID-19 with the BNT162b2 mRNA vaccine produced by Pfizer/BioNTech shortly after it became available and, by May 31, 2021, 5.1 million people had been fully vaccinated. With early reports of myocarditis occurring in association with receipt of the vaccine, the Ministry of Health initiated an active surveillance program and they now report the results covering the period of Dec. 30, 2020, through May 31, 2021.

As reported by Mevorach and colleagues, the surveillance program identified 142 cases, all but six of which were deemed to represent definite or probable myocarditis. During the same time period, 101 cases of myocarditis were identified among individuals who had never received the vaccine, but 29 of these had confirmed COVID-19. Of the 136 definite/probable cases, 91% of whom were male and 76% < 30 years of age, 129 (95%) presented with only mild symptoms. However, one case was fulminant, and that patient died. Nineteen (14%) of the 136 presented after the first vaccine dose, while 117 (86%) did so within 30 days after the second — most within the first six days. The standardized incidence ratio (observed vs. expected) relative to historical data was 5.34 (95% confidence interval [CI], 4.48 to 6.40), but in males 16-19 years of age, it was 13.60 (95% CI, 9.30 to 19.20). The incidence rate ratio (comparing fully vaccinated to unvaccinated individuals) 30 days after dose 2 was 2.35 (95% CI, 1.10 to 5.02) overall but, among males 16-19 years of age, it was 8.96 (95% CI, 4.50 to 17.83), with myocarditis occurring in one of the 6,637 patients in this group.

Separately, Witberg and colleagues examined the database of the largest healthcare organization in Israel and identified 54 cases of myocarditis among more than 2.5 million BNT162b2 mRNA vaccine recipients during Dec. 20, 2020, through May 24, 2021. To be counted, cases had to occur within 42 days after the first vaccine dose (and, thus, up to approximately 21 days after the second dose). Of the 54 cases, 41 were mild, 12 were intermediate in severity, and one, with cardiogenic shock, was fulminant. The median age of the patients was 27 years, and 94% were male. Sixty-nine percent occurred after the second vaccine dose, with a large proportion occurring in the seven days after the dose, but with cases continuing to occur for the full subsequent 21 days of observation. Fourteen patients had echocardiographic evidence of left ventricular dysfunction at the time of admission, but this had resolved in four patients at the time of discharge and in another five patients on follow-up. The overall incidence per 100,000 recipients of at least one vaccine dose was 2.13 (95% CI, 1.56 to 2.70), but in males 16-29 years of age, it was 10.69 (95% CI, 6.93 to 14.46).


Each of these studies from Israel, one using data from the largest healthcare organization in the country and the other using national surveillance data, came to the same conclusions. Although their estimates vary to some extent, it is evident that myocarditis may be an adverse effect of this mRNA vaccine, most often within a week after the second dose, and that the highest risk occurs in young males. Nonetheless, with some exceptions, the episodes of cardiac inflammation are mild, resolve quickly, and no intervention is required although at least one related death was recorded among the total of 190 cases in the combined series.

Nonetheless, Sweden, Norway, and Finland have put the use of the Moderna vaccine on hold in individuals younger than 30 years of age while further evaluating the data.

Myocarditis, which also may occur after receipt of the Moderna mRNA vaccine, mRNA-1273, should be suspected in patients with acute onset of chest pain, shortness of breath, or palpitations.1 If a diagnosis is made, consideration should be given to testing for alternative causes, such as acute viral infection, including with SARS-CoV-2. Cases of post-vaccination myocarditis or pericarditis should be reported through the Vaccine Adverse Event Reporting System.2


  1. Centers for Disease Control and Prevention. Vaccines and Immunizations. Clinical considerations: Myocarditis and pericarditis after mRNA COVID-19 vaccination. Clinical Considerations: Myocarditis and pericarditis after receipt of mRNA COVID-19 vaccines among adolescents and young adults.
  2. Vaccine Adverse Event Reporting System (VAERS).