A review of adverse events data in the United States from late 2020 through the summer of 2021 confirms that adolescent males and young male adults have the highest risk for myocarditis linked to Covid-19 vaccination with either of the messenger RNA (mRNA) vaccines—BNT162b2 and mRNA-1273—and that the risk is greatest after the second dose.

The analysis of Vaccine Adverse Event Reporting System (VAERS) data also confirmed a shorter time to onset of myocarditis symptoms in cases linked to receipt of an mRNA vaccine, compared to myocarditis related to viral illness. Symptoms associated with the heart muscle inflammation disorder were typically diagnosed within days of vaccination.

Major presenting symptoms, including chest pain (89%) and shortness of breath (29.6%), tended to resolve more quickly than more typical cases of myocarditis unrelated to Covid-19 vaccination, wrote Centers for Disease Control and Prevention researcher Matthew Oster, MD, Atlanta, Georgia, and colleagues. Their VAERS data study was published online Jan. 25 in JAMA.

In more than 192 million people in the U.S. receiving roughly 354 million mRNA-based Covid-19 vaccines between December 2020 and August 2021, 1,626 cases of vaccine-related myocarditis were reported to VAERS, with most occurring in young males.

“Even though almost all individuals with cases of myocarditis were hospitalized and clinically monitored, they typically experienced symptomatic recovery after receiving only pain management. In contrast, typical viral cases of myocarditis can have a more variable clinical course,” Oster and colleagues wrote, adding that up to 6% of “typical” viral myocarditis cases occurring in adolescents require heart transplant or lead to death.

The VAERS review identified 1,991 reports of myocarditis and 1,626 met the CDC’s case definition. The median age of reported cases was 21 years (IQR, 16-31 years) and the median time to symptom onset after the second vaccination dose was 2 days (IQR, 1-3 days). A full 90% of myocarditis events occurred within 7 days. When gender was reported, males accounted for 82% of the myocarditis cases.

“The crude reporting rates for cases of myocarditis within 7 days after Covid-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata,” the researchers wrote.

Among the main findings:

  • Myocarditis rates were highest after the second vaccination dose in young males between 12 and 15 years of age (70.7 per million doses of the BNT162b2 vaccine), in adolescent males age 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men age 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively).
  • There were 826 cases of myocarditis among those younger than 30 years of age, with almost all cases with available clinical information (98%) in this age group showing elevated troponin levels, 72% showing abnormal electrocardiogram results, and 72% having abnormal cardiac magnetic resonance imaging results.
  • Approximately 96% of cases ages 30 years and younger were hospitalized; in 87% of these cases, presenting symptoms had resolved by hospital discharge.
  • The most common treatment was nonsteroidal anti-inflammatory drugs (87%).

“There were no verified cases of myocarditis requiring a heart transplant, extracorporeal membrane oxygenation, or a ventricular assist device,” the researchers wrote, adding that long-term outcome data are not yet available for Covid-19 mRNA vaccine-associated myocarditis.

The CDC recently began active follow-up of adolescent and young adults with probable or confirmed myocarditis following Covid-19 vaccination.

In a separate study, published online Jan. 24 in Annals of Internal Medicine, researchers reported findings from one of the first case-control studies analyzing myocarditis and related carditis risk associated with the BNT162b2 vaccine and the CoronaVac inactivated virus vaccine.

The analysis of 160 myocarditis cases and 1,533 controls showed an elevated risk for carditis observed in recipients of BNT162b2 vaccine but not the inactivated virus vaccine. The incidence of carditis per 100,000 doses of CoronaVac and the mRNA vaccine administered respectively was estimated to be 0.31 (95% CI, 0.13-0.66) and 0.57 (CI, 0.36- 0.90), respectively. Multivariable analyses showed that recipients of the BNT162b2 vaccine had higher odds of carditis (adjusted odds ratio [OR], 3.57; 95% CI, 1.93-6.60) compared to people who were unvaccinated.

Compared to controls who did not develop carditis, the odds ratio (OR) for developing carditis was 4.68 (95% CI, 2.25-9.71) for males and 2.22 (CI, 0.57-8.69) for females receiving the BNT162b2 vaccine. For adults and adolescents receiving the BNT162b2 vaccine, ORs were 2.41 (95% CI, 1.18-4.90) and 13.79 (95% CI, 2.86-110.38), respectively.

In a sub-analysis, the odds ratio for myocarditis only was 9.29 (95% CI, 3.94-21.91) and 1.06 (95% CI, 0.35-3.22) for only pericarditis associated with receipt of the BNT162b2 vaccine, and the risk was mainly seen after the second dose of the mRNA vaccine.

“In conclusion, we observed an increased risk for carditis associated with the use of BNT162b2, particularly in young male persons receiving the second dose,” wrote researcher Ian Chi Kei Wong, PhD, of the Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, and Laboratory of Data Discovery for Health (D24H), Hong Kong Special Administrative Region, China, and the University College London, U.K., and colleagues. “Although the absolute risk is very low, this elevated risk should be made known to vaccine recipients and physicians and be weighed against the benefits of vaccination.”

Limitations of the study conducted by Oster et al include that VAERS is a passive reporting system with possibly incomplete data of variable quality, inability to obtain medical records or interview some physicians, and the lack of clinical review.

Limitations of the study from Wong et all include an insufficent sample size of adolescents resulting in relatively wide confidence intervals, dependence on ICD-9-CM codes to identify cases and thereby including only cases that required medical attention, the study’s observational nature, its predominatntly ethnic Chinese population, the lack of long-term postdischarge outcomes, the lack of data on overseas vaccine exposure, and that hospitalized control subjects may not be representative of risks.


The VAERS study was funded by the CDC, Boston Medical Center, Cincinnati Children’s Hospital Medical Center, and Vanderbilt University Medical Center with the US Centers for Disease Control and Prevention (CDC) Clinical Immunization Safety Assessment Project.

Oster reported no disclosures.

The case-control study was funded by a research grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region.

Wong reported receiving grants from Amgen, Bristol Myers Squibb, Pfizer, Jannssen, Bayer, GSK, Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund in Hong Kong, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia outside the submitted work; consulting fees from IQVIA outside the submitted work; payment for expert testimony from the Appeal Court in Hong Kong outside the submitted work; and membership in the Pharmacy and Poison Boards, Expert Committee on Clinical Events Assessment Following Covid-19 Immunization, and the Advisory Panel on Covid-19 Vaccines of the Hong Kong Government.



Salynn Boyles, Contributing Writer, BreakingMED™

Kaiser Health News

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