Myocarditis low after COVID-19 vaccination, but odds elevated in male teens, young adults
Despite low absolute rates, researchers observed elevated odds of cardiac injury among male adolescents and young adults after messenger RNA-based COVID-19 vaccination in a large U.S. study, as well as a smaller study in Hong Kong.
Among 192.4 million vaccinated adolescents and young adults in the U.S., researchers observed 1,991 cases of myocarditis after at least one dose.
According to the analysis published in JAMA, there were no confirmed cases of myocarditis among individuals younger than 30 years who died after receipt of a messenger RNA (mRNA)-based COVID-19 vaccination without another identifiable cause.
“Onset of myocarditis typically follows an inciting process, often a viral illness; however, no antecedent cause is identified in many cases,” Matthew E. Oster, MD, pediatric cardiologist at Children’s Healthcare of Atlanta, and colleagues wrote. “It has been hypothesized that vaccination can serve as a trigger for myocarditis; however, only the smallpox vaccine has previously been causally associated with myocarditis based on reports among U.S. military personnel, with cases typically occurring 7 to 12 days after vaccination.”
Using the Vaccine Adverse Event Reporting System (VAERS), the CDC and FDA passively monitor adverse events of special interest, such as myocarditis and pericarditis related to COVID-19 vaccination.
“As the reports of myocarditis after COVID-19 vaccination were reported to VAERS, the Clinical Immunization Safety Assessment Project, a collaboration between the CDC and medical research centers, which includes physicians treating infectious diseases and other specialists (eg, cardiologists), consulted on several of the cases,” the researchers wrote. “In addition, reports from several countries raised concerns that mRNA-based COVID-19 vaccines may be associated with acute myocarditis.”
To understand case characteristics, reporting rates and the clinical course of vaccine-related myocarditis, researchers conducted the present analysis using data obtained with VAERS.
Vaccine-related myocarditis in the U.S.
From Dec. 14, 2020, to Aug. 31, 2021, approximately 192.4 million individuals aged at least 12 years received more than 354 million mRNA-based COVID-19 vaccines (BNT162b2, Pfizer-BioNTech; mRNA-1273, Moderna), of which 1,991 cases of myocarditis were observed after at least one dose.
A total of 1,626 reports met the CDC’s definition of probable or confirmed myocarditis. Seventy-three percent of these individuals were younger than 30 years while 33% were younger than 18 years (median age, 21 years).
The researchers reported that among cases for which dosage information was reported, 82% occurred after the second vaccination dose, and that among cases for which dosage information and time to symptom onset were reported, 74% occurred within 7 days.
“The onset of myocarditis symptoms after exposure to a potential immunological trigger was shorter for COVID-19 vaccine-associated cases of myocarditis than is typical for myocarditis cases diagnosed after a viral illness,” the researchers wrote. “Cases of typical viral myocarditis can often have indolent courses with symptoms sometimes present for weeks to months after a trigger if the cause is ever identified.”
Men represented 82% of myocarditis cases, most of which were white (69%).
Among all age and sex strata, reported rates of myocarditis were highest after the second vaccination dose in:
- males aged 12 to 15 years (70.73 per 1 million doses of the BNT162b2 vaccine);
- males aged 16 to 17 years (105.86 per 1 million doses of the BNT162b2 vaccine);
- men aged 18 to 24 years (52.43 per 1 million doses of the BNT162b2 vaccine) and
- men aged 18 to 24 years who received the mRNA-1273 vaccine (56.31 per 1 million doses).
According to the study, reporting rates of myocarditis in females were lower compared with males across all age strata younger than 50 years:
- females aged 12 to 15 years (6.35 per 1 million doses of the BNT162b2 vaccine);
- females aged 16 to 17 years (10.98 per 1 million doses of the BNT162b2 vaccine);
- women aged 18 to 24 years (6.87 per 1 million doses of the mRNA-1273 vaccine); and
- women aged 25 to 29 years (8.22 per 1 million doses of the mRNA-1273 vaccine).
The researchers reported that the most common symptoms among verified cases of myocarditis included chest pain, pressure or discomfort (89%) and dyspnea or shortness of breath (30%).
Abnormal ECG findings were present in 72% of myocarditis cases and among patients who received a cardiac MRI, abnormal findings consistent with myocarditis were present in 72%.
Among the 721 patients who received an echocardiogram, 12% had reduced left ventricular ejection fraction.
Researchers found no cases of myocarditis that required heart transplant, extracorporeal membrane oxygenation or a ventricular assist device.
Moreover, resolution of the myocarditis symptoms was reached in 87% of patients by hospital discharge.
“For patients with myocarditis, the American Heart Association and the American College of Cardiology guidelines advise that patients should be instructed to refrain from competitive sports for 3 to 6 months, and that documentation of a normal electrocardiogram result, ambulatory rhythm monitoring and an exercise test should be obtained prior to resumption of sports,” the researchers wrote. “Further doses of mRNA-based COVID-19 vaccines should be deferred, but may be considered in select circumstances.”
Vaccine-related carditis in Hong Kong
A similar analysis, published in the Annals of Internal Medicine, was conducted in Hong Kong using the Clinical Data Analysis and Reporting System (CDARS), for which researchers evaluated the occurrence of carditis after receipt of the CoronaVac (Sinovac Life Sciences) or BNT162b2 vaccine.
More than 2 million doses of CoronaVac and nearly more than 3.5 million doses of BNT162b2 were administered in Hong Kong as of August.
Francisco Tsz Tsun Lai, PhD, from 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 colleagues matched 160 inpatients with carditis (14 unvaccinated) aged 12 years or older with nearly 1,600 control participants without carditis, defined as myocarditis or pericarditis.
According to the study, the cumulative incidence of carditis after vaccination in Hong Kong was 0.57 per 100,000 doses of BNT162b2 (first dose, 0.25 per 100,000; second dose, 1 per 100,000) and 0.31 per 100,000 doses of CoronaVac (first dose, 0.08 per 100,000; second dose, 0.6 per 100,000).
After BNT162b2 vaccination, carditis symptom onset occurred within the first week in 75% of cases. Among the seven patients with carditis who received CoronaVac, carditis onset occurred more than 30 days after vaccination.
Researchers reported that carditis was more likely to occur in those who received the BNT162b2 vaccine compared with those who were unvaccinated (adjusted OR = 3.57; CI, 1.93-6.6).
Similar to the U.S. study, males were more likely to develop carditis after vaccination compared with females (aOR for males = 4.68; 95% CI, 2.25-9.71; aOR for females = 2.22; CI, 0.57-8.69).
Researchers also observed elevated risk for carditis after vaccination among adults aged 18 years or older (OR = 2.41; CI, 1.18-4.9) and adolescents aged 12 to 17 years (OR = 13.79; CI, 2.86-110.38).
The odds of developing carditis after the first and second dose of BNT162b2 were greater compared with no vaccine (aOR for first dose = 2.23; 95% CI, 0.8-6.26; aOR for second dose = 4.41; 95% CI, 2.22-8.75).
Compared with unvaccinated patients, the odds of developing myocarditis after BNT162b2 vaccination were approximately 9.29 (95% CI, 3.94-21.91), but there were no elevated odds of developing pericarditis (OR = 1.06; 95% CI, 0.35-3.22), according to the study.
“The potential mechanism underlying this observed association between BNT162b2 and carditis is unclear,” the researchers wrote.
“Postvaccination carditis should be particularly closely monitored in persons receiving BNT162b2. From the observed onset distribution, more than 1 month after either dose of vaccine, vaccine recipients and physicians should be aware of symptoms related to probable carditis,” the researchers wrote. “The symptoms include chest pain, palpitation, shortness of breath and fatigue and the subsequent elevated risk for carditis, especially among the young and males. As some countries have already begun the rollout of the third dose, the associated risk for carditis and long-term safety profile of the vaccines should continue to be closely monitored.”