The estimated incidence of myocarditis among patients that have received at least one dose of the Pfizer-BioNTech (BNT162b2) mRNA vaccine against coronavirus disease 2019 (COVID-19) was 2.13 cases per 100,000 persons, primarily affecting young men and presenting mostly as mild or moderate illness, as demonstrated by a recent study published in the New England Journal of Medicine.
In the ongoing battle against the COVID-19 pandemic, Israel has conducted one of the fastest vaccination campaigns to date. More specifically, as of October 2021, more than 60% of the population has been fully vaccinated. Still, not much was known about the rare yet possible side effects of currently used vaccines.
On May 27, 2021, there was a statement from the US Centers for Disease Control and Prevention (CDC) on a possible link between vaccination and myocarditis (i.e., the inflammation of the heart muscle) – for both the Pfizer-BioNTech BNT162b2 vaccine and Moderna mRNA-1273 vaccine.
Six days later, the Israeli Ministry of Health disclosed that 148 cases of myocarditis had been recognized in Israel between December 2020 and May 2021, which coincided with the time when the vaccination program started. This was especially pertinent for the link between the second dose of the vaccine and myocarditis among male patients aged between 16 and 30 years.
This is why a research group from Israel, led by Dr. Guy Witberg from the Beilinson Hospital in Petah Tikva and Tel Aviv University, aimed to appraise both the burden and severity of myocarditis after vaccination in order to get more data on this issue.
Identifying myocarditis cases in vaccinees
This retrospective cohort study was based on the database of the single and largest health care institution in Israel – Clalit Health Services. By covering a total of 4.7 million patients (which accounts for 52% of the population), the aforementioned organization fully provides outpatient care, while inpatient care is provided by in-network and out-of-network hospitals.
The study population comprised individuals enrolled in Clalit Health Services and vaccinated between December 20, 2020, and May 24, 2021. The researchers have identified suspected myocarditis cases within 42 days after the first dose of the vaccine. Clinical course, presentation, and outcome have been extracted from the patients’ electronic health records.
The diagnosis of myocarditis has been established by using case definition in accordance with CDC. Moreover, myocarditis has been classified as either fulminant or non-fulminant, and the latter were further classified as mild or intermediate, taking into account all currently valid definitions.
Young men at the highest risk
In short, among more than 2.5 million vaccinated individuals over 16 years of age, there have been a total of 54 cases that met all the criteria necessary for establishing a diagnosis of myocarditis. This resulted in an estimated incidence of 2.13 cases per 100,000 individuals who had received at least one dose of the Pfizer-BioNTech (BNT162b2) mRNA vaccine.
The highest incidence of myocarditis, i.e., 10.69 cases per 100,000 individuals, has been reported in male patients aged between 16 and 29 years. Furthermore, a total of 76% of myocarditis cases has been mild and 22% intermediate, while there was one case linked with a life-threatening condition known as cardiogenic shock.
After a median follow-up period of 83 days, one patient had been readmitted to the hospital due to myocarditis, and one had died of an unknown cause. Moreover, of 14 patients with left ventricular dysfunction during admission, ten of them still had such dysfunction at the time of hospital discharge (and five of them underwent subsequent testing that revealed normal heart function).
Implications and the need for more studies
“Although we cannot directly compare the incidence of myocarditis after vaccination in our study with the incidence in other studies, our data may provide points of reference”, say the authors of this New England Journal of Medicine paper.
Still, the follow-up period in this patient cohort was relatively short to ascertain the long-term prognosis of patients with myocarditis after vaccination, and there are several other limitations of the study (such as the lack of a simultaneous comparator group, lack of myocarditis validation with biopsies, or lack of specific details in the hospital or discharge notes).
In any case, this study reinforces the need to continue with active surveillance of myocarditis cases after vaccination, as there may be an important association between mRNA vaccines and myocarditis in younger individuals.