Even though absolute rates of myocarditis remain low in recipients of mRNA COVID-19 vaccines, a new Canadian study suggested that vaccine type, age, and sex are important factors for vaccine providers to consider when seeking to reduce the risk of the adverse effect.

Specifically, the report in the Canadian Medical Association Journal recommended the preferential use of the BNT162b2 vaccine (Pfizer-BioNTech) over the mRNA-1273 (Moderna) vaccine for people aged 18 to 29 years.

Background information in the University of British Columbia–led study noted that postmarketing evaluations have linked myocarditis to SARS-CoV-2 mRNA vaccines. The study team sought to estimate the incidence of myocarditis after mRNA vaccination against SARS-CoV-2 and to compare the incidence with expected rates based on historical background rates in British Columbia.

To do that, researchers conducted an observational study using population health administrative data from the British Columbia COVID-19 cohort from December 15, 2020, to March 10, 2022. The primary exposure was defined as any dose of an mRNA vaccine against SARS-CoV-2, while the primary outcome was the incidence of hospital admission or emergency department visit for myocarditis or myopericarditis within 7 and 21 days postvaccination.

The study observed 99 incident cases of myocarditis within 7 days (0.97 cases per 100,000 vaccine doses; observed vs. expected ratio 14.81; 95% CI, 10.83-16.55) and 141 cases within 21 days (1.37 cases per 100,000 vaccine doses; observed vs. expected ratio 7.03; 95% CI, 5.92-8.29) postvaccination.

The researchers found that cases of myocarditis per 100 000 vaccine doses were higher for:

• Young people aged 12 to 17 years (2.64; 95% CI, 1.54-4.22) and aged 18 to 29 years (2.63; 95% CI, 1.94-3.50) than for older age groups
• For males compared with females (1.64; 95% CI, 1.30-2.04 vs. 0.35; 95% CI, 0.21-0.55)
• For those receiving a second dose compared with a third dose (1.90; 95% CI, 1.50-2.39 vs. 0.76; 95% CI, 0.45-1.30)
• For those who received the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer-BioNTech) vaccine (1.44; 95% CI, 1.06-1.91 vs. 0.74; 95% CI 0.56-0.98).

"The highest observed-to-expected ratio was seen after the second dose among males aged 18-29 years who received the mRNA-1273 vaccine (148.32; 95% CI, 95.03-220.69)," the authors advised.

The study recounts how postmarketing studies have suggested an association between mRNA SARS-CoV-2 vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) and myocarditis, among other adverse events after immunization. That has fed concerns about the safety of mRNA vaccines, especially among younger populations, the authors wrote.

"Most evidence comes from case reports and case series," the researchers stated. "Earlier data have suggested higher rates of myocarditis among young adults after the mRNA-1273 compared with the BNT162b2 vaccine. Limited data are available on the rate of myocarditis after the third dose, which is relevant as further boosters are planned. Given the important economic and health consequences of COVID-19, it is vital to further evaluate the likelihood of this signal."

The BC COVID-19 Cohort included more than 10.2 million doses of mRNA vaccines administered to people aged 12 years and older from December 15, 2020, to March 10, 2022. Almost 7 million were BNT162b2 (Pfizer-BioNTech) doses and 3.2 million were mRNA-1273 (Moderna) doses.

The study reports that, on average, the rate of myocarditis 21 days after vaccination was 1.37 per 100,000 people compared with an expected rate of 0.39 per 100,000 of unvaccinated people. "The highest rates of myocarditis were in males (rate: 2.15/100,000), among those aged 18-29 (rate: 2.97/100,000), after the second dose (rate: 2.27/100,000 doses) and in people vaccinated with mRNA-1273 (Moderna) (rate: 1.75/100,000). Among males aged 18-29 who received the mRNA-1273 (Moderna) vaccine, the rate was 22.9/100,000 doses. After the third dose, rates of myocarditis were lower, including among people aged 18-29," the researchers pointed out.

They added, "The overall rates of myocarditis per 100,000 doses were still very low for both vaccine products," emphasizing that the "benefits of vaccination against SARS-CoV-2 in reducing the severity of COVID-19, hospital admission and deaths far outweigh the risk of developing myocarditis...Thus, continued vaccination of this group, along with monitoring of adverse events, including myocarditis, should remain the preferred strategy."

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