Rare heart-related side effects higher with Moderna COVID vaccine

Though both complications were rare, data from Ontario show higher rates of myocarditis and pericarditis with the Moderna COVID-19 vaccine than with the Pfizer-BioNTech vaccine, but the rates were lower for both vaccines if the spacing between receiving two doses was extended, according to a study late last week in JAMA Network Open.

Myocarditis is an inflammation of the heart muscle, and pericarditis involves swelling of the thin membrane around the heart.

Five times higher rate with short dosing interval

For the study, researchers from Public Health Ontario, the University of Toronto, and the nonprofit ICES analyzed data on 19,740,741 doses of mRNA COVID vaccine administered in the province from Dec 14, 2020—when vaccines were first available—to Sep 4, 2021.

Ontario's electronic reporting system revealed 297 cases of myocarditis or pericarditis among those vaccine recipients, or only about 15 cases per million vaccine doses.

Of the 297 cases, 228 (76.8%) occurred in male recipients, and the median age of affected patients was 24 years (range, 12 to 81 years). Also, 207 (69.7%) of the cases occurred following the second vaccine dose.

Nearly all of the cases (290, or 97.6%) involved an emergency department visit, with 210 cases (70.7%) also requiring hospital admission. The number of hospitalizations was 87 (82.9%) for myocarditis, 33 (38.8%) for pericarditis, and 90 (84.1%) for people who had both conditions.

When the investigators focused solely on people who received their second dose during the period of enhanced passive surveillance (from Jun 1, 2021, onward), they found that the incidence of myocarditis or pericarditis was 62.5 cases per million doses after the second Moderna dose (95% confidence interval [CI], 42.4 to 88.6), compared with 29.0 cases per million doses (95% CI, 20.2 to 40.3) for Pfizer—or more than twice as high.

Men 18 to 24 years old had the highest rate: 299.5 cases per million doses after the second Moderna dose (95% CI, 171.2 to 486.4), compared with 59.2 cases per million doses (95% CI, 19.2 to 138.1) for Pfizer—or about five time higher with Moderna.

In assessing the effect of the interval between doses, the researchers found the incidence of either condition dropped by one-fifth for both vaccines when spacing was longer.

They recorded only 16.2 myocarditis or pericarditis cases per million Moderna doses when the interval was 56 days or longer, compared with 83.9 cases per million when the interval was 30 days or less. For the Pfizer vaccine, the longer interval was tied to 9.6 cases per million, compared with 52.1 cases per million for the shorter interval.

Study data also revealed that a Pfizer dose followed by a Moderna dose was associated with higher reported rates of myocarditis or pericarditis than were two consecutive doses of Moderna vaccine, a finding that the authors say requires further exploration.

'Still rare or very rare'

The authors write, "Several immunization advisory bodies, including those in Canada, the US, Australia, and the UK, have issued guidance outlining the considerations for or providing clear recommendations to use longer intervals between primary-series vaccine doses with the dual aims of improving the durability of the immune response and possibly reducing the rare risk of myocarditis or pericarditis."

In placing the risk in perspective, they add, "These findings need to be considered within the context of absolute risk because myocarditis and pericarditis are still rare or very rare events"

They conclude, "The findings of this study suggest that modifying mRNA COVID-19 vaccination programs to incorporate age-based product considerations and longer interdose intervals may reduce the risk of these events."

In a related commentary in the same journal, Eric Weintraub, MPH, with the US Centers for Disease Control and Prevention, Matthew Oster, MD, MPH, of Emory University, and Nicola Klein, MD, PhD, with the Kaiser Permanente Vaccine Study Center, note that the fewer side effects tied to a longer dosing interval are an important finding.

They write, "Although the absolute numbers were small, there was a consistent reduction in the rates of myocarditis or pericarditis with increasing intervals between doses, with the lowest rates occurring among individuals with interdose intervals of 56 days or more. In addition, data from other countries indicate that vaccine effectiveness may be higher with an interdose interval for mRNA vaccinations of 6 to 8 weeks compared with the 3- to 4-week interval that is recommended in the US.

"Therefore, an 8-week interval may be optimal for some people aged 12 years or older, especially for male individuals aged 12 to 39 years."

The commentators also note, "COVID-19 vaccination has prevented substantial morbidity and mortality and has been the most effective primary prevention strategy against COVID-19 infection and serious complications," but they add that scientists must remain vigilant in monitoring for myocarditis, pericarditis, and other adverse events.

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