Longer time between COVID shots may protect young men from heart inflammation

"Although myocarditis or pericarditis following receipt of mRNA vaccines is rare, 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," report Dr. Sarah Wilson of Public Health Ontario in Toronto and colleagues in JAMA Network Open.

Among roughly 19.7 million doses of mRNA vaccines administered in Ontario between December 14, 2020, and September 4, 2021, the study team identified 297 cases of myocarditis/pericarditis meeting criteria for levels 1 to 3 of the Brighton Collaboration case definitions after receipt of either the mRNA-1273 vaccine (Moderna Spikevax) or BNT162b2 (Pfizer-BioNTech Comirnaty) vaccine.

Consistent with other surveillance systems and studies, rates of myocarditis/pericarditis were highest among adolescent and young adult males following the second dose, with symptom onset usually occurring within the first week after vaccination.

Among males 18 to 24 years, rates of myocarditis/pericarditis following the second vaccine dose were higher with the Moderna than the Pfizer vaccine (299.5 vs 59.2 cases per one million doses).

The results also suggest that a longer time interval between the first and second dose in the primary vaccination series may be associated with a lower risk of myocarditis/pericarditis.

For both the Moderna and Pfizer mRNA vaccine products, rates of myocarditis/pericarditis were significantly higher when the interdose interval was 30 or fewer days (83.9 and 52.1 cases per one million doses), compared with 56 or more days (16.2 and 9.6 cases per million doses).

The authors of an editorial note that some data suggest vaccine effectiveness may be higher with an interdose interval for mRNA vaccinations of six to eight weeks compared with three to four weeks recommended in the United States.

"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," write Dr. Eric Weintraub with the U.S. Centers for Disease Control and Prevention (CDC) and co-authors.

The Ontario surveillance data also show that receipt of the Pfizer vaccine first and Moderna second was associated with higher rates of myocarditis/pericarditis compared with receipt of Moderna for both doses. This was not replicated, however, when comparing a heterologous vs homologous vaccine series for the Pfizer product, which had slightly higher rates of myocarditis/pericarditis with the homologous series.

Dr. Wilson and colleagues say studies are needed to confirm these findings and further explore the association of heterologous mRNA vaccine schedules and interdose intervals with the risk of myocarditis or pericarditis.

Dr. Weintraub and colleagues say these findings "add to the body of knowledge about the association of mRNA COVID-19 vaccination with myocarditis and pericarditis and offer additional insight into the differential risk between the 2 mRNA COVID-19 vaccine products and the possible association of the interdose interval with risk of myocarditis or pericarditis."

"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," they emphasize.

"As the epidemiology of the COVID-19 pandemic continues to evolve and as vaccination programs expand to include younger age groups and additional booster doses, vigilance in monitoring for myocarditis or pericarditis and other adverse events will be critical to ensuring that public health and regulatory authorities have timely and accurate safety data to weigh the benefits and risks of vaccination and make evidence-based recommendations to protect the public and mitigate the pandemic," they add.

The study had no commercial funding and the authors have declared no relevant conflicts of interest.