Longer Time Between COVID mRNA Doses May Cut Myocarditis Risk

Patrice Wendling

December 10, 2021

This is a summary of a preprint research study written by authors from Public Health Ontario and the University of Toronto on MedRxiv provided to you by Medscape. This study has not yet been peer-reviewed. The full text of the study can be found on  MedRxiv.org .

Key Takeaways

  • Rates of myocarditis or pericarditis among all ages and sexes combined were lower for those with a longer interval between dose 1 and 2 of an mRNA vaccine.

  • Rates of myocarditis or pericarditis were highest for young males following mRNA-1273 as the second dose than for BNT162b2 as the second dose.

Why This Matters

  • Studies in multiple countries have identified an association between myocarditis and pericarditis following COVID-19 mRNA vaccines, predominantly in young males.

  • Modifications to mRNA COVID-19 vaccine programs relating to age-based product considerations and the use of longer inter-dose intervals may reduce the risk for these events.

Study Design

  • This was a population-based study of all individuals in Ontario, Canada, who received at least one dose of COVID-19 mRNA vaccine between December 14, 2020, and September 4, 2021.

  • Researchers identified 19.7 million doses of mRNA-1273 (Spikevax, Moderna) or BNT162b2 (Pfizer/BioNTech) mRNA vaccines administered during the study period in the Ontario Ministry of Health's COVaxON database.

  • A total of 417 cases of myocarditis or pericarditis were reported in the provincial COVID-19 adverse events following immunization system.

  • Upon case-level review, 297 reports met the inclusion criteria based on the Brighton Collaboration definitions for myocarditis or pericarditis (levels 1-3).

  • Researchers examined reported rates of myocarditis/pericarditis following COVID-19 mRNA vaccines by age, sex, vaccine product, dose number, inter-dose interval, and homologous or heterologous vaccine schedule.

Key Results

  • Among all ages and sexes combined, myocarditis/pericarditis rates were higher for individuals with a shorter inter-dose interval (30 days vs 56 days) and were similar for the Moderna (rate ratio [RR], 5.2; 95% CI, 2.6 - 10.0) and Pfizer (RR, 5.5; 95% CI, 3.1 - 9.6) vaccines.

  • Rates of myocarditis or pericarditis were highest among young men, aged 18-24 years, following the second dose of mRNA vaccine (38.1%) vs the first dose.

  • The highest rate of myocarditis/pericarditis observed was in males aged 18-24 years following Moderna's mRNA-1273 vaccine as the second dose, which was 5.1 (95% CI, 1.9 - 15.5) times higher than that following Pfizer's BNT162b2 vaccine as the second dose (299 vs 59.2 per million doses).

  • There were no reported events in males aged 18-24 years who received a first dose of Moderna's mRNA-1273 followed by a second dose of Pfizer's BNT162b2; however, fewer than 9000 males in this age group received this schedule.


  • Data were from a passive vaccine safety surveillance system, which may stimulate reporting during a period of enhanced reporting.  

  • Several reporting rates for product and schedule combinations were based on small numbers, leading to very wide confidence intervals.

  • The Brighton Collaboration definition does not require a biopsy for the diagnosis of myocarditis.


  • The study was supported by Public Health Ontario; the Canadian Immunization Research Network (CIRN) through a grant from the Public Health Agency of Canada and the Canadian Institutes of Health Research; and ICES, which is funded by an annual grant from the Ontario Ministry of Health. Co-author Jeffrey C. Kwong is supported by a Clinician-Scientist Award from the University of Toronto.

  • The authors declare no conflicts of interest.

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