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Evaluation Video

Oral Presentation

Session: Vaccine Safety Across Ages & Platforms

Influence of mRNA Covid-19 Vaccine Dosing Interval on the Risk of Myocarditis

Monday, August 26, 2024
1:45 PM – 2:00 PM CEST
Location: Conv Hall I C

    Presenting Author(s)

  • SL

    Stéphane Le Vu

    EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France
    Saint-Denis, France

    Slides

    • Co-Author(s)

  • MB

    Marion Bertrand

    MSc
    EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France, France

  • Laura Semenzato, MSc (she/her/hers)

    Statistician - PhD candidate in Pharmacoepidemiology
    EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France
    Paris, France

  • Marie-Joelle Jabagi, PharmD PhD

    Epidemiologist
    EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France
    Paris, France

  • Jérémie Botton, PhD, PharmD, MPH

    PhD, PharmD, MPH
    EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France
    Saint-Denis, France

  • JD

    Jérôme Drouin

    EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France, France

  • Alain Weill, MD

    deputy director
    EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France, France

  • RD

    Rosemary Dray-Spira

    EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France, France

  • MZ

    Mahmoud Zureik, Phamacoepidemiology professor

    Phamacoepidemiology professor
    EPI-PHARE, French National Agency for Medicines and Health Products Safety (ANSM) and French National Health Insurance (CNAM), 143-147 Boulevard Anatole France, 93285, Saint-Denis, France
    Saint-Denis, France

Background: Myocarditis is the most salient serious adverse event of messenger RNA-based (mRNA) Covid-19 vaccines.

Objectives: To assess the relation between dosing interval and the risk of myocarditis, for both the two-dose primary series and the third dose (first booster).

Methods: We conducted a matched case-control study within the entire French population aged 12 or older, from December, 27, 2020 to November, 30, 2022. Data were obtained from the national databases on hospitalization and Covid-19 vaccination (SNDS). Cases were all patients admitted to French hospitals with a diagnosis of myocarditis. Each case was matched with 10 controls of same age, gender and area of residence. Exposure was defined by the receipt of an mRNA vaccine 0 to 7 days prior to the index date, and the time interval between two consecutive doses. We used conditional logistic regression models to estimate the odds ratios (OR) of myocarditis associated with exposure, adjusted for covariates. To also assess the nonlinear relationships between risk factors (dosing interval and age) and myocarditis, we implemented models based on restricted cubic splines.

Results: We included 7,911 cases of myocarditis and 10 matched control subjects per case, in a period where approximately 130 million mRNA-vaccine doses were administered.
Overall, the risk of myocarditis increased after receipt of each doses of both the BNT162b and mRNA-1273 vaccines, with OR ranging from 2.0 (95% confidence interval [CI], 1.5 to 2.6) for the first dose of BNT162b to 22 (95%CI, 16 to 30) for the second dose of mRNA-1273. OR were 4.2 (95%CI, 3.2 to 5.5) after the third dose of BNT162b and 4.6 (95%CI, 2.8 to 7.4) after the third dose of mRNA-1273 vaccine.
For both vaccines, OR tended to decrease as intervals grew longer. The highest risk was found after a second dose of mRNA-1273 administered less than 3 weeks apart from the first one (OR: 34; 95%CI, 17 to 67). For BNT162b vaccine, we identified a threshold of 5 weeks for the interval between dose 1 and 2 over which the risk was minimized in persons under age 50, and a corresponding threshold of 6 months between dose 2 and 3 in persons aged 50 or more. However, further extension of dosing intervals for the BNT162b booster or the primary doses of mRNA-1273 kept on providing a continuous reduction in risk in persons under age 50 (up to 4 times less).

Conclusions: This study brings new evidence suggesting that longer intervals between each consecutive dose, including booster doses, may decrease the occurrence of vaccine-associated myocarditis. A minimum 6-month interval might be required when scheduling additional booster vaccination, and could be extended further in healthy young adults at larger risk of adverse event. Our findings on Covid-19 vaccines may also apply to other oncoming mRNA-based viral vaccines.