Features of Inflammatory Heart Reactions Following mRNA COVID‐19 Vaccination at a Global Level

  1. Laurent Chouchana
  2. Alice Blet
  3. Mohammad Al‐Khalaf
  4. Tahir S. Kafil
  5. Girish Nair
  6. James Robblee
  7. Milou‐Daniel Drici
  8. Marie‐Blanche Valnet‐Rabier
  9. Joëlle Micallef
  10. Francesco Salvo
  11. Jean‐Marc Treluyer
  12. Peter P. Liu

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Abstract

Myocarditis and pericarditis may constitute adverse reactions of mRNA coronavirus disease 2019 (COVID‐19) vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case–non‐case design (also called disproportionality study) on inflammatory heart reactions reported with mRNA COVID‐19 vaccines within the World Health Organization (WHO) global safety database (VigiBase), up to June 30, 2021. Results are expressed using reporting odds ratios (RORs) and their 95% confidence interval (95% CI). Of 716,576 reports related to mRNA COVID‐19 vaccines, 2,277 were cases of inflammatory heart reactions, including 1241 (55%) myocarditis and 851 (37%) pericarditis. The main age group was 18–29 years (704, 31%), and mostly male patients (1,555, 68%). Pericarditis onset was delayed compared with myocarditis with a median time to onset of 8 (3–21) vs. 3 (2–6) days, respectively ( P  = 0.001). Regarding myocarditis, an important disproportionate reporting was observed in adolescents (ROR, 22.3, 95% CI 19.2–25.9) and in 18–29 years old (ROR, 6.6, 95% CI 5.9–7.5) compared with older patients, as well as in male patients (ROR, 9.4, 95% CI 8.3–10.6). Reporting rate of myocarditis was increased in young adults and adolescents. Inflammatory heart reactions may rarely occur shortly following mRNA COVID‐19 vaccination. Although an important disproportionate reporting of myocarditis was observed among adolescents and young adults, particularly in male patients, reporting rates support a very rare risk, that does not seem to compromise the largely positive benefit‐risk balance of these vaccines. Furthermore, this study confirmed the value of disproportionality analyses for estimation of relative risks among subgroups of patients.

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  1. Version published to 10.1002/cpt.2499
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    SciScore for 10.1101/2021.08.12.21261955: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Ethics: This study has obtained ethics approval from the Cochin university Hospital institutional review board (number AAA-2021-08039) in conformity with the French laws and regulations.33 All of the data used for analysis were de-identified, and only aggregate data are reported.
    Sex as a biological variableTherefore, our analyses assessed a potential difference of reporting of inflammatory heart reactions secondary to COVID-19 mRNA vaccines in male compared to female and in 12-17 years or 18-29 years old patients compared to patients over 30 years old.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This retrospective pharmacovigilance analysis has some limitations and strengths. VigiBase and VAERS are based on spontaneous reports. Anyone can submit a report, including parents and patients, which are analyzed and documented by national or regional pharmacovigilance centers. Spontaneous reports will likely feature under-reporting of total real world cases and variable data quality, all of which are inherent to any pharmacovigilance system.46 For instance, previous prospective study of the incidence of myocarditis/pericarditis following smallpox and influenza vaccination suggested significant underestimation of true incidence of these complications with passive surveillance alone.47 Hence, one major limitation of spontaneous reporting is that it is not possible to assess incidence of inflammatory heart reactions following COVID-19 vaccination and total number of cases is highly underestimated. However, VigiBase, covering more than 90% of the world’s population, provides a unique opportunity to analyze rare adverse events at a global scale. Furthermore, although we cannot eliminate residual confounders, disproportionality analysis on VigiBase has proven its value in detecting safety signal or increased risk of events.34 Our analysis highlights an increased risk of myocarditis reporting in young males. On one hand, myocarditis has suffered from a notoriety bias in relation with media communication which has probably increase its reporting in May and June 2021 compared to oth...

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    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2021.08.12.21261955v1 on medRxiv