Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis

  1. Mendel E. Singer
  2. Ira B. Taub
  3. David C Kaelber

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Abstract

Background

There have been recent reports of myocarditis (including myocarditis, pericarditis or myopericarditis) as a side-effect of mRNA-based COVID-19 vaccines, particularly in young males. Less information is available regarding the risk of myocarditis from COVID-19 infection itself. Such data would be helpful in developing a complete risk-benefit analysis for this population.

Methods

A de-identified, limited data set was created from the TriNetX Research Network, aggregating electronic health records from 48 mostly large U.S. Healthcare Organizations (HCOs). Inclusion criteria were a first COVID-19 diagnosis during the April 1, 2020 - March 31, 2021 time period, with an outpatient visit 1 month to 2 years before, and another 6 months to 2 years before that. Analysis was stratified by sex and age (12-17, 12-15, 16-19). Patients were excluded for any prior cardiovascular condition. Primary outcome was an encounter diagnosis of myocarditis within 90 days following the index date. Rates of COVID-19 cases and myocarditis not identified in the system were estimated and the results adjusted accordingly. Wilson score intervals were used for 95% confidence intervals due to the very low probability outcome.

Results

For the 12-17-year-old male cohort, 6/6,846 (0.09%) patients developed myocarditis overall, with an adjusted rate per million of 450 cases (Wilson score interval 206 - 982). For the 12-15 and 16-19 male age groups, the adjusted rates per million were 601 (257 - 1,406) and 561 (240 - 1,313).

For 12-17-year-old females, there were 3 (0.04%) cases of myocarditis of 7,361 patients. The adjusted rate was 213 (73 - 627) per million cases. For the 12-15- and 16-19-year-old female cohorts the adjusted rates per million cases were 235 (64 - 857) and 708 (359 - 1,397).

The outcomes occurred either within 5 days (40.0%) or from 19-82 days (60.0%).

Conclusions

Myocarditis (or pericarditis or myopericarditis) from primary COVID19 infection occurred at a rate as high as 450 per million in young males. Young males infected with the virus are up 6 times more likely to develop myocarditis as those who have received the vaccine.

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  1. Version published to 10.1101/2021.07.23.21260998v2 on medRxiv
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    SciScore for 10.1101/2021.07.23.21260998: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableWe considered three age cohorts: 12-17 years old to match US myocarditis data following mRNA COVID-19 vaccination, and 12-15 and 16-19 years old to align with common age groupings for vaccination policy and an Israeli report of especially high risk in males age 16-19 following mRNA COVID-19 vaccination.1,2,11 Given the demographics of earlier reports of mRNA vaccine-associated myocarditis, our report focuses on young males, but we include data for female cohorts for comparison purposes.
    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:
    Another limitation is the approach taken to account for missed cases of COVID-19. We assumed that infection rates are similar for 12-19-year-olds and the overall population, and that one-third of the extra COVID-19 cases not detected in the database were tested and seen by physicians with similar rates of myocarditis. There is no currently available data to support precise estimates. However, assuming no additional cases of myocarditis from any of the missed COVID-19 cases, rates of myocarditis in 12-17 year old males would still be nearly three times as great from COVID-19 infection than from the vaccine. With intense media and social media focus on COVID-19 vaccine side-effects, it is important to quantify and communicate to the public the risks of COVID-19 infection in young people. The ACIP report projected that mRNA vaccination in 12-17-year-old males would result in 215 fewer hospitalizations and 71 fewer intensive care unit stays. Benefits of the vaccine outweighed the risk of myocarditis from vaccination in all age groups, 12 years-old and up. Our results suggest that the risk of myocarditis from COVID-19 infection itself exceeds the known risk from vaccination by a considerable margin. In light of more infectious variants, the new school year nearing and many colleges now requiring COVID-19 vaccination (either for all students or just those living on campus), these results are especially timely. Whether considering all the risks and benefits of COVID-19 vaccination o...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

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

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

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  3. Version published to 10.1101/2021.07.23.21260998v1 on medRxiv