Analysis of Myocarditis Among 252 Million mRNA-1273 Recipients Worldwide
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Abstract
Background
Growing evidence indicates a causal relationship between SARS-CoV-2 infection and myocarditis. Post-authorization safety data have also identified myocarditis as a rare safety event following mRNA COVID-19 vaccination, particularly among adolescent and young-adult males after dose 2. We further evaluated the potential risk by querying the Moderna global safety database for myocarditis/myopericarditis reports among mRNA-1273 recipients worldwide.
Methods
Myocarditis/myopericarditis reports from 18 December 2020 to 15 February 2022 were reviewed and classified. The reported rate after any known mRNA-1273 dose was calculated according to age and sex, then compared with a population-based incidence rate to calculate observed-to-expected rate ratios (RRs).
Results
During the study period, 3017 myocarditis/myopericarditis cases among 252 million mRNA-1273 recipients who received at least 1 dose were reported to the Moderna global safety database. The overall reporting rate was 9.23 per 100 000 person-years, which was similar to the expected reference rate (9.0 cases per 100 000 person-years; RR [95% confidence interval (CI)], 1.03 [.97–1.08]). When stratified by sex and age, observed rates were highest for males aged <40 years, particularly those 18–24 years (53.76 per 100 000 person-years), which was higher than expected (RR [95% CI], 3.10 [2.68–3.58]). When considering only cases occurring within 7 days of a known dose, the observed rate was highest for males aged 18–24 years after dose 2 (4.23 per 100 000 doses administered).
Conclusions
Myocarditis/myopericarditis rates were not higher than expected for the overall population of mRNA-1273 recipients but were higher than expected in males aged 18–24 years, with most cases occurring 7 days after dose 2.
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SciScore for 10.1101/2021.11.11.21265536: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was based on data collected in the Moderna global safety database, mostly from adverse event reports submitted voluntarily, as part of routine ongoing post-authorization safety surveillance efforts by Moderna, Inc., as required by regulatory authorities; accordingly, a central institutional review board (IRB; Advarra) confirmed this study met criteria for an exemption from IRB oversight under 45 CFR 46.104(d)(4). Sex as a biological variable Although the reference rate was not stratified by age and sex in the published reference, the expected rate of 2.12 cases per 100,000 vaccine recipients was adjusted for lower prevalence among females aged 12–39 years relative to males by … SciScore for 10.1101/2021.11.11.21265536: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was based on data collected in the Moderna global safety database, mostly from adverse event reports submitted voluntarily, as part of routine ongoing post-authorization safety surveillance efforts by Moderna, Inc., as required by regulatory authorities; accordingly, a central institutional review board (IRB; Advarra) confirmed this study met criteria for an exemption from IRB oversight under 45 CFR 46.104(d)(4). Sex as a biological variable Although the reference rate was not stratified by age and sex in the published reference, the expected rate of 2.12 cases per 100,000 vaccine recipients was adjusted for lower prevalence among females aged 12–39 years relative to males by factor of 1.7326 as presented by the CDC.27 The observed reporting rate was divided by the expected rate and presented with an associated 95% confidence interval (CI) calculated as e(log(IRR)±1.96*SE(log(IRR)))). Randomization not detected. Blinding not detected. Power Analysis not 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:A key limitation of this analysis is that the information from the Moderna global safety database is primarily derived from passive, spontaneous adverse event reporting, which lack a denominator (to clearly define the number of individuals who have received the vaccine) and often provide limited details on the clinical features and outcomes of reported myocarditis cases. As such, chart reviews and follow-ups on case resolutions were precluded. In conclusion, our findings demonstrate that myocarditis in individuals receiving mRNA 1273 is a rare event; previous reports suggest these cases are likely generally mild and self-limiting.13-15, 17, 44 As noted in a recent update based on data presented to the ACIP, the benefits of mRNA COVID-19 vaccination (ie, prevention of COVID-19, hospitalization, intensive care unit admissions, and death) clearly outweigh the potential harm of vaccine-related myocarditis.15 In safely and effectively preventing COVID-19 disease and its complications (including myocarditis, a natural complication of SARS-CoV-2 infection), mRNA COVID-19 vaccines thus remain essential for controlling the COVID-19 pandemic.
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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