What is the clinical evidence from this study?

Study design: Cohort. Population: Myocarditis and pericarditis (n=35369669). Intervention: SARS-CoV-2 vaccines (Pfizer, AstraZeneca, Moderna, Janssen) vs. Pre-vaccination control period (60-day window). Primary outcome: First myocarditis diagnosis after second dose of Pfizer vaccine in individuals aged < 30 years (IRR 7.8, 95% CI 2.6-23.5).

November 24, 2022Open Access

Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries

Q: What are the key findings of this study?

The second dose of the Pfizer COVID-19 vaccine was associated with an increased risk of myocarditis in individuals aged < 30 years (IRR 7.8), although the absolute incidence remained low.

Key Result

The second dose of the Pfizer COVID-19 vaccine was associated with an increased risk of myocarditis in individuals aged < 30 years (IRR 7.8), although the absolute incidence remained low.

Study Design

Type

Cohort (n=35,369,669)

Multicenter

Yes

Structured PICO

Do COVID-19 vaccines increase the risk of myocarditis or pericarditis in the general population?

Population

35,369,669 individuals from four European countries (Italy, Spain, Netherlands, United Kingdom), 49.2% women, median age 39-49 years. Included individuals with at least 365 days of data availability prior to January 1, 2020.

Intervention

First and second dose of Pfizer/BioNTech, Moderna, AstraZeneca, and Janssen COVID-19 vaccines.

Comparator

Non-vaccinated person-time (for the cohort analysis) and a 60-day pre-vaccination control period (for the nested self-controlled risk interval analysis).

Outcome

First recorded diagnosis of myocarditis or pericarditis.safety

mRNA-based COVID-19 vaccines are associated with an increased risk of myocarditis in individuals under 30 years of age, though the absolute incidence remains very low.

Main Result

Effect estimate: IRR 7.8 (95% CI 2.6-23.5)

Limitations

Lag in data availability because data available for researchers was updated only periodically
Potential underestimation of background rates of myo-/pericarditis due to reduced access to care during lockdown periods
Data sources relying on GP data record information from specialists and hospitals with some delay
Limited power to estimate the effects of the AstraZeneca vaccine in persons aged below 30 and the Janssen vaccine in general due to low uptake
Vaccine exposure was limited in children aged 5-11 years, preventing estimation for this population

Abstract

Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39–49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed.

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