Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection

Abstract

Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1-28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1-28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.

Conflict of interest statement

A.S. is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group, the Scottish Government’s Standing Committee on Pandemics and AstraZeneca’s Thrombotic Thrombocytopenic Advisory Group. All roles are unremunerated. J.H.-C. reports grants from NIHR Biomedical Research Centre, Oxford, John Fell Oxford University Press Research Fund and Cancer Research United Kingdom (CR-UK) grant no. C5255/A18085, through the CR-UK Oxford Centre, and grants from the Oxford Wellcome Institutional Strategic Support Fund (204826/Z/16/Z) and other research councils during the conduct of the study. J.H.-C. is an unpaid director of QResearch, a not-for-profit organization that is a partnership between the University of Oxford and EMIS Health who supplied the QResearch database used for this work. J.H.-C. is a founder and shareholder of ClinRisk Ltd and was its medical director until 31 May 2019. ClinRisk Ltd produces open and closed source software to implement clinical risk algorithms (outside this work) into clinical computer systems. J.H.-C. is chair of the NERVTAG risk stratification subgroup and a member of Scientific Advisory Group for Emergencies COVID-19 groups and the NHS group advising on prioritization of use of monoclonal antibodies in SARS-CoV-2 infection. A.H. is a member of the Joint Committee on Vaccination and Immunisation. K.K. is a member of the Governments Scientific Advisory Group for Emergencies. All other authors declare no competing interests related to this paper.

© 2021. The Author(s).

Figures

Fig. 1. IRRs with 95% CIs for cardiac adverse events following each exposure.

IRRs are presented for predefined risk periods (0, 1–7, 8–14, 15–21 and 22–28 days) after first or second dose of ChAdOx1, BNT162b2 and mRNA-1273 vaccines and a SARS-CoV-2 positive test for the prerisk period (28 days before exposure). Horizontal bold line in each panel indicates 1.

Fig. 2. Number of excess events due to exposure per 1 million exposed, as reported in Supplementary Table 10.

When IRR did not show a significant increase of incidence over the 1–28 days postvaccination or a SARS-CoV-2 positive test, absolute measures are not given.

Extended Data Fig. 1. Incidence rate ratios (IRRs) with 95% confidence intervals associated with ChAdOx1 vaccine (sensitivity analyses).

Incidence rate ratios (IRRs) with 95% confidence intervals for single outcomes in predefined risk periods immediately before and after 1st and 2nd dose of ChAdOx1 vaccine computed using an underlying population of size n = 38,615,491 vaccinated individuals and different sensitivity analyses. Horizontal bold line indicates 1.

Extended Data Fig. 2. Incidence rate ratios (IRRs) with 95% confidence intervals associated with BNT162b2 vaccine (sensitivity analyses).

Incidence rate ratios (IRRs) with 95% confidence intervals for single outcomes in predefined risk periods immediately before and after 1st and 2nd dose of BNT162b2 vaccine computed using an underlying population of size n = 38,615,491 vaccinated individuals and different sensitivity analyses. Horizontal bold line indicates 1.

Extended Data Fig. 3. Incidence rate ratios (IRRs) with 95% confidence intervals associated with mRNA-1273 vaccine (sensitivity analyses).

Incidence rate ratios (IRRs) with 95% confidence intervals for single outcomes in predefined risk periods immediately before and after 1st and 2nd dose of mRNA-1273 vaccine computed using an underlying population of size n = 38,615,491 vaccinated individuals and different sensitivity analyses. Horizontal bold line indicates 1.

Extended Data Fig. 4. Number of admissions to hospital for single outcomes by month between April 2019 and August 2021.

Number of admissions to hospital for single outcomes by month between April 2019 and August 2021.

Extended Data Fig. 5. Schematic presentation of the SCCS study design.

Extended Data Fig. 5: Schematic presentation of the SCCS study design.

Extended Data Fig. 6. Number of hospital admissions or deaths for each outcome prior and post each vaccine dose by vaccine type.

Pink area shows the 28 prior to vaccination and yellow area shows the 28 days postvaccination.