Julia Stowe, Elizabeth Miller, Nick Andrews, Heather J. Whitaker
An increased risk of myocarditis or pericarditis after priming with mRNA Coronavirus Disease 2019 (COVID-19) vaccines has been shown but information on the risk post-booster is limited. With the now high prevalence of prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we assessed the effect of prior infection on the vaccine risk and the risk from COVID-19 reinfection.
The rapid development and global deployment of Coronavirus Disease 2019 (COVID-19) vaccines based on mRNA technology has been one of the outstanding successes of the response to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Licensed for human use for the first time in the pandemic, mRNA vaccines have proven highly effective at preventing severe morbidity and mortality from SARS-CoV-2 infection not only against the original Wuhan strain but subsequent variants of concern [1,2]. Overall, their safety profile has been good with no serious adverse events (SAEs) detected until the reports from Israel of temporally associated cases of acute myocarditis and pericarditis after primary vaccination with the BNT162b2 vaccine . Reported cases were predominantly in younger males after the second dose, with onset clustering in the first week after vaccination.
Materials and method
The study population comprised the resident population of 50 million individuals in England aged 12 years and older on the 31 August 2021. Age was defined as of 31 August 2021 as this best reflected eligibility for vaccination in the paediatric programme for 12 to 15 year olds that started after this date. Dates of admission for myocarditis or pericarditis were from 22 February 2021 to 6 February 2022.
There was a total of 3,124 hospital admissions in England with a diagnosis of myocarditis or pericarditis and 7,933 emergency care consultations between 22 February 2021 and 6 February 2022 (Table 1). Admission rates for myocarditis were generally higher than for pericarditis, whereas ECDS consultation rates were higher for pericarditis than myocarditis, particularly among those aged under 40 years. Confirmed SARS-CoV-2 infections in those admitted with myocarditis or pericarditis reflected the changing incidence of COVID-19 over the study period with a drop in the last 4 weeks due to delays in diagnostic coding and admissions not completed by the time of the data extract on 4 April 2022 (Fig 1). At least 1 dose of a COVID-19 vaccine had been received by 6,672 (84.1%) of those attending emergency care and 3,382 (86.2%) of those admitted to hospital. In both the ECDS and SUS datasets, admission rates per 100,000 person years in males were about double those in females and increased sharply with age between 12 and 19 years, remaining fairly constant thereafter. ECDS consultation and SUS admission rates were higher among black British, African, or Caribbean than other ethnic groups and higher among those with a CEV or other “at risk” flag than in those without.
Our study showed an increased risk of hospital admission with myocarditis 0 to 6 days after an mRNA vaccine, predominantly in males aged 16 to 39 years with the highest risk in those aged 16 to 24 years. An elevated risk was evident after each of the priming doses with higher risks after a second dose of the mRNA-1273 than the BNT162b2 vaccine. There was also evidence of an increased risk after a booster dose of each of the mRNA vaccines when given after a priming course of BNT162b2 but not after a primary course of ChAdOx1-S vaccine. The only elevated risk seen after the ChAdOx1-S vaccine was post-first dose in 16 to 39 year olds. An elevated risk of hospital admission after a second or booster dose of the mRNA vaccines was still present in individuals vaccinated after a confirmed SARS-CoV-2 infection, though RIs were lower than in those without a prior infection. Our study also showed an increased RI of myocarditis and pericarditis after a SARS-CoV-2 infection which was not abrogated by prior vaccination or previous infection and was evident after each infecting variant.
Citation: Stowe J, Miller E, Andrews N, Whitaker HJ (2023) Risk of myocarditis and pericarditis after a COVID-19 mRNA vaccine booster and after COVID-19 in those with and without prior SARS-CoV-2 infection: A self-controlled case series analysis in England. PLoS Med 20(6): e1004245. https://doi.org/10.1371/journal.pmed.1004245
Received: September 15, 2022; Accepted: May 22, 2023; Published: June 7, 2023
Copyright: © 2023 Stowe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The raw study data are protected and are not freely available due to data privacy laws. This work is carried out under Regulation 3 of The Health Service (Control of Patient Information) (Secretary of State for Health, 2002))(3) using patient identification information without individual patient consent. Data cannot be made publicly available for ethical and legal reasons, i.e. public availability would compromise patient confidentiality as data tables list single counts of individuals rather than aggregated data. Requests for the underlying data should be made via the UKHSA office for data release: https://www.gov.uk/government/publications/accessing-ukhsa-protected-data.
Funding: This work was supported by the UK Health Security Agency for authors NA, JS HJW via their employment. EM receives support from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with UKHSA (Grant Reference NIHR200929). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: CEV, clinically extremely vulnerable; CI, confidence interval; COVID-19, Coronavirus Disease 2019; dsRNA, double-stranded RNA; ECDS, Emergency Care Data Set; NHS, National Health Service; NIMS, National Immunisation Management System; RI, relative incidence; SAE, serious adverse event; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; SCCS, self-controlled case series; SGSS, Second Generation Surveillance System; SUS, Secondary Uses Service