Reports of myocarditis and pericarditis following mRNA COVID-19 vaccines: A systematic review of spontaneously reported data from the UK, Europe, and the US and of the literature

Objectives

To bring together spontaneously reported data from multiple countries to estimate reporting rate, and better understand risk factors for myocarditis and pericarditis following COVID-19 mRNA vaccines.

Design

Systematic review of spontaneously reported data from United Kingdom (UK), United States (US), and European Union/European Economic Area (EU/EEA) and of the literature.

Data sources

UK Yellow Card scheme, Vaccine Adverse Event Reporting System (VAERS), EudraVigilance were searched from date of vaccine launch to 14-16 March 2022. PubMed/MEDLINE and Embase were searched to 15 March 2022.

Eligibility criteria

We included publicly available spontaneous reporting data for “Myocarditis” and “Pericarditis” from UK, US, and EU/EEA following COVID-19 mRNA vaccines. Pharmacoepidemiological observational studies investigating myocarditis/pericarditis following mRNA COVID-19 vaccines were included (no restrictions on language or date). Critical Appraisal Skills Programme (CASP) tools assessed study quality.

Data extraction and synthesis

Two researchers extracted data. Spontaneously reported events of myocarditis and pericarditis were presented for each data source, stratified by vaccine, age, sex, and dose (where available). Reporting rates were calculated for myocarditis and pericarditis for each population. For published pharmacoepidemiological studies, design, participant characteristics, and study results were tabulated.

Results

Overall, 18,204 myocarditis and pericarditis events have been submitted to the UK, US, and EU/EEA regulators during the study period. Males represented 62.24% (n=11,331) of myocarditis and pericarditis reports. Most reports concerned vaccinees aged <40 years and were more frequent following a second dose. Reporting rates were consistent between the data sources. Thirty-two pharmacoepidemiological studies were included; results were consistent with our spontaneous report analyses.

Conclusions

Younger vaccinees more frequently report myocarditis and pericarditis following mRNA COVID-19 vaccines than older vaccinees. Results from published literature supported the results of our analyses.

Strengths and Limitations of the Study

• This is the first study to bring together spontaneously reported data from the United Kingdom, United States, and Europe on myocarditis and pericarditis following mRNA COVID-19 vaccines.

• Results from this study provide evidence on the frequency of reported events of myocarditis and pericarditis following mRNA vaccines in different age groups, and by sex and vaccine dose; analyses of spontaneous reports were consolidated with results of published literature, identified by systematic review.

• Results may have been influenced by biases including different vaccination policies in each region examined, and publicity on events of myocarditis and pericarditis following mRNA vaccines.

• The study relied on outputs from spontaneous reporting systems in which the level of detail differed between the systems examined; furthermore, it is not possible to estimate incidence rates using spontaneous reports due to the lack of data on the exposed population, and there is no unvaccinated comparison group.

• There is an urgent need for further pharmacoepidemiological studies to be conducted to provide more accurate estimates of the frequency, clinical course, long term outcome, effects of treatment and impact on quality of life, to address many of the limitations of spontaneous reporting.