Researchers in the UK have assessed data from around the world to better understand the frequency and risk factors for myocarditis and pericarditis following immunization with messenger RNA (mRNA)-based vaccines designed to protect against coronavirus disease 2019 (COVID-19).
A signal of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the sac surrounding the heart) following mRNA-based COVID-19 vaccination first emerged in Israel in May 2021 and further cases have since been reported in numerous other countries.
Now, Samantha Lane and Saad Shakir from the Drug Safety Research Unit in Southampton and have used spontaneous reporting systems from the UK, the United States, and the European Economic Area to estimate the frequency of these events following exposure to the mRNA-based COVID-19 vaccines developed by Pfizer-BioNTech and Moderna.
The reporting rates suggested that both events are very rare and that the typical clinical course is mild, with full recovery reached in most cases.
However, the reports also suggested that the events were more common amongst males, occurred more frequently following a second vaccine dose and mostly affected younger vaccinees.
Samantha Lane and Saad Shakir say that the results were consistent across the three data sources used.
“This is an important finding, because as vaccination programs around the world progress, rates of myocarditis and pericarditis are likely to increase,” they write. “Regulatory authorities should continue to monitor the effect that mRNA vaccination might have on the heart in the populations for which they are responsible.”
A pre-print version of the research paper is available on the medRxiv* server while the article undergoes peer review.
More about the emerging reports of myocarditis and pericarditis
Myocarditis and pericarditis have recently been recognized as very rare adverse events following vaccination with the COVID-19 vaccines developed by Pfizer-BioNTech and Moderna.
A signal of these events following mRNA-based vaccination was first identified in Israel in May 2021, where 148 cases of myocarditis were reported within 30 days of immunization, usually following a second dose.
This prompted the Israeli Ministry of Health to issue an investigation into any possible link between these cases of myocarditis and vaccination.
The results pointed to a possible link between the second vaccine dose and the onset of myocarditis among young men aged 16 to 30, with a stronger link identified among those aged 16 to 19.
Following the initial signal in Israel, further cases of myocarditis and pericarditis following mRNA-based vaccination were reported in numerous other countries.
The product information for both the Pfizer-BioNTech and Moderna vaccines was then updated to include myocarditis and pericarditis as an adverse event of unknown frequency in the UK, Europe, and the US.
“Although most cases appear to have mild severity, further follow-up of cases is ongoing to determine the long-term outcomes of myocarditis and pericarditis following mRNA vaccines,” say the researchers. “Individual regulatory authorities continue to monitor the events of myocarditis and pericarditis in their own spontaneous reporting systems.”
Assessing spontaneous reports from around the world
Lane and Shakir used spontaneous reporting outputs from the UK (Yellow Card scheme), the US (Vaccine Adverse Event Reporting System [VAERS]), and the European Economic Area (EudraVigilance) to estimate the frequency of reported cases of myocarditis and pericarditis following immunization with either the Pfizer-BioNTech or Moderna vaccine.
The data lock points were August 6th, 2021, for VAERS and EudraVigilance, and August 4th, 2021, for the Yellow Card scheme.
According to the reporting rates of spontaneous adverse reactions, myocarditis and pericarditis were very rare events across all three data sources.
Results for the UK
In the UK, 7.93 cases of myocarditis and 6.73 cases of pericarditis occurred per million recipients of at least one dose of the Pfizer-BioNTech vaccine. For the Moderna product, the corresponding figures were 2.07 and 1.79 cases per million.
No data were available regarding the age or sex of those reporting the events, or on which vaccine dose either of the events occurred.
The US findings
In the US, 6.47 cases of myocarditis and 3.53 cases of pericarditis were reported per million individuals who had received two doses of the Pfizer-BioNTech vaccine. For the Moderna product, the corresponding figures were 3.65 and 2.69 cases per million.
Of the 968 myocarditis events reported following Pfizer-BioNTech vaccination, 759 (78.4%) occurred in males. Reports of myocarditis were also more frequent in younger age groups, irrespective of gender. Similarly, while pericarditis was more frequently reported among males, this pattern was less pronounced among those older than 40 years.
Similar trends were observed for the Moderna vaccine.
Overall, the majority of both myocarditis and pericarditis events occurred following the second dose of either vaccine.
The European Economic Area
In the European Economic Area, 4.23 cases of myocarditis and 2.87 cases of pericarditis were reported per million individuals who had received at least one dose of the Pfizer-BioNTech vaccine. For the Moderna product, the corresponding figures were 6.15 cases and 3.84 cases per million.
For both mRNA vaccines, 71.56% of the myocarditis events and 53.46% of the pericarditis events were reported to have affected males.
Authorities must continue to monitor the effects on the heart
“This study adds to existing evidence that younger vaccinees more frequently report myocarditis and pericarditis following mRNA COVID-19 vaccines compared with older vaccinees, and reports are more frequent following the second dose,” said the researchers.
These very rare events with a typically mild disease course occur more frequently among males, they add.
Lane and Shakir say that the consistencies in the reporting rates and the trends within the three data sources suggest that the results may be generalizable to other populations.
“It is important that regulatory authorities continue to monitor the effects of mRNA vaccines on the heart, particularly as vaccine programs progress to include younger vaccinees in many parts of the world,” they write.
“Myocarditis and pericarditis following mRNA COVID-19 vaccines is an area which requires further research,” concludes the team.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.