Highlights
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Background
Myopericarditis is a rare complication of vaccination. However, there have been increasing reports of myopericarditis after COVID-19 vaccination, especially among adolescents and young adults. Our objective was to characterize the incidence of myopericarditis after COVID-19 vaccination and compare it with non-COVID-19 vaccination.
Methods
We did a systematic review and meta-analysis, searching four international databases from January 1, 1947 to December 31, 2021, for English-language studies reporting the incidence of myopericarditis after vaccination (the primary outcome).
We included studies that reported on people in the general population who had myopericarditis in temporal relation to receiving vaccines and excluded studies on a specific subpopulation of patients, non-human studies, and studies in which the number of doses was not reported.
Random-effects meta-analyses were performed (DerSimonian and Laird), and risk of intra-study bias (Joanna Briggs Institute checklist) and certainty of evidence (grade of recommendations, assessment, development and focus of assessments) were assessed. We analyzed the difference in the incidence of myopericarditis between subpopulations, stratifying by vaccine type (COVID-19 vs non-COVID-19) and age group (adult vs pediatric).
Among COVID-19 vaccines, we examined the effect of vaccine type (mRNA or non-mRNA), sex, age, and dose on the incidence of myopericarditis. This study was registered with PROSPERO (CRD42021275477).
Results
The overall incidence of myopericarditis from 22 studies (405,272,721 vaccine doses) was 33·3 cases (95% CI 15·3–72·6) per million vaccine doses, and did not differ significantly between people who received COVID-19 vaccines (18·2 [10·9–30·3], 11 studies [395,361,933 doses], high certainty) and those who received non-COVID-19 vaccines (56·0 [10·7– 293·7], 11 studies [9,910,788 doses], moderate certainty, p=0·20).
Compared with COVID-19 vaccination, the incidence of myopericarditis was significantly higher after smallpox vaccines (132·1 [81·3–214·6], p<0·0001) but was not significantly different after influenza vaccines (1·3 [ 0·0–884·1], p=0·43) or in studies reporting on vaccines other than smallpox (57·0 [1·1–3036· 6], p=0·58).
Among people who received COVID-19 vaccines, the incidence of myopericarditis was significantly higher in men (vs. women), in people younger than 30 years (vs. 30 years or older), after receiving an mRNA vaccine ( vs. a non-mRNA vaccine), and after a second vaccine dose (vs. a first or third dose).
Interpretation
The overall risk of myopericarditis after receiving a COVID-19 vaccine is low. However, younger men have a higher incidence of myopericarditis, particularly after receiving mRNA vaccines.
However, the risks of such rare adverse events must be weighed against the risks of COVID-19 infection (including myopericarditis).
Added value of this study
Our meta-analysis was performed to determine whether the increase in myopericarditis reporting was a true increase in incidence or the result of improved reporting systems and recall bias.
Among 260 million people who received more than 405 million vaccine doses as reported in studies and databases, we found that the incidence of myopericarditis was not elevated after COVID-19 vaccination (18 cases per million doses of vaccine) compared to after vaccination without COVID-19. 19 vaccination (56 cases per million vaccine doses) or relative to the pre-pandemic incidence rate of myopericarditis.
In people who received a COVID-19 vaccine, a significantly higher incidence of myopericarditis was found in men (vs. women), those under 30 years of age (vs. over 30 years of age), those who received a second dose of the vaccine (vs. a first or third dose), or those who receive an mRNA vaccine (vs. a non-mRNA vaccine). Using robust variance estimation methods to account for intra-study correlation, decreasing age (excluding persons younger than 12 years) was associated with a higher incidence of myopericarditis.
Implications of all available evidence
In the general population, the risk of myopericarditis after receiving the COVID-19 vaccine is low.
The incidence of myopericarditis from COVID-19 vaccination also appears to be lower than that from COVID-19 infection. However, the incidence of myopericarditis in young men after COVID-19 mRNA vaccination appears higher than expected. These findings could be of interest to policymakers determining national vaccination protocols, particularly as many countries will encourage booster vaccination during 2022.
Finally, our findings inform the general public about the rarity of myopericarditis, putting the risks in perspective and allowing for a more informed decision regarding COVID-19 vaccination.
Comments
The overall risk of myopericarditis after COVID-19 vaccination is very low, affecting 18 people per million vaccine doses. A new study published in The Lancet Respiratory Medicine confirms that this risk is comparable or lower after COVID-19 vaccination than other non-COVID-19 vaccines.
Researchers examined international databases, analyzing more than 400 million vaccination doses , to compare the risk of myopericarditis after vaccination against COVID-19 and other diseases such as influenza and smallpox.
They found no statistically significant difference between the incidence of myopericarditis after COVID-19 vaccination (18 cases per million doses) and other vaccines (56 cases per million doses).
“Our research suggests that the overall risk of myopericarditis does not appear to be different for this group of newly approved vaccines against COVID-19, compared to vaccines against other diseases. The risk of such rare events must be balanced with the risk of myopericarditis from infection and these findings should bolster public confidence in the safety of COVID-19 vaccines,” says Dr Kollengode Ramanathan, cardiac intensivist at National University Hospital, Singapore. , and Corresponding author.
Myopericarditis is a condition that causes inflammation of the heart muscle and, in some cases, serious permanent heart damage. Most often it is caused by viruses, but it can also occur after vaccination in rare cases. There have been reports of myopericarditis after mRNA-based COVID-19 vaccination, especially in adolescents and young adults. This study aimed to determine whether this increase in reporting was due to a true increase in incidence or the result of improved reporting systems and recall bias.
The researchers analyzed more than 20 studies from international databases with reported incidences of myopericarditis after any type of vaccination between January 1947 and December 2021. Of these, 11 studies specifically analyzed COVID-19 vaccines, covering more than 395 million doses of the COVID-19 vaccine, almost 300 million of which were mRNA vaccines. The rest of the studies covered other vaccines such as smallpox (2.9 million doses), influenza (1.5 million doses) and others [2] (5.5 million doses).
The rate of myopericarditis after COVID-19 vaccination was 18 cases per million doses. For all other viral vaccines combined, the rate of myopericarditis was 56 cases per million doses.
Among COVID-19 vaccines, the risk of myopericarditis was higher for those who received mRNA vaccines (22.6 cases per million doses) compared to non-mRNA vaccines (7.9 cases per million doses). Reported cases were also higher in people under 30 years of age (40.9 cases per million doses), men (23 cases per million doses), and after the second dose of the COVID-19 vaccine (31.1 cases per million doses). million doses).
To contextualize the findings with the risk of myopericarditis after COVID-19 infection, the authors conducted a post-study analysis. Among 2.5 million patients who were hospitalized with COVID-19, many of whom had clinical or radiological suspicion of myopericarditis, 1.1% had myopericarditis. However, although these figures provide a framework, the authors note that the results are not directly comparable with the number of myopericarditis cases after COVID-19 vaccination due to the different units of measurement.
“The occurrence of myopericarditis after vaccination without COVID-19 could suggest that myopericarditis is a side effect of the inflammatory processes induced by any vaccine and is not exclusive to the SARS-CoV-2 spike proteins in vaccines or the COVID-19 infection,” says Dr. Jyoti Somani, an infectious disease specialist at the National University Hospital of Singapore and co-author. “This also highlights that the risks of such rare adverse events must be offset by the benefits of vaccination, which include a “lower risk of infection, hospitalization, serious illness and death from COVID-19.”
The authors acknowledge some limitations of this study, in particular they note that the findings include only a small proportion of children under 12 years of age who have recently been eligible for vaccination, and that the results of this study cannot be generalized to this group of age. Additionally, comparisons have been made between different time periods for different vaccines. Diagnostic tools may have differed or been unavailable, leading to underreporting of cases in previous studies.
In a linked comment, Margaret Ryan of the Defense Health Agency and clinical professor at the University of California, San Diego, US, who was not involved in the study, said: “Reports of unexpected adverse events, although rare and limited to a subset of vaccine recipients – they have the potential to damage confidence in the vaccine at a critical point in the pandemic response.
Like Ling and colleagues, all professionals who have described myocarditis after COVID-19 vaccination have emphasized that the benefits of vaccination far outweigh the risks amid the current pandemic. However, scientific knowledge and public health strategies must continue to evolve. “Alternative vaccine platforms, vaccine doses, or vaccine schedules may reduce the risk of rare adverse events following immunization, and should be explored in the context of changing infection risk.”
