We have read with great interest the study by Wang et al.1 They performed a meta-analysis including 5 studies and have shown that incidence of myocarditis was 0.0011% (95% confidence interval [CI] 0.0005 to 0.0025) in subjects vaccinated with the Messenger RNA (mRNA) COVID-19 vaccine.1 Another meta-analysis including 7 studies done by Cordero et al2 demonstrated the incidence of myocarditis was 0.0035% (95% CI 0.0034 to 0.0035). These studies have shown a very low incidence of myocarditis after the COVID-19 mRNA vaccine. However, we still have some other concerns that were not analyzed in these systematic reviews: the risk difference between BNT162b2 and mRNA-1273 and the increased risk of acute myocarditis in the young population, especially after the second dose in male teenagers.1 , 2 However, several articles regarding this topic have been published since the database search of these systematic reviews. Therefore, we have increased the number of studies and added a subanalysis of the incidence of acute myocarditis by the types of vaccine administered and in young males who received the second dose of the mRNA vaccine.
On February 1, 2022, a literature search was performed using PubMed, Web of Science, the Cochrane library, and medRxiv by the search terms “COVID-19”, “SARS-CoV-2”, “vaccine”, “myocarditis”, and so on. We selected 13 eligible reports,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 including 3 reports demonstrating incidence of myocarditis after the second dose of mRNA vaccine in young males (16 to 19 years old).4 , 9 , 11 A total of 8 reports were from the United States,4, 5, 6 , 10, 11, 12, 13, 14 3 from Israel,3 , 9 , 15 1 from Denmark,7 and 1 from Hong Kong.8 Data of BNT162b2 or mRNA-1273 were assessed. The incidence of myocarditis was calculated using a random-model meta-analysis using the generic inverse variance method (RevMan version 5.4; Cochrane Collaboration, London, United Kingdom) Figure 1. demonstrated the results of a pooled meta-analysis. The incidence of myocarditis was 2.66 (95% CI 2.26 to 3.07) per 100,000 doses in an analysis regardless of age and gender (Figure 1); only 9.45 (95% CI: 5.35 to 13.55) among young males who received the second dose (Figure 1). Subgroup analyses suggested a trend toward higher event risk among those inoculated with mRNA-1273 (2.62, 95% CI, 0 to 6.23) than those with BNT162b2 (1.67, 95% CI, 0.59 to 2.75) (Figure 2 ). The heterogeneity of included data was substantial in these analyses (I2 >60%).
Figure 1.
Incidence of acute myocarditis/pericarditis after COVID-19 mRNA vaccination (A) Incidence of myocarditis was 2.66 (95% CI: 2.26 to 3.07) per 100,000 doses.(B) Incidence of myocarditis and 9.45 (95% CI: 5.35 to 13.55) per 100,000 doses after second dose in a young male.
Figure 2.
Incidence of acute myocarditis/pericarditis by the types of COVID-19 mRNA vaccination (A) Incidence of myocarditis was 1.67 (95% CI: 0.59 to 2.68) per 100,000 doses in BNT162b2. (B) Incidence of myocarditis and 2.62 (95% CI: 0 to 6.23) per 100.000 doses in mRNA-1273.
We have demonstrated that the incidence of acute myocarditis after the second dose of mRNA vaccine in adolescent males is higher than that of the general population but substantially lower than the incidence of myocardial injury or myocarditis caused by COVID-19 infection (1.000 to 1.400 per 100.000 patients with COVID-19).16 Typically, myocarditis can be diagnosed within days of mRNA vaccination. Symptoms are self-limiting and improve rapidly in almost all patients. The risk of occurrence of myocarditis is low and the short-term outcome is favorable. A recent study has shown that 76.3% of patients had an abnormal myocardial enhancement detectable on magnetic resonance imaging, indicating myocardial fibrosis/necrosis.17 The long-term effect of myocardial fibrosis/necrosis on the heart is unknown; therefore, monitoring of these populations is desirable. In addition, the risk of myocarditis after the booster shot is unknown, data accumulation is also desirable. In this situation, elevated risk of myocarditis after mRNA vaccine should be known to recipients, but it should be also noted that the benefit-risk analysis performed by the Centers for Disease Control and Prevention has shown a positive balance of vaccination for all age groups of both genders. Further studies that focus on evaluating risk factors and mechanisms of developing acute myocarditis are needed, especially among young male recipients, as mRNA vaccine will become more widely available in young children.
Disclosures
The authors have no conflicts of interest to declare.
References
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