Is there an increased incidence of COVID-related myocarditis in children?

Viruses are the most common cause of pediatric myocarditis. In general, the most common viruses causing pediatric myocarditis are Coxsackievirus B, other enteroviruses, influenza, rubella, and adenovirus.¹ During and after important viral outbreaks, including the original 2002 severe acute respiratory syndrome (SARS), 2012 Middle Eastern respiratory syndrome (MERS), and 2009 H1N1 influenza A, increases in cardiac abnormalities in adults (suggesting cardiac association with these viruses) have been reported.^2,3 

We are unable to find any articles addressing association between either the original 2002 SARS or MERS with myocarditis in children. Regarding the 2009/2010 H1N1 influenza outbreak, however, reports from pediatric ICUs in the United States and Japan suggested myocarditis incidence of around 1 to 2 percent in these patients (n=8 cases total).^4,5 

Clinically, the incidence of myocarditis is important to know. Animal studies have demonstrated that exercising with myocarditis is associated with an increase in viral replication, which can result in permanent cardiac scarring. Whether this translates to humans including children is unknown. However, myocarditis has been shown to account for 20 percent of nontraumatic sudden cardiac deaths among a military recruit cohort, suggesting that any children who acquire myocarditis may carry downstream risks into early adulthood.⁶ 

More recently, a systematic review specifically evaluated pediatric COVID-19–associated myocarditis.⁷ The authors found that, as of July 2020, there were 570 Centers for Disease Control and Prevention (CDC)–reported cases of pediatric multisystem inflammatory syndrome (PMIS). PMIS is more routinely referred to as MIS-C (multisystem inflammatory syndrome in children) in much of the emerging literature on this topic. The condition is a Kawasaki-like hyperinflammatory disease presentation involving multiple organ systems and often accompanying myocardial dysfunction. As of the end of July 2020, the authors calculated an incidence of CDC-reported MIS-C of approximately 0.2 to 0.6 percent of COVID-19 pediatric infections. In their systematic review, the authors identified 688 cases of MIS-C in the literature, with myocardial dysfunction documented in 340 of 688 of these cases (50.9 percent). Of note, isolated COVID-19–associated myocarditis cases have been reported in the literature, but most cases of myocarditis are related to MIS-C.

The overall incidence of COVID-19–associated myocarditis is difficult to estimate using these data, as these studies reported MIS-C patients in pediatric ICUs only. The incidence of less severe myocarditis is unknown in both patients with COVID-19 and influenza patients. 

Is COVID-19 especially likely to cause myocarditis? That remains unknown. The incidence of COVID-19–associated myocarditis may turn out to be similar to other viral pathogens, but due to the vast number of COVID-19 infections, the prevalence of COVID-19–associated myocarditis definitely appears to be higher. For this reason alone, myocarditis needs to be higher on practitioners’ differential diagnosis list when evaluating children in today’s clinical environment. 

While of uncertain clinical significance, there is a small amount of data on asymptomatic COVID-19–associated myocarditis in college student athletes (mean age of 20 years). A single study from Vanderbilt University evaluated 59 COVID-19–positive athletes, of whom 78 percent had mild symptoms and 22 percent were asymptomatic. These data were compared to results of 60 athlete controls and 27 healthy controls via cardiac magnetic resonance (CMR).⁸ The median time from COVID-19 detection to CMR was 21.5 days (range 10–162 days), and two of 59 (3 percent) COVID-19–positive patients met clinical criteria for myocarditis. Again, the clinical significance of these findings remains uncertain, and this study was not in children. Still, it does warrant consideration that something similar may be happening in children, too. 

Conclusion

We are unable to determine whether there is a higher incidence of COVID-19–associated myocarditis in children compared to other viral pathogens. However, the prevalence of myocarditis does appear to be higher, with the majority of cases appearing to be associated with MIS-C. 

References

1. Barach P, Lipshultz SE. Rethinking COVID-19 in children: lessons learned from pediatric viral and inflammatory cardiovascular diseases. Prog Pediatr Cardiol. 2020; 101233. 
2. Kochi AN, Tagliari AP, Forleo GB, et al. Cardiac and arrhythmic complications in patients with COVID-19. J Cardiovasc Electrophysiol. 2020;31(5):1003-1008.
3. Sellers SA, Hagan RS, Hayden FG, et al. The hidden burden of influenza: a review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017;11(5):372-393.
4. Tokuhira N, Shime N, Inoue M, et al. Mechanically ventilated children with 2009 pandemic influenza A/H1N1: results from the National Pediatric Intensive Care Registry in Japan. Pediatr Crit Care Med. 2012;13(5):e294-298.
5. Randolph AG, Vaughn F, Sullivan R, et al. Critically ill children during the 2009-2010 influenza pandemic in the United States. Pediatrics. 2011;128(6):e1450-1458.
6. Wilson MG, Hull JH, Rogers J, et al. Cardiorespiratory considerations for return-to-play in elite athletes after COVID-19 infection: a practical guide for sport and exercise medicine physicians. Br J Sports Med. 2020;54(19):1157-1161.
7. Rodriguez-Gonzalez M, Castellano-Martinez A, Cascales-Poyatos HM, et al. Cardiovascular impact of COVID-19 with a focus on children: a systematic review. World J Clin Cases. 2020;8(21):5250-5283.
8. Clark DE, Parikh A, Dendy JM, et al. COVID-19 Myocardial Pathology Evaluated through screEning Cardiac Magnetic Resonance (COMPETE CMR) [preprint]. medRxiv. 2020;2020.08.31.20185140.