Comparison of Multisystem Inflammatory Syndrome in Children–Related Myocarditis, Classic Viral Myocarditis, and COVID‐19 Vaccine‐Related Myocarditis in Children

BACKGROUND: Although rare, classic viral myocarditis in the pediatric population is a disease that carries significant morbidity and mortality. Since 2020, myocarditis has been a common component of multisystem inflammatory syndrome in children (MIS‐C) following SARS‐CoV‐2 infection. In 2021, myocarditis related to mRNA COVID‐19 vaccines was recognized as a rare adverse event. This study aims to compare classic, MIS‐C, and COVID‐19 vaccine‐related myocarditis with regard to clinical presentation, course, and outcomes. METHODS AND RESULTS: In this retrospective cohort study, we compared patients aged <21 years hospitalized at our institution with classic viral myocarditis from 2015 to 2019, MIS‐C myocarditis from March 2020 to February 2021, and vaccine‐related myocarditis from May 2021 to June 2021. Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS‐C myocarditis, and 9 had vaccine‐related myocarditis. At presentation, ejection fraction was lowest for those with classic myocarditis, with ejection fraction <55% present in 58% of patients. Nearly all patients with MIS‐C myocarditis (n=139, 93%) and all patients with vaccine‐related myocarditis (n=9, 100%) had normal left ventricular ejection fraction at the time of discharge compared with 70% (n=30) of the classic myocarditis group (P<0.001). At 3 months after discharge, of the 21 children discharged with depressed ejection fraction, none of the 10 children with MIS‐C myocarditis had residual dysfunction compared with 3 of the 11 (27%) patients in the classic myocarditis group. CONCLUSIONS: Compared with classic myocarditis, those with MIS‐C myocarditis had better clinical outcomes, including rapid recovery of cardiac function. Patients with vaccine‐related myocarditis had prompt resolution of symptoms and improvement of cardiac function.