Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children

Abstract

Background: Although rare, myocarditis in the pediatric population is a disease process that carries significant morbidity and mortality. Prior to the SARS-CoV-2 related (COVID-19) pandemic, enteroviruses were the most common cause of classic myocarditis. However, since 2020, myocarditis linked to multisystem inflammatory syndrome in children (MIS-C) is now common. In recent months, myocarditis related to COVID-19 vaccines has also been described. This study aims to compare these three different types of myocarditis with regards to clinical presentation, course, and outcomes. Methods: In this retrospective cohort study, we included all patients <21 years of age hospitalized at our institution with classic viral myocarditis from 2015-2019, MIS-C myocarditis from 3/2020-2/2021 and COVID-19 vaccine-related myocarditis from 5/2021-6/2021. We compared demographics, initial symptomatology, treatment, laboratory data, and echocardiogram findings. Results: Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS-C myocarditis, and 9 had COVID-19 vaccine-related myocarditis. Peak troponin was highest in the classic myocarditis group, whereas the MIS-C myocarditis group had the highest recorded brain natriuretic peptide (BNP). There were significant differences in time to recovery of normal left ventricular ejection fraction (LVEF) for the three groups: nearly all patients with MIS-C myocarditis (n=139, 93%) and all patients with COVID-19 vaccine-related myocarditis (n=9, 100%) had normal LVEF at the time of discharge, but a lower proportion of the classic myocarditis group (n=30, 70%) had a normal LVEF at discharge (p<0.001). Three months post-discharge, 18 of 40 children (45%) in the classic myocarditis group still required heart failure treatment, whereas only one of the MIS-C myocarditis patients and none of the COVID-19 vaccine-associated myocarditis patients did. Conclusions: Compared to those with classic myocarditis, those with MIS-C myocarditis had more significant hematologic derangements and worse inflammation at presentation, but had better clinical outcomes, including rapid recovery of cardiac function. Patients with COVID-19 vaccine-related myocarditis had similar clinical presentation to patients with classic myocarditis, but their pattern of recovery was similar to those with MIS-C, with prompt resolution of symptoms and improvement of cardiac function. Long-term follow-up should focus on cardiac and non-cardiac consequences of myocarditis associated with COVID-19 illness and vaccination. Key Words: MIS-C, myocarditis, COVID-19, mRNA vaccine

Reported cases of multisystem inflammatory syndrome in children aged 12–20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation

“…The investigation team sometimes provided suggestions for laboratory testing; however, clinical evaluation of alternative diagnoses was at the discretion of the treating clinicians. Individuals for whom the investigation team considered myocarditis as a plausible alternative diagnosis on the basis of clinical judgment received additional review with CISA cardiologists to differentiate between myocarditis and cardiac manifestations of MIS-C. 18 …”

The Burden of COVID-19 in Children and Its Prevention by Vaccination: A Joint Statement of the Israeli Pediatric Association and the Israeli Society for Pediatric Infectious Diseases

“…According to the CDC [130], vaccine-related myocarditis in young people is usually mild and is characterized by rapid recovery for the vast majority. Recovery from vaccine-related myocarditis is much faster than the course of recovery described in "classic" myocarditis and is characterized by rapid regression of symptoms and rapid recovery of cardiac function [131]. Thus, these findings further divert the risk-benefit balance of immunization in children and adolescents, as even myocarditis, the most severe known risk following immunization with mRNA vaccines, carries a benign clinical course in the vast majority of cases.…”

Myocarditis and Pericarditis following COVID-19 Vaccination: Evidence Syntheses on Incidence, Risk Factors, Natural History, and Hypothesized Mechanisms

“…Further, three patients had self-resolving mild intermittent chest pain after discharge, one had recurrent chest pain after discontinuing the NSAID prescribed at discharge, and three had recurrent symptoms that prompted emergency department visits post-discharge. In the series of nine patients, 50 none were on heart failure medication at 90 day follow-up. In the larger case series (n=43), 39 among cases of myocarditis and/or pericarditis (n=2) with long-term follow-up (n=24, mean follow-up time 89 days), the majority were males aged 12 to 17 years.…”