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Review 1: "Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children"

Reviewer: Michael Campbell (Duke University) | 📗📗📗📗◻️

Published onMay 07, 2022
Review 1: "Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children"
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key-enterThis Pub is a Review of
Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children

AbstractBackgroundAlthough 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.MethodsIn 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.ResultsOf 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.ConclusionsCompared 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.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.



Patel et al. compare pediatric patients with “classic” myocarditis (viral or idiopathic myocarditis presenting before 2020), myocarditis associated with the multi-system inflammatory syndrome (MIS-C) following SARS-CoV-2 infection, and vaccine-associated myocarditis following mRNA based COVID-19 vaccine. The clinical presentation, treatment, and follow-up of patients in these groups were compared. The main conclusions are:

1. MIS-C myocarditis patients have more hematologic abnormalities, higher inflammatory marker levels, and younger age at presentation when compared to “classic” myocarditis patients. MIS-C myocarditis patients are more likely to have recovery of left ventricular ejection fraction (LVEF) than “classic” myocarditis patients, with most MIS-C patients having normalization of LVEF.

2. COVID vaccine-associated myocarditis patients have a similar presentation to classic myocarditis but are more likely to have normalization of LVEF.

This study is impactful and increases the understanding of differences between recent forms of myocarditis (MIS-C and COVID-19 associated myocarditis) and “classic myocarditis”. An understanding of these differences will improve providers’ ability to correctly diagnose and appropriately treat these diseases. These conclusions support previously reported findings in smaller retrospective studies.

The study is a retrospective, single-institution study. The clinical evaluation, treatments, and follow-up provided to these patients were based on institutional practice patterns and protocols. Because of this, the findings may not translate to all. The study did not include cardiac MRI (CMR) data because many patients did not have follow-up CMR. I would anticipate this data will be added to the medical literature in the future and its inclusion will be critical.  

There are many unanswered questions regarding the etiology, pathogenesis, and long-term outcomes of MIS-C and COVID-19 associated myocarditis. This manuscript adds to current knowledge and moves the pediatric community to a better understanding of the cardiac effects of COVID-19.

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