Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children

Tarek Alsaied, MD, MSc; Adriana H. Tremoulet, MD; Jane C. Burns, MD; Arwa Saidi, MD; Audrey Dionne, MD; Sean M. Lang, MD; Jane W. Newburger, MD; Sarah de Ferranti, MD; Kevin G. Friedman, MD

Disclosures

Circulation. 2021;143(1):78-88. 

In This Article

Abstract and Introduction

Abstract

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with substantial cardiovascular implications. Although infection with SARS-CoV-2 is usually mild in children, some children later develop a severe inflammatory disease that can have manifestations similar to toxic shock syndrome or Kawasaki disease. This syndrome has been defined by the US Centers for Disease Control and Prevention as multisystem inflammatory syndrome in children. Although the prevalence is unknown, >600 cases have been reported in the literature. Multisystem inflammatory syndrome in children appears to be more common in Black and Hispanic children in the United States. Multisystem inflammatory syndrome in children typically occurs a few weeks after acute infection and the putative etiology is a dysregulated inflammatory response to SARS-CoV-2 infection. Persistent fever and gastrointestinal symptoms are the most common symptoms. Cardiac manifestations are common, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, and conduction abnormalities. Severe cases can present as vasodilatory or cardiogenic shock requiring fluid resuscitation, inotropic support, and in the most severe cases, mechanical ventilation and extracorporeal membrane oxygenation. Empirical treatments have aimed at reversing the inflammatory response using immunomodulatory medications. Intravenous immunoglobulin, steroids, and other immunomodulatory agents have been used frequently. Most patients recover within days to a couple of weeks and mortality is rare, although the medium- and long-term sequelae, particularly cardiovascular complications, are not yet known. This review describes the published data on multisystem inflammatory syndrome in children, focusing on cardiac complications, and provides clinical considerations for cardiac evaluation and follow-up.

Introduction

In late 2019, a novel coronavirus was isolated in Wuhan, China, as the cause of a cluster of severe cases of pneumonia and acute respiratory distress syndrome.[1] The virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease was called coronavirus disease 2019 (COVID-19). The virus rapidly spread worldwide, leading the World Health Organization (WHO) to declare a pandemic on March 11, 2020. As of this writing, COVID-19 has infected >58 million people and resulted in >1 million deaths.[2] Initial reports indicated that children were largely spared from the most severe symptoms of COVID-19 and were often asymptomatic.[3] In late April 2020, reports emerged from the United Kingdom of children presenting with fever and hyperinflammation temporally associated with COVID-19 and with clinical features similar to incomplete Kawasaki disease (KD), toxic shock syndrome, macrophage activating syndrome, or bacterial sepsis.[4] This new syndrome has been named multisystem inflammatory syndrome in children (MIS-C) by the US Centers for Disease Control and Prevention. This syndrome was also referred to as pediatric multisystem inflammatory syndrome and pediatric inflammatory multisystem syndrome.[5–7] In this article, we use the term MIS-C. Knowledge and experience in caring for patients with MIS-C is rapidly evolving. The objective of this review is to describe the current published data on MIS-C effects on the cardiovascular system and provide clinical considerations for cardiac evaluation and follow-up based on the available data.[8]

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