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Page 2 of 11 Misra et al. Vessel Plus 2022;6:14 https://dx.doi.org/10.20517/2574-1209.2021.89

Keywords: MIS-C, COVID-19, cardiac function, coronary artery dilation

INTRODUCTION
The 2019 coronavirus (COVID-19) pandemic has led to significant morbidity and mortality throughout the
world. During the initial phases of the COVID-19 pandemic, it was believed that children were not
susceptible to the severe illness that was primarily seen in adults; however, in April of 2020, there were
reports of Kawasaki like illness related to COVID-19 in children associated with significant multi-organ
dysfunction . This constellation of symptoms was named multisystem inflammatory syndrome in
[1-3]
children (MIS-C) associated with COVID-19 by the Centers for Disease Control (CDC) and other public
[4]
organizations . The CDC case definition of MIS-C includes the presence of fever, laboratory evidence of
inflammation, and multisystem organ involvement without alternative plausible diagnoses, as well as
evidence of COVID-19 infection or recent exposure to a COVID-19 case. In addition to the presentation
with persistent fever, asthenia, prominent gastrointestinal symptoms, and Kawasaki like disease, patients
with MIS-C have manifested widespread cardiovascular involvement, including cardiac dysfunction,
coronary artery dilation, myocarditis, myocardial stunning, and shock, with a majority of them requiring
[5,6]
intensive care therapy due to hemodynamic instability .
While the vast majority of patients recover from their illness, it is estimated that 6%-14% continue to have
myocardial dysfunction at discharge from their hospitalization, highlighting the need to closely follow these
patients as an outpatient to monitor for long-term sequelae .
[6]
In this article, we present the cardiovascular involvement in MIS-C, review the acute management and
discuss the cardiac outcomes of this illness as known to date.

METHODOLOGY FOR LITERATURE SEARCH
Each author reviewed available literature on MIS-C published between April 1, 2020, and June 30, 2021.
Papers were obtained by searching through PubMed and Google Scholar, focusing on manuscripts
discussing cardiovascular involvement with MIS-C and treatment. Particular emphasis was placed on
identifying multi-center studies given that the number of MIS-C patients at individual centers is low;
however, when applicable and related to the section, single-center studies were included. For each section,
the authors selected the papers they felt were most relevant to the subheading and shared them with the rest
of the authors for approval and discussion. There were no significant disagreements among the authors in
the selection of pertinent literature.

CARDIO-VASCULAR INVOLVEMENT IN MIS-C
Acute cardiovascular presentation
The clinical onset of MIS-C typically occurs at 2-6 weeks after the initial COVID-19 infection.
Cardiovascular involvement is common and can range from mild ventricular dysfunction to severe
[6]
refractory cardiogenic, vasodilatory shock, or significant arrhythmia .

The predominant initial presenting symptoms include fever and malaise, with is usually present in all
patients . Gastrointestinal manifestations, including abdominal pain, nausea, and vomiting, are also
[7-9]
[7-9]
present in most cases, with one case series of 70 patients noting up to 84% with these symptoms . In
addition, some patients have been noted to have Kawasaki-like features, which include rash, conjunctivitis,
and peeling of the skin; compared to their counterparts with Kawasaki, patients with MIS-C tended to be
older, have lower platelet counts, and a higher prevalence of cardiovascular involvement [10,11] .