NYMC Faculty Publications

Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children

Justin Lin, Labatt Family Heart Centre, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
Ashraf S. Harahsheh, Children's National Hospital, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Geetha Raghuveer, Children's Mercy Hospital, Kansas City, Missouri, USA.
Supriya Jain, Division of Pediatric Cardiology, Maria Fareri Children's Hospital of Westchester Medical Center, New York Medical College, Valhalla, New York, USA.
Nadine F. Choueiter, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, USA.
Luis Martin Garrido-Garcia, Pediatric Cardiology Department, Hospital Angeles Lomas, Huixquilucan, Mexico.
Nagib Dahdah, Division of Pediatric Cardiology, Sainte Justine University Hospital Center, University of Montreal, Montréal, Québec, Canada.
Michael A. Portman, Seattle Children's Hospital, Seattle, Washington, USA.
Nilanjana Misra, Cohen Children's Medical Center of New York, Northwell Health, New York, New York, USA.
Michael Khoury, Stollery Children's Hospital, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Marianna Fabi, Pediatric Emergency Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Matthew D. Elias, Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Audrey Dionne, Department of Cardiology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
Simon Lee, Children's Nationwide Hospital, Columbus, Ohio, USA.
Elif Seda Tierney, Division of Pediatric Cardiology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
Jean A. Ballweg, Helen DeVos Children's Hospital, Grand Rapids, Michigan, USA.
Cedric Manlhiot, Johns Hopkins University School of Medicine, Division of Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.
Brian W. McCrindle, Labatt Family Heart Centre, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada. Electronic address: brian.mccrindle@sickkids.ca.

Author Type(s)

Faculty

Journal Title

The Canadian Journal of Cardiology

First Page

793

Last Page

802

Document Type

Article

Publication Date

6-1-2023

Department

Pediatrics

Abstract

Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare delayed hyperinflammatory response to SARS-CoV-2 infection and causes severe morbidity in the pediatric age group. Although MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic, and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6 to12 years, and specific racial or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurologic complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein-as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens-are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C vs both acute SARS-CoV-2 infection and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine-associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.

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