Compelling evidence of a novel multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection

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Two studies totaling 66 previously unreported cases of MIS-C associated with SARS-CoV-2 infection in the US put meat on the bones of news reports and individual case notes. Several aspects of the studies make them clean and comparable, and their messages clear. Each reports 33 pediatric patients with confirmed SARS-CoV-2 infection (predominantly by antibody testing), over the same 4-week period from mid-March through mid-April, 2020 (ie, weeks following the peaks of community COVID-19 cases) from children’s medical centers in epicenters of COVID-19 in New Hyde Park, Queens (Capone et al) and 3 institutions in New York City (Kaushik et al). Both provide granular detail of patient characteristics, laboratory test results, management, and short-term outcomes. Although the spectrum of severity, especially that documented by precise measurement of cardiac dysfunction, was broad, the clinical manifestations and aberrations of the inflammatory response were unmistakable and similar.

In the 2 studies, median ages were 8.6 and 10 years, males 61%, underlying conditions 21% and 44%, and symptom duration prior to hospitalization 4 and 4.5 days. Fever was universal, gastrointestinal symptomatology (abdominal pain, diarrhea, or vomiting) universal, hypotension 63% (Kaushik et al), and shock requiring vasopressor therapy 76% (Capone et al). Although 64% of patients met criteria for complete Kawasaki disease in the study by Capone et al, for the most part patients did not have laboratory abnormalities or behave like patients with Kawasaki disease. Inflammatory markers were markedly elevated and cardiac function was markedly abnormal while coronary arteries were more likely to be normal or mildly abnormal. Medical therapies were varied in the studies reported herein, most focusing on halting the up-regulated inflammatory cytokines. Median lengths of hospital stay in these studies were remarkably short—4 days in the study by Capone et al that included PICU and non-PICU MIS-C cases and 4.7 days from shock to discharge from the PICU in the study by Kaushik et al. Although most patients with MIS-C have hypotension requiring vasopressor therapy, they are less ill appearing and less irritable than patients with the shock presentation of Kawasaki disease, and less ill and obtunded than patients with shock associated with bacterial infection (Associate Editor’s personal observation). Most remarkably, cardiac dysfunction in MIS-C usually is rapidly reversible, which distinguishes patients with MIS-C from patients with viral or post-infectious myocarditis/cardiomyopathy (Associate Editor’s personal observation).

MIS-C is a unique clinical entity seemingly of cytokine “toxicity” and thrombosis—an inflammatory syndrome, yes, but absent tissue inflammation such as vasculitis or myocarditis. Words matter. To take another opportunity for precision in language, MIS-C should not be referred to as COVID-associated since patients characteristically do not have the primary respiratory tract signs, symptoms, or outcomes of patients with COVID-19. MIS-C certainly is related to SARS-CoV-2 infection and it is unique.

Article pages 24 and 141

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