J Clin Invest


. 2020 Jul 30;140970.
doi: 10.1172/JCI140970. Online ahead of print.
Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2


Caroline Diorio 1 , Sarah E Henrickson 2 , Laura A Vella 1 , Kevin O McNerney 1 , Julie M Chase 1 , Chakkapong Burudpakdee 1 , Jessica H Lee 1 , Cristina Jasen 1 , Fran Balamuth 3 , David M Barrett 1 , Brenda Banwell 4 , Kathrin M Bernt 5 , Allison M Blatz 6 , Kathleen Chiotos 7 , Brian T Fisher 1 , Julie C Fitzgerald 7 , Jeffrey S Gerber 6 , Kandace Gollomp 8 , Christopher Gray 1 , Stephan A Grupp 5 , Rebecca M Harris 6 , Todd J Kilbaugh 7 , Audrey R Odom John 6 , Michele P Lambert 1 , Emily J Liebling 9 , Michele Paessler 10 , Whitney Petrosa 1 , Charles A Phillips 5 , Anne F Reilly 11 , Neil Romberg 1 , Alix E Seif 1 , Deborah Sesok-Pizzini 10 , Kathleen Sullivan 12 , Julie Vardaro 1 , Edward M Behrens 13 , David T Teachey 14 , Hamid Bassiri 11



Affiliations

Abstract

Background: Initial reports from the Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to Coronavirus Disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed Multisystem Inflammatory Syndrome in Children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.
Methods: We prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8 and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. Cts and burr cells on blood smears also differentiated between patients with severe COVID-19 and those with MIS-C.
Conclusion: Pediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and severe COVID-19.

Keywords: COVID-19; Cytokines.