• Caroline Diorio, Sarah E Henrickson, Laura A Vella, Kevin O McNerney, Julie Chase, Chakkapong Burudpakdee, Jessica H Lee, Cristina Jasen, Fran Balamuth, David M Barrett, Brenda L Banwell, Kathrin M Bernt, Allison M Blatz, Kathleen Chiotos, Brian T Fisher, Julie C Fitzgerald, Jeffrey S Gerber, Kandace Gollomp, Christopher Gray, Stephan A Grupp, Rebecca M Harris, Todd J Kilbaugh, Audrey R Odom John, Michele Lambert, Emily J Liebling, Michele E Paessler, Whitney Petrosa, Charles Phillips, Anne F Reilly, Neil D Romberg, Alix Seif, Deborah A Sesok-Pizzini, Kathleen E Sullivan, Julie Vardaro, Edward M Behrens, David T Teachey, and Hamid Bassiri.
• Immune Dysregulation Frontier Program.
• J. Clin. Invest. 2020 Nov 2; 130 (11): 5967-5975.

AbstractBACKGROUNDInitial 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.METHODSWe 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.RESULTSTwenty 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. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric 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 those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.

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