Journal Article

Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2

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

2020

Overview

BACKGROUNDInitial 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.

• Publisher: American Society for Clinical Investigation
• Subject: Adolescent / Betacoronavirus - metabolism / Child / Child, Preschool / Clinical Medicine / Complement Membrane Attack Complex - metabolism / Coronavirus Infections - blood / Coronavirus Infections - epidemiology / COVID-19 / Cytokines - blood / Diagnosis / Female / Hospital patients / Humans / Immunodiagnosis / Male / Medical examination / Pandemics / Pediatric multisystem inflammatory syndrome / Pediatric research / Pneumonia, Viral - blood / Pneumonia, Viral - epidemiology / Prospective Studies / SARS-CoV-2 / Severity of Illness Index / Systemic Inflammatory Response Syndrome - blood / Systemic Inflammatory Response Syndrome - epidemiology