TY - JOUR
T1 - Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2
AU - Diorio, Caroline
AU - Henrickson, Sarah E.
AU - Vella, Laura A.
AU - McNerney, Kevin O.
AU - Chase, Julie
AU - Burudpakdee, Chakkapong
AU - Lee, Jessica H.
AU - Jasen, Cristina
AU - Balamuth, Fran
AU - Barrett, David M.
AU - Banwell, Brenda L.
AU - Bernt, Kathrin M.
AU - Blatz, Allison M.
AU - Chiotos, Kathleen
AU - Fisher, Brian T.
AU - Fitzgerald, Julie C.
AU - Gerber, Jeffrey S.
AU - Gollomp, Kandace
AU - Gray, Christopher
AU - Grupp, Stephan A.
AU - Harris, Rebecca M.
AU - Kilbaugh, Todd J.
AU - Odom John, Audrey R.
AU - Lambert, Michele
AU - Liebling, Emily J.
AU - Paessler, Michele E.
AU - Petrosa, Whitney
AU - Phillips, Charles
AU - Reilly, Anne F.
AU - Romberg, Neil D.
AU - Seif, Alix
AU - Sesok-Pizzini, Deborah A.
AU - Sullivan, Kathleen E.
AU - Vardaro, Julie
AU - Behrens, Edward M.
AU - Teachey, David T.
AU - Bassiri, Hamid
N1 - Publisher Copyright:
© 2020, American Society for Clinical Investigation.
PY - 2020/11/2
Y1 - 2020/11/2
N2 - 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. RESULTS. 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. The presence of burr cells on blood smears, as well as Cts, 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 those with severe COVID-19. FUNDING. Financial 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.
AB - 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. RESULTS. 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. The presence of burr cells on blood smears, as well as Cts, 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 those with severe COVID-19. FUNDING. Financial 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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U2 - 10.1172/JCI140970
DO - 10.1172/JCI140970
M3 - Article
C2 - 32730233
AN - SCOPUS:85089155829
SN - 0021-9738
VL - 130
SP - 5967
EP - 5975
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 11
ER -
