Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2
Caroline Diorio, … , David T. Teachey, Hamid Bassiri
Caroline Diorio, … , David T. Teachey, Hamid Bassiri
Published July 30, 2020
Citation Information: J Clin Invest. 2020;130(11):5967-5975. https://doi.org/10.1172/JCI140970.
View: Text | PDF
Clinical Medicine COVID-19

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

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.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.

Authors

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, Hamid Bassiri

×

Figure 1

Cytokine architecture associated with SARS–CoV-2 infections in children.

Options: View larger image (or click on image) Download as PowerPoint
Cytokine architecture associated with SARS–CoV-2 infections in children....
(A) Heatmap of the 5 most differentially present cytokines in the plasma of pediatric SARS–CoV-2 infections. Comparison of patients with and without coinfections for each of the 3 clinical phenotypes of pediatric SARS–CoV-2 infection (n = 20). Patient IDs are listed above each column for reference. (B) Cytokine profiles for each patient (n = 15) were treated as a 5-dimensional vector and converted into unit vectors by dividing each component by the root sum square of the vector. Box-and-whisker plot of each unit vector with median values of each for MIS-C versus severe COVID-19 presentations (line). Whiskers represent maximum and minimum and boxes represent the 25th to 75th percentiles. Differences between phenotypes or phenotype/cytokine interaction were not significant by 2-way ANOVA. (C) Vector magnitudes of each cytokine profile were computed as the root sum square with values plotted for severe COVID-19 and MIS-C phenotypes (n = 15). Bar represents the median of each group. Differences were not significant by Mann-Whitney U test. (D) The sum of the IL-10 and TNF-α concentrations were computed for each patient and plotted for severe COVID-19 and MIS-C phenotypes (n = 15). Bar represents the median of each group with P values computed by Mann-Whitney U test.