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

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

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.