• Caroline Diorio, Kevin O McNerney, Michele Lambert, Michele Paessler, Elizabeth M Anderson, Sarah E Henrickson, Julie Chase, Emily J Liebling, Chakkapong Burudpakdee, Jessica H Lee, Frances B Balamuth, Allison M Blatz, Kathleen Chiotos, Julie C Fitzgerald, Therese M Giglia, Kandace Gollomp, Odom JohnAudrey RARDivision of Infectious Diseases, Department of Pediatrics., Cristina Jasen, Tomas Leng, Whitney Petrosa, Laura A Vella, Char Witmer, Kathleen E Sullivan, Benjamin L Laskin, Scott E Hensley, Hamid Bassiri, Edward M Behrens, and David T Teachey.
• Immune Dysregulation Frontier Program, Department of Pediatrics.
• Blood Adv. 2020 Dec 8; 4 (23): 6051-6063.

AbstractMost children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.© 2020 by The American Society of Hematology.

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