Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations
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- Caroline Diorio
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Kevin O. McNerney
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Michele Lambert
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Michele Paessler
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Elizabeth M. Anderson
- Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; and
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- Sarah E. Henrickson
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Julie Chase
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Emily J. Liebling
- Division of Rheumatology, Department of Pediatrics,
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- Chakkapong Burudpakdee
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Jessica H. Lee
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Frances B. Balamuth
- Division of Emergency Medicine, Department of Pediatrics,
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- Allison M. Blatz
- Division of Infectious Diseases, Department of Pediatrics,
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- Kathleen Chiotos
- Division of Infectious Diseases, Department of Pediatrics,
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- Julie C. Fitzgerald
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Therese M. Giglia
- Division of Cardiology, Department of Pediatrics, and
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- Kandace Gollomp
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Audrey R. Odom John
- Division of Infectious Diseases, Department of Pediatrics,
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- Cristina Jasen
- Division of Allergy and Immunology, Department of Pediatrics,
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- Tomas Leng
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Whitney Petrosa
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Laura A. Vella
- Division of Infectious Diseases, Department of Pediatrics,
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- Char Witmer
- Division of Hematology, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA;
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- Kathleen E. Sullivan
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Benjamin L. Laskin
- Division of Nephrology, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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- Scott E. Hensley
- Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; and
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- Hamid Bassiri
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- Edward M. Behrens
- Immune Dysregulation Frontier Program, Department of Pediatrics,
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- David T. Teachey
- Immune Dysregulation Frontier Program, Department of Pediatrics,
抄録
<jats:title>Abstract</jats:title> <jats:p>Most 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.</jats:p>
収録刊行物
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- Blood Advances
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Blood Advances 4 (23), 6051-6063, 2020-12-08
American Society of Hematology