Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations.

TitleEvidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations.
Publication TypeJournal Article
Year of Publication2020
AuthorsDiorio C, McNerney KO, Lambert M, Paessler M, Anderson EM, Henrickson SE, Chase J, Liebling EJ, Burudpakdee C, Lee JH, Balamuth FB, Blatz AM, Chiotos K, Fitzgerald JC, Giglia TM, Gollomp K, John AROdom, Jasen C, Leng T, Petrosa W, Vella LA, Witmer C, Sullivan KE, Laskin BL, Hensley SE, Bassiri H, Behrens EM, Teachey DT
JournalBlood Adv
Volume4
Issue23
Pagination6051-6063
Date Published2020 12 08
ISSN2473-9537
Abstract

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.

DOI10.1182/bloodadvances.2020003471
Alternate JournalBlood Adv
PubMed ID33290544
PubMed Central IDPMC7724906
Grant ListK08 AI136660 / AI / NIAID NIH HHS / United States
R01 CA193776 / CA / NCI NIH HHS / United States
R21 AI144472 / AI / NIAID NIH HHS / United States
K12 HS026393 / HS / AHRQ HHS / United States
R01 AI123433 / AI / NIAID NIH HHS / United States
T32 GM075766 / GM / NIGMS NIH HHS / United States
R01 AI103280 / AI / NIAID NIH HHS / United States
T32 AI007324 / AI / NIAID NIH HHS / United States
K23 DK119463 / DK / NIDDK NIH HHS / United States
K08 AI135091 / AI / NIAID NIH HHS / United States
R01 AI121250 / AI / NIAID NIH HHS / United States
UG1 CA233249 / CA / NCI NIH HHS / United States