Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations.
Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations.
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DOI：
10.1182/bloodadvances.2020003471
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发表时间：
2020-12-08
期刊：
影响因子：
7.5
通讯作者：
Teachey DT
中科院分区：
文献类型：
--
作者：
Diorio 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;Odom John AR;Jasen C;Leng T;Petrosa W;Vella LA;Witmer C;Sullivan KE;Laskin BL;Hensley SE;Bassiri H;Behrens EM;Teachey DT
sC 5 b 9血浆水平在SARS-CoV-2感染的儿童中升高，即使他们有最小的COVID-19症状。高比例的SARS-CoV-2感染儿童符合TMA的临床标准。大多数严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的儿童病情轻微或轻微，少数儿童发展为严重疾病或多系统炎症综合征（MIS-C）。补体介导的血栓性微血管病（TMA）与成人SARS-CoV-2感染有关，但尚未在儿科人群中进行研究。我们假设补体激活在儿童SARS-CoV-2感染中起重要作用，并试图了解TMA是否存在于这些患者中。我们入组了50例急性SARS-CoV-2感染（n = 21，2019年最小冠状病毒病[COVID-19]; n = 11，严重COVID-19）或MIS-C（n = 18）的住院儿科患者。作为补体激活和TMA的生物标志物，可溶性C5 b 9在血浆中测量了sC 5 b 9（正常值247 ng/mL），在轻微疾病患者中发现升高（中位数，392 ng/mL;四分位距[IQR]，244-622 ng/mL），重度疾病（中位数，646 ng/mL; IQR，203-728 ng/mL）和MIS-C（中位数，630 ng/mL; IQR，359-932 ng/mL）与26名健康对照受试者（中位数，57 ng/mL; IQR，9-163 ng/mL; P < .001）进行比较。较高的sC 5 b 9水平与较高的血清肌酐相关（P = 0.01），但与年龄无关。在19例有完整临床标准的患者中，17例（89%）符合TMA标准。在接受检测的SARS-CoV-2感染儿童中，有很高比例的人有补体激活的证据，并符合TMA的临床和诊断标准。未来的研究需要确定SARS-CoV-2住院儿童是否应该进行TMA筛查，TMA指导的管理是否有帮助，以及COVID-19或MIS-C儿童的补体激活和内皮损伤是否有任何短期或长期临床后果。
sC5b9 plasma levels are elevated in children with SARS-CoV-2 infection, even if they have minimal symptoms of COVID-19. A high proportion of children with SARS-CoV-2 infection met clinical criteria for TMA. 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.
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DOI：
10.1056/nejmoa1611391
发表时间：
2017-01-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kaddourah A;Basu RK;Bagshaw SM;Goldstein SL;AWARE Investigators
通讯作者：
AWARE Investigators
影响因子：
20.3
作者：
Jodele, Sonata;Davies, Stella M.;Laskin, Benjamin L.
通讯作者：
Laskin, Benjamin L.
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F
阻断 C5a-C5aR 轴可减轻感染 MERS-CoV 的 hDPP4 转基因小鼠的肺损伤。
影响因子：
13.2
作者：
Jiang Y;Zhao G;Song N;Li P;Chen Y;Guo Y;Li J;Du L;Jiang S;Guo R;Sun S;Zhou Y
通讯作者：
Zhou Y