Immune Dysregulation Frontier Program, Department of Pediatrics.
Division of Oncology, Department of Pediatrics, and.
Blood Adv. 2020 Dec 8;4(23):6051-6063. doi: 10.1182/bloodadvances.2020003471.
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.
大多数严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染的儿童患有轻度或轻度疾病，少数儿童发展为严重疾病或儿童多系统炎症综合征 (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，并试图了解这些患者是否存在 TMA。我们招募了 50 名患有急性 SARS-CoV-2 感染的住院儿科患者（n = 21，最小的 2019 年冠状病毒病 [COVID-19]；n = 11，严重 COVID-19）或 MIS-C（n = 18）。作为补体激活和 TMA 的生物标志物，测量了血浆中可溶性 C5b9（sC5b9，正常 247ng/mL），在患有轻度疾病的患者中发现了升高（中位数，392ng/mL；四分位距 [IQR]，244-622ng/mL）、严重疾病（中位数，646ng/mL；IQR，203-728ng/mL）和 MIS-C（中位数，630ng/mL；IQR，359-932ng/mL）与 26 名健康对照（中位数，57ng/mL；IQR，9-163ng/mL；P <.001）。较高的 sC5b9 水平与较高的血清肌酐相关（P =.01），但与年龄无关。在有完整临床标准的 19 名患者中，有 17 名（89%）符合 TMA 标准。很大比例接受 SARS-CoV-2 感染检测的儿童有补体激活的证据，并符合 TMA 的临床和诊断标准。需要进一步的研究来确定是否应筛查 SARS-CoV-2 感染的住院儿童是否存在 TMA，如果 TMA 定向治疗是否有帮助，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的临床后果。
