Immune Dysregulation Frontier Program.
Division of Oncology.
J Clin Invest. 2020 Nov 2;130(11):5967-5975. doi: 10.1172/JCI140970.
BACKGROUNDInitial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.METHODSWe prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data.RESULTSTwenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.
最初关于严重急性呼吸冠状病毒 2(SARS-CoV-2)大流行的报告表明,儿童比成年人不易感染 2019 年冠状病毒病(COVID-19)。随后,一种严重且新颖的儿科疾病,称为儿童多系统炎症综合征(MIS-C)出现了。我们报告了区分 COVID-19 和 MIS-C 的独特血液学和免疫学参数,并深入了解了病理生理学。
我们前瞻性招募了有 SARS-CoV-2 感染证据的住院患者,并将其分为 MIS-C 或 COVID-19。将 COVID-19 患者分为轻度或重度疾病。分析了细胞因子谱、病毒循环阈值(Cts)、血涂片和可溶性 C5b-9 值,并结合临床数据进行分析。
共纳入 20 例患者(9 例严重 COVID-19、5 例轻度 COVID-19 和 6 例 MIS-C)。有 5 种细胞因子(IFN-γ、IL-10、IL-6、IL-8 和 TNF-α)对分析有贡献。TNF-α和 IL-10 可区分 MIS-C 和严重 COVID-19 患者。血涂片上出现锯齿细胞以及 Cts 可区分严重 COVID-19 和 MIS-C 患者。
感染 SARS-CoV-2 的儿科患者有发生严重 COVID-19 和 MIS-C 等危重症的风险。细胞因子谱分析和外周血涂片检查可区分 MIS-C 和严重 COVID-19 患者。
这项研究得到了 CHOP 前沿计划免疫失调团队、美国国立过敏和传染病研究所、美国国立癌症研究所、白血病和淋巴瘤协会、为儿童癌症而做饼干、亚历克斯柠檬台基金会、儿童肿瘤学组、为癌症而站、Connor 团队、Amato 基金会、Burroughs Wellcome 基金 CAMS、临床免疫学学会、美国过敏、哮喘和免疫学学会、转化医学和治疗学研究所的支持。