Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China
Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China
复制标题
中国武汉市2019冠状病毒病（COVID-19）住院儿科患者的临床和免疫特征
DOI：
10.1001/jamanetworkopen.2020.10895
复制
发表时间：
2020-06-03
影响因子：
13.8
通讯作者：
Xiang, Yun
中科院分区：
文献类型：
--
作者：
Wu, Huan;Zhu, Hongmin;Xiang, Yun
问题2019冠状病毒病（COVID-19）引起的肺炎患儿的免疫学特征是什么？在这项涉及157名COVID-19儿科患者的单中心病例系列中，很少发生全身性炎症。与轻度疾病患者相比，中度疾病患者的白细胞介素10水平较高，中性粒细胞水平较低。本研究结果提示免疫反应失调可能参与了COVID-19的病理过程;更深入地了解中性粒细胞，CD 4（+）T细胞，和B细胞在严重急性呼吸综合征冠状病毒2型感染发病机制中的作用可能对COVID-1的临床管理很重要。19.本病例系列描述并比较了轻度和中度冠状病毒病的免疫学特征2019（COVID-19）在儿科患者中的应用。重要性2019年儿科冠状病毒病患者的流行病学和临床特征（COVID-19）的报道，但与疾病严重程度相关的免疫特征的信息很少。目的探讨和比较轻、中度COVID-19患儿的免疫学特征。设计、设置和参与者该单中心病例系列包括157名在武汉儿童医院住院的实验室确诊的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）儿科患者。数据收集时间为2020年1月25日至4月18日。暴露记录了SARS-CoV-2感染。主要结果和指标收集并分析临床和免疫学特征。观察结果直至2020年4月18日。结果157例COVID-19患儿中，轻型肺炎60例（38.2%），中型肺炎88例（56.1%），重型肺炎6例（3.8%），危重型肺炎3例（1.9%）。148名轻度或中度疾病儿童的中位（四分位距[IQR]）年龄为84（18-123）个月，其中88名（59.5%）为女孩。最常见的实验室异常是丙氨酸氨基转移酶（ALT）水平升高（中位数[IQR]，16.0 [12.0-26.0] U/L），天冬氨酸转氨酶（AST）（中位数[IQR]，30.0 [23.0-41.8] U/L），肌酸激酶MB（CK-MB）活性（中位数[IQR]，24.0 [18.0-34.0] U/L）和乳酸脱氢酶（LDH）（中位数[IQR]，243.0 [203.0-297.0] U/L），与肝脏和心肌损伤相关。与轻度病例相比，炎性细胞因子水平（包括白细胞介素6、肿瘤坏死因子α和干扰素γ）无变化，而免疫抑制性白细胞介素10水平在中度病例中显著升高（中位数[IQR]，3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = 0.048）。轻度和中度病例之间淋巴细胞（包括T细胞和B细胞）的绝对数量无统计学显著差异，但与轻度病例相比，中度病例与中性粒细胞水平降低相关（中位数[IQR]，2310/mu L [1680/mu L-3510/mu L] vs 3120/mu L [2040/mu L-4170/mu L]; P = 0.01）。免疫球蛋白G和中性粒细胞/淋巴细胞比值与肝脏和心肌损伤相关的生化指标呈负相关（免疫球蛋白G：ALT：r，-0.3579，AST：r，-0.5280，CK-MB活性：r，-0.4786，LDH：r，-0.4984，中性粒细胞/淋巴细胞比值：ALT：r，-0.1893，AST：r，-0.3912; CK-MB活性：r，-0.3428; LDH：r，-0.3234），而淋巴细胞计数、CD 4（+）T细胞计数和白细胞介素10呈正相关（淋巴细胞，ALT：r，0.2055; AST：r，0.3615; CK-MB活性：r，0.338; LDH：r，0.3309; CD 4（+）T细胞，AST：r，0.4701; CK-MB活性：r，0.4151; LDH：r，0.3309）r，0.4418;白细胞介素10，ALT：r，0.2595; AST：r，0.3386; CK-MB活性：r，0.3948; LDH：r，0.3794）。结论和相关性在该病例系列中，与在COVID-19成人患者中经常观察到的淋巴细胞减少和炎症反应加重相比，COVID-19儿科患者很少发生全身性炎症。深入了解中性粒细胞、CD 4（+）T细胞和B细胞在SARS-CoV-2感染发病机制中的作用，对于COVID-19的临床管理可能很重要。
Question What are the immunologic features of pediatric patients with pneumonia caused by coronavirus disease 2019 (COVID-19)? Findings In this single-center case series involving 157 pediatric patients with COVID-19, systemic inflammation rarely occurred. Patients with moderate disease had higher interleukin 10 levels and lower neutrophil levels than patients with mild disease. Meaning The results of this study suggest that dysregulation of immune response may be involved in the pathologic process of COVID-19; gaining a deeper understanding of the role of neutrophils, CD4(+) T cells, and B cells in the pathogenesis of severe acute respiratory syndrome coronavirus 2 infection could be important for the clinical management of COVID-19.This case series delineates and compares the immunologic features of mild and moderate coronavirus disease 2019 (COVID-19) in pediatric patients.Importance The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. Objective To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. Design, Setting, and Participants This single-center case series included 157 pediatric patients admitted to Wuhan Children's Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. Exposures Documented SARS-CoV-2 infection. Main Outcomes and Measures Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. Results Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor alpha, and interferon gamma were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/mu L [1680/mu L-3510/mu L] vs 3120/mu L [2040/mu L-4170/mu L]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, -0.3579; AST: r, -0.5280; CK-MB activity: r, -0.4786; LDH: r, -0.4984; and neutrophil to lymphocyte ratio, ALT: r, -0.1893; AST: r, -0.3912; CK-MB activity: r, -0.3428; LDH: r, -0.3234), while counts of lymphocytes, CD4(+) T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4(+) T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). Conclusions and Relevance In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4(+) T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.