埃及儿童和青少年 COVID-19 肺炎的细胞因子特征：一项多中心研究。
Cytokine profile in Egyptian children and adolescents with COVID-19 pneumonia: A multicenter study.
机构信息
Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Pediatrics, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
出版信息
Pediatr Pulmonol. 2021 Dec;56(12):3924-3933. doi: 10.1002/ppul.25679. Epub 2021 Sep 27.
BACKGROUND
To date, the cytokine profile in children and adolescent with novel coronavirus disease 2019 (COVID-19) has not been reported.
OBJECTIVES
We investigated serum levels of a panel of key cytokines in children and adolescent with COVID-19 pneumonia with a primary focus on "cytokine storm" cytokines such as interleukin (IL)-1β, IL-6, IL-17, IL-2, IL-4, IL-10, interferon (IFN-γ), tumor necrosis factor (TNF)-α, and two chemokines interferon-inducible protein-10 (IP-10) and IL-8. We also studied whether these cytokines could be potential markers for illness severity in COVID-19 pneumonia.
METHODS
Ninety-two symptomatic patients aged less than 18 years with confirmed COVID-19 pneumonia and 100 well-matched healthy controls were included in this multi-center study. For all patients, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory fluid specimens was detected by real-time reverse-transcriptase polymerase chain reaction. We measured serum concentrations of studied cytokines by using flow cytometry.
RESULTS
Patients with COVID-19 had significantly higher median IL-1β, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 serum levels than did control children (all p < 0.01). Patients with severe COVID-19 pneumonia had significantly higher median IL-1β, IL-6, and IP-10 serum levels as compared with those with moderate COVID-19 pneumonia; all p < 0.01. ROC analysis revealed that three of the studied markers (IL-6, IL-1β, and IP-10) could predict severe COVID-19 pneumonia cases with the largest AUC for IL-6 of 0.893 (95% confidence interval: 0.84-0.98; p < 0.01).
CONCLUSION
Our study shows that pediatric patients with COVID-19 pneumonia have markedly elevated serum IL-1β, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 levels at the initial phase of the illness indicating a cytokine storm following SARS-CoV-2 infection. Moreover, serum IL-6, IL-1β, and IP-10 concentrations were independent predictors for severe COVID-19 pneumonia.
背景
迄今为止，儿童和青少年新型冠状病毒病 2019（COVID-19）的细胞因子谱尚未报道。
目的
我们研究了 COVID-19 肺炎患儿血清中一系列关键细胞因子的水平，重点关注白细胞介素（IL）-1β、IL-6、IL-17、IL-2、IL-4、IL-10、干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α 和两种趋化因子干扰素诱导蛋白-10（IP-10）和 IL-8 等“细胞因子风暴”细胞因子。我们还研究了这些细胞因子是否可以作为 COVID-19 肺炎疾病严重程度的潜在标志物。
方法
本多中心研究纳入了 92 例年龄小于 18 岁且确诊为 COVID-19 肺炎的有症状患者和 100 例匹配良好的健康对照者。对于所有患者，通过实时逆转录酶聚合酶链反应检测呼吸道标本中严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的存在。我们使用流式细胞术测量了研究细胞因子的血清浓度。
结果
COVID-19 患者的血清 IL-1β、IL-6、IL-8、IL-10、IL-17、TNF-α 和 IP-10 水平中位数显著高于对照组儿童（均 p<0.01）。与中度 COVID-19 肺炎患者相比，重症 COVID-19 肺炎患者的血清 IL-1β、IL-6 和 IP-10 水平中位数显著升高；所有 p<0.01。ROC 分析显示，3 个研究标志物（IL-6、IL-1β 和 IP-10）可预测重症 COVID-19 肺炎病例，其中 IL-6 的 AUC 最大为 0.893（95%置信区间：0.84-0.98；p<0.01）。
结论
我们的研究表明，COVID-19 肺炎患儿在疾病的初始阶段，血清中 IL-1β、IL-6、IL-8、IL-10、IL-17、TNF-α 和 IP-10 水平显著升高，表明 SARS-CoV-2 感染后发生细胞因子风暴。此外，血清 IL-6、IL-1β 和 IP-10 浓度是重症 COVID-19 肺炎的独立预测因子。
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