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北非 COVID-19 患者的 T 细胞计数和血液中白细胞介素 6 浓度是重症和死亡的两个独立预后因素。

T cell counts and IL-6 concentration in blood of North African COVID-19 patients are two independent prognostic factors for severe disease and death.

机构信息

Immunology Department, Béni-Messous Teaching Hospital, University of Algiers, Algiers, Algeria.

Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.

出版信息

J Leukoc Biol. 2022 Jan;111(1):269-281. doi: 10.1002/JLB.4COVA1020-703R. Epub 2021 Feb 2.

Abstract

The immune system plays a crucial role in the response against severe acute respiratory syndrome coronavirus 2 with significant differences among patients. The study investigated the relationships between lymphocyte subsets, cytokines, and disease outcomes in patients with coronavirus disease 2019 (COVID-19). The measurements of peripheral blood lymphocytes subsets and cytokine levels were performed by flow cytometry for 57 COVID-19 patients. Patients were categorized into two groups according to the severity of the disease (nonsevere vs. severe). Total lymphocytes, T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells were decreased in COVID-19 patients and statistical differences were found among different severity of illness and survival states (P ˂ 0.01). The levels of IL-6 and IL-10 were significantly higher in severe and death groups and negatively correlated with lymphocyte subsets counts. The percentages of Th17 in the peripheral blood of patients were higher than those of healthy controls whereas the percentages of Th2 were lower. For the severe cases, the area under receiver operating characteristic (ROC) curve of IL-6 was the largest among all the immune parameters (0.964; 95% confidence interval: 0.927-1.000, P < 0.0001). In addition, the preoperative IL-6 concentration of 77.38 pg/ml was the optimal cutoff value (sensitivity: 84.6%, specificity: 100%). Using multivariate logistic regression analysis and ROC curves, IL-6 > 106.44 pg/ml and CD8+ T cell counts <150 cells/μl were found to be associated with mortality. Measuring the immune parameters and defining a risk threshold can segregate patients who develop a severe disease from those with a mild pathology. The identification of these parameters may help clinicians to predict the outcome of the patients with high risk of unfavorable progress of the disease.

摘要

免疫系统在对抗严重急性呼吸综合征冠状病毒 2 方面发挥着至关重要的作用,不同患者之间存在显著差异。本研究旨在探讨 2019 年冠状病毒病(COVID-19)患者淋巴细胞亚群、细胞因子与疾病结局之间的关系。通过流式细胞术检测 57 例 COVID-19 患者外周血淋巴细胞亚群和细胞因子水平。根据疾病严重程度(非重症与重症)将患者分为两组。COVID-19 患者总淋巴细胞、T 细胞、CD4+ T 细胞、CD8+ T 细胞、B 细胞和自然杀伤细胞计数均降低,不同疾病严重程度和生存状态之间存在统计学差异(P ˂ 0.01)。重症和死亡组患者的白细胞介素 6(IL-6)和白细胞介素 10(IL-10)水平显著升高,且与淋巴细胞亚群计数呈负相关。与健康对照组相比,患者外周血中 Th17 细胞的百分比更高,而 Th2 细胞的百分比更低。对于重症病例,IL-6 是所有免疫参数中 ROC 曲线下面积(AUC)最大的(0.964;95%置信区间:0.927-1.000,P ˂ 0.0001)。此外,IL-6 术前浓度为 77.38 pg/ml 是最佳截断值(敏感性:84.6%,特异性:100%)。多变量逻辑回归分析和 ROC 曲线显示,IL-6 ˃ 106.44 pg/ml 和 CD8+ T 细胞计数 ˂ 150 个/μl 与死亡率相关。通过测量免疫参数并定义风险阈值,可以将发生严重疾病的患者与发生轻度病理的患者区分开来。识别这些参数可能有助于临床医生预测疾病进展不良风险高的患者的预后。

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