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循环中白细胞介素-6 水平升高和 CD8 T 细胞耗竭与 COVID-19 的进展相关。

Increased circulating level of interleukin-6 and CD8 T cell exhaustion are associated with progression of COVID-19.

机构信息

Department of Hepatobiliary, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, 100039, China.

Department of Epidemiology, Second Military Medical University, Shanghai, 200433, China.

出版信息

Infect Dis Poverty. 2020 Nov 25;9(1):161. doi: 10.1186/s40249-020-00780-6.

DOI:10.1186/s40249-020-00780-6
PMID:33239109
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7686818/
Abstract

BACKGROUND

Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression.

METHODS

Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ test or the Fisher exact test (categorical variables) and independent group t test or Mann-Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19.

RESULTS

The mean incubation was 8.67 (95% confidence interval, 6.78-10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86-12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8 T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4 T cells, and CD8 T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8 lymphocyte count in pneumonia patients did not recover when discharged.

CONCLUSIONS

Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8 cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.

摘要

背景

2019 年冠状病毒病(COVID-19)正在全球流行。确定哪些 COVID-19 患者最有可能发展为重症至关重要。本研究旨在确定与肺炎发生相关的 COVID-19 患者的临床和流行病学特征,以及与疾病进展相关的因素。

方法

本研究纳入了 2019 年 12 月 27 日至 2020 年 3 月 12 日期间在北京解放军总医院收治的 70 例经病原学确诊的 COVID-19 患者,并对其进行了随访,直至 2020 年 3 月 16 日。采用 χ²检验或 Fisher 确切概率法(分类变量)和独立样本 t 检验或 Mann-Whitney U 检验(连续变量)比较了有肺炎和无肺炎 COVID-19 患者的临床和实验室检查结果差异。采用 Cox 比例风险模型和广义估计方程评价了预测 COVID-19 进展的因素。

结果

平均潜伏期为 8.67(95%置信区间:6.78-10.56)天。从首次检测到严重急性呼吸综合征冠状病毒 2 阳性到转为阳性的平均时间为 11.38(9.86-12.90)天。与无肺炎的患者相比,有肺炎的患者年龄大 16.5 岁,且高血压、发热和咳嗽的发生率更高,中性粒细胞比例、白细胞介素 6、CD8 T 细胞计数较低(<190/μl)和中性粒细胞/淋巴细胞比值更高。住院期间有 13 例患者病情恶化。Cox 回归分析表明,年龄较大和入院时血清白细胞介素 6、C 反应蛋白、降钙素原和乳酸水平较高,显著预测 COVID-19 进展。住院期间,肺炎患者的 T 淋巴细胞、CD4 T 细胞和 CD8 T 细胞计数较低,而中性粒细胞比例、中性粒细胞/淋巴细胞比值以及白细胞介素 6、C 反应蛋白和降钙素原水平较高。肺炎患者出院时 CD8 淋巴细胞计数未恢复。

结论

年龄较大、C 反应蛋白、降钙素原、白细胞介素 6 和乳酸水平较高可能预测 COVID-19 进展。T 淋巴细胞,尤其是 CD8 细胞介导的免疫,对 COVID-19 的恢复至关重要。本研究有助于预测疾病进展,并为 COVID-19 制定免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/7687755/1231ac9cd196/40249_2020_780_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/7687755/aac5ba8f3947/40249_2020_780_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/7687755/1231ac9cd196/40249_2020_780_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/7687755/aac5ba8f3947/40249_2020_780_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b68b/7687755/1231ac9cd196/40249_2020_780_Fig2_HTML.jpg

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