Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)
Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)
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DOI：
10.3389/fimmu.2020.00827
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发表时间：
2020-05-01
影响因子：
7.3
通讯作者：
Chen, Yongwen
中科院分区：
文献类型：
--
作者：
Diao, Bo;Wang, Chenhui;Chen, Yongwen
背景资料：由严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）爆发对人类健康构成了巨大威胁。T细胞在抗病毒免疫中起着至关重要的作用，但其数量和功能状态在COVID-19患者中仍不清楚。方法：我们回顾性分析了522例实验室确诊的COVID-19患者和40例健康对照者的T细胞计数和血清细胞因子浓度。结果：COVID-19患者T细胞总数、CD 4（+）和CD 8（+）T细胞数量显著减少，尤其是需要重症监护病房（ICU）护理的患者。总T细胞、CD 8（+）T细胞或CD 4（+）T细胞计数分别低于800、300或400/μ L与患者生存率呈负相关。T细胞数量与血清IL-6、IL-10和TNF-α浓度呈负相关，疾病缓解期患者的IL-6、IL-10和TNF-α浓度降低，T细胞计数恢复。来自COVID-19患者的T细胞具有显著更高水平的耗尽标志物PD-1。随着患者从前驱期进展到明显症状阶段，T细胞上的PD-1和Tim-3表达增加。结论：COVID-19患者的T细胞计数显著减少，存活的T细胞出现功能衰竭。总T细胞计数低于800/μ L的非ICU患者可能仍然需要紧急干预，即使由于病情进一步恶化的高风险而立即没有更严重的症状。
Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear.Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases.Results: The number of total T cells, CD4(+) and CD8(+) T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8(+) T cells or CD4(+) T cells lower than 800, 300, or 400/mu L, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-alpha concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-alpha concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages.Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/mu L may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.