Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells
Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells
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胸腺肽 Alpha 1 通过恢复淋巴细胞减少和恢复耗尽的 T 细胞来降低 2019 年严重冠状病毒病的死亡率
DOI：
10.1093/cid/ciaa630
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发表时间：
2020-10-15
影响因子：
11.8
通讯作者：
Chen, Yongwen
中科院分区：
文献类型：
--
作者：
Liu, Yueping;Pan, Yue;Chen, Yongwen
背景资料。胸腺素α1(Tα1)多年来一直作为免疫反应调节剂用于病毒感染的治疗。然而，Tα1治疗新冠肺炎的临床疗效和作用机制尚不清楚。我们回顾了2019年12月至2020年3月在武汉2家医院收治的76例重症新冠肺炎患者的临床转归。采用T细胞受体切除环法(TRECs)检测新冠肺炎患者外周血单个核细胞胸腺产量。用流式细胞仪检测CD8+T细胞上T细胞耗竭标志物程序性死亡-1(PD-1)和T细胞免疫球蛋白及粘蛋白结构域蛋白3(TIM-3)的水平。与未治疗组相比，Tα1治疗可显著降低重症新冠肺炎患者的死亡率(11.11%比30.00%，P=0.044)。严重淋巴细胞减少新冠肺炎患者外周血中T细胞数量增加。在这种条件下，Tα1也成功恢复了老年患者的CD8(+)和CD4(+)T细胞数量。同时，与未经治疗的患者相比，Tα1降低了重症新冠肺炎患者CD8+T细胞上PD-1和TIM-3的表达。值得注意的是，淋巴细胞减少和T细胞急性耗竭的恢复与TREC的上升大致平行。Tα1治疗显著降低了重症新冠肺炎患者的死亡率。循环中CD_8~+、CD_4~+T细胞分别低于400个/亩L和650个/亩L的新冠肺炎患者从Tα1中获益更多。在严重急性呼吸综合征-冠状病毒2型感染期间，Tα1通过促进胸腺输出而逆转T细胞衰竭，恢复免疫重建。
Background. Thymosin alpha 1 (T alpha 1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and the mechanism of T alpha 1 treatment for COVID-19 patients are still unclear.Methods. We retrospectively reviewed the clinical outcomes of 76 severe COVID-19 cases admitted to 2 hospitals in Wuhan, China, from December 2019 to March 2020. The thymus output in peripheral blood mononuclear cells from COVID-19 patients was measured by T-cell receptor excision circles (TRECs). The levels of T-cell exhaustion markers programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain protein 3 (Tim-3) on CD8(+) T cells were detected by flow cytometry.Results. Compared with the untreated group, T alpha 1 treatment significantly reduced the mortality of severe COVID-19 patients (11.11% vs 30.00%, P = .044). T alpha 1 enhanced blood T-cell numbers in COVID-19 patients with severe lymphocytopenia. Under such conditions, T alpha 1 also successfully restored CD8(+) and CD4(+) T-cell numbers in elderly patients. Meanwhile, T alpha 1 reduced PD-1 and Tim-3 expression on CD8(+) T cells from severe COVID-19 patients compared with untreated cases. It is of note that restoration of lymphocytopenia and acute exhaustion of T cells were roughly parallel to the rise of TRECs.Conclusions. T alpha 1 treatment significantly reduced mortality of severe COVID-19 patients. COVID-19 patients with counts of CD8(+) T cells or CD4(+) T cells in circulation less than 400/mu L or 650/mu L, respectively, gained more benefits from T alpha 1. T alpha 1 reversed T-cell exhaustion and recovered immune reconstitution through promoting thymus output during severe acute respiratory syndrome-coronavirus 2 infection.