Thymosin alpha 1 (Tα1) reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells.
Thymosin alpha 1 (Tα1) reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells.
复制标题
DOI：
--
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Yongwen Chen
中科院分区：
文献类型：
--
作者：
Yueping Liu;Yue Pang;Zhenhong Hu;Ming Wu;Chenhui Wang;Zeqing Feng;Congzheng Mao;Yingjun Tan;Ying Liu;Li Chen;Min Li;Gang Wang;Zilin Yuan;Bo Diao;Yuzhang Wu;Yongwen Chen
BACKGROUND: We previously reported that lymphocytopenia and T cell exhaustion is notable in acute COVID19 patients, especially in aged and severe cases. Thymosin alpha 1 (T&945;1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and mechanism of T&945;1 supplement to COVID-19 are still unclear. METHODS: We retrospectively reviewed the clinical outcomes of 76 severe cases with COVID-19 admitted into two hospitals in Wuhan from December 2019 to March 2020. The thymus output in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients was measured by T cell receptor excision circles (TREC). The levels of T cell exhaustion markers PD-1 and Tim-3 on CD8+ T cells were detected by flow cytometry. RESULTS: Compared with untreated group, T&945;1 treatment significantly reduces mortality of severe COVID-19 patients (11.11% vs. 30.00%, p=0.044). T&945;1 timely enhances blood T cell numbers in COVID-19 patients with severe lymphocytopenia (the counts of CD8+ T cells or CD4+ T cells in circulation lower than 400/�L or 650/�L, respectively). Under such conditions, T&945;1 also successfully restores CD8+ and CD4+ T cell numbers in aged patients. Meanwhile, T&945;1 reduces PD-1 and Tim-3 expression on CD8+ T cells from severe COVID-19 patients in comparison with untreated cases. It is of note that restoration of lymphocytopenia and acute exhaustion of T cells are roughly parallel to the rise of TRECs. CONCLUSIONS: T&945;1 supplement significantly reduce mortality of severe COVID-19 patients. COVID-19 patients with the counts of CD8+ T cells or CD4+ T cells in circulation lower than 400/�L or 650/�L, respectively, gain more benefits from T&945;1. T&945;1 reverses T cell exhaustion and recovers immune reconstitution through promoting thymus output during SARS-CoV-2 infection.
