Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells
Yueping Liu, Yue Pan, 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, Yueping Liu, Yue Pan, 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
Abstract
Background: Thymosin alpha 1 (Tα1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and the mechanism of Tα1 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, Tα1 treatment significantly reduced the mortality of severe COVID-19 patients (11.11% vs 30.00%, P = .044). Tα1 enhanced blood T-cell numbers in COVID-19 patients with severe lymphocytopenia. Under such conditions, Tα1 also successfully restored CD8+ and CD4+ T-cell numbers in elderly patients. Meanwhile, Tα1 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: Tα1 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/μL or 650/μL, respectively, gained more benefits from Tα1. Tα1 reversed T-cell exhaustion and recovered immune reconstitution through promoting thymus output during severe acute respiratory syndrome-coronavirus 2 infection.
Keywords: COVID-19; SARS-CoV-2; T-cell exhaustion; immune reconstitution; thymosin alpha 1.
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Source: PubMed