Yueping Liu1, Yue Pan2, Zhenhong Hu3, Ming Wu4,5, Chenhui Wang2, Zeqing Feng2, Congzheng Mao3, Yingjun Tan2, Ying Liu1, Li Chen1, Min Li1, Gang Wang1, Zilin Yuan1, Bo Diao1, Yuzhang Wu2, Yongwen Chen2. 1. Department of Medical Laboratory Center, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People's Republic of China. 2. Institute of Immunology, People's Liberation Army, Third Military Medical University, Chongqing, People's Republic of China. 3. Department of Respiratory and Critical Medicine, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People's Republic of China. 4. Intensive Care Unit, General Hospital of Central Theater Command, Wuhan, Hubei Province, People's Republic of China. 5. Intensive Care Unit, Wuhan Pulmonary Hospital, Wuhan, Hubei Province, People's Republic of China.
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.
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-19patients 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-19patients 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-19patients (11.11% vs 30.00%, P = .044). Tα1 enhanced blood T-cell numbers in COVID-19patients 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-19patients 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-19patients. COVID-19patients 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 2infection.
Authors: Max E Distler; Michelle H Teplensky; Katherine E Bujold; Caroline D Kusmierz; Michael Evangelopoulos; Chad A Mirkin Journal: J Am Chem Soc Date: 2021-08-19 Impact factor: 16.383
Authors: Roberto Lozano-Rodríguez; Verónica Terrón-Arcos; Raúl López; Juan Martín-Gutiérrez; Alejandro Martín-Quirós; Charbel Maroun-Eid; Elena Muñoz Del Val; Carlos Cañada-Illana; Alejandro Pascual Iglesias; Jaime Valentín Quiroga; Karla Montalbán-Hernández; José Carlos Casalvilla-Dueñas; Miguel A García-Garrido; Álvaro Del Balzo-Castillo; María A Peinado-Quesada; Laura Gómez-Lage; Carmen Herrero-Benito; Ray G Butler; José Avendaño-Ortiz; Eduardo López-Collazo Journal: J Clin Med Date: 2022-06-08 Impact factor: 4.964