{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:38:57Z","timestamp":1790519937339,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T00:00:00Z","timestamp":1590105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971478"],"award-info":[{"award-number":["81971478"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8177169"],"award-info":[{"award-number":["8177169"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Thymosin alpha 1 (T\u03b11) 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\u03b11 treatment for COVID-19 patients are still unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Compared with the untreated group, T\u03b11 treatment significantly reduced the mortality of severe COVID-19 patients (11.11% vs 30.00%, P = .044). T\u03b11 enhanced blood T-cell numbers in COVID-19 patients with severe lymphocytopenia. Under such conditions, T\u03b11 also successfully restored CD8+ and CD4+ T-cell numbers in elderly patients. Meanwhile, T\u03b11 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>T\u03b11 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\/\u03bcL or 650\/\u03bcL, respectively, gained more benefits from T\u03b11. T\u03b11 reversed T-cell exhaustion and recovered immune reconstitution through promoting thymus output during severe acute respiratory syndrome\u2013coronavirus 2 infection.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaa630","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T19:29:03Z","timestamp":1590002943000},"page":"2150-2157","source":"Crossref","is-referenced-by-count":132,"title":["Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells"],"prefix":"10.1093","volume":"71","author":[{"given":"Yueping","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Center, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Immunology, People\u2019s Liberation Army, Third Military Medical University, Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Medicine, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, General Hospital of Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"},{"name":"Intensive Care Unit, Wuhan Pulmonary Hospital, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Immunology, People\u2019s Liberation Army, Third Military Medical University, Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeqing","family":"Feng","sequence":"additional","affiliation":[{"name":"Institute of Immunology, People\u2019s Liberation Army, Third Military Medical University, Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congzheng","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Medicine, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute of Immunology, People\u2019s Liberation Army, Third Military Medical University, Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Center, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Center, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Center, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Center, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Center, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Diao","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Center, General Hospital of the Central Theater Command, Wuhan, Hubei Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Immunology, People\u2019s Liberation Army, Third Military Medical University, Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0022-6627","authenticated-orcid":false,"given":"Yongwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Immunology, People\u2019s Liberation Army, Third Military Medical University, Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,22]]},"reference":[{"key":"2020111907073032100_CIT0001","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"; 382:","author":"Zhu","year":"2020","journal-title":"N Engl J Med"},{"key":"2020111907073032100_CIT0002","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, 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