Thymosin alpha 1: A comprehensive review of the literature

This 2020 *World Journal of Virology* review synthesizes the clinical and mechanistic evidence on thymosin α-1 (thymalfasin) across its three-decade history of approved use. The authors document the regulatory landscape (over 35 countries with approval, principally for hepatitis B, hepatitis C as adjunct, and selected immunodeficiencies), the published RCT evidence in chronic viral hepatitis, the broader use cases as adjunct therapy in sepsis and serious infections, vaccine-enhancement applications particularly in immunosenescent older adults, and the emerging COVID-19 evidence. The mechanistic synthesis covers thymosin α-1's effects on T-cell maturation and differentiation, dendritic-cell function, natural killer activity, regulatory cytokine balance, and TLR-mediated innate immune signaling — framing it as an immunomodulator rather than a directional immunostimulant. A key COVID-19 finding cited is that thymosin α-1 prevented lymphopenia and supported T-cell proliferation in a cohort of 25 severely ill patients with SARS-CoV-2 infection. The review concludes by recommending further investigation into thymosin α-1's antiviral repositioning for severe coronavirus infections and long-COVID immune dysregulation.

This is a narrative review, not a systematic review or meta-analysis — there is no risk-of-bias methodology, no pooled effect sizes, and no quantitative synthesis. The journal (*World Journal of Virology*, Baishideng) is open-access with broader editorial standards than the leading hepatology journals where most of the primary thymosin α-1 trials were published; readers seeking the strongest individual primary trials should follow citations from this review to the underlying papers (Andreone et al. *J Hepatol* 1996/2000, You et al. on the interferon-comparison trials, the Cochrane review on chronic hepatitis B). The chronic hepatitis B and C indications are where the most rigorous evidence sits, but the post-DAA-era role of thymosin α-1 in HCV is essentially superseded for routine treatment; readers should not infer current first-line standing from this review's historical synthesis. The COVID-19 evidence cited here is small-cohort observational; the long-COVID program is still maturing.