复杂的免疫系统变化和免疫介导的多器官损伤在宿主对SARS-CoV-2感染的应答和COVID-19的发病机制中起关键作用，并与不良结局有关。胸腺肽α1（Tα1）是COVID-19治疗中使用的分子之一，因为它具有在感染和癌症期间恢复免疫系统稳态的能力。在中国和COVID-19患者中，使用Tα1已得到广泛应用。研究表明，它可以减少住院率，特别是对于病情更严重的患者，并通过恢复淋巴细胞减少死亡率，特别是T细胞减少的患者。持续的失调导致天然B和T细胞亚群的耗竭和记忆T细胞的扩增，表明在SARS-CoV-2感染后后遗症患者中存在免疫反应的慢性刺激。我们的离体研究显示，在免疫反应持续改变的PASC患者中，Tα1可以恢复适当的免疫应答，尤其在急性期需要呼吸支持的严重病例和具有特定全身和精神症状的PASC患者中表现最为明显，证实Tα1治疗在感染并发症患者中更为有效。这些结果以及关于最近在COVID-19患者中Tα1治疗试验的有希望的报告，为那些存在长期炎症症状和后继感染症状的患者介入治疗提供了新的见解。版权所有©2023 Elsevier B.V.。保留所有权利。

The complex alterations of the immune system and the immune-mediated multiorgan injury plays a key role in host response to SARS-CoV-2 infection and in the pathogenesis of COVID-19, being also associated with adverse outcomes. Thymosin alpha 1 (Tα1) is one of the molecules used in the treatment of COVID-19, as it is known to restore the homeostasis of the immune system during infections and cancer. The use of Tα1 in COVID-19 patients had been widely used in China and in COVID-19 patients, it has been shown to decrease hospitalization rate, especially in those with greater disease severity, and reduce mortality by restoring lymphocytopenia and more specifically, depleted T cells. Persistent dysregulation with depletion of naive B and T cell subpopulations and expansion of memory T cells suggest a chronic stimulation of the immune response in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Our data obtained from an ex vivo study, showed that in PASC individuals with a chronically altered immune response, Tα1 improve the restoration of an appropriate response, most evident in those with more severe illness and who need respiratory support during acute phase, and in those with specific systemic and psychiatric symptoms of PASC, confirming Tα1 treatment being more effective in compromised patients. The results obtained, along with promising reports on recent trials on Tα1 administration in patients with COVID-19, offer new insights into intervention also for those patients with long-lasting inflammation with post-infectious symptoms, some of which have a delayed onset.Copyright © 2023 Elsevier B.V. All rights reserved.