Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing pandemic coronavirus disease 2019 (COVID-19). The majority of patients with COVID-19 have a good prognosis, but variable percentages in different countries develop pneumonia associated with lymphocytopenia and severe inflammatory response due to uncontrolled release of cytokines. These immune mediators are transcriptionally regulated by JAK-STAT molecular pathways, which can be disabled by small molecules. Here, we provide evidences on the efficacy of baricitinib, a JAK1/JAK2 inhibitor, in correcting the immune abnormalities observed in patients hospitalized with COVID-19. Indeed, we demonstrate a significant reduction in serum levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)α, a rapid recovery in circulating T and B cell frequencies and an increased antibody production against SARS-CoV-2 spike protein in baricitinib-treated patients. Moreover, treated patients underwent a rapid reduction in oxygen flow need and progressive increase in the P/F. Our work provides the basis on developing effective treatments against COVID-19 pathogenesis using on-target therapy.

中文翻译：

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Baricitinib抑制COVID-19患者的免疫失调

严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）是正在进行的2019年大流行性冠状病毒疾病（COVID-19）的病原体。大多数COVID-19患者的预后良好，但由于细胞因子释放不受控制，不同国家中有不同百分比的人患上与淋巴细胞减少症相关的肺炎和严重的炎症反应。这些免疫介体受JAK-STAT分子途径的转录调控，而JAK-STAT分子途径可被小分子禁用。在这里，我们提供了JAK1 / JAK2抑制剂Baricitinib纠正在COVID-19住院患者中观察到的免疫异常的功效的证据。实际上，我们证明了血清白介素（IL）-6，IL-1β和肿瘤坏死因子（TNF）α的水平显着降低，在接受Baricitinib治疗的患者中，循环T和B细胞频率的快速恢复以及针对SARS-CoV-2突突蛋白的抗体产生增加。此外，接受治疗的患者的氧气流量需求迅速减少，P / F逐渐增加。我们的工作为使用靶向疗法开发针对COVID-19发病机理的有效疗法提供了基础。