Internal Medicine Residency Program, Cleveland Clinic, Cleveland, OH 44195, USA.
Division of Cardiology, Department of Medicine, New York University Langone Health, New York, NY 10016, USA.
Cells. 2022 Jan 17;11(2):306. doi: 10.3390/cells11020306.
Acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection continues to be a worldwide public health crisis. Among the several severe manifestations of this disease, thrombotic processes drive the catastrophic organ failure and mortality in these patients. In addition to a well-established cytokine storm associated with the disease, perturbations in platelets, endothelial cells, and the coagulation system are key in triggering systemic coagulopathy, involving both the macro- and microvasculatures of different organs. Of the several mechanisms that might contribute to dysregulation of these cells following SARS-CoV-2 infection, the current review focuses on the role of activated Janus kinase (JAK) signaling in augmenting thrombotic processes and organ dysfunction. The review concludes with presenting the current understanding and emerging controversies concerning the potential therapeutic applications of JAK inhibitors for ameliorating the inflammation-thrombosis phenotype in COVID-19 patients.
急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染仍然是全球公共卫生危机。在这种疾病的几种严重表现中,血栓形成过程导致这些患者灾难性的器官衰竭和死亡。除了与疾病相关的已确立的细胞因子风暴外,血小板、内皮细胞和凝血系统的紊乱是触发全身性凝血功能障碍的关键,涉及不同器官的大血管和微血管。在可能导致 SARS-CoV-2 感染后这些细胞失调的几种机制中,本综述重点介绍了激活的 Janus 激酶(JAK)信号在增强血栓形成过程和器官功能障碍中的作用。该综述最后介绍了关于 JAK 抑制剂在改善 COVID-19 患者炎症-血栓形成表型方面的潜在治疗应用的当前理解和新兴争议。