Department of Cellular and Molecular Biology, University of Texas Health Science Centre at Tyler, Tyler, Texas; Texas Lung Injury Institute, University of Texas Health Science Centre at Tyler, Tyler, Texas; Department of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine, Pulmonary Injury and Repair Center, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Department of Medicine and Anesthesia, University of California San Francisco, San Francisco, California.
Physiol Rev. 2020 Jul 1;100(3):1065-1075. doi: 10.1152/physrev.00013.2020. Epub 2020 Mar 27.
Patients with hypertension, diabetes, coronary heart disease, cerebrovascular illness, chronic obstructive pulmonary disease, and kidney dysfunction have worse clinical outcomes when infected with SARS-CoV-2, for unknown reasons. The purpose of this review is to summarize the evidence for the existence of elevated plasmin(ogen) in COVID-19 patients with these comorbid conditions. Plasmin, and other proteases, may cleave a newly inserted furin site in the S protein of SARS-CoV-2, extracellularly, which increases its infectivity and virulence. Hyperfibrinolysis associated with plasmin leads to elevated D-dimer in severe patients. The plasmin(ogen) system may prove a promising therapeutic target for combating COVID-19.
患有高血压、糖尿病、冠心病、脑血管病、慢性阻塞性肺疾病和肾功能不全的患者在感染 SARS-CoV-2 时临床结局更差,但原因不明。本综述的目的是总结 COVID-19 合并这些合并症患者中存在升高的纤溶酶原(ogen)的证据。纤溶酶和其他蛋白酶可能在 SARS-CoV-2 的 S 蛋白的新插入的弗林蛋白酶切割位点,从而增加其感染性和毒力。与纤溶相关的纤溶酶原导致严重患者的 D-二聚体升高。纤溶酶原系统可能成为治疗 COVID-19 的有希望的治疗靶点。