Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport

• Published in: Biomedicine & pharmacotherapy Vol. 163; p. 114863
• Main Authors: Fu, Yunmei, Xue, Hao, Wang, Tingyu, Ding, Yan, Cui, Yong, Nie, Hongguang
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.07.2023; The Author(s). Published by Elsevier Masson SAS; Elsevier
• Subjects: COVID-19; Epithelial sodium channel; Fibrinolytic system; Humans; Ion Transport; Plasmin; Review; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19; SARS-CoV-2; Fibrinolytic system; Epithelial sodium channel; Plasmin
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.114863

Lifeways of worldwide people have changed dramatically amid the coronavirus disease 2019 (COVID-19) pandemic, and public health is at stake currently. In the early stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, fibrinolytic system is mostly inhibited, which is responsible for the development of hypofibrinolysis, promoting disseminated intravascular coagulation, hyaline membrane formation, and pulmonary edema. Whereas the common feature and risk factor at advanced stage is a large amount of fibrin degradation products, including D-dimer, the characteristic of hyperfibrinolysis. Plasmin can cleave both SARS-CoV-2 spike protein and γ subunit of epithelial sodium channel (ENaC), a critical element to edematous fluid clearance. In this review, we aim to sort out the role of fibrinolytic system in the pathogenesis of COVID-19, as well as provide the possible guidance in current treating methods. In addition, the abnormal regulation of ENaC in the occurrence of SARS-CoV-2 mediated hypofibrinolysis and hyperfibrinolysis are summarized, with the view of proposing an innovative view of epithelial ion transport in preventing the dysfunction of fibrinolytic system during the progress of COVID-19. [Display omitted] •Plasmin cleaves the furin sites both in γ subunit of epithelial sodium channel (ENaC) and SARS-CoV-2 spike protein.•In the early stage, reduced uPA and elevated PAI-1 create a hypofibrinolytic state with low ENaC activation.•Increased plasmin and tPA cause hyperfibrinolysis with the overactivation of ENaC at advanced stage.