Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility

• Published in: Physiological reviews Vol. 100; no. 3; pp. 1065 - 1075
• Main Authors: Ji, Hong-Long, Zhao, Runzhen, Matalon, Sadis, Matthay, Michael A
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.07.2020
• Subjects: Betacoronavirus - metabolism; Betacoronavirus - pathogenicity; Cardiovascular disease; Chronic obstructive pulmonary disease; Comorbidity; Coronary artery disease; Coronavirus Infections - blood; Coronavirus Infections - epidemiology; Coronavirus Infections - mortality; Coronavirus Infections - physiopathology; Coronaviruses; COVID-19; Diabetes mellitus; Disease Susceptibility - blood; Fibrinolysin - metabolism; Furin; Heart diseases; Host-Pathogen Interactions - physiology; Humans; Infectivity; Kidney diseases; Lung diseases; Obstructive lung disease; Pandemics; Plasmin; Plasminogen - metabolism; Pneumonia, Viral - blood; Pneumonia, Viral - epidemiology; Pneumonia, Viral - mortality; Pneumonia, Viral - physiopathology; Respiratory Distress Syndrome - blood; Respiratory Distress Syndrome - physiopathology; Respiratory Distress Syndrome - virology; Review; Risk Factors; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Therapeutic applications; Virulence; COVID-19; fibrinolysis; plasmin(ogen); SARS-CoV-2; comorbidity
• ISSN: 0031-9333; 1522-1210; 1522-1210
• DOI: 10.1152/physrev.00013.2020

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.