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

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.

Keywords: COVID-19; SARS-CoV-2; comorbidity; fibrinolysis; plasmin(ogen).

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Betacoronavirus / metabolism
  • Betacoronavirus / pathogenicity
  • Comorbidity
  • Coronavirus Infections / blood*
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / mortality
  • Coronavirus Infections / physiopathology
  • Disease Susceptibility / blood*
  • Fibrinolysin / metabolism*
  • Host-Pathogen Interactions / physiology*
  • Humans
  • Pandemics
  • Plasminogen / metabolism*
  • Pneumonia, Viral / blood*
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / mortality
  • Pneumonia, Viral / physiopathology
  • Respiratory Distress Syndrome, Adult / blood
  • Respiratory Distress Syndrome, Adult / physiopathology
  • Respiratory Distress Syndrome, Adult / virology
  • Risk Factors


  • Plasminogen
  • Fibrinolysin

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2