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- Title
Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19.
- Authors
Tetiana Yatsenko; Rios, Ricardo; Nogueira, Tatiane; Salama, Yousef; Satoshi Takahashi; Yoko Tabe; Toshio Naito; Kazuhisa Takahashi; Koichi Hattori; Heissig, Beate
- Abstract
Patients with coronavirus disease-2019 (COVID-19) have an increased risk of thrombosis and acute respiratory distress syndrome (ARDS). Thrombosis is often attributed to increases in plasminogen activator inhibitor-1 (PAI-1) and a shut-down of fibrinolysis (blood clot dissolution). Decreased urokinase-type plasminogen activator (uPA), a protease necessary for cell-associated plasmin generation, and increased tissue-type plasminogen activator (tPA) and PAI-1 levels have been reported in COVID-19 patients. Because these factors can occur in free and complexed forms with differences in their biological functions, we examined the predictive impact of uPA, tPA, and PAI-1 in their free forms and complexes as a biomarker forCOVID-19 severity and the development of ARDS. In this retrospective study of 69 Japanese adults hospitalized with COVID-19 and 20 healthy donors, we found elevated free, non-complexed PAI-1 antigen, low circulating uPA, and uPA/ PAI-1 but not tPA/PAI-1 complex levels to be associatedwith COVID-19 severity and ARDS development. This biomarker profile was typical for patients in the complicated phase. Lack of PAI-1 activity in circulation despite free, noncomplexed PAI-1 protein and plasmin/a2anti-plasmin complex correlated with suPAR and sVCAM levels, markers indicating endothelial dysfunction. Furthermore, uPA/PAI-1 complex levels positively correlated with TNFa, a cytokine reported to trigger inflammatory cell death and tissue damage. Those levels also positively correlated with lymphopenia and the pro-inflammatory factors interleukin1b (IL1b), IL6, and C-reactive protein, markers associated with the anti-viral inflammatory response. These findings argue for using uPA and uPA/PAI-1 as novel biomarkers to detect patients at risk of developing severe COVID-19, including ARDS.
- Subjects
PLASMINOGEN activators; TISSUE plasminogen activator; ENDOTHELIUM diseases; LYMPHOPENIA; THROMBOSIS; ADULT respiratory distress syndrome; JAPANESE people
- Publication
Frontiers in Immunology, 2024, p01
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1299792