Is plasminogen activator inhibitor-1 level a prognostic marker in COVID-19?

Year 2024, Volume: 3 Issue: 4, 137 - 145, 27.12.2024

Güler İnönü Oğuzhan Zengin , Esra Fırat Oğuz , Enes Seyda Şahiner , İhsan Ateş

Abstract

INTRODUCTION: We aimed to investigate the relationship of plasminogen activator inhibitor-1 (PAI-1) level, which is the main inhibitor of the fibrinolytic system, with COVID – 19 severities.

METHODS: A total of 88 cases diagnosed with COVID – 19, 42 with mild pneumonia and 46 with severe pneumonia, were prospectively included in the study. Serum PAI-1 level was studied by ELISA method. COVID – 19 diagnosis was made by reverse transcriptase-polymerase chain reaction test.

RESULTS: PAI – 1 level was found to be higher in the group with severe pneumonia compared to the group with mild pneumonia (72.1 ng/mL vs 64.1 ng/mL, respectively; p=0.005). In the multivariate regression analysis high level of serum PAI – 1 was associated with severe pneumoniae (OR: 1.073; CI: 1.003 – 1.147; p=0.040). The cut off value of PAI – 1 for severe pneumoniae was determined as 65.8 ng/mL with 52.2% sensitivity, specificity of 78.6%, positive predictive value of 72.7% and negative predictive value of 60%. The patients whose PAI – 1 level were over 65.8 ng/mL were found to have 4.646 times increased risk of severe pneumoniae compared to the ones who had PAI – 1 lower than 65.8 ng/mL (OR: 4.646; CI: 1.186 – 18.202; p= 0.027).

DISCUSSION AND CONCLUSION: In this study, we found out that the serum level of PAI – 1 was higher in patients with severe pneumoniae than the ones with mild pneumoniae. High level of serum PAI – 1 was associated with severe pneumoniae.

Keywords

COVID-19, plasminogen activator inhibitor-1, prognostic marker in COVID-19

References

• 1. Goh, K.J., M.C. Choong, E.H. Cheong, S. Kalimuddin, S.D. Wen, G.C. Phua, K.S. Chan, and S.H. Mohideen (2020) Rapid progression to acute respiratory distress syndrome: Review of current understanding of critical illness from coronavirus disease 2019 (COVID-19) infection. Ann Acad Med Singapore 49: 108-118.
• 2. Iba, T., J.H. Levy, J.M. Connors, T.E. Warkentin, J. Thachil, and M. Levi (2020) The unique characteristics of COVID-19 coagulopathy. Critical care 24: 1-8.
• 3. Klok, F., M. Kruip, N. Van der Meer, M. Arbous, D. Gommers, K. Kant, F. Kaptein, J. van Paassen, M. Stals, and M. Huisman (2020) Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis research 191: 145-147.
• 4. Cesari, M., M. Pahor, and R.A. Incalzi (2010) Plasminogen activator inhibitor‐1 (PAI‐1): a key factor linking fibrinolysis and age‐related subclinical and clinical conditions. Cardiovascular therapeutics 28: e72-e91.
• 5. Tipoe, T.L., W.K. Wu, L. Chung, M. Gong, M. Dong, T. Liu, L. Roever, J. Ho, M.C. Wong, and M.T. Chan (2018) Plasminogen activator inhibitor 1 for predicting sepsis severity and mortality outcomes: a systematic review and meta-analysis. Frontiers in immunology 9: 1218.
• 6. Hoshino, K., T. Kitamura, Y. Nakamura, Y. Irie, N. Matsumoto, Y. Kawano, and H. Ishikura (2017) Usefulness of plasminogen activator inhibitor-1 as a predictive marker of mortality in sepsis. Journal of intensive care 5: 1-8.
• 7. Song, Y., S.V. Lynch, J. Flanagan, H. Zhuo, W. Tom, R.H. Dotson, M.S. Baek, A. Rubio-Mills, G. Singh, and E. Kipnis (2007) Increased plasminogen activator inhibitor-1 concentrations in bronchoalveolar lavage fluids are associated with increased mortality in a cohort of patients with Pseudomonas aeruginosa. The Journal of the American Society of Anesthesiologists 106: 252-261.
• 8. Wright, F.L., T.O. Vogler, E.E. Moore, H.B. Moore, M.V. Wohlauer, S. Urban, T.L. Nydam, P.K. Moore, and R.C. McIntyre Jr (2020) Fibrinolysis shutdown correlation with thromboembolic events in severe COVID-19 infection. Journal of the American College of Surgeons 231: 193-203. e191.
• 9. Kang, S., T. Tanaka, H. Inoue, C. Ono, S. Hashimoto, Y. Kioi, H. Matsumoto, H. Matsuura, T. Matsubara, and K. Shimizu (2020) IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome. Proceedings of the National Academy of Sciences 117: 22351-22356.
• 10. Han, M. and D. Pandey (2021) ZMPSTE24 regulates SARS-CoV-2 spike protein–enhanced expression of endothelial PAI-1. American journal of respiratory cell and molecular biology 65: 300-308.
• 11. Tang, B.S., K.-h. Chan, V.C. Cheng, P.C. Woo, S.K. Lau, C.C. Lam, T.-l. Chan, A.K. Wu, I.F. Hung, and S.-y. Leung (2005) Comparative host gene transcription by microarray analysis early after infection of the Huh7 cell line by severe acute respiratory syndrome coronavirus and human coronavirus 229E. Journal of virology 79: 6180-6193.
• 12. Zhao, X., J.M. Nicholls, and Y.-G. Chen (2008) Severe acute respiratory syndrome-associated coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-β signaling. Journal of Biological Chemistry 283: 3272-3280.
• 13. Ortega‐Paz, L., D. Capodanno, G. Montalescot, and D.J. Angiolillo (2021) Coronavirus disease 2019–associated thrombosis and coagulopathy: review of the pathophysiological characteristics and implications for antithrombotic management. Journal of the American Heart Association 10: e019650.
• 14. Zuo, Y., M. Warnock, A. Harbaugh, S. Yalavarthi, K. Gockman, M. Zuo, J.A. Madison, J.S. Knight, Y. Kanthi, and D.A. Lawrence (2021) Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients. Scientific reports 11: 1580.
• 15. Masi, P., G. Hékimian, M. Lejeune, J. Chommeloux, C. Desnos, M. Pineton De Chambrun, I. Martin-Toutain, A. Nieszkowska, G. Lebreton, and N. Bréchot (2020) Systemic inflammatory response syndrome is a major contributor to COVID-19–associated coagulopathy: insights from a prospective, single-center cohort study. Circulation 142: 611-614.
• 16. Placencio, V.R. and Y.A. DeClerck (2015) Plasminogen activator inhibitor-1 in cancer: rationale and insight for future therapeutic testing. Cancer research 75: 2969-2974.
• 17. Umemura, Y., K. Yamakawa, T. Kiguchi, T. Nishida, M. Kawada, and S. Fujimi (2020) Hematological phenotype of COVID-19-induced coagulopathy: far from typical sepsis-induced coagulopathy. Journal of Clinical Medicine 9: 2875.
• 18. Yin, M., L. Si, W. Qin, C. Li, J. Zhang, H. Yang, H. Han, F. Zhang, S. Ding, and M. Zhou (2018) Predictive value of serum albumin level for the prognosis of severe sepsis without exogenous human albumin administration: a prospective cohort study. Journal of intensive care medicine 33: 687-694.
• 19. Hoeboer, S.H., H.M.O.-v. Straaten, and A.J. Groeneveld (2015) Albumin rather than C-reactive protein may be valuable in predicting and monitoring the severity and course of acute respiratory distress syndrome in critically ill patients with or at risk for the syndrome after new onset fever. BMC pulmonary medicine 15: 1-13.
• 20. Huang, J., A. Cheng, R. Kumar, Y. Fang, G. Chen, Y. Zhu, and S. Lin (2020) Hypoalbuminemia predicts the outcome of COVID‐19 independent of age and co‐morbidity. Journal of medical virology 92: 2152-2158.
• 21. Bellmann-Weiler, R., L. Lanser, R. Barket, L. Rangger, A. Schapfl, M. Schaber, G. Fritsche, E. Wöll, and G. Weiss (2020) Prevalence and predictive value of anemia and dysregulated iron homeostasis in patients with COVID-19 infection. Journal of clinical medicine 9: 2429.
• 22. Wang, C., H. Zhang, X. Cao, R. Deng, Y. Ye, Z. Fu, L. Gou, F. Shao, J. Li, and W. Fu (2020) Red cell distribution width (RDW): a prognostic indicator of severe COVID-19. Annals of translational medicine 8:
• 23. Li, C., J. Ye, Q. Chen, W. Hu, L. Wang, Y. Fan, Z. Lu, J. Chen, Z. Chen, and S. Chen (2020) Elevated lactate dehydrogenase (LDH) level as an independent risk factor for the severity and mortality of COVID-19. Aging (Albany NY) 12: 15670.
• 24. Whyte, C.S., G.B. Morrow, J.L. Mitchell, P. Chowdary, and N.J. Mutch (2020) Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID‐19. Journal of Thrombosis and Haemostasis 18: 1548-1555.
• 25. Iwasaki, M., J. Saito, H. Zhao, A. Sakamoto, K. Hirota, and D. Ma (2021) Inflammation triggered by SARS-CoV-2 and ACE2 augment drives multiple organ failure of severe COVID-19: molecular mechanisms and implications. Inflammation 44: 13-34.
• 26. Oualim, S., S. Abdeladim, A. El Ouarradi, I. Bensahi, S. Hafid, A. Naitlho, E. Bouaiti, and M. Sabry (2020) Elevated levels of D-dimer in patients with COVID-19: prognosis value. The Pan African Medical Journal 35:
• 27. Ferroni, P., M. Roselli, I. Portarena, V. Formica, S. Riondino, F. La Farina, L. Costarelli, A. Melino, G. Massimiani, and F. Cavaliere (2014) Plasma plasminogen activator inhibitor-1 (PAI-1) levels in breast cancer–relationship with clinical outcome. Anticancer research 34: 1153-1161.