Plasma gradient of soluble urokinase-type plasminogen activator receptor is linked to pathogenic plasma proteome and immune transcriptome and stratifies outcomes in severe COVID-19

Sarif, J.; Raychaudhuri, D.; D'Rozario, R.; Bandopadhyay, P.; Singh, P.; Mehta, P.; Hoque, M. A.; Sinha, B. P.; Kushwaha, M.; Sahni, S.; Devi, P.; Chattopadhyay, P.; Paul, S. R.; Ray, Y.; Chaudhuri, K.; Banerjee, S.; Majumdar, D.; Saha, B.; Sharma Sarkar, B.; Bhattacharya, P.; Chatterjee, S.; Paul, S.; Ghosh, P.; Pandey, R.; Sengupta, S.; Ganguly, D.

Disease caused by SARS-CoV-2 coronavirus (COVID-19) has resulted in significant morbidity and mortality world-wide. A systemic hyper-inflammation characterizes the severe COVID-19 disease often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. In the present study we report higher plasma abundance of soluble urokinase-type plasminogen activator receptor (sUPAR), expressed by an abnormally expanded circulating myeloid cell population, in severe COVID-19 patients with ARDS. Plasma sUPAR level was found to be linked to a characteristic proteomic signature of plasma, linked to coagulation disorders and complement activation. Receiver operator characteristics curve analysis identified a cut-off value of sUPAR at 1996.809 pg/ml that could predict survival in our cohort (Odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower sUPAR level than this threshold concentration was associated with a differential expression of the immune transcriptome as well as favourable clinical outcomes, both in terms of survival benefit (Hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus we identified sUPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.