Circulating Soluble Urokinase Plasminogen Activator Receptor as a Predictive Indicator for COVID-19-Associated Acute Kidney Injury and Mortality: Clinical and Bioinformatics Analysis.

Urokinase receptors regulate the interplay between inflammation, immunity, and blood clotting. The soluble urokinase plasminogen activator system is an immunologic regulator affecting endothelial function and its related receptor; the soluble urokinase plasminogen activator receptor (suPAR) has been reported to impact kidney injury. This work aims to measure serum levels of suPAR in COVID-19 patients and correlate the measurements with variable clinicolaboratory parameters and patient outcomes. In this prospective cohort study, 150 COVID-19 patients and 50 controls were included. The circulating suPAR levels were quantified by Enzyme-linked immunosorbent assay (ELISA). Routine COVID-19 laboratory assessments, including CBC, CRP, LDH, serum creatinine, and estimated glomerular filtration rates, were performed. The need for oxygen therapy, CO-RAD score, and survival rates was assessed. Bioinformatic analysis and molecular docking were run to explore the urokinase receptor structure/function and to characterize molecules as potential anti-suPAR therapeutic targets, respectively. We found higher circulating suPAR levels in COVID-19 patients vs. controls (p < 0.001). Circulating suPAR levels positively correlated with COVID-19 severity, the need for O2 therapy, the total leukocytes count, and the neutrophils to lymphocyte ratio, while they were negatively correlated with the O2 saturation level, albumin, blood calcium, lymphocytic count, and GFR. In addition, the suPAR levels were associated with poor prognostic outcomes such as a high incidence of acute kidney injury (AKI) and mortality rate. Kaplan-Meier curves showed a lower survival rate with higher suPAR levels. The logistic regression analysis confirmed the significant association of suPAR levels with the occurrence of AKI related to COVID-19 and with increased mortality probability within three months of COVID-19 follow-up. Some compounds that can act similarly to uPAR were discovered and tested by molecular docking to identify the possible ligand-protein interactions. In conclusion, higher circulating suPAR levels were associated with COVID-19 severity and could be considered a putative predictor of AKI development and mortality.

Neutrophil to lymphocytic ratio and other inflammatory markers as adverse outcome predictor in hospitalized COVID-19 patients.

Early risk classification of coronavirus disease 2019 (COVID-19) patients admitted to hospital is a critical key for providing optimal interventions. We investigated whether neutrophil-to-lymphocyte ratio (NLR) levels and other inflammatory and coagulation markers could be predictors for the severity and mortality of hospitalized COVID-19 patients. This cross-sectional study included 155 COVID-19 patients diagnosed by the reverse transcription polymerase chain reaction (RT-PCR) using oropharyngeal swabs. All patients had clinical examination, routine laboratory investigation, and chest computerized tomography scan. O2 saturation, serum D dimer, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and serum ferritin were assessed. NLR can predict the adverse outcome (e.g., disease deterioration and shock) at cut-off 6.65, with 92% sensitivity and 20.7% specificity. LDH at cut-off value of 364.5 had 79.3% sensitivity and 47% specificity. Ferritin at a cut-off value of 1036 had 60.9% sensitivity and 60.6% specificity. NLR alone was not an independent predictor for ICU, however, combining NLR with ferritin and LDH predicted the need for ICU. Total leucocytic count (TLC), neutrophil count, lymphocytic count, D dimer, and CRP were independent predictors for the need of ICU admission (P < 0.05). Admitted patients to ICU and dead patients had higher COVID-19 Reporting and Data System, length of stay, LDH, and ferritin and lower O2 saturation than non-admitted and alive ones. We concluded that NLR with ferritin and LDH markers had higher degree of sensitivity and specificity in detecting adverse outcomes in COVID-19 patients. Other inflammatory biomarkers such as TLC, neutrophil, lymphocyte, D dimer, and CRP were predictive in this case.