تقييم الخلل البطاني للأوعية الدموية بواسطة المستقبل المنشط لإنزيم الحال للبروتين -1 PAR- لدى مرضى كوفيد-19

Assessment of Vessels Endothelial Dysfunction by Protease- Activated Receptors (PARs) Signaling in COVID-19 Patients

Background: One of the major factors in the development of thromboembolism in COVID-19 has become recognized to be endothelial dysfunction. Acute venous thromboembolism is another significant complication that significantly contributes to the substantial morbidity and mortality in patients with COVID-19. Despite of the fact that hypoxic respiratory failure caused by viral pneumonia and acute respiratory distress syndrome remains the leading cause of death in patients with COVID-19. The level of protease-activated receptors (PARs) would be correlated with the common coagulation and inflammation markers of COVID-19 because protease-activated receptor type 1 (PAR1) is the primary thrombin receptor and may reflect an important connection between coagulation and inflammation in the pathophysiology of COVID- 19.
Methodology: A cross-sectional study for a total of 93 patient samples, including critical, severe, and post-COVID19 patient samples at Al-Shehid Hassan Al-Hatmy Hospital in Al-Najaf Governorate, Iraq. This study was done during 3 months. Serum biomarkers levels were measured for the following parameter: PAR-1, thrombin and prothrombin levels were measured using the ELISA technique.; D-Dimer assay was performed by sandwich chemiluminescence immunoassay; Complete blood count was done by XP-300™ Automated hematology analyzer Sysmex. The association between biochemical markers and disease severity was evaluated. The efficiency of the predicting value was assessed using the receiver operating characteristic (ROC) curve.
Results: Levels of hematological parameters were varied based on severity of the disease. Serum PAR-1 level was quietly increased in post COVID-19 and critical cases. Levels of thrombin were shown a massive significant increase in severe and critical cases (p <0.05). In critical cases, a weakly correlation was confirmed between D-dimer and PAR-1. Also, a significant positive correlation was confirmed between Platelet-Lymphocyte Ratio (PLR) and Neutrophil-Lymphocyte Ratio (NLR) [r = 0.55, P <0.001]
Results of the receiver operating curve (ROC) curve , area under the curve (AUC) analysis for the PAR-1 and Thrombin levels as possible diagnostic parameters. Both parameters were shown a good diagnostic performance for the prediction critical cases of COVID-19 Patients compared to severe and post cases group. PAR-1 levels: (sensitivity = 96%, specificity = 92%) at a level = 596, while thrombin levels: (sensitivity = 0.96%, specificity = 0.76%) at a level = 39.5.
Conclusion: Levels of PAR-1 were statistically significant among groups of COVID-19 patients. Among the three groups of COVID-19 patients (severe, critical and post cases), D-dimer and PAR-1 levels were demonstrated a high prognosis value through the confirming results that obtained by the ROC curves for the prediction of coagulopathy in post cases of COVID-19.