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Abstract The novel coronavirus (COVID-19) was declared as a global pandemic by the World Health Organization (WHO) on March 11, 2020. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact worldwide. COVID-19 exhibits heterogeneous disease patterns due to variable clinical factors, including age, gender, comorbidities, genetic makeup, and acquired immune differences. Mapping virus-host interactions is critical to understand disease progression. High mortality due to COVID-19 disease has been a serious concern. COVID-19 is a multisystemic disease regulated by an interplay of immunological, inflammatory, and coagulative cascades. Patients with the severe form of coronavirus disease have been frequently found to suffer from both arterial and venous thrombotic events due to the presence of a hypercoagulable state. This phenomenon, termed COVID-19– associated coagulopathy. At first, the vascular insults may be limited to the pulmonary microvasculature, as the disease progresses, systemic involvement occurs, culminating in distant organ thrombosis and multiorgan dysfunction syndrome. SARS-CoV-2 infection occurs through the interaction of the viral protein Spike with the angiotensin II receptor (ACE 2), leading to an increase of angiotensin II and activation of nicotinamide adenine dinucleotide phosphate oxidase2 (NOX2), resulting in the release of both reactive oxygen species (ROS) and inflammatory molecules. Also, NOX2 activated by the RNA viruse as consequence of upregulation of TLR-7. The role of NOX2 in the promoting the coagulation state appeared in upregulating endothelial- TF activation, activation of leucocytes induced thrombomodulin oxidation, platelet activation and induction of vascular wall inflammation. Tissue factor (TF) is a high-affinity transmembrane protein receptor and interact with factor (F)VII/VIIa. The TF-FVIIa complex is Summary and Conclusion 121 the primary initiator of blood coagulation and plays an essential role in hemostasis. TF-mediated extrinsic coagulation activation may be the underlying cause of COVID-19 associated coagulopathy. Exposure to pathogens results in rapid and transient upregulation of TF expression in immune cells and non-immune cells (endothelial and epithelial cells). Expression of TF on endothelial cells and leukocytes combined with endothelial microinjuries (which expose subendothelial TF) results in increased fibrin generation and formation of microthrombi. The present study aimed to find out the relation between NADPH oxidase and the thrombotic complications in COVID-19 infection in Egyptian patients. The current study was carried out on 180 subjects, 100 adult hospital admitted COVID-19 patients and 80 apparently healthy subjects. COVID-19 patients were classified into two groups; patients with TEEs included 29 patients and patients without TEEs included 71 patients. They were subjected to complete history taking, clinical examination and assessment of hematological profile, biochemical profile, inflammatory markers, coagulation profile, IL-6, tissue factor and NOX2. The highest incidance of TEEs were appeared among criticaly ill patients. COVID-19 patients with TEEs had significant higher levels of WBCs count, neutrophil count, ALT, AST, urea, creatinine, LDH, CRP, ferritin, procalcitonin, IL-6, INR, APTT, D-dimer, TF and NOX2 than patients without TEEs. However, serum albumin level was significantly lower in patients with TEEs. NOX2 and TF were significantly positively correlated with each other and positively correlated with laboratory variables such as IL-6, procalcitonin, APTT and D-dimer. In contrast, they were significantly negatively correlated with platelet count. Patients who developed stroke complications had significant higher levels of TF and NOX2 than other types of TEEs. ICU- admitted patients and non- survived patients had significant higher levels of TF and Summary and Conclusion 122 NOX2. Also, patients with TEEs had lower survival rate when compared with patients without TEEs. It was found that the prognostic performance of NOX2 when combined with IL-6 to predict thromboembolic events showed the highest senstivity and specificity which were slightly higher than NOX2 alone. It was found that the prognostic performance of NOX2 when combined with IL-6 and TF when combined with IL-6 to predict mortality showed the highest senstivity, while NOX2 level had the highest specificity to predict mortality. from this study, we concluded that: High levels of NADPH oxidase2, tissue factor and IL-6 are associated with increased incidances of the thromboembolic complications, ICU admission and mortality rates in COVID-19 patients. Therefore, they should be regularly investigated as predictor biomarkers of COVID-19 bad outcome. |