الفهرس 
Introduction and Aim of the workOnly 14 pages are availabe for public view
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Abstract
On March 11, 2020, the World Health Organization classified the coronavirus (SARS-CoV-2) to be a pandemic. The virus is known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is the cause of the coronavirus disease (Covid-19) outbreak of severe respiratory sickness. After starting in Wuhan, China, this epidemic quickly spread to every continent and nearly every nation in the world. It has become a hazard to global health.The virus spreads through direct and contact transmission and is thought to have a zoonotic origin. Fever, coughing, and myalgia are signs of the symptomatic phase, which progresses to severe respiratory failure. Since the SARS-CoV-2 outbreaks, there have been more than 242 million confirmed illnesses and approximately 5 million fatalities worldwide.SARS-CoV-2 is reported to use the angiotensin converting enzyme 2 (ACE2) receptor for host cell entry. ACE2 is a cell-surface receptor with N-terminal and C-terminal domains. ACE2 is found in the epithelium of the nose, mouth, and lungs. Aim of the work:The aim of the present study was to evaluate the association of ACE2 expression and markers of oxidative stress, with clinical severity in patients with COVID-19. Methods and results: The present study was performed at the Medical Biochemistry Department, Mansoura Nephrology and Dialysis Unit and Zoology Department, Faculty of Science, Mansoura University, Egypt and approved by the Mansoura University Summary 70 ethics committee (Institutional Research Board; R.20.10.1). All patients provided signed informed consent. The present study comprised 40 patients with COVID-19 and 40 age-matched and sex-matched apparently healthy controls recruited between September 2021 and March 2022. Study participants were assigned to one of two groups: group 1: comprising 40 patients (22 males and 18 females) with severe COVID-19 infection who were admitted to the Intensive Care Unit (ICU) at the time of the study and may have received remdesivir and/or inotropes. All patients had a confirmed diagnosis of COVID-19 based on their clinical profile and a positive PCR test. group 2: comprised 40 healthy controls who had no previous history of COVID-19 infection, chronic pulmonary disease, or autoimmune disease. Patients with mild respiratory symptoms or were pregnant with COVID-19 were excluded from the present study. Blood sampling: Venesection was performed for all participants to obtain 7 ml of whole blood that was divided into two collection tubes; Blood samples (4 ml) were collected in EDTA-containing tubes for isolation of peripheral blood mononuclear cells. The remaining blood sample (3 ml) was collected in plain tubes and used for serum biochemical analyses. Clinical investigations:1-Age 2- Sex 3-Admission duration 4-Systolic blood pressure (SBP)5- Diastolic blood pressure (DBP)6- MAP 7-Heart rate 8-Temperature 9- Respiratory rate 10-GCS Laboratory investigations:1-Serum sodium 2- Serum potassium3-RBS 4- Liver function (ALT, AST, Serum albumin, serum total bilirubin) 5- Kidney function (serum creatinine and serum LDH) 6- Inflammatory marker (c-reactive protein, CRP) Molecular investigations:Real time PCR of (ACE2) gene expression. Statistical analysis: Data were analyzed using IBM-SPSS software (IBM Corp. Released 2019. IBM-SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp) and MedCalc® Statistical Software version 20 (MedCalc Software Ltd, Ostend, Belgium, 2021). Qualitative data are presented as n (%). Quantitative data were initially tested for normality using Shapiro–Wilk’s test Quantitative data. Qualitative data were compared between groups using the Chi-Square (2) test. Quantitative data were compared between two groups using the independent-samples t-test. The Summary 72 one-sample Wilcoxon signed ranks test was used to compare non-normally distributed quantitative data against a hypothetical median. Spearman’s correlation was used to assess the direction and strength of association between two non-normally distributed continuous variables. Point biserial correlation was used to assess the association between a dichotomous variable and a continuous variable. Receiver operating characteristic (ROC) curves were used to categorize continuous variables into two categories based on a cutoff value with the area under the curve (AUC) reported. The results are summarized as follows: Patients with COVID-19 had a mean age of 60.7 ± 9.29 years while, healthy control subjects had a mean age of 59.6 ± 9.31 years. There was no significant difference in sex or age between the two groups (P < 0.361 and P < 0.590, respectively). Serum levels of ACE2 mRNA was compared between the two study groups, with the one-sample Wilcoxon signed ranks test demonstrating significantly lower expression levels of ACE2 in COVID-19 patients compared to a hypothesized value (1.0) for controls. Serum levels of TAC and MLT were significantly lower in COVID-19 patients compared to controls (P > 0.001). On the other hand, patients with COVID-19 had significantly higher serum levels of MDA (P > 0.001) compared to healthy controls. A statistically significant negative correlation between serum MDA levels and both diastolic blood pressure (DBP) and Glasgow coma scale (GCS) scores. Serum MLT levels were significantly and positively correlated with DBP, MAP, and respiratory rate. Serum levels of TAC were positively correlated with GCS scores.A statistically significant negative correlation was observed between serum TAC and creatinine levels, between serum ACE2 and total bilirubin levels, and between serum MDA and potassium levels. A statistically significant and positive correlation was observed between serum MLT and potassium levels. Serum ACE2 levels did not correlate with any complete blood count (CBC) parameter. Moreover, serum TAC levels were significantly and positively correlated with mean platelet volume (P = 0.008). Serum ACE2 levels and studied redox state markers were not correlated with arterial blood gas (ABG) parameters. Patients with COVID-19 who were treated with remdesivir had significantly lower serum levels of MLT (P = 0.025) compared to the control group (Table 4). Serum MLT levels were lower in patients treated with inotropes (median serum MLT level, 22.7) compared to patients not treated with inotropes (median serum MLT level, 74.4).ROC curve analysis was performed to assess the diagnostic performance of serum ACE2 levels and the studied oxidative markers for COVID-19 infection and demonstrated serum ACE2 levels and the studied oxidative markers could discriminate COVID-19 patients from healthy controls. In conclusion, the present study demonstrated that increased levels of oxidative stress markers, decreased levels of antioxidant indicators, and lower serum ACE2 levels are correlated with disease severity and poor outcomes in hospitalized patients with COVID-19. These findings indicate ACE2 and oxidative stress may represent therapeutic targets for severe COVID-19.