الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
COVID-19 pandemic caused by SARS-CoV-2 has emerged as a major threat to humans. Majority of patients with COVID-19 are asymptomatic or experienced mild symptoms. However, severe to fatal cases with systemic manifestations like sepsis, septic shock, and multiple organ dysfunction syndromes have also been observed. So, early recognition of severe forms is essential for timely triaging of patients and for effective management.
PD-1 expression, a critical checkpoint for T cell exhaustion, can be modulated by interleukin-10, which also mediates apoptotic T cell cytopenia and plays a significant role in the immunopathology of COVID-19.
This study aimed to measure the level of PD-1 expression as a characteristic marker of T cell exhaustion and investigate the correlation between the level of expression of PD-1and IL-10 serum level in modulating T cell effector proliferation and function, correlating the results with disease severity.
A total of 40 patients with COVID-19, admitted to Ain Shams University Hospitals, were enrolled in this study during the period from July to October 2020 and stratified into moderate and severe groups. The numbers of males and females were 21 (52.5%) and 19 (47.5%), respectively, and their mean age was 49.38 ± 15.65. While there were 20 healthy control subjects in the control group; they were equally divided into both sexes with a mean age of 44.35 ± 14.47.
EDTA anti-coagulated blood samples were collected for all study participants. The expression of PD-1 was determined on CD8+ T lymphocytes and CD4+ T lymphocytes by flowcytometry. Serum samples were also tested for IL-10 levels using ELISA technique.
We found a remarkable decrease in T cell counts with functionally exhausted surviving T cells in the patient groups, especially in patients with severe disease. PD-1 expression increased significantly in CD4+, CD8+, and total T cells, showing a higher expression in CD8+ T cells. The patient groups had significantly higher serum IL-10 levels than the control group. The ROC analysis demonstrated the predictive role of IL-10 levels in disease severity (65% sensitivity, 80% specificity, and AUC = 0.806). IL-10 serum levels and PD-1 expression in total T cells were positively correlated, suggesting that IL-10 participates in T cell exhaustion.
Thus, IL-10 might represent an important target for lowering the mortality of COVID-19 by blocking its pathological pro-inflammatory function. Accordingly, it may be important to select the right time to block the activity of IL-10 in severe and critical cases.
Also, blockade of the PD-1 pathway in CD8+CD279+ subpopulation might open a new therapeutic avenue for abrogating functional exhaustion in these cells, and reinstating vigorous T cell cytotoxicity against the viral antigen.