Abstract

Coronavirus disease 2019 (COVID-19), which is a major global concern, is characterized by a progressive disease pattern involving diverse host immune responses. Programmed cell death marker-1(PD-1) expression, a critical checkpoint for T cell exhaustion, can be modulated by interleukin-10, which also mediates apoptotic T cell cytopenia. We aimed to measure the level of PD-1 expression and to investigate its correlation with IL-10 serum levels in modulating T cell effector function, correlating the results with the level of severity of the disease. This study involved 40 patients with COVID-19 and 20 healthy controls. Using flow cytometry, the expression of PD-1 was determined on CD8+ T lymphocytes and CD4+ T lymphocytes. ELISA was used to determine the levels of IL-10 in the serum. 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.

Highlights

  • Coronavirus disease 2019 (COVID-19)is considered to be a worldwide pandemic with 2,597,381 deaths and 116,874,912 confirmed COVID-19 cases globally according to the report of the World Health Organization (WHO) dated March 9, 20211,2

  • All the studied groups were subjected to blood sample collection, and the expression of Programmed Cell Death 1 (PD-1) was measured using flow cytometric analysis, and IL-10 serum levels were measured using enzyme-linked immunosorbent assay (ELISA)

  • These results were similar to those of Zhang et al.[17], who found that patients with COVID-19 had significantly lower CD4+, CD8+, and total T cell counts, in those suffering from severe disease

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Summary

Introduction

Coronavirus disease 2019 (COVID-19)is considered to be a worldwide pandemic with 2,597,381 deaths and 116,874,912 confirmed COVID-19 cases globally according to the report of the World Health Organization (WHO) dated March 9, 20211,2. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of this pandemic, is a new beta corona virus belonging to the order Nidovirales, with a positive single-stranded RNA3,4. Critical cases rapidly develop acute respiratory distress syndrome, metabolic acidosis, multiorgan failure, coagulation disorders, septic shock, and death[1,5]. This heterogeneous disease pattern of acute SARS-CoV-2 infection presents with differential cytokine patterns that may be directed by variable immunological responses to the virus and investigating these responses is a critical step toward precision medicine in this disease[4]. T cell exhaustion refers to impaired T cell function, occurring throughout infections and malignancies, described as continuously expressed inhibitory receptors and weak effector function, which is distinct from functional effector T cells in terms of transcriptional state[6,7]

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