Decrease of Tregs cells and increase of exhausted Treg cells as the predictors of COVID19 severity

Abstract

Background: T cells and regulatory T cells (Tregs) play a critical role in viral infectious immunity. Exhaustion of T cells during infection and decreased Tregs both contribute to the exacerbation of the disease. In the present study, we assessed T cells and regulatory T cells of COVID-19 patients and a control group according to the expression of the PD-1 molecule. Methods: Forty-two COVID-19 patients and 40 controls were enrolled in the study. In COVID-19 patients, blood samples were collected on the first day of their hospitalization. Regulatory T cells (CD4+, CD25+, FOXP3+), CD4+PD-1+, and PD-1+ regulatory T cells were assessed by flow cytometry. Results: The percentage of CD4+PD-1 + T cells in COVID-19 patients was significantly higher compared to the control group (P < 0.0001). The percentage of PD-1+ regulatory T cells was significantly increased in the patient group compared to the control group (P < 0.0001). However, the Treg percentage was significantly decreased in the patient group compared to the control group (P < 0.0001). The frequency of CD4+PD-1 + T cells, Tregs, and PD-1+ Tregs had acceptable sensitivity and specificity for assisting in the diagnosis of severe/critical COVID-19. The declined Tregs and enhanced CD4+CD25+, CD4+PD-1+, and PD-1 + T cells were associated with disease severity. Conclusion: The decrease in Tregs and the increase in exhaustion of these cells and T cells play an important role in COVID-19 pathogenesis. These immune parameters could be used as meaningful indicators for assisting in the diagnosis of severe/critical COVID-19.

Keywords

• COVID-19
• Regulatory T-cells
• PD1
• Exhausted T cells
• Activated T cells