Lymphocyte Inhibition Mechanisms and Immune Checkpoints in COVID-19: Insights into Prognostic Markers and Disease...

Background and Objectives: Immune checkpoint inhibitors such as PD-1 and TIM-3 play an important role in regulating the host immune response and are proposed as potential prognostic markers and therapeutic targets in severe cases of COVID-19. We evaluated the expression of PD-1 and TIM-3 on T cells, as well as the concentration of sPD-1 in plasma, to clarify the role of these molecules in patients infected with SARS-CoV-2. Materials and Methods: In this retrospective observational study, we analysed the expression of PD-1 and TIM-3 on CD4⁺ and CD8⁺ T cells upon admission and after 7 days of hospitalisation in 770 adult patients. We also evaluated sPD-1 levels in the plasma of 145 patients at different stages of COVID-19 and of 11 control subjects. Molecules were determined using conventional flow cytometry and ELISA and the data were statistically processed. Results: We observed a significantly higher expression of PD-1 on CD4⁺ cells in deceased patients than in those with mild-to-moderate disease. All patients with COVID-19 exhibited a significantly higher expression of TIM-3 on both CD4⁺ and CD8⁺ T cells compared to controls. After 1 week of hospitalisation, there was no significant change in PD-1 or TIM-3 expression on CD4⁺ or CD8⁺ T cells across the studied groups. sPD-1 concentrations were not significantly different between survivors and non-survivors. Plasma sPD-1 levels did not correlate with PD-1 expression on T cells, but a significant correlation was observed between CD4⁺ PD-1 and CD8⁺ PD-1. Using machine-learning algorithms, we supported our observations and confirmed immunological variables capable of predicting survival, with AUC = 0.786. Conclusions: Analysis of the immune response may be useful for monitoring and predicting the course of COVID-19 upon admission. However, it is essential to evaluate complex immune parameters in conjunction with other key clinical and laboratory indicators.