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

• Published in: Medicina (Kaunas, Lithuania) Vol. 61; no. 2; p. 189
• Main Authors: Schniederova, Martina, Bobcakova, Anna, Grendar, Marian, Markocsy, Adam, Ceres, Andrej, Cibulka, Michal, Dobrota, Dusan, Jesenak, Milos
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.01.2025; MDPI
• Subjects: Adult; Aged; Algorithms; B cells; Biomarkers - blood; Blood & organ donations; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; China; COVID-19; COVID-19 - blood; COVID-19 - immunology; COVID-19 - mortality; Cytotoxicity; Data analysis; Data mining; Diseases; Enzyme-linked immunosorbent assay; Female; Health aspects; Hepatitis A Virus Cellular Receptor 2 - analysis; Hepatitis A Virus Cellular Receptor 2 - blood; Humans; Immune checkpoint inhibitors; immune predictors; Immune response; Immune system; Immunology; Infections; Length of stay; Leukocytes; Lymphocytes; Machine learning; machine-learning algorithm; Male; Middle Aged; Plasma; Prognosis; Programmed Cell Death 1 Receptor - analysis; Programmed Cell Death 1 Receptor - blood; Retrospective Studies; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Slovakia; T cells; Variables; China; Slovakia; United Kingdom > UK; United States > US; COVID-19; machine-learning algorithm; immune checkpoint inhibitors; immune predictors
• ISSN: 1648-9144; 1010-660X; 1648-9144
• DOI: 10.3390/medicina61020189

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.