Lymphocyte Inhibition Mechanisms and Immune Checkpoints in COVID-19: Insights into Prognostic Markers and Disease Severity
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,...
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| Published in | Medicina (Kaunas, Lithuania) Vol. 61; no. 2; p. 189 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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Switzerland
MDPI AG
22.01.2025
MDPI |
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| Online Access | Get full text |
| ISSN | 1648-9144 1010-660X 1648-9144 |
| DOI | 10.3390/medicina61020189 |
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| Abstract | 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. |
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| AbstractList | 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. 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.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. 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. : 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. 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. 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. 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. 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[sup.+] and CD8[sup.+] 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[sup.+] 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[sup.+] and CD8[sup.+] T cells compared to controls. After 1 week of hospitalisation, there was no significant change in PD-1 or TIM-3 expression on CD4[sup.+] or CD8[sup.+] 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[sup.+] PD-1 and CD8[sup.+] 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. |
| Audience | Academic |
| Author | Ceres, Andrej Markocsy, Adam Cibulka, Michal Grendar, Marian Schniederova, Martina Dobrota, Dusan Bobcakova, Anna Jesenak, Milos |
| AuthorAffiliation | 2 Department of Pulmonology and Phthisiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia 4 Biomed—Centre for Biomedicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03659 Martin, Slovakia 6 Department of Clinical Biochemisty, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia 1 Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; martina.schniederova@unm.sk (M.S.); anna.bobcakova@jfmed.uniba.sk (A.B.); adam.markocsy@unm.sk (A.M.); michal.cibulka@uniba.sk (M.C.) 3 Department of Paediatrics and Adolescent Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia 5 Department of Medical Biochemistry |
| AuthorAffiliation_xml | – name: 2 Department of Pulmonology and Phthisiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia – name: 6 Department of Clinical Biochemisty, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia – name: 3 Department of Paediatrics and Adolescent Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia – name: 5 Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03659 Martin, Slovakia; dusan.dobrota@uniba.sk – name: 1 Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; martina.schniederova@unm.sk (M.S.); anna.bobcakova@jfmed.uniba.sk (A.B.); adam.markocsy@unm.sk (A.M.); michal.cibulka@uniba.sk (M.C.) – name: 4 Biomed—Centre for Biomedicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03659 Martin, Slovakia |
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| Keywords | COVID-19 machine-learning algorithm immune checkpoint inhibitors immune predictors |
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| Snippet | 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... : 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... 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... |
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| Title | Lymphocyte Inhibition Mechanisms and Immune Checkpoints in COVID-19: Insights into Prognostic Markers and Disease Severity |
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