{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:41:16Z","timestamp":1759970476397,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["ITMS: 313011AFG4"],"award-info":[{"award-number":["ITMS: 313011AFG4"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/medicina61020189","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T09:52:20Z","timestamp":1737539540000},"page":"189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lymphocyte Inhibition Mechanisms and Immune Checkpoints in COVID-19: Insights into Prognostic Markers and Disease Severity"],"prefix":"10.3390","volume":"61","author":[{"given":"Martina","family":"Schniederova","sequence":"first","affiliation":[{"name":"Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Bobcakova","sequence":"additional","affiliation":[{"name":"Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"},{"name":"Department of Pulmonology and Phthisiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"},{"name":"Department of Paediatrics and Adolescent Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Grendar","sequence":"additional","affiliation":[{"name":"Biomed\u2014Centre for Biomedicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03659 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Markocsy","sequence":"additional","affiliation":[{"name":"Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"},{"name":"Department of Pulmonology and Phthisiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrej","family":"Ceres","sequence":"additional","affiliation":[{"name":"Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9245-9991","authenticated-orcid":false,"given":"Michal","family":"Cibulka","sequence":"additional","affiliation":[{"name":"Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"},{"name":"Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03659 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dusan","family":"Dobrota","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03659 Martin, Slovakia"},{"name":"Department of Clinical Biochemisty, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7976-2523","authenticated-orcid":false,"given":"Milos","family":"Jesenak","sequence":"additional","affiliation":[{"name":"Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"},{"name":"Department of Pulmonology and Phthisiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"},{"name":"Department of Paediatrics and Adolescent Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/nsr\/nwaa041","article-title":"Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients","volume":"7","author":"Zhou","year":"2020","journal-title":"Natl. 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Mak., 22.","DOI":"10.1186\/s12911-021-01742-0"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/2\/189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:33:47Z","timestamp":1759919627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/2\/189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,22]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["medicina61020189"],"URL":"https:\/\/doi.org\/10.3390\/medicina61020189","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2025,1,22]]}}}