{"title":"Immune checkpoint molecules as predictive markers of COVID-19 severity: A comprehensive univariable and multivariable analysis","authors":"Adam Majchrzak , Paulina Niedźwiedzka-Rystwej , Dominika Bębnowska , Bogusz Aksak-Wąs , Malwina Karasińska-Cieślak , Danuta Cembrowska-Lech , Karolina Skonieczna-Żydecka , Kaja Mielczak , Anna Urbańska , Rafał Hrynkiewicz , Filip Lewandowski , Miłosz Parczewski","doi":"10.1016/j.imlet.2025.107089","DOIUrl":null,"url":null,"abstract":"<div><div>Immune dysregulation plays a key role in the deterioration of COVID-19. This study evaluated immune checkpoint molecules (ICMs) as markers of disease severity. Immunophenotyping of 525 hospitalised patients with moderate (n=464) and severe (n=61) COVID-19 was performed at admission and analysed alongside clinical, laboratory, and imaging data. The strongest correlations with severe outcomes and mortality were found for CD200R+CD3+ T and CD19+ B cells. Significant differences in PD-1+ and PD-L1+ lymphocyte subsets were observed between severity groups. Machine learning (SHAP) confirmed that ICM expression was at least as predictive as conventional risk factors. These findings suggest that markers of immune exhaustion, especially PD-1, PD-L1, and CD200R, may help predict COVID-19 severity. Further research is needed to determine whether targeting immune checkpoints could improve outcomes.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107089"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunology letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0165247825001221","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Immune dysregulation plays a key role in the deterioration of COVID-19. This study evaluated immune checkpoint molecules (ICMs) as markers of disease severity. Immunophenotyping of 525 hospitalised patients with moderate (n=464) and severe (n=61) COVID-19 was performed at admission and analysed alongside clinical, laboratory, and imaging data. The strongest correlations with severe outcomes and mortality were found for CD200R+CD3+ T and CD19+ B cells. Significant differences in PD-1+ and PD-L1+ lymphocyte subsets were observed between severity groups. Machine learning (SHAP) confirmed that ICM expression was at least as predictive as conventional risk factors. These findings suggest that markers of immune exhaustion, especially PD-1, PD-L1, and CD200R, may help predict COVID-19 severity. Further research is needed to determine whether targeting immune checkpoints could improve outcomes.
期刊介绍:
Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings.
Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.