{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T22:08:00Z","timestamp":1789250880416,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DFG Open Access Publication"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In patients with COVID-19, broad panels of immune checkpoint molecules (ICPMs) and the purinergic signaling have not been studied in parallel. We aimed to perform in-depth immunophenotyping of major cell subsets present in human peripheral blood of COVID-19 patients and controls using PD1, TIM3, LAG3, TIGIT, and CD200R, as well as CD39, as markers for the purinergic signaling pathway. We studied 76 COVID-19 patients and 12 healthy controls using peripheral blood mononuclear cells on flow cytometry. Univariable and multivariable statistics were performed. All ICPMs studied were significantly overexpressed on different cell subsets of COVID-19 patients when compared with healthy controls. Elevated lactate dehydrogenase; C-reactive protein; age; and high expression of CD45+, CD39+CD45+, TIM3+CD39+CD4+CD45+, and TIM3+CD39+CD8+CD3+CD4+ cells were significantly associated with severe COVID-19. On multivariable analysis, however, only high expression of CD39+CD45+ (OR 51.4, 95% CI 1.5 to 1763) and TIM3+CD39+CD4+CD3+CD45+ (OR 22.6, 95% CI 1.8 to 277) cells was an independent predictor for severe COVID-19. In conclusion, numerous ICPMs are overexpressed in COVID-19 patients when compared with healthy controls, suggesting a pathophysiological role of these molecules in SARS-CoV-2 infection. However, only TIM3 in co-expression with CD39 remained as a significant independent prognostic ICPM on multivariable analysis. The flow cytometric evaluation of TIM3+CD39+CD4+CD3+CD45+, as well as CD39+CD45+, is a powerful tool for the prognostication of COVID-19 patients on hospital admission.<\/jats:p>","DOI":"10.3390\/v16050810","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T03:26:27Z","timestamp":1716261987000},"page":"810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Prospective Study Investigating Immune Checkpoint Molecule and CD39 Expression on Peripheral Blood Cells for the Prognostication of COVID-19 Severity and Mortality"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7862-3695","authenticated-orcid":false,"given":"Thilo","family":"Gambichler","sequence":"first","affiliation":[{"name":"Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"},{"name":"Department of Dermatology, Hospital Dortmund, Faculty of Health\/School of Medicine, Witten-Herdecke University, 44137 Dortmund, Germany"},{"name":"Department of Dermatology, Christian Hospital Unna, 59423 Unna, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0315-1496","authenticated-orcid":false,"given":"Jonas","family":"R\u00fcth","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Goesmann","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"H\u00f6xtermann","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Skrygan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Susok","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"},{"name":"Department of Dermatology, Christian Hospital Unna, 59423 Unna, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen C.","family":"Becker","sequence":"additional","affiliation":[{"name":"Translational Skin Cancer Research, DKTK Partner Site Essen\/D\u00fcsseldorf, West German Cancer Center, Dermatology, University Duisburg-Essen, 45122 Essen, Germany"},{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5736-3513","authenticated-orcid":false,"given":"Oliver","family":"Overheu","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine, Ruhr-University Bochum, 44791 Bochum, Germany"},{"name":"Department for Hematology and Onoclogy with Palliative Care Unit, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Reinacher-Schick","sequence":"additional","affiliation":[{"name":"Department for Hematology and Onoclogy with Palliative Care Unit, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"ref_1","unstructured":"(2024, May 02). 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