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We investigated the enzymatic activities of CD39 (NTPDase1) and CD73 (ecto-5\u2019-nucleotidase) as potential biomarkers of disease severity. Patients with RT-PCR-confirmed COVID-19 were enrolled between August 1st, 2020, and August 1st, 2021, and stratified into mild to moderate (MM,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200955) or severe to critical (SC,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200930) groups according to WHO criteria. Serum samples were collected on days 1, 3, and 7 following Emergency Department (ED) admission. CD39 and CD73 activities were measured by HPLC using etheno-fluorescent nucleotide substrates and compared to healthy volunteers (HV,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200930) matched for age and sex. Serum CD73 activity was significantly elevated in COVID-19 patients compared to HV (MM: 76\u2009\u00b1\u20099.4; SC: 99\u2009\u00b1\u200921 vs. HV: 25\u2009\u00b1\u20092.7 pmol\/min\/\u00b5L;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), particularly in patients requiring\u2009\u2265\u20096\u00a0L\/min oxygen (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005) or with a respiratory rate\u2009&gt;\u200920\/min (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02). CD73 activity remained elevated throughout hospitalization. Conversely, febrile patients (\u2265\u200938\u00a0\u00b0C) and those with CRP\u2009\u2265\u2009100\u00a0mg\/L exhibited significantly lower CD73 activity (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.023 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.004, respectively). CD39 activity was undetectable in 28.2% of patients and showed no association with disease severity or outcome. The lowest CD73 levels were observed in patients requiring oxygen therapy for \u2265\u200930 days and in those who died before day 7. Serum CD73 activity is associated with hypoxemia and oxygen requirements upon ED admission. Conversely, low CD73 activity reflects a hyperinflammatory state and worse outcomes, supporting its potential use in biomarker-based risk stratification for COVID-19.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-41023-2","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T08:53:26Z","timestamp":1772096006000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum CD73 activity as a biomarker of hypoxemia in COVID-19 patients"],"prefix":"10.1038","volume":"16","author":[{"given":"Pierrick","family":"Le Borgne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Bilbault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Clere-Jehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Favre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Lefebvre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Ubeaud-S\u00e9quier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatiha El","family":"Ghazouani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Demiselle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Toti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferhat","family":"Meziani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Kauffenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"41023_CR1","unstructured":"WHO Coronavirus (COVID-19. ) Dashboard | WHO Coronavirus (COVID-19) Dashboard With Vaccination Data. 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