{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T13:35:06Z","timestamp":1772372106409,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>COVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis, yet the key players driving this association remain unclear. It is generally assumed that organ damage causes toxic acidosis, but since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes, we asked if metabolic acidosis mediated by the glycolytic neutrophils is associated with lung damage and impaired oxygen delivery in critically ill patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Based on prospective mortality outcome, critically ill COVID-19 patients were divided into ICU- survivors and ICU-non-survivors. Samples were analyzed to explore if correlations exist between neutrophil counts, lung damage, glycolysis, blood lactate, blood pH, hemoglobin oxygen saturation, and mortality outcome. We also interrogated isolated neutrophils, platelets, and PBMCs for glycolytic activities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Arterial blood gas analyses showed remarkable hypoxemia in non-survivors with no consistent differences in PCO<jats:sub>2<\/jats:sub> or [HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>]. The hemoglobin oxygen dissociation curve revealed a right-shift, consistent with lower blood-pH and elevated blood lactate in non-survivors. Metabolic analysis of different blood cells revealed increased glycolytic activity only when considering the total number of neutrophils.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This indicates the role of neutrophilia in hyperlactatemia and lung damage, subsequently contributing to mortality outcomes in severe SARS-CoV-2 infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmolb.2024.1510592","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T05:16:43Z","timestamp":1736140603000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The role of neutrophilia in hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality outcome in critically ill COVID-19 patients"],"prefix":"10.3389","volume":"11","author":[{"given":"Basma A.","family":"Yasseen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya A.","family":"Elkhodiry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajar","family":"El-sayed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Zidan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azza G.","family":"Kamel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed A.","family":"Badawy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa S.","family":"Hamza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riem M.","family":"El-Messiery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"El Ansary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Engy A.","family":"Abdel-Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sameh S.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1080\/10715762.2020.1856376","article-title":"Autism spectrum disorder (ASD)-associated mitochondrial deficits are revealed in children\u2019s platelets but unimproved by hyperbaric oxygen therapy","volume":"55","author":"Abdel-Rahman","year":"2021","journal-title":"Free Radic. 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