{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T13:23:55Z","timestamp":1772717035988,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Innovation Program IVACE-i Promoci\u00f3n de Talento Innodocto","award":["INNTA3\/2024\/3"],"award-info":[{"award-number":["INNTA3\/2024\/3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>COVID-19 is known to impair red blood cell (RBC) function, which may affect oxygen transport and disease progression. However, the metabolic consequences of SARS-CoV-2 infection on RBCs and how these changes relate to disease severity and sex differences, have not been systematically explored. Here, we compared RBC metabolomic profiles from healthy controls and individuals with COVID-19 using nuclear magnetic resonance (NMR) to gain insight into disease mechanisms and potential biomarkers. Multivariate and univariate analyses were performed within the men and women cohorts, and clinical factors, including body mass index, comorbidities, and critical clinical status were considered. We found that COVID-19 induces significant metabolic remodeling in RBCs of all patients, including reduced glycolytic and pentose phosphate pathway (PPP) intermediates, consistent with impaired energetic and antioxidant capacity. However, we also observed differences between men and women in the pattern and extent of these changes. Female patients showed changes in metabolites implicated in oxygen release and amino sugar metabolism, including 2,3-BPG, suggesting a distinct metabolic adaptation. By contrast, male patients exhibited a broader set of RBC-specific metabolic disruptions, most evident in severe disease, characterized by decreased amino acid levels, altered glycolytic activity, and weakened antioxidant responses. Overall, these findings identify RBC metabolism as a component of COVID-19 pathophysiology and support its potential as a source of biomarkers.<\/jats:p>","DOI":"10.3390\/biology15050422","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:52:11Z","timestamp":1772711531000},"page":"422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-Dependent Metabolic Alterations in Red Blood Cells During COVID-19"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7178-3290","authenticated-orcid":false,"given":"Jos\u00e9 Raul","family":"Herance","sequence":"first","affiliation":[{"name":"Molecular Imaging and Therapy Research Group, Vall d\u2019Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Idoia","family":"\u00c1lvarez-Ajuria","sequence":"additional","affiliation":[{"name":"Moldrug AI Systems SL, Parque Tecnol\u00f3gico de Valencia, 46980 Paterna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Aparicio-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Molecular Imaging and Therapy Research Group, Vall d\u2019Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Giralt-Arnaiz","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Research Group, Biochemical Core Facilities, Vall d\u2019Hebron University Hospital, Autonomous University Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia","family":"Moya-Latorre","sequence":"additional","affiliation":[{"name":"ProtoQSAR SL, Parque Tecnol\u00f3gico de Valencia, 46980 Paterna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6904-8833","authenticated-orcid":false,"given":"Rita","family":"Ortega-Vallbona","sequence":"additional","affiliation":[{"name":"ProtoQSAR SL, Parque Tecnol\u00f3gico de Valencia, 46980 Paterna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Palomino-Sch\u00e4tzlein","sequence":"additional","affiliation":[{"name":"Moldrug AI Systems SL, Parque Tecnol\u00f3gico de Valencia, 46980 Paterna, Spain"},{"name":"ProtoQSAR SL, Parque Tecnol\u00f3gico de Valencia, 46980 Paterna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). 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