biostudies-literatureEscarcega RDNIA NIH HHSNIMH NIH HHSU.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)461https://www.ebi.ac.uk/biostudies/studies/S-EPMC9106988biostudies-literatureUnknown13(5)Coronavirus disease (COVID-19), caused by SARS-CoV-2, leads to symptoms ranging from asymptomatic disease to death. Although males are more susceptible to severe symptoms and higher mortality due to COVID-19, patient sex has rarely been examined. Sex-associated metabolic changes may implicate novel biomarkers and therapeutic targets to treat COVID-19. Here, using serum samples, we performed global metabolomic analyses of uninfected and SARS-CoV-2-positive male and female patients with severe COVID-19. Key metabolic pathways that demonstrated robust sex differences in COVID-19 groups, but not in controls, involved lipid metabolism, pentose pathway, bile acid metabolism, and microbiome-related metabolism of aromatic amino acids, including tryptophan and tyrosine. Unsupervised statistical analysis showed a profound sexual dimorphism in correlations between patient-specific clinical parameters and their global metabolic profiles. Identification of sex-specific metabolic changes in severe COVID-19 patients is an important knowledge source for researchers striving for development of potential sex-associated biomarkers and druggable targets for COVID-19 patients.Cell death & diseaseSex differences in global metabolomic profiles of COVID-19 patients.PMC9106988R01 MH1278561RF1AG068292RF1 AG068292Tsvetkov ASEscarcega RDTorres GJuneja STabor NGanesh BPMcCullough LDHonarpisheh PColpo GDCouture LOrtiz GJAhnstedt HWSollome JLiu FChoi HAfalseSex differences in global metabolomic profiles of COVID-19 patients.Coronavirus disease (COVID-19), caused by SARS-CoV-2, leads to symptoms ranging from asymptomatic disease to death. Although males are more susceptible to severe symptoms and higher mortality due to COVID-19, patient sex has rarely been examined. Sex-associated metabolic changes may implicate novel biomarkers and therapeutic targets to treat COVID-19. Here, using serum samples, we performed global metabolomic analyses of uninfected and SARS-CoV-2-positive male and female patients with severe COVID-19. Key metabolic pathways that demonstrated robust sex differences in COVID-19 groups, but not in controls, involved lipid metabolism, pentose pathway, bile acid metabolism, and microbiome-related metabolism of aromatic amino acids, including tryptophan and tyrosine. Unsupervised statistical analysis showed a profound sexual dimorphism in correlations between patient-specific clinical parameters and their global metabolic profiles. Identification of sex-specific metabolic changes in severe COVID-19 patients is an important knowledge source for researchers striving for development of potential sex-associated biomarkers and druggable targets for COVID-19 patients.2022-01-01T00:00:00Z2022 May2025-05-29T22:25:13.063Z2025-04-04T19:42:28.054ZS-EPMC91069883556870610.1038/s41419-022-04861-2