Sex differences in global metabolomic profiles of COVID-19 patients
Rocio Diaz Escarcega, Pedram Honarpisheh, Gabriela Delevati Colpo, Hilda Ahnstedt, Lucy Couture, Shivanki Juneja, Glenda Torres, Guadalupe J. Ortiz, James Sollome, Natalie Tabor, Bhanu Priya Ganesh, H. Alex Choi, Fudong Liu, Louise D. McCullough, Andrey S. Tsvetkov
Abstract
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.