SARS-CoV-2 infection dysregulates the metabolomic and lipidomic profiles of serum

Bruzzone, Chiara; Bizkarguenaga, Maider; Gil-Redondo, Rubén; Diercks, Tammo; Arana, Eunate; García de Vicuña, Aitor; Seco, Marisa; Bosch, Alexandre; Palazón, Asís; San Juan, Itxaso; Laín, Ana; Gil-Martínez, Jon; Bernardo-Seisdedos, Ganeko; Fernández-Ramos, David; Lopitz-Otsoa, Fernando; Embade, Nieves; Lu, Shelly; Mato, José M.; Millet, Oscar

COVID-19 is a systemic infection that exerts significant impact on the metabolism. Yet, there is little information on how SARS-CoV-2 affects metabolism. Using NMR spectroscopy, we measured the metabolomic and lipidomic serum profile from 263 (training cohort) + 135 (validation cohort) symptomatic patients hospitalized after positive PCR testing for SARS-CoV-2 infection. We also established the profiles of 280 persons collected before the coronavirus pandemic started. PCA analyses discriminated both cohorts, highlighting the impact that the infection has in overall metabolism. The lipidomic analysis unraveled a pathogenic redistribution of the lipoprotein particle size and composition to increase the atherosclerotic risk. In turn, metabolomic analysis reveals abnormally high levels of ketone bodies (acetoacetic acid, 3-hydroxybutyric acid and acetone) and 2-hydroxybutyric acid, a readout of hepatic glutathione synthesis and marker of oxidative stress. Our results are consistent with a model in which SARS-CoV-2 infection induces liver damage associated with dyslipidemia and oxidative stress.