SARS-CoV-2 Infection Dysregulates the Metabolomic and Lipidomic Profiles of Serum
Chiara Bruzzone, Maider Bizkarguenaga, Rubén Gil‐Redondo, Tammo Diercks, Eunate Arana‐Arri, Aitor García de Vicuña, Marisa Seco, Alexandre Bosch, Asís Palazón, Itxaso San Juan, Ana Laín, Jon Gil‐Martínez, Ganeko Bernardo‐Seisdedos, David Fernández‐Ramos, Fernando Lopitz‐Otsoa, Nieves Embade, Shelly C. Lu, José M. Mato, Óscar Millet
Abstract
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. Principal-component analysis discriminated both cohorts, highlighting the impact that the infection has on 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.