Cancer Immunology and Immunotherapy Lab, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain
Asís Palazón
Cancer Immunology and Immunotherapy Lab, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain
Itxaso San Juan
Precision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain
Ana Laín
Precision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain
Jon Gil-Martínez
Precision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain
Ganeko Bernardo-Seisdedos
ATLAS Molecular Pharma S. L., 48160 Derio, Spain
David Fernández-Ramos
Precision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain; CIBERehd, Instituto de Salud Carlos III Madrid, Spain
Fernando Lopitz-Otsoa
Precision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain
Nieves Embade
Precision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain
Shelly Lu
Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, US
José M. Mato
Precision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain
Oscar Millet
Precision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance, 48160 Derio, Spain; ATLAS Molecular Pharma S. L., 48160 Derio, Spain; Corresponding author
Summary: 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.