SARS-CoV-2 Infection Dysregulates the Metabolomic and Lipidomic Profiles of Serum

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. 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.

COVID-19 convalescent plasma composition and immunological effects in severe patients

“…We found a differential metabolomic profile of recovered COVID-19 patients compared with pre-pandemic controls and severe COVID-19 patients. Consistent with previous reports, ours confirmed that COVID-19 patients are characterized by lipid dysregulation in fatty acids, glycerophospholipids, glycerolipids, and sphingolipids, which has been associated with dyslipidemia and oxidative stress [ 30 , 31 ]. Recovered patients regulated the most prominent metabolic perturbations that were associated with SARS-CoV-2 infection on metabolic function, such as a decrease in lipid levels, along with an increase in ketone bodies.…”

Dissecting lipid metabolism alterations in SARS-CoV-2

“…The bio-fluid analysed, the number of samples, the platform used and the main altered lipid species are shown. Bio-fluid N. of samples Platform Main altered lipids Reference Serum 108 High-Res MS Glycerophospholipids Shen et al [ 136 ] Serum 50 QQQ GM3s, free fatty acids Song et al [ 137 ] Plasma 35 QQQ NEFAs, TAGs, PCs Wu et al [ 148 ] Serum 57 QQQ PUFAs and lipid mediators Schwarz et al [ 141 ] Plasma 161 High-Res MS PCs, LPCs, PEs, LPEs, NEFAs Barberis et al [ 144 ] Serum 49 High-Res MS Acylcarnitines, NEFAs Thomas et al [ 138 ] Serum 236 NMR Short chain fatty acids Bruzzone et al [ 146 ] Plasma 102 High-Res MS and QQQ TAGs, PCs Overmyer et al [ 145 ] …”

“…Finally, lipids alterations were detected using NMR spectroscopy by Bruzzone et al [ 146 ]. The authors analysed 263 symptomatic patients, and they found a pathogenic rearrangement of the lipoprotein particle size and composition.…”

“…COVID-19 patients are also characterized by an increase of serum TAG, TAG-VLDL, TAG-IDL (IDL, intermediate density lipoproteins), TAG-LDL (LDL, low-density lipoproteins) and TAG-HDL (HDL, high density lipoproteins) [ 146 ]. At the same time, the total cholesterol (TC) was decreased.…”

Lipidome is lipids regulator in gastrointestinal tract and it is a life collar in COVID-19: A review

“…Also, higher increase of 2-hydroxybutyric acid (an indication of hepatic glutathione synthesis and oxidative stress marker). So, SARS-CoV-2 infection caused liver damage correlated with dyslipidemia and oxidative stress[ 71 ]. The viral infection is depended on the lipid metabolism of the infected cells.…”