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. 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.

A metabolic readout of the urine metabolome of COVID-19 patients

“…Previous studies on urinary proteomics of COVID-19 patients also indicate that they present aminoaciduria (Dewulf et al, 2022 ). This increase in ketone bodies would be in line with the increase in these substances found in the blood (Bruzzone et al, 2020a ). Ketosis is generated in the liver because there has been a metabolic shift to a state of gluconeogenesis.…”

“…In different studies carried out with analyzes of COVID-19 patients, it could be deduced that the metabolism was changing to this situation of ketosis and type II diabetes or a certain resistance to insulin (Bruzzone et al, 2020a ; Ghini et al, 2022 ). This metabolism alteration would be supported by the increase in the concentration of TMAO (trimethylamine N-oxide).…”

“…Therefore, the decrease in this metabolite could be indicating that this detoxification process is not working properly, which would cause liver damage. In other words, the infection itself could be affecting the liver's detoxifying capacity, which would explain the liver damage observed in COVID-19 patients (Bruzzone et al, 2020a ). These results should be confirmed by further investigations focused on hepatic metabolism.…”

“…The effect of certain drugs, such as glucocorticoids, is being studied with promising results for the treatment of the disease, albeit due to the complexity of the illness, drug-disease interactions are still incompletely understood (Spick et al, 2022 ). Although much is still unknown about the molecular aspects of the disease, important advances have been made studying the metabolism of COVID-19 patients, mainly at the serological level (Bruzzone et al, 2020a ; Costanzo et al, 2022 ; Ghini et al, 2022 ; Li et al, 2022 ; Shen et al, 2020 ; Thomas et al, 2020 ; Wu et al, 2020 ; Xu et al, 2021 ; Zhang et al, 2021 ). In urine samples from COVID-19 patients, alterations in certain biomarkers, such as glucose, kynurenines and proteins, have been found to reflect the metabolic alterations caused by the disease and to assess its severity (Bi et al, 2022 ; Dewulf et al, 2022 ; Liu et al, 2020a ; Morell-Garcia et al, 2021 ).…”

Novel COVID-19 biomarkers identified through multi-omics data analysis: N-acetyl-4-O-acetylneuraminic acid, N-acetyl-L-alanine, N-acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate

“…Dataset I (Spain dataset): NMR analysis Dataset I (dataset from Spain) refers to plasma samples from COVID-19 patients (n = 261) diagnosed by RT-PCR and from healthy volunteers (n = 280) with negative COVID-19 RT-PCR test results [21]. Samples from healthy volunteers were collected during the period of routine examinations (check-up) that occurred before the start of the pandemic (2018-2019).…”