The specific metabolome profiling of patients infected by SARS-COV-2 supports the key role of tryptophan-nicotinamide pathway and cytosine metabolism

Abstract

The biological mechanisms involved in SARS-CoV-2 infection are only partially understood. Thus we explored the plasma metabolome of patients infected with SARS-CoV-2 to search for diagnostic and/or prognostic biomarkers and to improve the knowledge of metabolic disturbance in this infection. We analyzed the plasma metabolome of 55 patients infected with SARS-CoV-2 and 45 controls by LC-HRMS at the time of viral diagnosis (D0). We first evaluated the ability to predict the diagnosis from the metabotype at D0 in an independent population. Next, we assessed the feasibility of predicting the disease evolution at the 7th and 15th day. Plasma metabolome allowed us to generate a discriminant multivariate model to predict the diagnosis of SARS-CoV-2 in an independent population (accuracy > 74%, sensitivity, specificity > 75%). We identified the role of the cytosine and tryptophan-nicotinamide pathways in this discrimination. However, metabolomic exploration modestly explained the disease evolution. Here, we present the first metabolomic study in SARS-CoV-2 patients which showed a high reliable prediction of early diagnosis. We have highlighted the role of the tryptophan-nicotinamide pathway clearly linked to inflammatory signals and microbiota, and the involvement of cytosine, previously described as a coordinator of cell metabolism in SARS-CoV-2. These findings could open new therapeutic perspectives as indirect targets.

Targeted Metabolomics Identifies High Performing Diagnostic and Prognostic Biomarkers for COVID-19

“…While earlier COVID-19 studies have proposed panels of up to ten metabolites to identify infected patients from healthy individuals 13,16 , and still other studies have proposed individual diagnostic metabolites 12 or metabolite ratios 14 , the metabolite panels offered here have some advantages. In particular we have identi ed metabolite-only and metabolite + clinical feature panels that can: 1) reliably distinguish between mildly COVID-19 positive patients and COVID-19 negative patients; and 2) differentiate among three different levels of COVID-19 severity.…”

The Uniqueness of Tryptophan in Biology: Properties, Metabolism, Interactions and Localization in Proteins

“…Perhaps the most enigmatic aspect of Trp metabolism that has defied a clear molecular explanation for years is its intersection with various normal and pathological conditions, such as cancer, multiple sclerosis, transplantation, peripheral and CNS disorders, and recently in SARS-CoV-2 infection [ 47 , 48 , 49 , 50 , 109 , 110 , 111 ]. For the sake of brevity, the focus in this review is on selected branches of immune regulation, a key character in which is indole 2,3-dioxygenase (IDO), the rate-limiting first enzyme in the kynurenine pathway of Trp degradation ( Figure 2 ).…”

Comprehensive Meta-Analysis of COVID-19 Global Metabolomics Datasets

“…Powered by the growing applications of high-resolution mass spectrometry (MS), metabolomics has become a key member of the omics toolkit in biomedical research. Multiple metabolomics studies have been recently conducted across the world to study COVID-19, revealing key metabolic dysregulations during the disease’s progression [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. For instance, several amino acids have been observed to be positively correlated with the severity of COVID-19 as key indicators of clinical prognosis of the disease [ 8 , 9 , 12 , 13 , 14 ].…”