¹H qNMR-Based Metabolomics Discrimination of Covid-19 Severity

Abstract

The coronavirus disease 2019 (Covid-19), which caused respiratory problems in many patients worldwide, led to more than 5 million deaths by the end of 2021. Experienced symptoms vary from mild to severe illness. Understanding the infection severity to reach a better prognosis could be useful to the clinics, and one study area to fulfill one piece of this biological puzzle is metabolomics. The metabolite profile and/or levels being monitored can help predict phenotype properties. Therefore, this study evaluated plasma metabolomes of 110 individual samples, 57 from control patients and 53 from recent positive cases of Covid-19 (IgM 98% reagent), representing mild to severe symptoms, before any clinical intervention. Polar metabolites from plasma samples were analyzed by quantitative 1 H NMR. Glycerol, 3-aminoisobutyrate, formate, and glucuronate levels showed alterations in Covid-19 patients compared to those in the control group (Tukey’s HSD p -value cutoff = 0.05), affecting the lactate, phenylalanine, tyrosine, and tryptophan biosynthesis and d -glutamine, d -glutamate, and glycerolipid metabolisms. These metabolic alterations show that SARS-CoV-2 infection led to disturbance in the energetic system, supporting the viral replication and corroborating with the severe clinical conditions of patients. Six polar metabolites (glycerol, acetate, 3-aminoisobutyrate, formate, glucuronate, and lactate) were revealed by PLS-DA and predicted by ROC curves and ANOVA to be potential prognostic metabolite panels for Covid-19 and considered clinically relevant for predicting infection severity due to their straight roles in the lipid and energy metabolism. Thus, metabolomics from samples of Covid-19 patients is a powerful tool for a better understanding of the disease mechanism of action and metabolic consequences of the infection in the human body and may corroborate allowing clinicians to intervene quickly according to the needs of Covid-19 patients.

Integrated Metabolic and Inflammatory Signatures Associated with Severity of, Fatality of, and Recovery from COVID-19

“…As reported by independent studies, we observed increased abundance of phenylalanine with SARS-CoV-2 infection ( 32 , 49 , 50 ). Although differences between categories of severity did not reach statistical significance, phenylalanine has been implicated as a biomarker of COVID-19 severity ( 51 – 53 ).…”

Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome (LTCS) patients

“…Several studies on mild/moderate and acute COVID-19 patients have implicated the important functions of lipoproteins in disease development [12; 33; 36; 44; 45; 46; 47]. In our study, the four cohort groups were partially separated by the PCA (Fig.…”

“…Of note, a previously launched in vitro diagnostics research (IVDr) NMR analytical platform demonstrated that for given samples this method can discover quantitative data on metabolite and lipoprotein levels in analysed solutions from either blood serum and plasma (Letertre et al, 2021). The IVDr nMR platform had been already successfully implemented for COVID-19 phenotyping [12; 22; 28; 29; 30; 31; 32; 33; 34; 35]. The samples were collected dated from June 2020 to February 2021 and correspond to the wildtype/alpha mutant of the virus based on epidemiological knowledge.…”

Stratification of COVID-19 Severity Using SeptiCyte RAPID, a Novel Host Immune Response Test

“…We conducted ROC curve analyses to compare SeptiCyte RAPID to other single biomarkers, specifically CRP, D-dimer, lactate, monocytes, and CD16-positive monocytes, for discriminating (critical + severe) vs. (moderate + mild) cases. These biomarkers have all been used previously by clinicians and investigators to assess the severity of COVID-19 clinical trajectories [ 21 , 28 , 29 , 30 , 31 , 32 ].…”