Metabolomic Profiling of Plasma Reveals Differential Disease Severity Markers in COVID-19 Patients

Abstract

The severity, disabilities, and lethality caused by the coronavirus 2019 (COVID-19) disease have dumbfounded the entire world on an unprecedented scale. The multifactorial aspect of the infection has generated interest in understanding the clinical history of COVID-19, particularly the classification of severity and early prediction on prognosis. Metabolomics is a powerful tool for identifying metabolite signatures when profiling parasitic, metabolic, and microbial diseases. This study undertook a metabolomic approach to identify potential metabolic signatures to discriminate severe COVID-19 from non-severe COVID-19. The secondary aim was to determine whether the clinical and laboratory data from the severe and non-severe COVID-19 patients were compatible with the metabolomic findings. Metabolomic analysis of samples revealed that 43 metabolites from 9 classes indicated COVID-19 severity: 29 metabolites for non-severe and 14 metabolites for severe disease. The metabolites from porphyrin and purine pathways were significantly elevated in the severe disease group, suggesting that they could be potential prognostic biomarkers. Elevated levels of the cholesteryl ester CE (18:3) in non-severe patients matched the significantly different blood cholesterol components (total cholesterol and HDL, both p < 0.001) that were detected. Pathway analysis identified 8 metabolomic pathways associated with the 43 discriminating metabolites. Metabolomic pathway analysis revealed that COVID-19 affected glycerophospholipid and porphyrin metabolism but significantly affected the glycerophospholipid and linoleic acid metabolism pathways (p = 0.025 and p = 0.035, respectively). Our results indicate that these metabolomics-based markers could have prognostic and diagnostic potential when managing and understanding the evolution of COVID-19.

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

“…Recent literature reported altered amino acid and lipid precursors in plasma from COVID-19 patients, with metabolite levels correlating with disease severity and risk of hospitalization, suggesting that the implementation of a KD may improve patient health. 50,51,59,60,[67][68][69][70][71][72][73][74][75] However, robust followup clinical studies are needed to translate these findings into clinical recommendations.…”

Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19

“…All these contributions highlight the critical role that kynerurate pathway has in the metabotype associated to the disease severity ( D’Amora et al, 2021 ; Marín-Corral et al, 2021 ; Roberts et al, 2022 ). Dysregulated amino acids ( Ibarra-gonza et al, 2022 ), alterations in intermediates of amino acid catabolism ( Páez-Franco et al, 2021 ) and elevated porphyrins ( San Juan et al, 2020 ; Oliveira et al, 2022 ) are also linked to severe phenotypes of the disease.…”

Crosstalk between COVID-19 Infection and Kidney Diseases: A Review on the Metabolomic Approaches

“…Particularly, altered energy metabolism and hepatic dysfunction are brought on by malic acid of the TCA cycle as well as the carbamoyl phosphate of the urea cycle [ 176 ]. Another metabolomic pathway analysis revealed that the individuals affected with COVID-19 were found to have an impact on glycerophospholipid and the porphyrin metabolism but at the same time showed a significant effect on the glycerophospholipid and linoleic acid metabolism pathways [ 177 ]. Shen et al, analyzed the proteome and metabolome of the sera from several COVID-19 patients by applying proteomics and metabolomics to test whether any characteristic molecular changes are induced by SARS-CoV-2.…”