Diagnostic, Prognostic and Mechanistic Biomarkers of COVID-19 Identified by Mass Spectrometric Metabolomics

Abstract

A number of studies have assessed the impact of SARS-CoV-2 infection and COVID-19 severity on the metabolome of exhaled air, saliva, plasma, and urine to identify diagnostic and prognostic biomarkers. In spite of the richness of the literature, there is no consensus about the utility of metabolomic analyses for the management of COVID-19, calling for a critical assessment of the literature. We identified mass spectrometric metabolomic studies on specimens from SARS-CoV2-infected patients and subjected them to a cross-study comparison. We compared the clinical design, technical aspects, and statistical analyses of published studies with the purpose to identify the most relevant biomarkers. Several among the metabolites that are under- or overrepresented in the plasma from patients with COVID-19 may directly contribute to excessive inflammatory reactions and deficient immune control of SARS-CoV2, hence unraveling important mechanistic connections between whole-body metabolism and the course of the disease. Altogether, it appears that mass spectrometric approaches have a high potential for biomarker discovery, especially if they are subjected to methodological standardization.

Lipidome is a valuable tool for the severity prediction of coronavirus disease 2019

“…Metabolomic and lipidomic approaches have elucidated numerous circulating lipids that are directly associated with the severity of COVID-19, indicating that lipid metabolism could be a potential target for therapeutic strategies in the treatment and management of the disease (21,22). Circulating lipids play a key function in the pathogenesis of SARS-CoV-2.…”

Meta-Analysis of COVID-19 Metabolomics Identifies Variations in Robustness of Biomarkers

“…Looking beyond possible literature biases, the wide variety of biomarkers identified is strongly suggestive of confounding variables. One such variable is severity with extensive overlap between biomarkers identified as prognostic and diagnostic [ 9 ]. Danlos et al identified reductions in plasma tryptophan levels and increases in levels of the immunosuppressive metabolite kynurenine in critical care patients as compared to mild cases [ 46 ].…”

“…Later, as reverse transcription polymerase chain reaction (RT-PCR) and rapid antigen testing (RAT) capacity increased dramatically, the focus of metabolomics work shifted to identifying dysregulated pathways and markers for patient vulnerabilities and potential treatment candidates. Whilst many metabolomics studies have been conducted in a variety of matrices including breath [ 5 ], sebum [ 6 ], urine [ 7 ], and saliva [ 8 ], the majority of tests have used peripheral blood as a sampling matrix [ 9 , 10 ]. Whilst more invasive than breath or sebum, for example, peripheral blood has the advantage of being homeostatically regulated and less subject to contamination.…”