Cross-Validation of Metabolic Phenotypes in SARS-CoV-2 Infected Subpopulations Using Targeted Liquid Chromatography–Mass Spectrometry (LC-MS)

• DOI: 10.1021/acs.jproteome.3c00797
• Publication Date: 2024-03-14T23:33:16Z
• Authors: Luke Whiley; Nathan G. Lawler; Annie Xu Zeng; Alex Lee; Sung-Tong Chin; Maider Bizkarguenaga; Chiara Bruzzone; Nieves Embade; Julien Wist; Elaine Holmes; Oscar Millet; Jeremy K. Nicholson; Nicola Gray
• Keywords: Bile Acids and Salts; Phenotype; SARS-CoV-2; Tandem Mass Spectrometry; Liquid Chromatography-Mass Spectrometry; Humans; COVID-19; Chromatography, Liquid

To ensure biological validity in metabolic phenotyping, findings must be replicated independent sample sets. Targeted workflows have long been heralded as ideal platforms for such validation due to their robust quantitative capability. We evaluated the capability of liquid chromatography-mass spectrometry (LC-MS) assays targeting organic acids and bile validate phenotypes SARS-CoV-2 infection. Two sets were collected: (1) Australia: plasma, positive (n = 20), noninfected healthy controls 22) COVID-19 disease-like symptoms but negative infection 22). (2) Spain: serum, 33) 39). Multivariate modeling using orthogonal projections latent structures discriminant analyses (OPLS-DA) classified from (Australia; R2 0.17, ROC-AUC 1; Spain 0.20, 1). Univariate revealed 23 significantly different (p < 0.05) metabolites between individuals across both cohorts. Significant consistent perturbations cellular energy metabolism (pyruvic acid, 2-oxoglutaric acid), oxidative stress (lactic 2-hydroxybutyric hypoxia (2-hydroxyglutaric 5-aminolevulinic liver activity (primary acids), host-gut microbial cometabolism (hippuric phenylpropionic indole-3-propionic acid). These data support targeted LC-MS phenotyping