Metabolomics profiles associated with SARS-CoV-2 -IgG serostatus as an alternative diagnostic approach

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, showed a wide range of host responses from no symptoms to severe illness, highlighting the urgent need for better diagnostic and therapeutic solutions. Untargeted metabolomics offers a way to uncover molecular and biochemical changes linked to immune differences, potentially identifying biomarkers for early detection and treatment monitoring. METHOD: This cross-sectional observational study recruited 49 individuals. Samples were stratified using the SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) into two groups SARS-CoV-2 IgG-negative (n = 26) and SARS-CoV-2 IgG-positive (n = 23). Samples were analyzed using LC/MS-based untargeted metabolomics. The data were processed using a standard pipeline that included multivariate statistical analysis, molecular annotation, pathway and network analyses. RESULTS: Metabolomic analysis of SARS-CoV-2 IgG-positive and SARS-CoV-2 IgG-negative groups revealed 319 dysregulated metabolites, comprising 218 up- and 101 down-regulated metabolites. ROC analysis revealed the metabolites 4-hydroxysphinganine and Ganglioside GM1 (18:1/22:0), with the highest AUC of 0.883 and 0.95, respectively. The significantly affected metabolic pathways identified to be dysregulated between the two groups belonged to ubiquinone, tyrosine, pyrimidine, and glutathione metabolism. Network pathway analysis demonstrated that the identified metabolites together were involved in regulating lipid metabolism, small molecule biochemistry, and cell-cell signaling and interaction, and were centered around dysregulation of TNF, IL-23, JNK, IL-1β, and CRP signaling pathways. The top metabolites identified in the interaction network pathway were L-Fucose, phosphorylcholine, cerotic acid, 5-hydroxydecanoic acid, and paired immunoglobulin-like type 2 receptor beta (PILRB). CONCLUSION: Our findings identify metabolomic alterations associated with SARS-CoV-2 infection between IgG-positive and IgG-negative individuals. The identified metabolites are involved in regulating lipid metabolism, immune response, and the inflammatory signaling pathways. The results offer preliminary hypothesis generating insights into the underlying changes that may inform future research on host-immune interactions in COVID-19. Changes in these metabolites need to be validated in larger and independent cohorts.