Omics-driven systems interrogation of metabolic dysregulationin COVID-19 pathogenesis
Systematic analyses of metabolic alterations during COVID-19 pathogenesis will uncover candidate pathways implicated in disease progression. We utilize a combination of targeted and untargeted tandem mass spectrometry for quantitative profiling of plasma lipidome and metabolome in mild, moderate and severe COVID-19 patients and healthy controls. We found that the plasma lipidome of COVID-19 resembled that of monosialodihexosyl gangliosides (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s. We conducted systems evaluation of metabolic dysregulation in COVID-19 using multiscale embedded differential correlation networks, and uncovered two lipid modules implicating bis(monoacylglyero)phosphate (BMPs)-mediated lipid sorting in multivesicular bodies (MVBs), and the negative co-regulation between GM3s and phosphatidylserines (PSs) in COVID-19 pathogenesis. We validated our postulations drawn based on plasma lipid changes using exosomes isolated from the same cohort. We measured exosome lipids and demonstrated that GM3s were increasingly enriched in the exosomes of COVID-19 patients with elevating disease severity. The levels of lipids and metabolotes are presented in the attached excel file. The level of lipids was expressed as nmol/L, while the level of polar metabolites was expressed as peak area (intensity).