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Omics-Driven Systems Interrogation of Metabolic Dysregulation in COVID-19 Pathogenesis #MMPMID32610096
Song JW; Lam SM; Fan X; Cao WJ; Wang SY; Tian H; Chua GH; Zhang C; Meng FP; Xu Z; Fu JL; Huang L; Xia P; Yang T; Zhang S; Li B; Jiang TJ; Wang R; Wang Z; Shi M; Zhang JY; Wang FS; Shui G
Cell Metab 2020[Aug]; 32 (2): 188-202.e5 PMID32610096show ga
The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to analyze the plasma lipidome and metabolome in mild, moderate, and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma lipidome of COVID-19 resembled that of monosialodihexosyl ganglioside (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs). Systems evaluation of metabolic dysregulation in COVID-19 was performed using multiscale embedded differential correlation network analyses. Using exosomes isolated from the same cohort, we demonstrated that exosomes of COVID-19 patients with elevating disease severity were increasingly enriched in GM3s. Our work suggests that GM3-enriched exosomes may partake in pathological processes related to COVID-19 pathogenesis and presents the largest repository on the plasma lipidome and metabolome distinct to COVID-19.