Omics-driven Systems Interrogation of Metabolic Dysregulation in COVID-19 Pathogenesis
Jinwen Song, Sin Man Lam, Xing Fan, Wenjing Cao, Siyu Wang, He Tian, Gek Huey Chua, Chao Zhang, Fanping Meng, Zhe Xu, Junliang Fu, Lei Huang, Peng Xia, Tao Yang, Shaohua Zhang, Bowen Li, Tianjun Jiang, Raoxu Wang, Zehua Wang, Ming Shi, Jiyuan Zhang, Fusheng Wang, Guanghou Shui
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 analyse 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 gangliosides (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.