Title: Omics-driven systems interrogation of metabolic dysregulation in COVID-19 pathogenesis.
Author: Jin-Wen Song, Sin Man Lam, Xing Fan, Wen-Jing Cao, Si-Yu Wang, He Tian, Gek Huey Chua, Chao Zhang, Fan-Ping Meng, Zhe Xu, Jun-Liang Fu, Lei Huang, Peng Xia, Tao Yang, Shaohua Zhang, Bowen Li, Tian-Jun Jiang, Raoxu Wang, Zehua Wang, Ming Shi, Ji-Yuan Zhang, Fu-Sheng Wang, Guanghou Shui
Abstract: 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.