Omics-Driven Systems Interrogation of Metabolic Dysregulation in COVID-19 Pathogenesis

• Published in: Cell metabolism Vol. 32; no. 2; pp. 188 - 202.e5
• Main Authors: Song, Jin-Wen, Lam, Sin Man, Fan, Xing, Cao, Wen-Jing, Wang, Si-Yu, Tian, He, Chua, Gek Huey, Zhang, Chao, Meng, Fan-Ping, Xu, Zhe, Fu, Jun-Liang, Huang, Lei, Xia, Peng, Yang, Tao, Zhang, Shaohua, Li, Bowen, Jiang, Tian-Jun, Wang, Raoxu, Wang, Zehua, Shi, Ming, Zhang, Ji-Yuan, Wang, Fu-Sheng, Shui, Guanghou
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.08.2020
• Subjects: Adult; Aged; Betacoronavirus; biomarker; bis(monoacylglyero)phosphates; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; Coronavirus Infections - blood; Coronavirus Infections - pathology; COVID-19; Diglycerides - blood; exosomes; Exosomes - metabolism; Female; G(M3) Ganglioside - blood; Gangliosides - blood; Humans; lipidomics; Male; Metabolome - physiology; metabolomics; Metabolomics - methods; Middle Aged; monosialodihexosyl gangliosides; Pandemics; phosphatidylserines; Pneumonia, Viral - blood; Pneumonia, Viral - pathology; SARS-CoV-2; Sphingomyelins - blood; Tandem Mass Spectrometry; Young Adult; COVID-19; phosphatidylserines; metabolomics; exosomes; bis(monoacylglyero)phosphates; biomarker; lipidomics; monosialodihexosyl gangliosides
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2020.06.016

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. [Display omitted] •Quantitative lipidomic and metabolomic profiling of COVID-19 plasma•Plasma metabolite panel distinguished COVID-19 from healthy controls (AUC = 0.975)•Differential correlation analyses uncovered metabolic dysregulation in COVID-19•GM3-enriched exosomes are positively correlated with COVID-19 pathogenesis Plasma metabolite panel effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma monosialodihexosyl gangliosides (GM3s) were negatively correlated with CD4+ T cell count in COVID-19 patients, and GM3-enriched exosomes were positively correlated with disease severity. These observations suggest that GM3-enriched exosomes may participate in pathological processes associated with COVID-19 progression.