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

Cell Metab. 2020 Aug 4;32(2):188-202.e5. doi: 10.1016/j.cmet.2020.06.016. Epub 2020 Jun 24.

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 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.

Keywords: COVID-19; biomarker; bis(monoacylglyero)phosphates; exosomes; lipidomics; metabolomics; monosialodihexosyl gangliosides; phosphatidylserines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Betacoronavirus
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • COVID-19
  • Coronavirus Infections / blood*
  • Coronavirus Infections / pathology*
  • Diglycerides / blood
  • Exosomes / metabolism*
  • Female
  • G(M3) Ganglioside / blood*
  • Gangliosides / blood*
  • Humans
  • Male
  • Metabolome / physiology
  • Metabolomics / methods
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / blood*
  • Pneumonia, Viral / pathology*
  • SARS-CoV-2
  • Sphingomyelins / blood
  • Tandem Mass Spectrometry
  • Young Adult

Substances

  • Diglycerides
  • G(M3) Ganglioside
  • Gangliosides
  • Sphingomyelins
  • sialogangliosides