Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment

Matt Spick, Amy Campbell, Ivona Baricevic-Jones, Johanna von Gerichten, Holly May Lewis, Cecile F. Frampas, Katie Longman, Alexander Stewart, Deborah Dunn-Walters, Debra J. Skene, Nophar Geifman, Anthony D. Whetton, Melanie J. Bailey

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Treatments for COVID-19 infections have improved dramatically since the beginning of the pandemic, and glucocorticoids have been a key tool in improving mortality rates. The UK’s National Institute for Health and Care Excellence guidance is for treatment to be targeted only at those requiring oxygen supplementation, however, and the interactions between glucocorticoids and COVID-19 are not completely understood. In this work, a multi-omic analysis of 98 inpatient-recruited participants was performed by quantitative metabolomics (using targeted liquid chromatography-mass spectrometry) and data-independent acquisition proteomics. Both ‘omics datasets were analysed for statistically significant features and pathways differentiating participants whose treatment regimens did or did not include glucocorticoids. Metabolomic differences in glucocorticoid-treated patients included the modulation of cortisol and bile acid concentrations in serum, but no alleviation of serum dyslipidemia or increased amino acid concentrations (including tyrosine and arginine) in the glucocorticoid-treated cohort relative to the untreated cohort. Proteomic pathway analysis indicated neutrophil and platelet degranulation as influenced by glucocorticoid treatment. These results are in keeping with the key role of platelet-associated pathways and neutrophils in COVID-19 pathogenesis and provide opportunity for further understanding of glucocorticoid action. The findings also, however, highlight that glucocorticoids are not fully effective across the wide range of ‘omics dysregulation caused by COVID-19 infections.

Original languageEnglish
Article number12079
JournalInternational Journal of Molecular Sciences
Volume23
Issue number20
DOIs
StatePublished - 1 Oct 2022
Externally publishedYes

Keywords

  • COVID-19
  • dexamethasone
  • glucocorticoid
  • mass spectrometry
  • metabolomics
  • multi-omics
  • proteomics

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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