Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12079 |
| _version_ | 1797472842666737664 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Matt Spick |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:06:52Z |
| format | Article |
| id | doaj.art-8dac2462bc9743d19bd440d3df7a5ac9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:06:52Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8dac2462bc9743d19bd440d3df7a5ac92023-11-24T00:28:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201207910.3390/ijms232012079Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid TreatmentMatt Spick0Amy Campbell1Ivona Baricevic-Jones2Johanna von Gerichten3Holly-May Lewis4Cecile F. Frampas5Katie Longman6Alexander Stewart7Deborah Dunn-Walters8Debra J. Skene9Nophar Geifman10Anthony D. Whetton11Melanie J. Bailey12Faculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, UKStoller Biomarker Discovery Centre, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NQ, UKStoller Biomarker Discovery Centre, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NQ, UKFaculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, UKFaculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, UKFaculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, UKFaculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, UKFaculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UKFaculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UKFaculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UKSchool of Health Sciences, University of Surrey, Guildford GU2 7XH, UKSchool of Veterinary Medicine, School of Biosciences and Medicine, University of Surrey, Guildford GU2 7XH, UKFaculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, UKTreatments 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.https://www.mdpi.com/1422-0067/23/20/12079glucocorticoiddexamethasoneCOVID-19proteomicsmetabolomicsmass spectrometry |
| spellingShingle | 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 Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment International Journal of Molecular Sciences glucocorticoid dexamethasone COVID-19 proteomics metabolomics mass spectrometry |
| title | Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment |
| title_full | Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment |
| title_fullStr | Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment |
| title_full_unstemmed | Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment |
| title_short | Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment |
| title_sort | multi omics reveals mechanisms of partial modulation of covid 19 dysregulation by glucocorticoid treatment |
| topic | glucocorticoid dexamethasone COVID-19 proteomics metabolomics mass spectrometry |
| url | https://www.mdpi.com/1422-0067/23/20/12079 |
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