Frontiers in Immunology (Sep 2022)
Blood gene expression predicts intensive care unit admission in hospitalised patients with COVID-19
- Rebekah Penrice-Randal,
- Rebekah Penrice-Randal,
- Xiaofeng Dong,
- Andrew George Shapanis,
- Aaron Gardner,
- Nicholas Harding,
- Jelmer Legebeke,
- Jelmer Legebeke,
- Jenny Lord,
- Andres F. Vallejo,
- Stephen Poole,
- Stephen Poole,
- Nathan J. Brendish,
- Nathan J. Brendish,
- Catherine Hartley,
- Anthony P. Williams,
- Gabrielle Wheway,
- Marta E. Polak,
- Marta E. Polak,
- Fabio Strazzeri,
- James P. R. Schofield,
- Paul J. Skipp,
- Paul J. Skipp,
- Julian A. Hiscox,
- Julian A. Hiscox,
- Julian A. Hiscox,
- Tristan W. Clark,
- Tristan W. Clark,
- Diana Baralle,
- Diana Baralle
Affiliations
- Rebekah Penrice-Randal
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Rebekah Penrice-Randal
- TopMD Precision Medicine Ltd, Southampton, United Kingdom
- Xiaofeng Dong
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Andrew George Shapanis
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Aaron Gardner
- TopMD Precision Medicine Ltd, Southampton, United Kingdom
- Nicholas Harding
- TopMD Precision Medicine Ltd, Southampton, United Kingdom
- Jelmer Legebeke
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Jelmer Legebeke
- National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University Hospital Southampton National Health Service (NHS) Foundation Trust, University of Southampton, Southampton, United Kingdom
- Jenny Lord
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Andres F. Vallejo
- School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Stephen Poole
- National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University Hospital Southampton National Health Service (NHS) Foundation Trust, University of Southampton, Southampton, United Kingdom
- Stephen Poole
- School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Nathan J. Brendish
- National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University Hospital Southampton National Health Service (NHS) Foundation Trust, University of Southampton, Southampton, United Kingdom
- Nathan J. Brendish
- School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Catherine Hartley
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Anthony P. Williams
- Cancer Sciences Division, Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom
- Gabrielle Wheway
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Marta E. Polak
- School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Marta E. Polak
- Institute for Life Sciences, University of Southampton, Southampton, United Kingdom
- Fabio Strazzeri
- TopMD Precision Medicine Ltd, Southampton, United Kingdom
- James P. R. Schofield
- TopMD Precision Medicine Ltd, Southampton, United Kingdom
- Paul J. Skipp
- TopMD Precision Medicine Ltd, Southampton, United Kingdom
- Paul J. Skipp
- Centre for Proteomic Research, School of Biological Sciences, University of Southampton, Southampton, United Kingdom
- Julian A. Hiscox
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Julian A. Hiscox
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom
- Julian A. Hiscox
- 0ASTAR Infectious Diseases Laboratories (ASTAR ID Labs), Agency for Science, Technology and Research (ASTAR) Singapore, Singapore, Singapore
- Tristan W. Clark
- National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University Hospital Southampton National Health Service (NHS) Foundation Trust, University of Southampton, Southampton, United Kingdom
- Tristan W. Clark
- School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Diana Baralle
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- Diana Baralle
- National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University Hospital Southampton National Health Service (NHS) Foundation Trust, University of Southampton, Southampton, United Kingdom
- DOI
- https://doi.org/10.3389/fimmu.2022.988685
- Journal volume & issue
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Vol. 13
Abstract
BackgroundThe COVID-19 pandemic has created pressure on healthcare systems worldwide. Tools that can stratify individuals according to prognosis could allow for more efficient allocation of healthcare resources and thus improved patient outcomes. It is currently unclear if blood gene expression signatures derived from patients at the point of admission to hospital could provide useful prognostic information.MethodsGene expression of whole blood obtained at the point of admission from a cohort of 78 patients hospitalised with COVID-19 during the first wave was measured by high resolution RNA sequencing. Gene signatures predictive of admission to Intensive Care Unit were identified and tested using machine learning and topological data analysis, TopMD.ResultsThe best gene expression signature predictive of ICU admission was defined using topological data analysis with an accuracy: 0.72 and ROC AUC: 0.76. The gene signature was primarily based on differentially activated pathways controlling epidermal growth factor receptor (EGFR) presentation, Peroxisome proliferator-activated receptor alpha (PPAR-α) signalling and Transforming growth factor beta (TGF-β) signalling.ConclusionsGene expression signatures from blood taken at the point of admission to hospital predicted ICU admission of treatment naïve patients with COVID-19.
Keywords