iScience (Jan 2022)
Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19
- Julie C. Wilson,
- David Kealy,
- Sally R. James,
- Tobias Plowman,
- Katherine Newling,
- Christopher Jagger,
- Kara Filbey,
- Elizabeth R. Mann,
- Joanne E. Konkel,
- Madhvi Menon,
- Sean B. Knight,
- Angela Simpson,
- Aliya Prihartadi,
- Greg Forshaw,
- Neil Todd,
- David R.A. Yates,
- John R. Grainger,
- Tracy Hussell,
- Paul M. Kaye,
- Nathalie Signoret,
- Dimitris Lagos
Affiliations
- Julie C. Wilson
- Department of Mathematics, University of York, York YO10 5DD, UK
- David Kealy
- Hull York Medical School, University of York, Wentworth Way, York YO10 5DD, UK; York Biomedical Research Institute, University of York, York YO10 5DD, UK
- Sally R. James
- York Biosciences Technology Facility, University of York, Wentworth Way, York YO10 5DD, UK
- Tobias Plowman
- Hull York Medical School, University of York, Wentworth Way, York YO10 5DD, UK; York Biomedical Research Institute, University of York, York YO10 5DD, UK
- Katherine Newling
- York Biosciences Technology Facility, University of York, Wentworth Way, York YO10 5DD, UK
- Christopher Jagger
- Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Room 2.16, 46 Grafton Street, Manchester M13 9PL, UK
- Kara Filbey
- Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Room 2.16, 46 Grafton Street, Manchester M13 9PL, UK
- Elizabeth R. Mann
- Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Room 2.16, 46 Grafton Street, Manchester M13 9PL, UK; Maternal and Fetal Health Centre, Division of Developmental Biology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 5th Floor St. Mary's Hospital, Oxford Road, Manchester M13 9WL, UK
- Joanne E. Konkel
- Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Room 2.16, 46 Grafton Street, Manchester M13 9PL, UK
- Madhvi Menon
- Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Room 2.16, 46 Grafton Street, Manchester M13 9PL, UK
- Sean B. Knight
- Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Room 2.16, 46 Grafton Street, Manchester M13 9PL, UK; Respiratory Department, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK
- Angela Simpson
- Division of Infection, Immunity and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK
- Aliya Prihartadi
- Hull York Medical School, University of York, Wentworth Way, York YO10 5DD, UK
- Greg Forshaw
- York and Scarborough Teaching Hospitals NHS Foundation Trust, York YO31 8HE, UK
- Neil Todd
- York and Scarborough Teaching Hospitals NHS Foundation Trust, York YO31 8HE, UK
- David R.A. Yates
- Hull York Medical School, University of York, Wentworth Way, York YO10 5DD, UK; The Members of the Coronavirus Immune Response and Clinical Outcomes (CIRCO) Collaborative Group
- John R. Grainger
- Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Room 2.16, 46 Grafton Street, Manchester M13 9PL, UK
- Tracy Hussell
- Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Room 2.16, 46 Grafton Street, Manchester M13 9PL, UK
- Paul M. Kaye
- Hull York Medical School, University of York, Wentworth Way, York YO10 5DD, UK; York Biomedical Research Institute, University of York, York YO10 5DD, UK
- Nathalie Signoret
- Hull York Medical School, University of York, Wentworth Way, York YO10 5DD, UK; York Biomedical Research Institute, University of York, York YO10 5DD, UK
- Dimitris Lagos
- Hull York Medical School, University of York, Wentworth Way, York YO10 5DD, UK; York Biomedical Research Institute, University of York, York YO10 5DD, UK; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 1
p. 103672
Abstract
Summary: Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present with different disease severity. Here, we determined 171 microRNAomes from 58 hospitalized COVID-19 patients (Cohort 1) and levels of 25 cytokines and chemokines (CC) in the same samples. Combining microRNA (miRNA) and CC measurements allowed for discrimination of severe cases with greater accuracy than using miRNA or CC levels alone. Severity group-specific associations between miRNAs and COVID-19-associated CC (e.g., IL6, CCL20) or clinical hallmarks of COVID-19 (e.g., neutrophilia, hypoalbuminemia) separated patients with similar CC levels but different disease severity. Analysis of an independent cohort of 108 patients from a different center (Cohort 2) demonstrated feasibility of CC/miRNA profiling in leftover hospital blood samples with similar severe disease CC and miRNA profiles, and revealed CCL20, IL6, IL10, and miR-451a as key correlates of fatal COVID-19. These findings highlight that systemic miRNA/CC networks underpin severe COVID-19.
