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; CIRCO Collaborative Group; Aliya Prihartadi; Greg Forshaw; Neil Todd; David R A Yates; John R Grainger; Tracy Hussell; Paul M Kaye; Nathalie Signoret; Dimitris Lagos

doi:10.1016/j.isci.2021.103672

Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19

iScience. 2022 Jan 21;25(1):103672. doi: 10.1016/j.isci.2021.103672. Epub 2021 Dec 20.

Authors

Julie C Wilson¹, David Kealy^{2

3}, Sally R James⁴, Tobias Plowman^{2

3}, Katherine Newling⁴, Christopher Jagger⁵, Kara Filbey⁵, Elizabeth R Mann^{5

6}, Joanne E Konkel⁵, Madhvi Menon⁵, Sean B Knight^{5

7}, Angela Simpson⁸; CIRCO Collaborative Group; Aliya Prihartadi², Greg Forshaw⁹, Neil Todd⁹, David R A Yates^{2

10}, John R Grainger⁵, Tracy Hussell⁵, Paul M Kaye^{2

3}, Nathalie Signoret^{2

3}, Dimitris Lagos^{2

3}

Affiliations

¹ Department of Mathematics, University of York, York YO10 5DD, UK.
² Hull York Medical School, University of York, Wentworth Way, York YO10 5DD, UK.
³ York Biomedical Research Institute, University of York, York YO10 5DD, UK.
⁴ York Biosciences Technology Facility, University of York, Wentworth Way, York YO10 5DD, UK.
⁵ 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.
⁶ 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.
⁷ Respiratory Department, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK.
⁸ Division of Infection, Immunity and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK.
⁹ York and Scarborough Teaching Hospitals NHS Foundation Trust, York YO31 8HE, UK.
¹⁰ The Members of the Coronavirus Immune Response and Clinical Outcomes (CIRCO) Collaborative Group.

Abstract

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.

Keywords: Clinical finding; Complex system biology; Health sciences.

Abstract

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