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

Julie C. Wilson, David James Kealy, Sally Rachel James, Tobias Plowman, Katherine Newling, Christopher Jagger, Kara Filbey, Elizabeth Mann, Joanne Konkel, Madvi Menon, Sean Knight, Angela Simpson, CIRCO Collaborative Group, Aliyah Prihartadi, Greg Forshaw, Neil Todd, David Yates, John Grainger, Tracy Hussell, Paul KayeNathalie Yvonne Micheline Signoret, Dimitris Lagos

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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.
Original languageEnglish
Article number103672
Number of pages23
Issue number1
Early online date20 Dec 2021
Publication statusPublished - 21 Jan 2022

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