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

TY - JOUR

T1 - Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19

AU - Wilson, Julie C.

AU - Kealy, David James

AU - James, Sally Rachel

AU - Plowman, Tobias

AU - Newling, Katherine

AU - Jagger, Christopher

AU - Filbey, Kara

AU - Mann, Elizabeth

AU - Konkel, Joanne

AU - Menon, Madvi

AU - Knight, Sean

AU - Simpson, Angela

AU - Collaborative Group, CIRCO

AU - Prihartadi, Aliyah

AU - Forshaw, Greg

AU - Todd, Neil

AU - Yates, David

AU - Grainger, John

AU - Hussell, Tracy

AU - Kaye, Paul

AU - Signoret, Nathalie Yvonne Micheline

AU - Lagos, Dimitris

N1 - © 2021 The Author(s)

PY - 2022/1/21

Y1 - 2022/1/21

N2 - 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.

AB - 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.

KW - Clinical finding

KW - Complex system biology

KW - Health sciences

UR - http://www.scopus.com/inward/record.url?scp=85122400485&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2021.103672

DO - 10.1016/j.isci.2021.103672

M3 - Article

AN - SCOPUS:85122400485

SN - 2589-0042

VL - 25

JO - iScience

JF - iScience

IS - 1

M1 - 103672

ER -