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Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of
Julie C Wilson1, David Kealy2,3, Sally R James4
1Department of Mathematics, University of York, York YO10 5DD, UK.
Insights
This study reveals that combining microRNA (miRNA) and cytokine/chemokine (CC) measurements improves COVID-19 severity prediction. Systemic miRNA/CC networks are key drivers of severe COVID-19 pathology.
Area of Science:
- Immunology
- Genomics
- Virology
Background:
- Inflammatory cytokines and chemokines (CC) are implicated in COVID-19 pathology.
- Disease severity varies significantly among patients despite similar CC levels.
Purpose of the Study:
- To investigate the combined role of microRNAs (miRNAs) and CCs in predicting COVID-19 severity.
- To identify specific miRNA-CC networks associated with severe COVID-19.
Main Methods:
- Profiling of 171 microRNAomes and 25 cytokines/chemokines in hospitalized COVID-19 patients (Cohort 1).
- Analysis of an independent cohort (Cohort 2) to validate findings.
- Statistical analysis to identify associations between miRNAs, CCs, and clinical outcomes.
Main Results:
- Combined miRNA and CC profiling enhanced discrimination of severe COVID-19 cases compared to individual measurements.
- Severity group-specific miRNA-CC associations were identified, differentiating patients with similar CC levels but varying severity.
- CCL20, IL6, IL10, and miR-451a were identified as key correlates of fatal COVID-19 in an independent cohort.
Conclusions:
- Systemic miRNA and CC networks are crucial in determining COVID-19 severity.
- Combined miRNA-CC profiling offers a more accurate approach for assessing COVID-19 disease progression.
- These findings provide insights into the molecular mechanisms underlying severe COVID-19.
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.
