Integrated miRNA/Cytokine/Chemokine Profiling Reveals Severity-Associated Step Changes and Principal Correlates of Fatality in COVID-19

Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present different disease severity. Here, we determined 171 microRNAomes from 58 hospitalised (Cohort 1) of 25 in the same samples. Combining microRNA (miRNA) measurements allowed for discrimination severe cases greater accuracy than using miRNA or alone. Severity group-specific associations between miRNAs COVID-19-associated (e.g. IL6, CCL20) clinical hallmarks neutrophilia, hypoalbuminemia) separated but Critically, analysis an independent cohort 108 a centre 2) demonstrated feasibility CC/miRNA profiling leftover blood samples profiles, revealed CCL20, IL10, miR-451a as key correlates fatal COVID-19. These findings highlight that systemic miRNA/CC networks underpin COVID-19. Funding: The study was funded by UKRI MRC/NIHR award to UK Coronavirus Immunology Consortium (UK-CIC, MR/V028448/1). Sample collection at Manchester NHS Trusts supported NIHR Biomedical Research Centre (TH AS) 3M Global Giving (JRG TH). York Scarborough Trust Wellcome (ISSF grant WT204829 through Future Health University York) Hull Medical School. JRG is senior fellowship Kennedy Rheumatology Research. This report contains research North West Lung Charity Clinical Facility Wythenshawe Hospital. Declaration Interests: authors declare no competing interests. Ethics Approval Statement: For 1, ethics approval obtained West-Haydock Ethics Committee ManARTS (reference 15/NW/0409) Wales 4 NCARC 18/WA/0368). 2, Yorkshire & Humber - Leeds (REC reference 19/YH/0394 approved 26 SA002 amendment IRAS project 269597).