Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in 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 hospitalised 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 centre (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.

Altered microRNA expression in severe COVID-19: potential prognostic and pathophysiological role

“…Secondly, most of the miRNAs associated with severe COVID-19 were found to be downregulated. This is in agreement with a recent study where a paralleled downregulation of miRNA expression in severe COVID-19 was reported [47]. Bartoszewski et al suggested that the SARS-CoV-2 genome acts as miRNA sponge to reduce cellular miRNA levels [48].…”

Altered microRNA expression in severe COVID‐19: Potential prognostic and pathophysiological role

“…A paralleled down‐regulation of miRNA expression in severe COVID‐19 was reported lately. 1 RNA silencing pathways have been identified as antiviral defense mechanisms in plants and insects, and possibly in mammalian cells. 2 To escape this antiviral defense, plant and insect viruses possess virus‐encoded suppressors of RNA interference, and this may extend to mammalian cells.…”

miRNA expression in COVID-19

“…Their results have indicated that miR-30b/c/e, miR-6080, miR-181a-5p, miR-199a-3p, and miR-339 are highly specific for determination of severity and mortality rate of COVID-19 ( Gustafson et al, 2022 ). In addition, Wilson et al have shown correlations between levels of CCL20, IL-6, IL-10, and miR-451a and mortality of COVID-19 patients ( Wilson et al, 2022 ). Besides, miR-133a and miR-122 have been found to be correlated with 28 day mortality of COVID-19 patients.…”