Plasma miR‐1‐3p levels predict severity in hospitalized COVID‐19 patients

Background and Purpose Accumulating evidence suggests circulating microRNAs (miRNAs) are important regulators of biological processes involved in COVID‐19 complications. We sought to assess whether circulating miRNAs are associated with COVID‐19 clinical phenotype and outcome. Experimental Approach To discover signatures of circulating miRNAs associated with COVID‐19 disease severity and mortality, miRNA quantification was performed on plasma samples collected at hospital admission from a cohort of 106 patients with mild or severe COVID‐19. Variable importance projection scoring with partial least squared discriminant analysis and Random Forest Classifier were employed to identify key miRNAs associated with COVID‐19 severity. ROC analysis was performed to detect promising miRNA able to discriminate between mild and severe COVID status. Key Results Hsa‐miR‐1‐3p was the most promising miRNA in differentiating COVID‐19 patients who developed severe, rather than mild, disease. Hsa‐miR‐1‐3p levels rose with increasing disease severity, and the highest levels were associated with prolonged hospital length of stay and worse survival. Longitudinal miRNA profiling demonstrated that plasma hsa‐miR‐1‐3p expression levels were significantly increased in patients during acute infection compared with those observed 6 months after the disease onset. Specific blockade of miR‐1‐3p in SARS‐CoV‐2–infected endothelial cells decreased up‐regulation of genes involved in endothelial‐to‐mesenchymal transition, inflammation and thrombosis. Furthermore, miR‐1‐3p inhibition reversed the impaired angiogenic capacity induced by plasma from patients with severe COVID‐19. Conclusion and Implications Our data establish a novel role for miR‐1‐3p in the pathogenesis of COVID‐19 infection and provide a strong rationale for its usefulness as early prognostic biomarkers of severity status and survival.