Association of plasma microRNAs with COVID-19 severity and outcome.

Objective: As one of the remarkable host responses to SARS-CoV-2 infection, circulating microRNAs (miRNAs) represent important diagnostic and prognostic diseases biomarkers. The study is a step towards highlighting the role of miRNAs in COVID-19 pathogenesis and severity.

Methods: In this case-control study, miRCURY LNA miRNA PCR plasma panel (168 miRNAs) was applied and the expression of the altered miRNAs was then analysed by quantitative real time PCR for 120 COVID-19 patients (30 mild, 30 moderate, 30 severe, and 30 critical) and 30 healthy subjects.

Results: The initial screening showed that 30 miRNAs displayed altered expression, out of them, only eleven miRNAs (miR-885-5p, miR-141-3p, miR-21-5p, miR-127-3p, miR-99b-5p, let-7d-3p, miR-375, miR-1260a, miR-139-5p, miR-28-5p and miR-34a-5p) were dysregulated in the plasma of COVID-19 patients; all of them were significantly overexpressed. By applying ROC curve analysis, AUC for the eleven miRNAs were ranged from 0.65 to 0.83, and the AUC for the combined miRNAs was 0.93. Ten miRNAs (miR-141-3p, miR-181a-5p, miR-221-3p, miR-223-5p, miR99b-5p, Let-7d-3p, miR-375, miR-199a-5p, miR-139-5p and miR-28-5p) exhibited a significant change in their expression between different severity groups. Patients with positive outcome were found to have increased miR-375 and decreased miR-99b-5p expression levels. Bioinformatic prediction showed that, out of the eleven dysregulated miRNAs, five miRNAs (miR-139-5p, -34a-5p, -28-5p, -21-5p and -885-5p) have the ability to regulate at least two genes related to COVID-19 according to KEGG database.

Conclusion: miRNAs are dysregulated in COVID-19 patients and associated with severity degree and patients' outcome.