Potential translation of plasma microRNA signatures in the risk stratification of COVID-19 patients admitted to the ICU

Background: The investigation clinical indicators provided by emerging omics technologies may shed light on the development of novel tools for the management of COVID-19. Aim: to explore the potential role and clinical significance of the plasma microRNA (miRNA) profile as a source of biomarkers of disease severity. Methods: Observational and multicenter study. Eighty-four patients with a positive for SARS-CoV-2 recruited during the first pandemic wave in Spain were included. The patients were divided according to the severity of the disease into the following groups: i) hospitalized patients without requiring critical care, and ii) hospitalized patients admitted to the ICU. An additional study including ICU nonsurvivors and survivors was performed. Plasma miRNA profiling was analyzed using RT-qPCR. Results: Ten miRNAs were dysregulated in ICU patients compared to ward patients. The multivariable analysis identified a signature of three miRNAs (miR-148a-3p, miR-451a and miR-486-5p) that displayed an optimal discriminatory ability to distinguish between ICU and ward patients (AUC=0.89). Among critically ill patients, six miRNAs showed significant suppression in patients who did not survive the ICU stay. The multivariable analysis selected a signature based on two miRNAs, miR-192-5p and miR-323a-3p, that was a relevant predictor of mortality during the ICU stay (AUC = 0.80). The discriminatory potential of the miRNA signature was higher than that observed for clinical laboratory parameters such as CRP, D-dimer or leukocyte counts (maximum AUC=0.73). Conclusions: Plasma miRNA signatures may be useful for risk-based patient stratification over current tests.