Bronchial Aspirate-Based Profiling Identifies MicroRNA Signatures Associated With COVID-19 and Fatal Disease in Critically Ill Patients

dc.contributor.authorMolinero, Marta
dc.contributor.authorBenítez, Iván
dc.contributor.authorGonzález, Jessica
dc.contributor.authorGort Paniello, Clara
dc.contributor.authorMoncusí Moix, Anna
dc.contributor.authorRodríguez Jara, Fátima
dc.contributor.authorGarcía Hidalgo, María Coronada
dc.contributor.authorTorres, Gerard
dc.contributor.authorVengoechea Aragoncillo, José Javier
dc.contributor.authorGómez Falguera, Silvia
dc.contributor.authorCabo Gambín, Ramón
dc.contributor.authorCaballero, Jesús
dc.contributor.authorBermejo Martin, Jesús F.
dc.contributor.authorCeccato, Adrián
dc.contributor.authorFernández Barat, Laia
dc.contributor.authorFerrer, Ricard
dc.contributor.authorGarcía Gasulla, Darío
dc.contributor.authorMenéndez, Rosario
dc.contributor.authorMotos, Anna
dc.contributor.authorPeñuelas, Oscar
dc.contributor.authorRiera, Jordi
dc.contributor.authorTorres, Antoni
dc.contributor.authorBarbé Illa, Ferran
dc.contributor.authorde Gonzalo Calvo, David
dc.description.abstractBackground: The pathophysiology of COVID-19-related critical illness is not completely understood. Here, we analyzed the microRNA (miRNA) profile of bronchial aspirate (BAS) samples from COVID-19 and non-COVID-19 patients admitted to the ICU to identify prognostic biomarkers of fatal outcomes and to define molecular pathways involved in the disease and adverse events. Methods: Two patient populations were included (n = 89): (i) a study population composed of critically ill COVID-19 and non-COVID-19 patients; (ii) a prospective study cohort composed of COVID-19 survivors and non-survivors among patients assisted by invasive mechanical ventilation (IMV). BAS samples were obtained by bronchoaspiration during the ICU stay. The miRNA profile was analyzed using RT-qPCR. Detailed biomarker and bioinformatics analyses were performed. Results: The deregulation in five miRNA ratios (miR-122-5p/miR-199a-5p, miR-125a-5p/miR-133a-3p, miR-155-5p/miR-486-5p, miR-214-3p/miR-222-3p, and miR-221-3p/miR-27a-3p) was observed when COVID-19 and non-COVID-19 patients were compared. In addition, five miRNA ratios segregated between ICU survivors and nonsurvivors (miR-1-3p/miR-124-3p, miR-125b-5p/miR-34a-5p, miR-126-3p/miR-16-5p, miR-199a-5p/miR-9-5p, and miR-221-3p/miR-491-5p). Through multivariable analysis, we constructed a miRNA ratio-based prediction model for ICU mortality that optimized the best combination of miRNA ratios (miR-125b-5p/miR-34a-5p, miR-199a-5p/miR-9-5p, and miR-221-3p/miR-491-5p). The model (AUC 0.85) and the miR-199a-5p/miR-9-5p ratio (AUC 0.80) showed an optimal discrimination value and outperformed the best clinical predictor for ICU mortality (days from first symptoms to IMV initiation, AUC 0.73). The survival analysis confirmed the usefulness of the miRNA ratio model and the individual ratio to identify patients at high risk of fatal outcomes following IMV initiation. Functional enrichment analyses identified pathological mechanisms implicated in fibrosis, coagulation, viral infections, immune responses and inflammation. Conclusions: COVID-19 induces a specific miRNA signature in BAS from critically ill patients. In addition, specific miRNA ratios in BAS samples hold individual and collective potential to improve risk-based patient stratification following IMV initiation in COVID-19-related critical illness. The biological role of the host miRNA profiles may allow a better understanding of the different pathological axes of the disease.ca_ES
dc.description.sponsorshipThis work was supported by Instituto de Salud Carlos III (COV20/00110), co-funded by European Regional Development Fund (ERDF)/A way to make Europe. CIBERES is an initiative of the Instituto de Salud Carlos III. Supported by: Programa de donaciones estar preparados; UNESPA (Madrid, Spain). DdG-C (Miguel Servet 2020: CP20/00041) and MM (PFIS: FI21/00187) have received financial support from the Instituto de Salud Carlos III, co-funded by the European Social Fund (ESF)/Investing in your future. MM is the recipient of a predoctoral fellowship (PERIS, PIF-Salut, SLT017/20/000142) from the Department de Salut (Generalitat de Catalunya). MG-H is the recipient of a predoctoral fellowship from University of Lleida.ca_ES
dc.publisherFrontiers Mediaca_ES
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofFrontiers In Medicine, 2022, vol. 8, p. 1-15ca_ES
dc.rightscc-by (c) Authors, 2022ca_ES
dc.subjectAcute respiratory distress syndromeca_ES
dc.subjectMechanical ventilationca_ES
dc.titleBronchial Aspirate-Based Profiling Identifies MicroRNA Signatures Associated With COVID-19 and Fatal Disease in Critically Ill Patientsca_ES
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