2026-04-05T12:46:45Zhttps://recercat.cat/oai/requestoai:recercat.cat:10459.1/832512024-12-05T21:24:30Zcom_2072_3622col_2072_479130
RECERCAT
author
Molinero, Marta
author
Benítez, Iván
author
González, Jessica
author
Gort Paniello, Clara
author
Moncusí Moix, Anna
author
Rodríguez Jara, Fátima
author
García Hidalgo, María Coronada
author
Torres, Gerard
author
Vengoechea Aragoncillo, José Javier
author
Gómez Falguera, Silvia
author
Cabo Gambín, Ramón
author
Caballero, Jesús
author
Bermejo Martin, Jesús F.
author
Ceccato, Adrián
author
Fernández Barat, Laia
author
Ferrer, Ricard
author
García Gasulla, Darío
author
Menéndez, Rosario
author
Motos, Anna
author
Peñuelas, Oscar
author
Riera, Jordi
author
Torres, Antoni
author
Barbé Illa, Ferran
author
de Gonzalo Calvo, David
2024-12-05T21:24:30Z
2024-12-05T21:24:30Z
2022-05-10T07:35:25Z2022-05-10T07:35:25Z2022
http://hdl.handle.net/10459.1/83251
Background: 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.This 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.
cc-by (c) Authors, 2022 info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/
COVID-19
SARS-CoV-2
Acute respiratory distress syndrome
Mechanical ventilation
MicroRNA
Bronchial Aspirate-Based Profiling Identifies MicroRNA Signatures Associated With COVID-19 and Fatal Disease in Critically Ill Patients
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion