@misc{10498/29728,
year = {2023},
month = {6},
url = {http://hdl.handle.net/10498/29728},
abstract = {Background: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. Methods: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. Results: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. Conclusions: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.},
publisher = {Springer},
keywords = {COVID-19},
keywords = {Biomarker},
keywords = {ICU},
keywords = {microRNA},
keywords = {Prognosis},
keywords = {SARS-CoV-2},
title = {A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study},
doi = {10.1186/s12931-023-02462-x},
author = {de Gonzalo Calvo, David and Molinero, Marta and Benítez, Iván D. and Perez Pons, Manel and García Mateo, Nadia and Ortega, Alicia and Postigo, Tamara and García Hidalgo, María C. and Belmonte, Thalía and Rodríguez Muñoz, Carlos and González, Jessica and Torres, Gerard and Gort Paniello, Clara and Moncusí Moix, Anna and Estella García, Ángel and Tamayo Lomas, Luis and Martínez de la Gándara, Amalia and Socias, Lorenzo and Peñasco, Yhivian and de la Torre, María del Carmen and Bustamante Munguira, Elena and Gallego Curto, Elena and Martínez Varela, Ignacio and Martín Delgado, María Cruz and Vidal Cortés, Pablo and López Messa, Juan and Pérez García, Felipe and Caballero, Jesús and Añón, José Manuel and Loza Vázquez, Ana and Carbonell, Nieves and Marin Corral, Judith and Jorge García, Ruth Noemí and Barberà, Carmen and Ceccato, Adrián and Fernández Barat, Laia and Ferrer, Ricard and García Gasulla, Dario and Lorente Balanza, Jose Ángel and Menéndez, Rosario and Motos, Ana and Peñuelas, Oscar and Riera, Jordi and Bermejo Martin, Jesús F. and Torres, Antoni and Barbé, Ferrán},
}