A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study

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...

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Detalles Bibliográficos
Autores: de Gonzalo Calvo, David, Molinero, Marta, Benítez, Iván, Perez-Pons, Manel, García Mateo, Nadia, Ortega, Alicia, Postigo, Tamara, García Hidalgo, María Coronada, Belmonte, Thalía, Rodríguez Muñoz, Carlos, González, Jessica, Torres, Gerard, Gort Paniello, Clara, Moncusí Moix, Anna, Estella, Ángel, Tamayo Lomas, Luis, Martínez de la Gándara, Amalia, Socias, Lorenzo, Peñasco, Yhivian, de la Torre, Maria del Carmen, Bustamante Munguira, Elena, Gallego, Elena, Martínez Varela, Ignacio, Martin Delgado, María Cruz, Vidal Cortés, Pablo, López Messa, Juan, Pérez García, Felipe, Caballero, Jesús, Añón, José M., Loza Vázquez, Ana, Carbonell, Nieves, Marin Corral, Judith, Jorge García, Ruth Noemí, Barberà, Carme, Ceccato, Adrián, Fernández Barat, Laia, Ferrer, Ricard, García Gasulla, Darío, Lorente-Balanza, Jose Ángel, Menéndez, Rosario, Motos, Anna, Peñuelas, Oscar, Riera, Jordi, Bermejo Martin, Jesús F., Torres, Antoni, Barbé Illa, Ferran
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/464293
Acceso en línea:https://doi.org/10.1186/s12931-023-02462-x
https://hdl.handle.net/10459.1/464293
Access Level:acceso abierto
Palabra clave:Biomarker
COVID-19
ICU
microRNA
Prognosis
SARS-CoV-2
Descripción
Sumario: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.

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