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 principales: de Gonzalo-Calvo, David, Molinero, Marta, Benítez, Iván D., Perez-Pons, Manel, García-Mateo, Nadia, Ortega, Alicia, Postigo, Tamara, García-Hidalgo, María C., Belmonte, Thalia, 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 Curto, 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, Carmen, Ceccato, Adrián, Fernández-Barat, Laia, Ferrer, Ricard, Garcia-Gasulla, Dario, Lorente-Balanza, Jose Ángel, Menéndez, Rosario, Motos, Ana, Peñuelas, Oscar, Riera, Jordi, Bermejo-Martin, Jesús F., Torres, Antoni, Barbé, Ferran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276486/
https://www.ncbi.nlm.nih.gov/pubmed/37328754
http://dx.doi.org/10.1186/s12931-023-02462-x
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. CONCLUSIONS: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-023-02462-x.

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