학술논문
A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study.
Document Type
Article
Author
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
Source
Subject
*COVID-19
*GENE expression
*SARS disease
*MICRORNA
*CRITICALLY ill
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Language
ISSN
1465-9921
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. [ABSTRACT FROM AUTHOR]