A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
Authors
Gonzalo Calvo, David de; Molinero, Marta; Benítez, Iván D; Pérez Pons, Manel; García Mateo, Nadia; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/60933DOI: 10.1186/s12931-023-02462-x
ISSN: 1465-9921
Date
2023-06-17Funders
Instituto de Salud Carlos III
Universidad de Lleida
Centro de Investigación Biomédica en Red
Fundació La Marató
Bibliographic citation
Respiratory Research, 2023, v. 24, n. 1, p. -
Keywords
Biomarker
COVID-19
ICU
microRNA
Prognosis
SARS-CoV-2
Description / Notes
11 p.
Project
info:eu-repo/grantAgreement/ISCIII//PFIS2021/ES//
info:eu-repo/grantAgreement/ISCIII//FI21%00187/ES//
info:eu-repo/grantAgreement/ISCIII//CD21%00087/ES//
info:eu-repo/grantAgreement/ISCIII//COV20%00110/ES//
info:eu-repo/grantAgreement/ISCIII//202108-30%-31/ES//
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© The Author(s) 2023
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
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.
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