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

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  • dc.contributor.author Gonzalo-Calvo, David de
  • dc.contributor.author Marin Corral, Judith
  • dc.contributor.author Barbé, Ferran
  • dc.date.accessioned 2024-04-11T05:46:52Z
  • dc.date.available 2024-04-11T05:46:52Z
  • dc.date.issued 2023
  • dc.description.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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Gonzalo-Calvo D, Molinero M, Benítez ID, Perez-Pons M, García-Mateo N, Ortega, A et al. A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study. Respir Res. 2023 Jun 17;24(1):159. DOI: 10.1186/s12931-023-02462-x
  • dc.identifier.doi http://dx.doi.org/10.1186/s12931-023-02462-x
  • dc.identifier.issn 1465-9921
  • dc.identifier.uri http://hdl.handle.net/10230/59728
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof Respir Res. 2023 Jun 17;24(1):159
  • dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Biomarker
  • dc.subject.keyword COVID-19
  • dc.subject.keyword ICU
  • dc.subject.keyword Prognosis
  • dc.subject.keyword SARS-CoV-2
  • dc.subject.keyword microRNA
  • dc.title A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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