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

DOI record: { "DOI": "10.1186/s12931-023-02462-x", "ISSN": [ "1465-993X" ], "URL": "http://dx.doi.org/10.1186/s12931-023-02462-x", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR &lt; 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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.</jats:p>\n </jats:sec>", "alternative-id": [ "2462" ], "article-number": "159", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "20 February 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "25 May 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "17 June 2023" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "The study protocol was approved by the respective ethics committee of each participating hospital. The study was designed and conducted in compliance with the Declaration of Helsinki and national and international law on data protection." }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "The authors declare no competing interests." } ], "author": [ { "affiliation": [], "family": "de Gonzalo-Calvo", "given": "David", "sequence": "first" }, { "affiliation": [], "family": "Molinero", "given": "Marta", "sequence": "additional" }, { "affiliation": [], "family": "Benítez", "given": "Iván D.", "sequence": "additional" }, { "affiliation": [], "family": "Perez-Pons", "given": "Manel", "sequence": "additional" }, { "affiliation": [], "family": "García-Mateo", "given": "Nadia", "sequence": "additional" }, { "affiliation": [], "family": "Ortega", "given": "Alicia", "sequence": "additional" }, { 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