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

{ 'indexed': {'date-parts': [[2023, 6, 18]], 'date-time': '2023-06-18T04:17:40Z', 'timestamp': 1687061860095}, 'reference-count': 30, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2023, 6, 17]], 'date-time': '2023-06-17T00:00:00Z', 'timestamp': 1686960000000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2023, 6, 17]], 'date-time': '2023-06-17T00:00:00Z', 'timestamp': 1686960000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ { 'DOI': '10.13039/501100004587', 'name': 'Instituto de Salud Carlos III', 'doi-asserted-by': 'crossref', 'award': ['CP20/00041']}, { 'DOI': '10.13039/501100009410', 'name': 'Universitat de Lleida', 'doi-asserted-by': 'crossref'}, {'name': 'European Development Regional Fund'}, {'name': 'CIBERES', 'award': ['COV20/00110']}, {'name': 'UNESPA'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, '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\xa0h 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\u2009&lt;\u20090.05). 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>', 'DOI': '10.1186/s12931-023-02462-x', 'type': 'journal-article', 'created': {'date-parts': [[2023, 6, 17]], 'date-time': '2023-06-17T03:31:29Z', 'timestamp': 1686972689000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a ' 'multicenter validation study', 'prefix': '10.1186', 'volume': '24', 'author': [ {'given': 'David', 'family': 'de Gonzalo-Calvo', 'sequence': 'first', 'affiliation': []}, {'given': 'Marta', 'family': 'Molinero', 'sequence': 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Mortality comparison between the first and ' 'second/third waves among 3,795 critical COVID-19 patients with pneumonia ' 'admitted to the ICU: a multicentre retrospective cohort study. Lancet ' 'Reg Health-Eur. 2021;11:100243.', 'journal-title': 'Lancet Reg Health-Eur'}, { 'key': '2462_CR30', 'doi-asserted-by': 'publisher', 'first-page': '121', 'DOI': '10.3389/fmolb.2022.858702', 'volume': '9', 'author': 'Y Devaux', 'year': '2022', 'unstructured': 'Devaux Y, Pinet F, de Gonzalo-Calvo D, Editorial. The non-coding ' 'transcriptome as a New Player in Intercellular Communication. 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The study was designed and conducted in compliance with ' 'the Declaration of Helsinki and national and international law on data ' 'protection.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'Not applicable.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare no competing interests.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '159'}