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

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...

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Published in:Respiratory research 2023-06, Vol.24 (1), p.159-159, Article 159
Main Authors: 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, Bustamante-Munguira, Elena, Gallego Curto, Elena, Martínez Varela, Ignacio, Martin Delgado, María Cruz, Vidal-Cortés, Pablo, López Messa, Juan, Pérez-García, Felipe, Caballero, Jesús, Añón, José M, Loza-Vázquez, Ana, Carbonell, Nieves, Marin-Corral, Judith, Jorge García, Ruth Noemí, Barberà, Carmen, Ceccato, Adrián, Fernández-Barat, Laia, Ferrer, Ricard, Garcia-Gasulla, Dario, Lorente-Balanza, Jose Ángel, Menéndez, Rosario, Motos, Ana, Peñuelas, Oscar, Riera, Jordi, Bermejo-Martin, Jesús F, Torres, Antoni, Barbé, Ferran
Format: Article
Language:English
Subjects:
Analysis
Biological markers
Biomarker
Biomarkers
Blood
Classifiers
COVID-19
Decision making
Functional analysis
ICU
Inflammation
Intensive care units
Laboratories
MicroRNA
MicroRNAs
miRNA
Mortality
Patients
Predictions
Prognosis
Regression analysis
Ribonucleic acid
Risk
RNA
SARS-CoV-2
Services
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container_end_page 159
container_issue 1
container_start_page 159
container_title Respiratory research
container_volume 24
creator 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
Bustamante-Munguira, Elena
Gallego Curto, Elena
Martínez Varela, Ignacio
Martin Delgado, María Cruz
Vidal-Cortés, Pablo
López Messa, Juan
Pérez-García, Felipe
Caballero, Jesús
Añón, José M
Loza-Vázquez, Ana
Carbonell, Nieves
Marin-Corral, Judith
Jorge García, Ruth Noemí
Barberà, Carmen
Ceccato, Adrián
Fernández-Barat, Laia
Ferrer, Ricard
Garcia-Gasulla, Dario
Lorente-Balanza, Jose Ángel
Menéndez, Rosario
Motos, Ana
Peñuelas, Oscar
Riera, Jordi
Bermejo-Martin, Jesús F
Torres, Antoni
Barbé, Ferran
description 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. 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. Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR 
doi_str_mv 10.1186/s12931-023-02462-x
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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. 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. 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. A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.</description><identifier>ISSN: 1465-993X</identifier><identifier>ISSN: 1465-9921</identifier><identifier>EISSN: 1465-993X</identifier><identifier>EISSN: 1465-9921</identifier><identifier>DOI: 10.1186/s12931-023-02462-x</identifier><identifier>PMID: 37328754</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Biological markers ; Biomarker ; Biomarkers ; Blood ; Classifiers ; COVID-19 ; Decision making ; Functional analysis ; ICU ; Inflammation ; Intensive care units ; Laboratories ; MicroRNA ; MicroRNAs ; miRNA ; Mortality ; Patients ; Predictions ; Prognosis ; Regression analysis ; Ribonucleic acid ; Risk ; RNA ; SARS-CoV-2 ; Services</subject><ispartof>Respiratory research, 2023-06, Vol.24 (1), p.159-159, Article 159</ispartof><rights>2023. The Author(s).</rights><rights>COPYRIGHT 2023 BioMed Central Ltd.</rights><rights>2023. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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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. 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. 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. A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.</description><subject>Analysis</subject><subject>Biological markers</subject><subject>Biomarker</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>Classifiers</subject><subject>COVID-19</subject><subject>Decision making</subject><subject>Functional analysis</subject><subject>ICU</subject><subject>Inflammation</subject><subject>Intensive care units</subject><subject>Laboratories</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Mortality</subject><subject>Patients</subject><subject>Predictions</subject><subject>Prognosis</subject><subject>Regression analysis</subject><subject>Ribonucleic acid</subject><subject>Risk</subject><subject>RNA</subject><subject>SARS-CoV-2</subject><subject>Services</subject><issn>1465-993X</issn><issn>1465-9921</issn><issn>1465-993X</issn><issn>1465-9921</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdUstuEzEUHSEQLYUfYIEssWEz4Lc9bFAUXpEqKiGK2FkeP1JHM-Nge6rm73GSUloWlq_tc4_vufc0zUsE3yIk-buMcEdQCzGpi3Lc3jxqThHlrO068uvxvfikeZbzBkIkpGBPmxMiCK4RPW3KAvRDjBaMwaT4_dsCmEHnHHxwCfiYQLlyYJucDaaEOIHowWp5CcaYih5C2YEwgeXFz9XHFnVgq0twU8nvgQbjPJRg6qnyXFeo1Yf8XGa7e9488XrI7sXtftZcfv70Y_m1Pb_4slouzlvDMCstoZZ4YhnqIZI99oQwWtUwQx11TlouBMLU4J6JjnsDrWHQItsLb73kmpCzZnXktVFv1DaFUaedijqow0VMa6VTrXJwqocOdVBKxrylnnstLRbUwN5YKhh2levDkWs796Oze2VJDw9IH75M4Uqt47VCEAtOJa8Mb24ZUvw9u1zUGLJxw6AnF-essMQCMyloV6Gv_4Nu4pym2qsDCiFWR_kPtdZVQZh8rB-bPalaCEYwh5Dvm4CPqDrfnJPzdzUjqPY-UkcfqeojdfCRuqlJr-6rvUv5axzyB7Xpwws</recordid><startdate>20230617</startdate><enddate>20230617</enddate><creator>de Gonzalo-Calvo, David</creator><creator>Molinero, Marta</creator><creator>Benítez, Iván D</creator><creator>Perez-Pons, Manel</creator><creator>García-Mateo, Nadia</creator><creator>Ortega, Alicia</creator><creator>Postigo, Tamara</creator><creator>García-Hidalgo, María C</creator><creator>Belmonte, Thalia</creator><creator>Rodríguez-Muñoz, Carlos</creator><creator>González, Jessica</creator><creator>Torres, Gerard</creator><creator>Gort-Paniello, Clara</creator><creator>Moncusí-Moix, Anna</creator><creator>Estella, Ángel</creator><creator>Tamayo Lomas, Luis</creator><creator>Martínez de la Gándara, Amalia</creator><creator>Socias, Lorenzo</creator><creator>Peñasco, Yhivian</creator><creator>de la Torre, Maria Del Carmen</creator><creator>Bustamante-Munguira, Elena</creator><creator>Gallego Curto, Elena</creator><creator>Martínez Varela, Ignacio</creator><creator>Martin Delgado, María Cruz</creator><creator>Vidal-Cortés, Pablo</creator><creator>López Messa, Juan</creator><creator>Pérez-García, Felipe</creator><creator>Caballero, Jesús</creator><creator>Añón, José M</creator><creator>Loza-Vázquez, Ana</creator><creator>Carbonell, Nieves</creator><creator>Marin-Corral, Judith</creator><creator>Jorge García, Ruth Noemí</creator><creator>Barberà, Carmen</creator><creator>Ceccato, Adrián</creator><creator>Fernández-Barat, Laia</creator><creator>Ferrer, Ricard</creator><creator>Garcia-Gasulla, Dario</creator><creator>Lorente-Balanza, Jose Ángel</creator><creator>Menéndez, Rosario</creator><creator>Motos, Ana</creator><creator>Peñuelas, Oscar</creator><creator>Riera, Jordi</creator><creator>Bermejo-Martin, Jesús F</creator><creator>Torres, Antoni</creator><creator>Barbé, Ferran</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20230617</creationdate><title>A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study</title><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 ; Bustamante-Munguira, Elena ; Gallego Curto, Elena ; Martínez Varela, Ignacio ; Martin Delgado, María Cruz ; Vidal-Cortés, Pablo ; López Messa, Juan ; Pérez-García, Felipe ; Caballero, Jesús ; Añón, José M ; Loza-Vázquez, Ana ; Carbonell, Nieves ; Marin-Corral, Judith ; Jorge García, Ruth Noemí ; Barberà, Carmen ; Ceccato, Adrián ; Fernández-Barat, Laia ; Ferrer, Ricard ; Garcia-Gasulla, Dario ; Lorente-Balanza, Jose Ángel ; Menéndez, Rosario ; Motos, Ana ; Peñuelas, Oscar ; Riera, Jordi ; Bermejo-Martin, Jesús F ; Torres, Antoni ; Barbé, Ferran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-34d3f3d51b018b2f33549935c4e4ee8d677124c2b5796fc0dc50d1db7fdf86a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Biological markers</topic><topic>Biomarker</topic><topic>Biomarkers</topic><topic>Blood</topic><topic>Classifiers</topic><topic>COVID-19</topic><topic>Decision making</topic><topic>Functional analysis</topic><topic>ICU</topic><topic>Inflammation</topic><topic>Intensive care units</topic><topic>Laboratories</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>miRNA</topic><topic>Mortality</topic><topic>Patients</topic><topic>Predictions</topic><topic>Prognosis</topic><topic>Regression analysis</topic><topic>Ribonucleic acid</topic><topic>Risk</topic><topic>RNA</topic><topic>SARS-CoV-2</topic><topic>Services</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Gonzalo-Calvo, David</creatorcontrib><creatorcontrib>Molinero, Marta</creatorcontrib><creatorcontrib>Benítez, Iván D</creatorcontrib><creatorcontrib>Perez-Pons, Manel</creatorcontrib><creatorcontrib>García-Mateo, Nadia</creatorcontrib><creatorcontrib>Ortega, Alicia</creatorcontrib><creatorcontrib>Postigo, Tamara</creatorcontrib><creatorcontrib>García-Hidalgo, María C</creatorcontrib><creatorcontrib>Belmonte, Thalia</creatorcontrib><creatorcontrib>Rodríguez-Muñoz, Carlos</creatorcontrib><creatorcontrib>González, Jessica</creatorcontrib><creatorcontrib>Torres, Gerard</creatorcontrib><creatorcontrib>Gort-Paniello, Clara</creatorcontrib><creatorcontrib>Moncusí-Moix, Anna</creatorcontrib><creatorcontrib>Estella, Ángel</creatorcontrib><creatorcontrib>Tamayo Lomas, Luis</creatorcontrib><creatorcontrib>Martínez de la Gándara, Amalia</creatorcontrib><creatorcontrib>Socias, Lorenzo</creatorcontrib><creatorcontrib>Peñasco, Yhivian</creatorcontrib><creatorcontrib>de la Torre, Maria Del Carmen</creatorcontrib><creatorcontrib>Bustamante-Munguira, Elena</creatorcontrib><creatorcontrib>Gallego Curto, Elena</creatorcontrib><creatorcontrib>Martínez Varela, Ignacio</creatorcontrib><creatorcontrib>Martin Delgado, María Cruz</creatorcontrib><creatorcontrib>Vidal-Cortés, Pablo</creatorcontrib><creatorcontrib>López Messa, Juan</creatorcontrib><creatorcontrib>Pérez-García, Felipe</creatorcontrib><creatorcontrib>Caballero, Jesús</creatorcontrib><creatorcontrib>Añón, José M</creatorcontrib><creatorcontrib>Loza-Vázquez, Ana</creatorcontrib><creatorcontrib>Carbonell, Nieves</creatorcontrib><creatorcontrib>Marin-Corral, Judith</creatorcontrib><creatorcontrib>Jorge García, Ruth Noemí</creatorcontrib><creatorcontrib>Barberà, Carmen</creatorcontrib><creatorcontrib>Ceccato, Adrián</creatorcontrib><creatorcontrib>Fernández-Barat, Laia</creatorcontrib><creatorcontrib>Ferrer, Ricard</creatorcontrib><creatorcontrib>Garcia-Gasulla, Dario</creatorcontrib><creatorcontrib>Lorente-Balanza, Jose Ángel</creatorcontrib><creatorcontrib>Menéndez, Rosario</creatorcontrib><creatorcontrib>Motos, Ana</creatorcontrib><creatorcontrib>Peñuelas, Oscar</creatorcontrib><creatorcontrib>Riera, Jordi</creatorcontrib><creatorcontrib>Bermejo-Martin, Jesús F</creatorcontrib><creatorcontrib>Torres, Antoni</creatorcontrib><creatorcontrib>Barbé, Ferran</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; 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Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest Health &amp; Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health &amp; Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Respiratory research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Gonzalo-Calvo, David</au><au>Molinero, Marta</au><au>Benítez, Iván D</au><au>Perez-Pons, Manel</au><au>García-Mateo, Nadia</au><au>Ortega, Alicia</au><au>Postigo, Tamara</au><au>García-Hidalgo, María C</au><au>Belmonte, Thalia</au><au>Rodríguez-Muñoz, Carlos</au><au>González, Jessica</au><au>Torres, Gerard</au><au>Gort-Paniello, Clara</au><au>Moncusí-Moix, Anna</au><au>Estella, Ángel</au><au>Tamayo Lomas, Luis</au><au>Martínez de la Gándara, Amalia</au><au>Socias, Lorenzo</au><au>Peñasco, Yhivian</au><au>de la Torre, Maria Del Carmen</au><au>Bustamante-Munguira, Elena</au><au>Gallego Curto, Elena</au><au>Martínez Varela, Ignacio</au><au>Martin Delgado, María Cruz</au><au>Vidal-Cortés, Pablo</au><au>López Messa, Juan</au><au>Pérez-García, Felipe</au><au>Caballero, Jesús</au><au>Añón, José M</au><au>Loza-Vázquez, Ana</au><au>Carbonell, Nieves</au><au>Marin-Corral, Judith</au><au>Jorge García, Ruth Noemí</au><au>Barberà, Carmen</au><au>Ceccato, Adrián</au><au>Fernández-Barat, Laia</au><au>Ferrer, Ricard</au><au>Garcia-Gasulla, Dario</au><au>Lorente-Balanza, Jose Ángel</au><au>Menéndez, Rosario</au><au>Motos, Ana</au><au>Peñuelas, Oscar</au><au>Riera, Jordi</au><au>Bermejo-Martin, Jesús F</au><au>Torres, Antoni</au><au>Barbé, Ferran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study</atitle><jtitle>Respiratory research</jtitle><addtitle>Respir Res</addtitle><date>2023-06-17</date><risdate>2023</risdate><volume>24</volume><issue>1</issue><spage>159</spage><epage>159</epage><pages>159-159</pages><artnum>159</artnum><issn>1465-993X</issn><issn>1465-9921</issn><eissn>1465-993X</eissn><eissn>1465-9921</eissn><abstract>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. 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. 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. A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>37328754</pmid><doi>10.1186/s12931-023-02462-x</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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ispartof Respiratory research, 2023-06, Vol.24 (1), p.159-159, Article 159
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source PubMed (Medline); Publicly Available Content (ProQuest); EZB Electronic Journals Library
subjects Analysis
Biological markers
Biomarker
Biomarkers
Blood
Classifiers
COVID-19
Decision making
Functional analysis
ICU
Inflammation
Intensive care units
Laboratories
MicroRNA
MicroRNAs
miRNA
Mortality
Patients
Predictions
Prognosis
Regression analysis
Ribonucleic acid
Risk
RNA
SARS-CoV-2
Services
title A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
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