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

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, Angel; Tamayo Lomas, Luis; Martínez de la Gándara, Amalia; Socias, Lorenzo; Peñasco, Yhivian; de la Torre, María Del Carmen; Bustamante-Munguira, Elena; Gallego Curto, Elena; Martínez Varela, Ignacio; Martin Delgado, María Cruz; Vidal-Cortes, Pablo; López Messa, Juan; Pérez-García, Felipe; Caballero, Jesús; Añón, José Manuel; Loza-Vázquez, Ana; Carbonell, Nieves; Marin-Corral, Judith; Jorge García, Ruth Noemí; Barberà, Carme; Ceccato, Adrián; Fernández-Barat, Laia; Ferrer, Ricard; Garcia-Gasulla, Dario; Lorente-Balanza, Jose Ángel; Menéndez, Rosario; Motos, Ana; Peñuelas, Oscar; Riera, Jordi; Bermejo-Martin, Jesus F.; Torres, Antoni; Barbé, Ferran

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...

Descripción completa

Detalles Bibliográficos
Autores:	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, Angel, Tamayo Lomas, Luis, Martínez de la Gándara, Amalia, Socias, Lorenzo, Peñasco, Yhivian, de la Torre, María Del Carmen, Bustamante-Munguira, Elena, Gallego Curto, Elena, Martínez Varela, Ignacio, Martin Delgado, María Cruz, Vidal-Cortes, Pablo, López Messa, Juan, Pérez-García, Felipe, Caballero, Jesús, Añón, José Manuel, Loza-Vázquez, Ana, Carbonell, Nieves, Marin-Corral, Judith, Jorge García, Ruth Noemí, Barberà, Carme, Ceccato, Adrián, Fernández-Barat, Laia, Ferrer, Ricard, Garcia-Gasulla, Dario, Lorente-Balanza, Jose Ángel, Menéndez, Rosario, Motos, Ana, Peñuelas, Oscar, Riera, Jordi, Bermejo-Martin, Jesus F., Torres, Antoni, Barbé, Ferran
Tipo de recurso:	artículo
Fecha de publicación:	2023
País:	España
Institución:	Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:	Docusalut
Idioma:	inglés
OAI Identifier:	oai:docusalut.com:20.500.13003/19054
Acceso en línea:	https://hdl.handle.net/20.500.13003/19054
Access Level:	acceso abierto
Palabra clave:	Intensive Care Units Prospective Studies Biomarkers MicroRNAs Critical Illness Humans COVID-19 Retrospective Studies Humanos Estudios Prospectivos Biomarcadores Enfermedad Crítica Estudios Retrospectivos MicroARNs Unidades de Cuidados Intensivos

id	ES_ad9326c8f7aa6ff878a41bc76a72f1b0
oai_identifier_str	oai:docusalut.com:20.500.13003/19054
network_acronym_str	ES
network_name_str	España
repository_id_str
spelling	A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation studyde Gonzalo-Calvo, DavidMolinero, MartaBenítez, Iván D.Perez-Pons, ManelGarcía-Mateo, NadiaOrtega, AliciaPostigo, TamaraGarcía-Hidalgo, María CBelmonte, ThaliaRodríguez-Muñoz, CarlosGonzález, JessicaTorres, GerardGort-Paniello, ClaraMoncusí-Moix, AnnaEstella, AngelTamayo Lomas, LuisMartínez de la Gándara, AmaliaSocias, LorenzoPeñasco, Yhiviande la Torre, María Del CarmenBustamante-Munguira, ElenaGallego Curto, ElenaMartínez Varela, IgnacioMartin Delgado, María CruzVidal-Cortes, PabloLópez Messa, JuanPérez-García, FelipeCaballero, JesúsAñón, José ManuelLoza-Vázquez, AnaCarbonell, NievesMarin-Corral, JudithJorge García, Ruth NoemíBarberà, CarmeCeccato, AdriánFernández-Barat, LaiaFerrer, RicardGarcia-Gasulla, DarioLorente-Balanza, Jose ÁngelMenéndez, RosarioMotos, AnaPeñuelas, OscarRiera, JordiBermejo-Martin, Jesus F.Torres, AntoniBarbé, FerranIntensive Care UnitsProspective StudiesBiomarkersMicroRNAsCritical IllnessHumansCOVID-19Retrospective StudiesHumanosEstudios ProspectivosBiomarcadoresEnfermedad CríticaEstudios RetrospectivosCOVID-19MicroARNsUnidades de Cuidados IntensivosThe 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 < 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.BMC20232023-06-1720232023-06-17research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/19054reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/190542026-06-22T12:44:07Z
dc.title.none.fl_str_mv	A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
title	A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
spellingShingle	A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study de Gonzalo-Calvo, David Intensive Care Units Prospective Studies Biomarkers MicroRNAs Critical Illness Humans COVID-19 Retrospective Studies Humanos Estudios Prospectivos Biomarcadores Enfermedad Crítica Estudios Retrospectivos COVID-19 MicroARNs Unidades de Cuidados Intensivos
title_short	A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
title_full	A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
title_fullStr	A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
title_full_unstemmed	A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
title_sort	A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
dc.creator.none.fl_str_mv	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, Angel Tamayo Lomas, Luis Martínez de la Gándara, Amalia Socias, Lorenzo Peñasco, Yhivian de la Torre, María Del Carmen Bustamante-Munguira, Elena Gallego Curto, Elena Martínez Varela, Ignacio Martin Delgado, María Cruz Vidal-Cortes, Pablo López Messa, Juan Pérez-García, Felipe Caballero, Jesús Añón, José Manuel Loza-Vázquez, Ana Carbonell, Nieves Marin-Corral, Judith Jorge García, Ruth Noemí Barberà, Carme Ceccato, Adrián Fernández-Barat, Laia Ferrer, Ricard Garcia-Gasulla, Dario Lorente-Balanza, Jose Ángel Menéndez, Rosario Motos, Ana Peñuelas, Oscar Riera, Jordi Bermejo-Martin, Jesus F. Torres, Antoni Barbé, Ferran
author	de Gonzalo-Calvo, David
author_facet	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, Angel Tamayo Lomas, Luis Martínez de la Gándara, Amalia Socias, Lorenzo Peñasco, Yhivian de la Torre, María Del Carmen Bustamante-Munguira, Elena Gallego Curto, Elena Martínez Varela, Ignacio Martin Delgado, María Cruz Vidal-Cortes, Pablo López Messa, Juan Pérez-García, Felipe Caballero, Jesús Añón, José Manuel Loza-Vázquez, Ana Carbonell, Nieves Marin-Corral, Judith Jorge García, Ruth Noemí Barberà, Carme Ceccato, Adrián Fernández-Barat, Laia Ferrer, Ricard Garcia-Gasulla, Dario Lorente-Balanza, Jose Ángel Menéndez, Rosario Motos, Ana Peñuelas, Oscar Riera, Jordi Bermejo-Martin, Jesus F. Torres, Antoni Barbé, Ferran
author_role	author
author2	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, Angel Tamayo Lomas, Luis Martínez de la Gándara, Amalia Socias, Lorenzo Peñasco, Yhivian de la Torre, María Del Carmen Bustamante-Munguira, Elena Gallego Curto, Elena Martínez Varela, Ignacio Martin Delgado, María Cruz Vidal-Cortes, Pablo López Messa, Juan Pérez-García, Felipe Caballero, Jesús Añón, José Manuel Loza-Vázquez, Ana Carbonell, Nieves Marin-Corral, Judith Jorge García, Ruth Noemí Barberà, Carme Ceccato, Adrián Fernández-Barat, Laia Ferrer, Ricard Garcia-Gasulla, Dario Lorente-Balanza, Jose Ángel Menéndez, Rosario Motos, Ana Peñuelas, Oscar Riera, Jordi Bermejo-Martin, Jesus F. Torres, Antoni Barbé, Ferran
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv	Intensive Care Units Prospective Studies Biomarkers MicroRNAs Critical Illness Humans COVID-19 Retrospective Studies Humanos Estudios Prospectivos Biomarcadores Enfermedad Crítica Estudios Retrospectivos COVID-19 MicroARNs Unidades de Cuidados Intensivos
topic	Intensive Care Units Prospective Studies Biomarkers MicroRNAs Critical Illness Humans COVID-19 Retrospective Studies Humanos Estudios Prospectivos Biomarcadores Enfermedad Crítica Estudios Retrospectivos COVID-19 MicroARNs Unidades de Cuidados Intensivos
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 < 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.
publishDate	2023
dc.date.none.fl_str_mv	2023 2023-06-17 2023 2023-06-17
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/20.500.13003/19054
url	https://hdl.handle.net/20.500.13003/19054
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	BMC
publisher.none.fl_str_mv	BMC
dc.source.none.fl_str_mv	reponame:Docusalut instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str	Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str	Docusalut
collection	Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869416469868052480
score	15.198674

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

Similares en LA Referencia