A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universitat de Lleida (UdL) |
| Repositorio: | Repositori Obert UdL |
| OAI Identifier: | oai:repositori.udl.cat:10459.1/464293 |
| Acceso en línea: | https://doi.org/10.1186/s12931-023-02462-x https://hdl.handle.net/10459.1/464293 |
| Access Level: | acceso abierto |
| Palabra clave: | Biomarker COVID-19 ICU microRNA Prognosis SARS-CoV-2 |
| id |
ES_ada3cedda2b4b04df48be7e398318b95 |
|---|---|
| oai_identifier_str |
oai:repositori.udl.cat:10459.1/464293 |
| 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, IvánPerez-Pons, ManelGarcía Mateo, NadiaOrtega, AliciaPostigo, TamaraGarcía Hidalgo, María CoronadaBelmonte, ThalíaRodríguez Muñoz, CarlosGonzález, JessicaTorres, GerardGort Paniello, ClaraMoncusí Moix, AnnaEstella, ÁngelTamayo Lomas, LuisMartínez de la Gándara, AmaliaSocias, LorenzoPeñasco, Yhiviande la Torre, Maria del CarmenBustamante Munguira, ElenaGallego, ElenaMartínez Varela, IgnacioMartin Delgado, María CruzVidal Cortés, PabloLópez Messa, JuanPérez García, FelipeCaballero, JesúsAñón, José M.Loza Vázquez, AnaCarbonell, NievesMarin Corral, JudithJorge García, Ruth NoemíBarberà, CarmeCeccato, AdriánFernández Barat, LaiaFerrer, RicardGarcía Gasulla, DaríoLorente-Balanza, Jose ÁngelMenéndez, RosarioMotos, AnnaPeñuelas, OscarRiera, JordiBermejo Martin, Jesús F.Torres, AntoniBarbé Illa, FerranBiomarkerCOVID-19ICUmicroRNAPrognosisSARS-CoV-2Background: 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.BMJ2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1186/s12931-023-02462-xhttps://hdl.handle.net/10459.1/464293reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésReproducció del document publicat a: https://doi.org/10.1186/s12931-023-02462-xRespiratory Research, 2023, vol. 24, núm. 159cc-by (c)The authors, 2023Attribution 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:repositori.udl.cat:10459.1/4642932026-06-24T12:42:17Z |
| 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 Biomarker COVID-19 ICU microRNA Prognosis SARS-CoV-2 |
| 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 Perez-Pons, Manel García Mateo, Nadia Ortega, Alicia Postigo, Tamara García Hidalgo, María Coronada Belmonte, Thalía 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, 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, Carme Ceccato, Adrián Fernández Barat, Laia Ferrer, Ricard García Gasulla, Darío Lorente-Balanza, Jose Ángel Menéndez, Rosario Motos, Anna Peñuelas, Oscar Riera, Jordi Bermejo Martin, Jesús F. Torres, Antoni Barbé Illa, Ferran |
| author |
de Gonzalo Calvo, David |
| author_facet |
de Gonzalo Calvo, David Molinero, Marta Benítez, Iván Perez-Pons, Manel García Mateo, Nadia Ortega, Alicia Postigo, Tamara García Hidalgo, María Coronada Belmonte, Thalía 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, 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, Carme Ceccato, Adrián Fernández Barat, Laia Ferrer, Ricard García Gasulla, Darío Lorente-Balanza, Jose Ángel Menéndez, Rosario Motos, Anna Peñuelas, Oscar Riera, Jordi Bermejo Martin, Jesús F. Torres, Antoni Barbé Illa, Ferran |
| author_role |
author |
| author2 |
Molinero, Marta Benítez, Iván Perez-Pons, Manel García Mateo, Nadia Ortega, Alicia Postigo, Tamara García Hidalgo, María Coronada Belmonte, Thalía 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, 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, Carme Ceccato, Adrián Fernández Barat, Laia Ferrer, Ricard García Gasulla, Darío Lorente-Balanza, Jose Ángel Menéndez, Rosario Motos, Anna Peñuelas, Oscar Riera, Jordi Bermejo Martin, Jesús F. Torres, Antoni Barbé Illa, 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.subject.none.fl_str_mv |
Biomarker COVID-19 ICU microRNA Prognosis SARS-CoV-2 |
| topic |
Biomarker COVID-19 ICU microRNA Prognosis SARS-CoV-2 |
| description |
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. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://doi.org/10.1186/s12931-023-02462-x https://hdl.handle.net/10459.1/464293 |
| url |
https://doi.org/10.1186/s12931-023-02462-x https://hdl.handle.net/10459.1/464293 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1186/s12931-023-02462-x Respiratory Research, 2023, vol. 24, núm. 159 |
| dc.rights.none.fl_str_mv |
cc-by (c)The authors, 2023 Attribution 4.0 International info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ |
| rights_invalid_str_mv |
cc-by (c)The authors, 2023 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
BMJ |
| publisher.none.fl_str_mv |
BMJ |
| dc.source.none.fl_str_mv |
reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL) |
| instname_str |
Universitat de Lleida (UdL) |
| reponame_str |
Repositori Obert UdL |
| collection |
Repositori Obert UdL |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869416475388805120 |
| score |
15.811543 |