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0 0.5 1 1.5 2+ Mortality 38% Improvement Relative Risk HCQ  de Gonzalo-Calvo et al.  ICU PATIENTS Is very late treatment with HCQ beneficial for COVID-19? Retrospective 491 patients in Spain (March 2020 - February 2021) Lower mortality with HCQ (not stat. sig., p=0.23) de Gonzalo-Calvo et al., Respiratory R.., Jun 2023 Favors HCQ Favors control

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

de Gonzalo-Calvo et al., Respiratory Research, doi:10.1186/s12931-023-02462-x, NCT04457505
Jun 2023  
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Retrospective 491 ICU patients in Spain showing lower mortality with HCQ without statistical significance in unadjusted results. This study is excluded in the after exclusion results of meta analysis: unadjusted results with no group details.
risk of death, 37.6% lower, RR 0.62, p = 0.23, treatment 6 of 32 (18.8%), control 138 of 459 (30.1%), NNT 8.8.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
de Gonzalo-Calvo et al., 17 Jun 2023, retrospective, Spain, peer-reviewed, median age 65.0, 46 authors, study period March 2020 - February 2021, trial NCT04457505 (history).
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A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
David De Gonzalo-Calvo, Marta Molinero, Iván D Benítez, Manel Perez-Pons, Nadia García-Mateo, Alicia Ortega, Tamara Postigo, María C García-Hidalgo, Thalia Belmonte, Carlos Rodríguez-Muñoz, Jessica González, Gerard Torres, Clara Gort-Paniello, Anna Moncusí-Moix, Ángel Estella, Luis Tamayo Lomas, Amalia Martínez De La Gándara, Lorenzo Socias, Yhivian Peñasco, Maria Del Carmen De La Torre, Elena Bustamante-Munguira, Elena Gallego Curto, Ignacio Martínez Varela, María Cruz Martin Delgado, Pablo Vidal-Cortés, Juan López Messa, Felipe Pérez-García, Jesús Caballero, José M Añón, Ana Loza-Vázquez, Nieves Carbonell, Judith Marin-Corral, Ruth Noemí Jorge García, Carmen Barberà, Adrián Ceccato, Laia Fernández-Barat, Ricard Ferrer, Dario Garcia-Gasulla, Jose Ángel Lorente-Balanza, Rosario Menéndez, Ana Motos, Oscar Peñuelas, Jordi Riera, Jesús F Bermejo-Martin, Antoni Torres, Ferran Barbé
Respiratory Research, doi:10.1186/s12931-023-02462-x
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
Abbreviations Declarations Ethics approval and consent to participate 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. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Late treatment
is less effective
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