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

Respir Res. 2023 Jun 17;24(1):159. doi: 10.1186/s12931-023-02462-x.

Abstract

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.

Conclusions: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.

Keywords: Biomarker; COVID-19; ICU; Prognosis; SARS-CoV-2; microRNA.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Biomarkers
  • COVID-19* / diagnosis
  • COVID-19* / genetics
  • Critical Illness
  • Humans
  • Intensive Care Units
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Prospective Studies
  • Retrospective Studies

Substances

  • MicroRNAs
  • Biomarkers