Endothelin-1 in combination with CRB-65 enhance risk stratification in COVID-19 patients.

Background: COVID-19 continuously causes severe disease conditions and significant mortality. We evaluate whether easily accessible biomarkers can improve risk prediction of severe disease outcomes. Methods: Our study analysed 426 COVID-19 patients collected by German CAPNETZ and PROGRESS study grou...

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Published in:Infection Vol. 53; no. 6; pp. 2769 - 2779
Main Authors: Farhat, Imrana, Rosolowski, Maciej, Ahrens, Katharina, Lienau, Jasmin, Ahnert, Peter, Pletz, Mathias, Rohde, Gernot, Rupp, Jan, Witzenrath, Martin, Scholz, Markus
Format: equations & formulas research tables/charts Journal Article
Published: Springer Nature Dec2025
Online Access:View this record in EBSCOhost
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      dt: Dec2025
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s15010-025-02627-4
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        atl: Endothelin-1 in combination with CRB-65 enhance risk stratification in COVID-19 patients.
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        au:
          Farhat, Imrana
          Rosolowski, Maciej
          Ahrens, Katharina
          Lienau, Jasmin
          Ahnert, Peter
          Pletz, Mathias
          Rohde, Gernot
          Rupp, Jan
          Witzenrath, Martin
          Scholz, Markus
        affil: https://ror.org/03s7gtk40 Institute for Medical Informatics, Statistics, and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
      sug:
        subj:
          COVID-19 Mortality
          Endothelins Blood
          Biological Markers Blood
          Clinical Prediction Rules
          Intensive Care Units
          Patient Admission
          Risk Assessment
          Human
          Funding Source
          Male
          Female
          Middle Age
          Prospective Studies
          Vaccination Status
          Nonexperimental Studies
          Enzyme-Linked Immunosorbent Assay
          Comparative Studies
          Mann-Whitney U Test
          ROC Curve
          Logistic Regression
          Data Analysis Software
          Descriptive Statistics
          Prediction Models
          Troponin Blood
          Calcitonin Blood
          Natriuretic Peptide, Brain Blood
          Proteins Blood
          Carrier Proteins Blood
          Germany
          Inpatients
          Confidence Intervals
          Machine Learning
          Middle Aged: 45-64 years
          Male
          Female
      ab: Background: COVID-19 continuously causes severe disease conditions and significant mortality. We evaluate whether easily accessible biomarkers can improve risk prediction of severe disease outcomes. Methods: Our study analysed 426 COVID-19 patients collected by German CAPNETZ and PROGRESS study groups between 2020 and 2021. Troponin T high-sensitive (TnT-hs), procalcitonin (PCT), N-terminal pro brain natriuretic peptide, angiopoietin-2, copeptin, endothelin-1 (ET-1) and lipocalin-2 were measured at enrolment and related to 28d mortality/ICU admission endpoint. Logistic and relaxed LASSO regression were used to evaluate the added value of biomarkers compared to the CRB-65 score and to develop a combined risk prediction model for our endpoint. Results: Of the 426 COVID-19 patients, 64 (15%) reached the endpoint. Among individual biomarkers, ET-1 showed the highest predictive performance (AUC = 0.76, 95% CI: 0.70–0.82). CRB-65 alone had an AUC of 0.63 (95% CI: 0.56–0.70). Our machine learning method identified CRB-65 + ET-1 to be optimal for prediction performance and model sparsity (AUC = 0.77, 95% CI: 0.71–0.83). Decision curve analysis demonstrated its greater net benefit over CRB-65 across large range of risk thresholds. The generalizability of our non-COVID CAP model (CRB-65 + TnT-hs + PCT) to COVID-19 patients was also assessed, yielding an AUC of 0.67 (95% CI: 0.60–0.74) for our primary endpoint. For 28d mortality alone as endpoint, it performed remarkably well (AUC = 0.90, 95% CI: 0.85–0.95). Conclusion: Combining the already established clinical CRB-65 score with ET-1 significantly improves risk prediction of intensive care requirement or death within 28 days in hospitalized COVID-19 patients.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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