Biomarkers of COVID-19 short-term worsening: a multiparameter analysis within the prospective multicenter COVIDeF cohort

Eur J Emerg Med. 2024 Dec 1;31(6):429-437. doi: 10.1097/MEJ.0000000000001175. Epub 2024 Sep 12.

Abstract

Background: During a pandemic like COVID-19, hospital resources are constrained and accurate severity triage of the patients is required.

Objective: The objective of this study is to estimate the predictive performances of candidate biomarkers for short-term worsening (STW) of COVID-19.

Design: Prospective, multicenter (20 hospitals in Paris) cohort study of consecutive COVID-19 patients with systematic biobanking at admission, during the first waves of COVID-19 in France in 2020 (COVIDeF cohort).

Setting and participants: Consecutive COVID-19 patients were screened for inclusion. They were excluded in presence of severity criteria defined by either an ICU admission, mechanical ventilation (including noninvasive ventilation), acute respiratory distress, or in-hospital death before sampling. Routine blood tests measured during usual care and centralized systematic measurement of creatine kinase, C-reactive protein (CRP), procalcitonin, soluble urokinase plasminogen activator receptor (suPAR), high-sensitive troponin T (TnT-hs), N terminal pro-B natriuretic peptide (NT-proBNP), calprotectin, platelet factor 4, mid-regional pro-adrenomedullin (MR-proADM), and proendothelin were performed.

Outcome measures and analyses: The primary outcome was STW, defined by a severity criteria within 7 days. A backward stepwise logistic regression model and a 'best subset' approach were used to identify independent association, and the area under the receiving operator characteristics (AUROC) was computed.

Results: Five hundred and eleven patients were analyzed, of whom 60 (11.7%) experienced STW. Median time to occurrence of a severity criteria was 3 days. At admission, lower values of eosinophils, lymphocytes, platelets, alanine aminotransferase, and higher values of neutrophils, creatinine, urea, CRP, TnT-hs, suPAR, NT-proBNP, calprotectin, procalcitonin, MR-proADM, and proendothelin were predictive of worsening. Stepwise logistic regression identified three biomarkers significantly associated with worsening: CRP [adjusted odds ratio (aOR): 1.10, 95% confidence interval (95% CI): 1.06-1.15 for a 10-unit increase, AUROC: 0.73 (0.66-0.79)], procalcitonin [aOR: 0.42, 95% CI: 0.22-0.81, AUROC: 0.69 (0.64-0.88)], and MR-proADM [aOR: 2.85, 95% CI: 1.74-4.69, AUROC: 0.75 (0.69-0.81)]. These biomarkers outperformed clinical variables except diabetes and cancer comorbidities.

Conclusion: In this multicenter prospective study that assessed a large panel of biomarkers for COVID-19 patients, CRP, procalcitonin, and MR-proADM were independently associated with the risk of STW.

Trial registration: ClinicalTrials.gov NCT04352348.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Biomarkers* / blood
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • COVID-19* / blood
  • COVID-19* / diagnosis
  • Cohort Studies
  • Female
  • France / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Pandemics
  • Peptide Fragments / blood
  • Procalcitonin / blood
  • Prospective Studies
  • SARS-CoV-2
  • Severity of Illness Index
  • Troponin T / blood

Substances

  • Biomarkers
  • C-Reactive Protein
  • Procalcitonin
  • Troponin T
  • Natriuretic Peptide, Brain
  • pro-brain natriuretic peptide (1-76)
  • Peptide Fragments

Associated data

  • ClinicalTrials.gov/NCT04352348