Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients

Angiogenesis. 2020 Nov;23(4):611-620. doi: 10.1007/s10456-020-09730-0. Epub 2020 May 27.


Background: Coronavirus disease-2019 (COVID-19), a respiratory disease has been associated with ischemic complications, coagulation disorders, and an endotheliitis.

Objectives: To explore endothelial damage and activation-related biomarkers in COVID-19 patients with criteria of hospitalization for referral to intensive care unit (ICU) and/or respiratory worsening.

Methods: Analysis of endothelial and angiogenic soluble markers in plasma from patients at admission.

Results: Study enrolled 40 consecutive COVID-19 patients admitted to emergency department that fulfilled criteria for hospitalization. Half of them were admitted in conventional wards without any ICU transfer during hospitalization; whereas the 20 others were directly transferred to ICU. Patients transferred in ICU were more likely to have lymphopenia, decreased SpO2 and increased D-dimer, CRP and creatinine levels. In those patients, soluble E-selectin and angiopoietin-2 were significantly increased (p value at 0.009 and 0.003, respectively). Increase in SELE gene expression (gene coding for E-selectin protein) was confirmed in an independent cohort of 32 patients using a whole blood gene expression profile analysis. In plasma, we found a strong association between angiopoetin-2 and CRP, creatinine and D-dimers (with p value at 0.001, 0.001 and 0.003, respectively). ROC curve analysis identified an Angiopoietin-2 cut-off of 5000 pg/mL as the best predictor for ICU outcome (Se = 80.1%, Sp = 70%, PPV = 72.7%, NPV = 77%), further confirmed in multivariate analysis after adjustment for creatinine, CRP or D-dimers.

Conclusion: Angiopoietin-2 is a relevant predictive factor for ICU direct admission in COVID-19 patients. This result showing an endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction.

Keywords: Angiogenesis; Angiopoietin-2; Biomarker; COVID-19; E-selectin; Endothelial.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiopoietin-2 / blood*
  • Betacoronavirus
  • Biomarkers / blood
  • COVID-19
  • Coronavirus Infections / blood*
  • Coronavirus Infections / therapy*
  • Critical Care / methods
  • E-Selectin / blood
  • Endothelium, Vascular / metabolism*
  • Female
  • Gene Expression Profiling
  • Hospitalization
  • Humans
  • Intensive Care Units*
  • Male
  • Middle Aged
  • Pandemics
  • Patient Admission
  • Pneumonia, Viral / blood*
  • Pneumonia, Viral / therapy*
  • Prospective Studies
  • Respiration, Artificial
  • SARS-CoV-2


  • ANGPT2 protein, human
  • Angiopoietin-2
  • Biomarkers
  • E-Selectin

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