Observational studyAngiogenesis2020
Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients.
Observational study in Angiogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 7 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
168 citing papers in PubMed, 7 syntheses or guidelines pooled it, 262 citations in OpenAlex.
- VEGF-A in COVID-19: a systematic review and meta-analytical approach to its prognostic value.Clinical and experimental medicine · 2025Pooled it
- Endotheliopathy in Acute COVID-19 and Long COVID.International journal of molecular sciences · 2023Pooled it
- D-dimer, disease severity, and deaths (3D-study) in patients with COVID-19: a systematic review and meta-analysis of 100 studies.Scientific reports · 2021Pooled it
- A systematic review and meta-analysis of regional risk factors for critical outcomes of COVID-19 during early phase of the pandemic.Scientific reports · 2021Pooled it
- Chronic Diseases as a Predictor for Severity and Mortality of COVID-19: A Systematic Review With Cumulative Meta-Analysis.Frontiers in medicine · 2021Pooled it
- Can we predict the severe course of COVID-19 - a systematic review and meta-analysis of indicators of clinical outcome?PloS one · 2021Pooled it
- Hemostatic System (Fibrinogen Level, D-Dimer, and FDP) in Severe and Non-Severe Patients With COVID-19: A Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisPooled it
- sST2 is a key outcome biomarker in COVID-19: insights from discovery randomized trial.Scientific reports · 2025Trial
- Multidimensional Proteomic Approach of Endothelial Progenitors Demonstrate Expression of KDR Restricted to CD19 Cells.Stem cell reviews and reports · 2021Trial
- Dissecting the pathobiology of suspected sepsis through a comparative analysis of endothelial inflammatory and clinical prediction models.Scientific reports · 2026Article
- Beyond the infusion: nursing at the vanguard of cytokine release syndrome rescue in CAR-T cell therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Endothelial Activation Phenotypes and Interleukin-6 Response After Therapeutic Plasma Exchange in Severe COVID-19-Associated Sepsis: A Retrospective Cohort Study.Diseases (Basel, Switzerland) · 2026Article
- Integrated Analysis of Parenchymal and Vascular HRCT Patterns with Circulating Biomarkers in Severe COVID-19 Pneumonia.Diagnostics (Basel, Switzerland) · 2026Article
- Renal microthrombosis and thrombomodulin deficiency in COVID-19-associated acute kidney injury.BMC nephrology · 2026Observational
- Circulating Angiopoietin-like proteins in Strongyloides Stercoralis infection and reversal following treatment.PLoS neglected tropical diseases · 2025Article
- Divergent biological pathways distinguish community-acquired pneumonia from COVID-19 despite similar plasma cytokine profiles.Respiratory research · 2025Article
- Inflammatory, fibrotic and endothelial biomarker profiles in COVID-19 patients during and following hospitalization.Scientific reports · 2025Article
- Cathepsin K cleavage of angiopoietin-2 creates detrimental Tie2 antagonist fragments in sepsis.The Journal of clinical investigation · 2025Article
- Predictive biosignatures for hospitalization in patients with virologically confirmed COVID-19.Journal of the Chinese Medical Association : JCMA · 2025Article
- An analysis of novel endothelial biomarkers to ascertain their role as prognostic indicators in severe COVID-19 illness.The Indian journal of medical research · 2025Article
108 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCoronavirus disease-2019 (COVID-19), a respiratory disease has been associated with ischemic complications, coagulation disorders, and an endotheliitis.
objectivesTo 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.
methodsAnalysis of endothelial and angiogenic soluble markers in plasma from patients at admission.
resultsStudy 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.
conclusionAngiopoietin-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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.