Title:The Role of Endothelial Related Circulating Biomarkers in
COVID-19. A Systematic Review and Meta-analysis
Volume: 29
Issue: 21
Author(s): Stamatios Lampsas, Paraskevas Tsaplaris, Panteleimon Pantelidis, Evangelos Oikonomou*, Georgios Marinos, Georgios Charalambous, Nektarios Souvaliotis, Vasiliki-Chara Mystakidi, Athina Goliopoulou, Efstratios Katsianos, Gerasimos Siasos, Michael-Andrew Vavuranakis, Costas Tsioufis, Manolis Vavuranakis and Dimitrios Tousoulis
Affiliation:
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest
Disease Hospital, Athens, Greece
- 1st Department of Cardiology, National and Kapodistrian University
of Athens, Medical School, Hippokration General Hospital, Athens, Greece
- Emergency Department, Hippokration' General Hospital, Athens, Greece
Keywords:
COVID-19, SARS-CoV-2, endothelial dysfunction, biomarkers, adhesion molecules, disease severity.
Abstract:
Background: Several studies have revealed the link between Coronavirus Disease
2019 (COVID-19) and endothelial dysfunction. To better understand the global pattern
of this relationship, we conducted a meta-analysis on endothelial biomarkers related
to COVID-19 severity.
Methods: We systematically searched the literature up to March 10, 2021, for studies investigating
the association between COVID-19 severity and the following endothelial biomarkers:
Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion
Molecule 1 (VCAM-1), E-selectin, P-selectin, Von Willebrand Factor Antigen (VWFAg),
soluble Thrombomodulin (sTM), Mid-regional pro-adrenomedullin (MR-proADM),
and Angiopoietin-2 (Ang-2). Pooled estimates and mean differences (PMD) for each biomarker
were reported.
Results: A total of 27 studies (n=2213 patients) were included. Critically ill patients presented
with higher levels of MR-proADM (PMD: 0.71 nmol/L, 95% CI: 0.22 to 1.20
nmol/L, p=0.02), E-selectin (PMD: 13,32 pg/ml, 95% CI: 4,89 to 21,75 pg/ml, p=0.008),
VCAM-1 (PMD: 479 ng/ml, 95% CI: 64 to 896 ng/ml, p=0.03), VWF-Ag (PMD: 110.5
IU/dl, 95% CI: 44.8 to 176.1 IU/dl, p=0.04) and Ang-2 (PMD: 2388 pg/ml, 95% CI:
1121 to 3655 pg/ml, p=0.003), as compared to non-critically ill ones. ICAM-1, P-selectin
and thrombomodulin did not differ between the two groups (p>0.05).
Conclusion: Endothelial biomarkers display significant heterogeneity in COVID-19 patients,
with higher MR-proADM, E-selectin, VCAM-1, VWF-Ag, and Ang-2 levels being
associated with increased severity. These findings strengthen the evidence on the key
role of endothelial dysfunction in disease progress.