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 Pages 3790 - 3805 ( 16 )
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.
COVID-19, SARS-CoV-2, endothelial dysfunction, biomarkers, adhesion molecules, disease severity.
3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 1st Department of Cardiology, 'Hippokration' General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece; General Practice Department, Laiko Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens