ABSTRACT
Coronavirus disease (COVID-19) is a respiratory disease, although arterial function involvement has been documented. We assess the impact of a post-acute COVID-19 rehabilitation program on endothelium-dependent vasodilation and arterial wall properties. We enrolled 60 convalescent patients from COVID-19 and one-month post-acute disease, who were randomized at a 1:1 ratio in a 3-month cardiopulmonary rehabilitation program (study group) or not (control group). Endothelium-dependent vasodilation was evaluated by flow-mediated dilation (FMD), and arterial wall properties were evaluated by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx) at 1 month and at 4 months post-acute disease. FMD was significantly improved in both the study (6.2 ± 1.8% vs. 8.6 ± 2.4%, p < 0.001) and control groups (5.9 ± 2.2% vs. 6.6 ± 1.8%, p = 0.009), but the improvement was significantly higher in the study group (rehabilitation) (p < 0.001). PWV was improved in the study group (8.2 ± 1.3 m/s vs. 6.6 ± 1.0 m/s, p < 0.001) but not in the control group (8.9 ± 1.8 m/s vs. 8.8 ± 1.9 m/s, p = 0.74). Similarly, AIx was improved in the study group (25.9 ± 9.8% vs. 21.1 ± 9.3%, p < 0.001) but not in the control group (27.6 ± 9.2% vs. 26.2 ± 9.8 m/s, p = 0.15). Convalescent COVID-19 subjects of the study group (rehabilitation) with increased serum levels of circulating IL-6 had a greater reduction in FMD. Conclusively, a 3-month cardiopulmonary post-acute COVID-19 rehabilitation program improves recovery of endothelium-dependent vasodilation and arteriosclerosis.
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.