Impaired left ventricular deformation and ventricular-arterial coupling in post-COVID-19: association with autonomic dysregulation.

Coronavirus disease-19 (COVID-19) has extended implications namely the long COVID-19 syndrome. We assessed over-time changes in left ventricular (LV) function, aortic stiffness, autonomic function, and ventricular-arterial coupling (VAC) in post-COVID-19 patients. We followed 34 post-COVID-19 subjects, up to 6 months post-hospital discharge. Subjects without COVID-19 served as control. We evaluated LV global longitudinal strain (LV-GLS), arterial stiffness [carotid-femoral pulse wave velocity (cf-PWV)], and heart rate variability -standard deviation of normal RR intervals (SDNN). VAC was estimated as the ratio of cf-PWV to LV-GLS. Post-COVID-19 individuals (1-month post-hospital discharge) presented with impaired LV-GLS [-18.4%(3.1) vs. -22.0%(2.7), P < 0.001], cf-PWV [12.1 m/s (3.2) vs. 9.6 m/s (1.9), P < 0.001], SDNN [111.3 ms (22.6) vs. 147.2 ms (14.0), P < 0.001], and VAC [-0.68 (0.22) vs. -0.44 (0.10), P < 0.001] compared to control. LV-GLS, SDNN, and VAC improved at the 6-month follow-up however they did not reach control levels. In post-COVID-19 subjects, SDNN and VAC were correlated at the 1-month (R = 0.499, P = 0.003) and 6-month (R = 0.372, P = 0.04) follow-up. Long COVID-19 syndrome was associated with impaired LV-GLS, SDNN, and VAC. Post-COVID-19 subjects presented with autonomic dysregulation associated with aortic stiffness, ventricular-arterial impairment, and LV dysfunction, even 6-months post-hospital discharge. These abnormalities may be related to the presence of long COVID-19 syndrome.

Endothelial dysfunction in acute and long standing COVID-19: A prospective cohort study.

BACKGROUND: Coronavirus disease-19 (COVID-19) is implicated by active endotheliitis, and cardiovascular morbidity. The long-COVID-19 syndrome implications in atherosclerosis have not been elucidated yet. We assessed the immediate, intermediate, and long-term effects of COVID-19 on endothelial function. METHODS: In this prospective cohort study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled and followed up to 6 months post-hospital discharge. Medical history and laboratory examinations were performed while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Comparison with propensity score-matched cohort (control group) was performed at the acute (upon hospital admission) and follow-up (1 and 6 months) stages. RESULTS: Seventy-three patients diagnosed with COVID-19 (37% admitted in ICU) were recruited. FMD was significantly (p < 0.001) impaired in the COVID-19 group (1.65 ± 2.31%) compared to the control (6.51 ± 2.91%). ICU-treated subjects presented significantly impaired (p = 0.001) FMD (0.48 ± 1.01%) compared to those treated in the medical ward (2.33 ± 2.57%). During hospitalization, FMD was inversely associated with Interleukin-6 and Troponin I (p < 0.05 for all). Although, a significant improvement in FMD was noted during the follow-up (acute: 1.75 ± 2.19% vs. 1 month: 4.23 ± 2.02%, vs. 6 months: 5.24 ± 1.62%; p = 0.001), FMD remained impaired compared to control (6.48 ± 3.08%) at 1 month (p < 0.001) and 6 months (p = 0.01) post-hospital discharge. CONCLUSION: COVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.

Vaccination Against SARS-CoV-2 Protects from COVID-19-induced Endothelial Dysfunction.

BACKGROUND: Coronavirus Disease-19 (COVID-19) is implicated in endotheliitis, which adversely affects cardiovascular events. The impact of vaccination with COVID-19 on the clinical outcome of patients is documented. OBJECTIVE: To evaluate the impact of vaccination with COVID-19 on the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection-related endothelial impairment. METHODS: We enrolled 45 patients hospitalized for COVID-19 (either vaccinated or not against SARS-CoV-2). Clinical and laboratory data were collected, and brachial artery flow-mediated dilation (FMD) was evaluated. Subjects without COVID-19 were used as the control group. RESULTS: There was no difference in age (64.7 ± 7.5 years vs. 61.2 ± 11.1 years vs. 62.4 ± 9.5, p = 0.28), male sex (49% vs. 60% vs. 52%, p = 0.71), control subjects, vaccinated, and unvaccinated subjects with COVID-19, respectively. Of the patients with COVID-19, 44% were vaccinated against SARS-CoV-2. Unvaccinated COVID-19 patients had significantly impaired FMD compared to vaccinated COVID-19 patients and Control subjects (2.05 ± 2.41 % vs. 7.24 ± 2.52% vs. 7.36 ± 2.94 %, p <0.001). Importantly, post hoc tests revealed that unvaccinated COVID-19 patients had significantly impaired FMD from both Vaccinated COVID-19 subjects (p <0.001) and from Control subjects (p <0.001). There was no difference in FMD between the control group and the vaccinated COVID-19 group (p = 0.99). CONCLUSION: Hospitalized patients with COVID-19 present endothelial dysfunction in the acute phase of the disease. Endothelial function in unvaccinated patients with COVID-19 is impaired compared to control subjects as well compared to vaccinated patients with COVID-19. Vaccinated hospitalized subjects with COVID-19 do not show endothelial dysfunction, strengthening the protective role of vaccination against SARS-CoV-2.

The Role of Endothelial Related Circulating Biomarkers in COVID-19. A Systematic Review and Meta-analysis.

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.