Clinical Assessment of Endothelial Function in Convalescent COVID-19 Patients Undergoing Multidisciplinary Pulmonary Rehabilitation

Abstract

Background: Growing evidence points to a key role of endothelial dysfunction in the pathogenesis of COVID-19. In this study, we evaluated changes in endothelium-dependent flow-mediated dilation (FMD) in a cohort of convalescent COVID-19 patients undergoing pulmonary rehabilitation (PR). Methods: After swab test negativization, convalescent COVID-19 patients referring to a post-acute care facility for PR were consecutively screened for inclusion. Study procedures were performed at the time of hospitalization and discharge. Results: We enrolled 82 convalescent COVID-19 patients (85.4% males, mean age 60.4 years). After PR, a significant improvement in most pulmonary function tests and exercise capacity was documented. FMD changed from 2.48% ± 2.01 to 4.24% ± 2.81 (p < 0.001), corresponding to a 70.9% increase. Significantly higher changes in FMD were found in patients without a history of vascular events as compared to those with (+2.04% ± 2.30 vs. +0.61% ± 1.83, p = 0.013). Values of forced expiratory volume in 1 s (FEV1%), forced vital capacity (FVC%) and diffusion capacity for carbon monoxide (DLCO%) significantly and directly correlated with FMD both at baseline and after PR. Patients with normal FEV1% (≥80% predicted) during the overall study period or those normalizing FEV1% after PR showed a more significant FMD change as compared to patients with persistently impaired FEV1% (<80% predicted) (p for trend = 0.029). This finding was confirmed in a multivariate analysis. Conclusions: Clinically evaluated endothelial function improves after PR in convalescent COVID-19 patients. A direct and persistent association between the severity of pulmonary and vascular disease can be hypothesized. Endothelial function testing may be useful in the follow-up of convalescent COVID-19 patients.

Persistent Endothelial Dysfunction in Post-Acute COVID-19 Syndrome: A Case-Control Study

“…The literature evidence of a better prognosis and a lower incidence of CV outcomes among female COVID-19 patients is consistent with the latter result [59,60]. Finally, in line with the previous evidence of a direct and persistent correlation between the severity of pulmonary and vascular disease in this clinical setting [30], we also found that FMD values directly correlated with pulmonary function tests in our post-COVID-19 population. Of particular interest is the correlation between FMD and DLCO%, which may be justified by the functional and structural role of the endothelium within the alveolar-capillary barrier [61].…”

“…A high incidence of stroke and thromboembolic complications has been reported during the acute phase [39,40], with the risk of arrhythmic and ischemic complications [41][42][43] and subsequent hemodynamic instability [44,45]. Moreover, it has been suggested that such increased CV risk may persist during convalescence [30], as confirmed by the evidence of magnetic resonance and echocardiographic alterations [41,46] with a non-negligible incidence of venous and arterial thrombotic events [47]. However, the physiopathology of these manifestations has not been fully elucidated [48].…”

“…The COPD Assessment Test (CAT) [30] and the Barthel scale [31] were also administered to all convalescent COVID-19 patients to determine the impact of the disease on the level of functioning and activities of daily living. Exercise capacity was tested by measuring the six-minute walking distance (6MWD) [32].…”

“…Procedures for evaluating vascular reactivity parameters have been detailed elsewhere [30]. In brief, patients undergoing FMD examination were requested to abstain from food, tobacco, alcohol, and caffeine for no less than 12 h prior to the test.…”

Indications of Persistent Glycocalyx Damage in Convalescent COVID-19 Patients: A Prospective Multicenter Study and Hypothesis

“…These results demonstrate for the first time elevated SDC-1 levels as an indication of persistent impairment of glycocalyx after COVID-19 infection with mild disease progression without hospitalization. These results support the work of Ambrosino et al on hospitalized convalescent COVID-19 patients 2 months after severe or critical disease progression (WHO classification III/IV), in whom sex-dependent signs of endothelial damage were also found [24,25]. The study population, especially females, had significantly decreased endothelium-dependent flow-mediated dilation (FMD) compared with matched controls (demographics, previous disease).…”