The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated a worldwide emergency, until the declaration of the pandemic in March 2020. SARS-CoV-2 could be responsible for coronavirus disease 2019 (COVID-19), which goes from a flu-like illness to a potentially fatal condition that needs intensive care. Furthermore, the persistence of functional disability and long-term cardiovascular sequelae in COVID-19 survivors suggests that convalescent patients may suffer from post-acute COVID-19 syndrome, requiring long-term care and personalized rehabilitation. However, the pathophysiology of acute and post-acute manifestations of COVID-19 is still under study, as a better comprehension of these mechanisms would ensure more effective personalized therapies. To date, mounting evidence suggests a crucial endothelial contribution to the clinical manifestations of COVID-19, as endothelial cells appear to be a direct or indirect preferential target of the virus. Thus, the dysregulation of many of the homeostatic pathways of the endothelium has emerged as a hallmark of severity in COVID-19. The aim of this review is to summarize the pathophysiology of endothelial dysfunction in COVID-19, with a focus on personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction as an attractive therapeutic option in this clinical setting.

Background: Endothelial dysfunction has been proposed as the common pathogenic background of most manifestations of coronavirus disease 2019 (COVID-19). Among these, some authors also reported an impaired exercise response during cardiopulmonary exercise testing (CPET). We aimed to explore the potential association between endothelial dysfunction and the reduced CPET performance in COVID-19 survivors. Methods: 36 consecutive COVID-19 survivors underwent symptom-limited incremental CPET and assessment of endothelium-dependent flow-mediate dilation (FMD) according to standardized protocols. Results: A significantly higher FMD was documented in patients with a preserved, as compared to those with a reduced, exercise capacity (4.11% ± 2.08 vs. 2.54% ± 1.85, p = 0.048), confirmed in a multivariate analysis (β = 0.899, p = 0.038). In the overall study population, FMD values showed a significant Pearson’s correlation with two primary CPET parameters, namely ventilation/carbon dioxide production (VE/VCO2) slope (r = −0.371, p = 0.026) and end-tidal carbon dioxide tension (PETCO2) at peak (r = 0.439, p = 0.007). In multiple linear regressions, FMD was the only independent predictor of VE/VCO2 slope (β = −1.308, p = 0.029) and peak PETCO2 values (β = 0.779, p = 0.021). Accordingly, when stratifying our study population based on their ventilatory efficiency, patients with a ventilatory class III-IV (VE/VCO2 slope ≥ 36) exhibited significantly lower FMD values as compared to those with a ventilatory class I-II. Conclusions: The alteration of endothelial barrier properties in systemic and pulmonary circulation may represent a key pathogenic mechanism of the reduced CPET performance in COVID-19 survivors. Personalized pharmacological and rehabilitation strategies targeting endothelial function may represent an attractive therapeutic option.

Background: Fractional exhaled nitric oxide (FeNO) measurement is a simple and non‐invasive method for monitoring eosinophilic airway inflammation. New portable analyzers for FeNO measurements are constantly being developed. The aim of our study was to evaluate the agreement of FeNO values measured by new portable analyzers. Materials and methods: FeNO was measured in 20 healthy subjects, 20 asthmatic and 20 chronic obstructive pulmonary disease patients using the analyzers Niox-VERO, Vivatmo-PRO and HypAir-FeNO. A linear relationship was estimated with Pearson’s coefficient (r), and absolute agreement by the intraclass correlation coefficient (ICC) and bias with the limits of agreement (95% of paired differences) were assessed according to the Bland–Altman method. Results: In the study population (58 ± 14 years, 20 females), mean values of FeNO with their 95% confidence interval were 24.0 (18.6–29.4) with the Niox-VERO, 19.6 (13.6–25.7) with the Vivatmo-PRO and 20.4 (15.7–25.1) with the HypAir-FeNO. FeNO measured with the Niox-VERO was higher than the Vivatmo-PRO (mean difference of paired values +4.3; limits −16.0 to 25.7 ppb) and the HypAir-FeNO (+3.6; −12.2 to 19.4 ppb); the Vivatmo-PRO and HypAir-FeNO showed large variability of paired differences (−0.7; −16.5 to 15.0 ppb). Measurements linearly correlated with an imperfect absolute agreement: Niox-VERO versus Vivatmo-PRO r = 0.90 and ICC = 0.87; Niox-VERO versus HypAir-FeNO r = 0.93 and ICC = 0.90, Vivatmo-PRO versus HypAir-FeNO r = 0.96 and ICC = 0.93. Most of the disagreement was greater in some asthmatic patients at high values of FeNO. Conclusions: The present study indicates that absolute exhaled NO measurements may differ to a clinically relevant extent using the Niox-VERO, Vivatmo-PRO and HypAir-FeNO analyzers. The devices cannot be used interchangeably.

Chronic obstructive pulmonary disease (COPD) is characterized by respiratory symptoms and non-reversible airflow limitation with recurrent episodes of acute exacerbations. The concurrent presence of bronchiectasis in patients with COPD is associated with reduced respiratory function as well as increased exacerbation risk. Adiponectin is a promising biomarker in COPD, as greater high molecular weight (HMW) oligomer levels have been observed among COPD patients. Here, we investigate adiponectin levels in two groups of COPD patients characterized by the presence or absence of bronchiectasis (BCO), comparing both groups to healthy controls. We evaluated serum adiponectin levels in COPD patients, those with BCO, and healthy subjects and characterized the pattern of circulating adiponectin oligomers. We found that forced volume capacity % (FVC%) and forced expiratory volume % (FEV1%) were lower for BCO patients than for COPD patients. COPD patients had higher levels of adiponectin and its HMW oligomers than healthy controls. Interestingly, BCO patients had higher levels of adiponectin than COPD patients. We showed that expression levels of IL-2, -4, and -8, IFN-γ, and GM-CSF were significantly higher in BCO patients than in healthy controls. Conversely, IL-10 expression levels were lower in BCO patients. Our data suggest that the increased levels of adiponectin detected in the cohort of BCO patients compared to those in COPD patients without bronchiectasis might be determined by their worse airway inflammatory state. This hypothesis suggests that adiponectin could be considered as a biomarker to recognize advanced COPD patients with bronchiectasis.

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