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

Abstract

Background: Endothelial dysfunction has a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its disabling complications. We designed a case-control study to assess the alterations of endothelium-dependent flow-mediated dilation (FMD) among convalescent COVID-19 patients. Methods: COVID-19 patients referred to a Pulmonary Rehabilitation Unit within 2 months from swab test negativization were consecutively evaluated for inclusion and compared to controls matched for age, gender, and cardiovascular risk factors. Results: A total of 133 convalescent COVID-19 patients (81.2% males, mean age 61.6 years) and 133 matched controls (80.5% males, mean age 60.4 years) were included. A significantly lower FMD was documented in convalescent COVID-19 patients as compared to controls (3.2% ± 2.6 vs. 6.4% ± 4.1 p < 0.001), confirmed when stratifying the study population according to age and major clinical variables. Among cases, females exhibited significantly higher FMD values as compared to males (6.1% ± 2.9 vs. 2.5% ± 1.9, p < 0.001). Thus, no significant difference was observed between cases and controls in the subgroup analysis on females (6.1% ± 2.9 vs. 5.3% ± 3.4, p = 0.362). Among convalescent COVID-19 patients, FMD showed a direct correlation with arterial oxygen tension (rho = 0.247, p = 0.004), forced expiratory volume in 1 s (rho = 0.436, p < 0.001), forced vital capacity (rho = 0.406, p < 0.001), and diffusing capacity for carbon monoxide (rho = 0.280, p = 0.008). Overall, after adjusting for major confounders, a recent COVID-19 was a major and independent predictor of FMD values (β = −0.427, p < 0.001). Conclusions: Post-acute COVID-19 syndrome is associated with a persistent and sex-biased endothelial dysfunction, directly correlated with the severity of pulmonary impairment.

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).…”

“…The overrepresentation of women in the healthy cohort must be considered as a limitation of our study. Compared with the collective of healthy controls of Karampoor et al, the control collective used in this study showed comparable mean syndecan-1 levels (Karampoor et al 24 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32) ng/mL versus 31.6 (17.1-54.7) ng/mL in our study) [20]. Endothelial damage correlated significantly with the severity of lung dysfunction (arterial oxygen tension, forced expiratory volume in 1 s, forced vital capacity, diffusing capacity for carbon monoxide).…”

Persistent Endothelial Dysfunction in Coronavirus Disease-2019 Survivors Late After Recovery

“…Therefore, the brachial artery FMD during reactive hyperemia reflects an endothelial nitric oxide activity and is the marker of endothelial function ( 19 ). Unexpectedly, there are only few reports published on FMD measures in patients suffering from COVID-19, so far ( 11 – 15 , 20 , 21 ). Oliveira et al reported an endothelial vascular dysfunction assessed by FMD at early stage of illness in patients hospitalized for COVID-19 ( 20 ), and Ambrosino et al documented a significant improvement in FMD in patients with convalescent COVID-19 after a stay of 23 days in hospital ( 11 ).…”

Post-COVID 19 neurological syndrome: The need to define a cut-off score between the acute and post-COVID 19 phases

“…The COVID-19 pandemic is increasingly raising questions about the prognosis of underlying disease and the sequelae of COVID-19 disease, which depend on the phenotype developed by this condition. Post-COVID-19 syndrome has been defined as the persistence or de novo appearance of signs and/or symptoms which may or may not have been present during the acute phase of COVID-19, which are associated with target organ damage and affect the performance of activities of daily living [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] ]. So far, there is scarce and low-level (IV–V) evidence [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] ], which has discussed this concept and which highlights the importance of investigating the burden of disease it may cause, although there are studies that have shown that mortality and the risk of dying from multi-organ involvement after the acute phase of COVID-19, in the range of 30–90 days, is high [ [5] , [6] , [7] , [8] , [9] ].…”