Nitric oxide-mediated cutaneous microvascular function is not altered in middle-aged-to-older adults following mild SARS-CoV-2 infection: A pilot study.

We tested the hypothesis that post-COVID-19 adults (PC) would have impaired cutaneous nitric oxide (NO)-mediated vasodilation compared to controls (CON). We performed a cross-sectional study including 10 (10 F/0 M, 69 ± 7 years) CON and 7 (2 F/5 M, 66 ± 8 years) PC (223 ± 154 days post-diagnosis). COVID-19 symptoms severity (survey) was assessed (0-100 scale for 18 common symptoms). NO-dependent cutaneous vasodilation was induced by a standardized 42°C local heating protocol and quantified via perfusion of 15 mM NG-nitro-L-arginine methyl ester during the plateau of the heating response (intradermal microdialysis). Red blood cell flux was measured with laser-Doppler flowmetry. Cutaneous vascular conductance (CVC = flux/mm Hg) was presented as a percentage of maximum (28 mM sodium nitroprusside +43°C). All data are means ± SD. The local heating plateau (CON: 71 ± 23% CVCmax vs. PC: 81 ± 16% CVCmax , p = 0.77) and NO-dependent vasodilation (CON: 56 ± 23% vs. PC: 60 ± 22%, p = 0.77) were not different between groups. In the PC group neither time since diagnosis nor peak symptom severity (46 ± 18 AU) correlated with NO-dependent vasodilation (r < 0.01, p = 0.99 and r = 0.42, p = 0.35, respectively). In conclusion, middle-aged and older adults who have had COVID-19 did not have impaired NO-dependent cutaneous vasodilation. Additionally, in this cohort of PC, neither time since diagnosis nor symptomology were related to microvascular function.

Impaired ß 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019.

AIM: The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown. METHODS: Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample. RESULTS: One hundred and one participants (60 men) aged 47.8 ±â€Š14.1 (mean ±â€ŠSD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n  = 34) and those recovered from mild symptoms of COVID-19 ( n  = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P  = 0.001). In a sub-sample ( n  = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P  = 0.006) with no significant difference between hospitalized ( n  = 12) and nonhospitalized participants ( n  = 10). CONCLUSIONS: In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

Endothelial glycocalyx in hepatopulmonary syndrome: An indispensable player mediating vascular changes.

Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes respiratory insufficiency in patients with chronic liver diseases. HPS is characterized by two central pathogenic features-intrapulmonary vascular dilatation (IPVD) and angiogenesis. Endothelial glycocalyx (eGCX) is a gel-like layer covering the luminal surface of blood vessels which is involved in a variety of physiological and pathophysiological processes including controlling vascular tone and angiogenesis. In terms of lung disorders, it has been well established that eGCX contributes to dysregulated vascular contraction and impaired blood-gas barrier and fluid clearance, and thus might underlie the pathogenesis of HPS. Additionally, pharmacological interventions targeting eGCX are dramatically on the rise. In this review, we aim to elucidate the potential role of eGCX in IPVD and angiogenesis and describe the possible degradation-reconstitution equilibrium of eGCX during HPS through a highlight of recent literature. These studies strongly underscore the therapeutic rationale in targeting eGCX for the treatment of HPS.

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.

Tracking peripheral vascular function for six months in young adults following SARS-CoV-2 infection.

SARS-CoV-2 infection is known to instigate a range of physiologic perturbations, including vascular dysfunction. However, little work has concluded how long these effects may last, especially among young adults with mild symptoms. To determine potential recovery from acute vascular dysfunction in young adults (8 M/8F, 21 ± 1 yr, 23.5 ± 3.1 kg⋅m-2 ), we longitudinally tracked brachial artery flow-mediated dilation (FMD) and reactive hyperemia (RH) in the arm and hyperemic response to passive limb movement (PLM) in the leg, with Doppler ultrasound, as well as circulating biomarkers of inflammation (interleukin-6, C-reactive protein), oxidative stress (thiobarbituric acid reactive substances, protein carbonyl), antioxidant capacity (superoxide dismutase), and nitric oxide bioavailability (nitrite) monthly for a 6-month period post-SARS-CoV-2 infection. FMD, as a marker of macrovascular function, improved from month 1 (3.06 ± 1.39%) to month 6 (6.60 ± 2.07%; p < 0.001). FMD/Shear improved from month one (0.10 ± 0.06 AU) to month six (0.18 ± 0.70 AU; p = 0.002). RH in the arm and PLM in the leg, as markers of microvascular function, did not change during the 6 months (p > 0.05). Circulating markers of inflammation, oxidative stress, antioxidant capacity, and nitric oxide bioavailability did not change during the 6 months (p > 0.05). Together, these results suggest some improvements in macrovascular, but not microvascular function, over 6 months following SARS-CoV-2 infection. The data also suggest persistent ramifications for cardiovascular health among those recovering from mild illness and among young, otherwise healthy adults with SARS-CoV-2.

Post COVID-19 syndrome with impairment of flow-mediated epicardial vasodilation and flow reserve.

AIMS: The aim of this study is to evaluate whether post-acute sequelae of COVID-19 cardiovascular syndrome (PASC-CVS) is associated with alterations in coronary circulatory function. MATERIALS AND METHODS: In individuals with PASC-CVS but without known cardiovascular risk factors (n = 23) and in healthy controls (CON, n = 23), myocardial blood flow (MBF) was assessed with 13 N-ammonia and PET/CT in mL/g/min during regadenoson-stimulated hyperemia, at rest, and the global myocardial flow reserve (MFR) was calculated. MBF was also measured in the mid and mid-distal myocardium of the left ventricle (LV). The Δ longitudinal MBF gradient (hyperemia minus rest) as a reflection of an impairment of flow-mediated epicardial vasodilation, was calculated. RESULTS: Resting MBF was significantly higher in PASC-CVS than in CON (1.29 ± 0.27 vs. 1.08 ± 0.20 ml/g/min, p ≤ .024), while hyperemic MBFs did not differ significantly among groups (2.46 ± 0.53 and 2.40 ± 0.34 ml/g/min, p = .621). The MFR was significantly less in PASC-CVS than in CON (1.97 ± 0.54 vs. 2.27 ± 0.43, p ≤ .031). In addition, there was a Δ longitudinal MBF gradient in PASC-CVS, not observed in CON (-0.17 ± 0.18 vs. 0.04 ± 0.11 ml/g/min, p < .0001). CONCLUSIONS: Post-acute sequelae of COVID-19 cardiovascular syndrome may be associated with an impairment of flow-mediated epicardial vasodilation, while reductions in coronary vasodilator capacity appear predominantly related to increases in resting flow in women deserving further investigations.

Lower brachial artery flow-mediated dilation is associated with a worse prognosis and more lung parenchymal involvement in Covid-19: Prospective observational study.

Severe acute respiratory syndrome coronavirus-2 is a highly infectious pathogenic coronavirus, which has appeared toward the end of 2019. The virus seen all over the world caused a pandemic of an acute respiratory disease named coronavirus disease 2019 (Covid-19). It has been shown that the virus that uses angiotensin-converting enzyme 2 receptors is causing endothelial dysfunction resulting in vascular inflammation and coagulopathy. It is possible to assess endothelial dysfunction by the flow-mediated dilatation (FMD) technique. Our study aimed to demonstrate the effect of endothelial dysfunction assessed using the FMD on prognosis and mortality in the patients hospitalized with the diagnosis of Covid-19. In this prospective observational study, endothelial functions of 94 patients hospitalized due to the Covid-19 in the ward or intensive care unit (ICU) were evaluated by FMD. The relationship among endothelial dysfunction and prognosis of disease, biochemical parameters, lung involvement, and mortality was investigated. We found that the FMD% values of the Covid-19 ICU patients compared to those followed up in the ward (2.66 ± 0.62 vs. 5.23 ± 1.46/P < .001) and those who died due to Covid-19 compared to those who were discharged alive (2.57 ± 0.22 vs. 4.66 ± 1.7/P < .001) were significantly lower. There were moderate negative correlation between FMD% and peak values of D-dimer (r = -0.52, P < .001), troponin (r = -0.45, P < .001), ferritin (r = -0.47, P < .001), lactate dehydrogenase (r = -0.49, P < .001), and white blood cells count (r = -0.23, P = .024). Lower FMD% was associated with higher lung parenchymal involvement (P < .001). The optimum cutoff point of FMD in predicting mortality was found to be 3.135% (sensitivity: 1, selectivity: 0.70). According to our results, lower FMD% was associated with higher lung parenchyma involvement, ICU admission, and mortality rate in Covid-19 patients. The best cutoff point for predicting mortality of FMD was 3.135%. Nevertheless, largescale, multicenter studies are needed to evaluate lower FMD values as a risk factor for mortality in Covid-19.

Evaluation of Endothelial Dysfunction in COVID-19 With Flow-Mediated Dilatation. / Avaliação da Disfunção Endotelial em Casos de COVID-19 com Dilatação Fluxo-Mediada.

BACKGROUND: Inflammation is known to play a crucial role in many diseases, including COVID-19. OBJECTIVE: Using flow-mediated dilatation (FMD), we aimed to assess the effects of inflammation on endothelial function in COVID-19 patients. METHODS: This study was conducted with a total of 161 subjects, of whom 80 were diagnosed with COVID-19 within the last six months (comprising 48 women and 32 men with a mean age of 32.10 ± 5.87 years) and 81 were healthy controls (comprising 45 women and 36 men with a mean age of 30.51 ± 7.33 years). We analyzed the findings of transthoracic echocardiography and FMD in all subjects. All results were considered statistically significant at the level of p < 0.05. RESULTS: The echocardiography and FMD of the COVID-19 group were performed 35 days (range: 25-178) after diagnosis. There was no statistically significant difference in echocardiographic parameters. Differently, FMD (%) was significantly higher in the control group (9.52 ± 5.98 vs. 12.01 ± 6.18, p=0.01). In multivariate analysis with the forward stepwise model, FMD was significantly different in the control group compared to the COVID-19 group (1.086 (1.026 - 1.149), p=0.04). A Spearman's correlation test indicated that FMD (r=0.27, p=0.006) had a weak positive correlation with the presence of COVID-19. CONCLUSION: Our findings point to COVID-19-induced endothelial dysfunction, as assessed by FMD, in the early recovery phase.

FUNDAMENTO: Sabe-se que a inflamação desempenha um papel crucial em muitas doenças, incluindo a COVID-19. OBJETIVO: Utilizando a dilatação fluxo-mediada (DFM), objetivou-se avaliar os efeitos da inflamação na função endotelial de pacientes com COVID-19. MÉTODOS: Este estudo foi realizado com um total de 161 indivíduos, dos quais 80 foram diagnosticados com COVID-19 nos últimos seis meses (48 mulheres e 32 homens com idade média de 32,10±5,87 anos) e 81 eram controles saudáveis (45 mulheres e 36 homens com idade média de 30,51±7,33 anos). Os achados do ecocardiograma transtorácico e da DFM foram analisados em todos os indivíduos. Resultados com p<0,05 foram considerados estatisticamente significantes. RESULTADOS: O ecocardiograma e a DFM do grupo COVID-19 foram realizados 35 dias (intervalo: 25­178) após o diagnóstico. Não houve diferença estatisticamente significativa nos parâmetros ecocardiográficos. Em contraste, a DFM (%) foi significativamente maior no grupo controle (9,52±5,98 versus 12,01±6,18; p=0,01). Na análise multivariada com o modelo stepwise progressivo, a DFM foi significativamente diferente no grupo controle em relação ao grupo COVID-19 (1,086 (1,026­1,149), p=0,04). O teste de correlação de Spearman indicou que a DFM (r=0,27; p=0,006) apresentou correlação positiva fraca com a presença de COVID-19. CONCLUSÃO: Os achados deste estudo apontam para disfunção endotelial induzida por COVID-19, avaliada por DFM, na fase inicial de recuperação.

Carotid intima-media thickness and flow-mediated dilation do not predict acute in-hospital outcomes in patients hospitalized with COVID-19.

Studies have suggested a potential role of endothelial dysfunction and atherosclerosis in the pathophysiology of COVID-19. Herein, we tested whether brachial flow-mediated dilation (FMD) and carotid intima-media thickness (cIMT) measured upon hospital admission are associated with acute in-hospital outcomes in patients hospitalized with COVID-19. A total of 211 patients hospitalized with COVID-19 were submitted to assessments of FMD and mean and maximum cIMT (cIMTmean and cIMTmax) within the first 72 h of hospital admission. Study primary outcome was a composite of intensive care unit admission, mechanical ventilation, or death during the hospitalization. These outcomes were also considered independently. Thrombotic events were included as a secondary outcome. Odds ratios (ORs) and confidence intervals (CIs) were calculated using unadjusted and adjusted multivariable logistic regression models. Eighty-eight (42%) participants demonstrated at least one of the composite outcomes. cIMTmean and cIMTmax were predictors of mortality and thrombotic events in the univariate analysis (cIMTmean and mortality: unadjusted OR 12.71 [95% CI 1.71-94.48]; P = 0.014; cIMTmean and thrombotic events: unadjusted OR 11.94 [95% CI 1.64-86.79]; P = 0.015; cIMTmax and mortality: unadjusted OR 8.47 [95% CI 1.41-51.05]; P = 0.021; cIMTmax and thrombotic events: unadjusted OR 12.19 [95% CI 2.03-73.09]; P = 0.007). However, these associations were no longer present after adjustment for potential confounders (P > 0.05). In addition, FMD% was not associated with any outcome. In conclusion, cIMT and FMD are not independent predictors of clinical outcomes in patients hospitalized with COVID-19. These results suggest that subclinical atherosclerosis and endothelial dysfunction may not be the main drivers of COVID-19 complications in patients hospitalized with COVID-19.NEW & NOTEWORTHY Studies have suggested a role of endothelial dysfunction and atherosclerosis in COVID-19 pathophysiology. In this prospective cohort study, we assessed the prognostic value of carotid intima-media thickness (IMT) and flow-mediated dilation (FMD) in patients with COVID-19. Carotid IMT and FMD were not independent predictors of major outcomes. These results suggest that other risk factors may be the main drivers of clinical outcomes in patients with COVID-19.

Nitric oxide-mediated cutaneous microvascular function is not altered in young adults following mild-to-moderate SARS CoV-2 infection.

Vascular dysfunction has been reported in adults who have recovered from COVID-19. To date, no studies have investigated the underlying mechanisms of persistent COVID-19-associated vascular dysfunction. Our purpose was to quantify nitric oxide (NO)-mediated vasodilation in healthy adults who have recovered from SARS-CoV-2 infection. We hypothesized that COVID-19-recovered adults would have impaired NO-mediated vasodilation compared with adults who have not had COVID-19. In methods, we performed a cross-sectional study including 10 (5 men/5 women, 24 ± 4 yr) healthy control (HC) adults who were unvaccinated for COVID-19, 11 (4 men/7 women, 25 ± 6 yr) healthy vaccinated (HV) adults, and 12 (5 men/7 women, 22 ± 3 yr) post-COVID-19 (PC, 19 ± 14 wk) adults. COVID-19 symptoms severity (survey) was assessed. A standardized 39°C local heating protocol was used to assess NO-dependent vasodilation via perfusion (intradermal microdialysis) of 15 mM NG-nitro-l-arginine methyl ester during the plateau of the heating response. Red blood cell flux was measured (laser-Doppler flowmetry) and cutaneous vascular conductance (CVC = flux/mmHg) was expressed as a percentage of maximum (28 mM sodium nitroprusside + 43°C). In results, the local heating plateau (HC: 61 ± 20%, HV: 60 ± 19%, PC: 67 ± 19%, P = 0.80) and NO-dependent vasodilation (HC: 77 ± 9%, HV: 71 ± 7%, PC: 70 ± 10%, P = 0.36) were not different among groups. Neither symptom severity (25 ± 12 AU) nor time since diagnosis correlated with the NO-dependent vasodilation (r = 0.46, P = 0.13; r = 0.41, P = 0.19, respectively). In conclusion, healthy adults who have had mild-to-moderate COVID-19 do not have altered NO-mediated cutaneous microvascular function.NEW & NOTEWORTHY Healthy young adults who have had mild-to-moderate COVID-19 do not display alterations in nitric oxide-mediated cutaneous microvascular function. In addition, healthy young adults who have COVID-19 antibodies from the COVID-19 vaccinations do not display alterations in nitric oxide-mediated cutaneous microvascular function.

Determinants of endothelial dysfunction in noncritically ill hospitalized COVID-19 patients: A cross-sectional study.

OBJECTIVE: The aim of this study was to identify determinants of endothelial dysfunction in patients hospitalized with acute COVID-19. METHODS: A total of 109 hospitalized COVID-19 patients in noncritical status were cross-sectionally studied. Clinical data (age, sex, comorbidities, and medications) and BMI were assessed. Laboratory tests included serum hemoglobin, leukocytes, lymphocytes, platelets, C-reactive protein, ferritin, D-dimer, and creatinine. Physical status was evaluated using a handgrip dynamometer. Endothelial function was assessed noninvasively using the flow-mediated dilation (FMD) method. RESULTS: The sample average age was 51 years, 51% of patients were male, and the most frequent comorbidity was obesity (62%). Univariate analysis showed association of lower FMD with higher BMI, hypertension, use of oral antihypertensive, higher blood levels of creatinine, and larger baseline artery diameter. After adjusting for confounders, the multivariate analysis showed BMI (95% CI: -0.26 to -0.11; p < 0.001) as the major factor associated with FMD. Other factors associated with FMD were baseline artery diameter (95% CI: -1.77 to -0.29; p = 0.007) and blood levels of creatinine (95% CI: -1.99 to -0.16; p = 0.022). CONCLUSIONS: Increased BMI was the major factor associated with endothelial dysfunction in noncritically hospitalized COVID-19 patients. This may explain one of the pathways in which obesity may increase the risk for severe COVID-19.

PostCOVID effect on endothelial function in hypertensive patients: A new research opportunity.

SARS-CoV-2 is causing devastation both in human lives and economic resources. When the world seems to start overcoming the pandemics scourge, the threat of long-term complications of COVID-19 is rising. Reports show that some of these long-term effects may contribute to the main cause of morbimortality worldwide: the vascular diseases. Given the evidence of damage in the endothelial cells due to SARS-CoV-2 and that endothelial dysfunction precedes the development of arteriosclerosis, the authors propose to measure endothelial function around 6-12 months after acute disease in hypertensive patients, especially if they have other cardiovascular risk factors or overt vascular disease. The methods the authors propose are cost-effective and can be made available to any hypertension unit. These methods could be the "in vivo" assessment of endothelial function by flow mediated vasodilatation after ischemia by Laser-Doppler flowmetry and the measurement of plasma free circulating DNA and microparticles of endothelial origin.

Vascular alterations among young adults with SARS-CoV-2.

While SARS-CoV-2 primarily affects the lungs, the virus may be inflicting detriments to the cardiovascular system, both directly through angiotensin-converting enzyme 2 receptor and initiating systemic inflammation. Persistent systemic inflammation may be provoking vascular dysfunction, an early indication of cardiovascular disease risk. To establish the potential effects of SARS-CoV-2 on the systemic vasculature in the arms and legs, we performed a cross-sectional analysis of young healthy adults (control: 5 M/15 F, 23.0 ± 1.3 y, 167 ± 9 cm, 63.0 ± 7.4 kg) and young adults who, 3-4 wk prior to testing, had tested positive for SARS-CoV-2 (SARS-CoV-2: 4 M/7 F, 20.2 ± 1.1 y, 172 ± 12 cm, 69.5 ± 12.4 kg) (means ± SD). Using Doppler ultrasound, brachial artery flow-mediated dilation (FMD) in the arm and single passive limb movement (sPLM) in the leg were assessed as markers of vascular function. Carotid-femoral pulse wave velocity (PWVcf) was asvsessed as a marker of arterial stiffness. FMD was lower in the SARS-CoV-2 group (2.71 ± 1.21%) compared with the control group (8.81 ± 2.96%) (P < 0.01) and when made relative to the shear stimulus (SARS-CoV-2: 0.04 ± 0.02 AU, control: 0.13 ± 0.06 AU, P < 0.01). The femoral artery blood flow response, as evidenced by the area under the curve, from the sPLM was lower in the SARS-CoV-2 group (-3 ± 91 mL) compared with the control group (118 ± 114 mL) (P < 0.01). PWVcf was higher in the SARS-CoV-2 group (5.83 ± 0.62 m/s) compared with the control group (5.17 ± 0.66 m/s) (P < 0.01). Significantly lower systemic vascular function and higher arterial stiffness are evident weeks after testing positive for SARS-CoV-2 among young adults compared with controls.NEW & NOTEWORTHY This study was the first to investigate the vascular implications of contracting SARS-CoV-2 among young, otherwise healthy adults. Using a cross-sectional design, this study assessed vascular function 3-4 wk after young adults tested positive for SARS-CoV-2. The main findings from this study were a strikingly lower vascular function and a higher arterial stiffness compared with healthy controls. Together, these results suggest rampant vascular effects seen weeks after contracting SARS-CoV-2 in young adults.

Blunted peripheral but not cerebral vasodilator function in young otherwise healthy adults with persistent symptoms following COVID-19.

Recent findings suggest that COVID-19 causes vascular dysfunction during the acute phase of the illness in otherwise healthy young adults. To date, to our knowledge, no studies have investigated the longer-term effects of COVID-19 on vascular function. Herein, we hypothesized that young, otherwise healthy adults who are past the acute phase of COVID-19 would exhibit blunted peripheral [brachial artery flow-mediated dilation (FMD) and reactive hyperemia] and cerebral vasodilator function (cerebral vasomotor reactivity to hypercapnia; CVMR) and increased central arterial stiffness. Sixteen young adults who were at least 4 wk past a COVID-19 diagnosis and 12 controls who never had COVID-19 were studied. Eight subjects with COVID-19 were symptomatic (SYM) and eight were asymptomatic (ASYM) at the time of testing. FMD and reactive hyperemia were not different between COVID and control groups. However, FMD was lower in SYM (3.8 ± 0.6%) compared with ASYM (6.8 ± 0.9%; P = 0.007) and control (6.8 ± 0.6%; P = 0.003) with no difference between ASYM and control. Similarly, peak blood velocity following cuff release was lower in SYM (47 ± 8 cm/s) compared with ASYM (64 ± 19 cm/s; P = 0.025) and control (61 ± 14 cm/s; P = 0.036). CVMR and arterial stiffness were not different between any groups. In summary, peripheral macrovascular and microvascular function, but not cerebral vascular function or central arterial stiffness were blunted in young adults symptomatic beyond the acute phase of COVID-19. In contrast, those who were asymptomatic had similar vascular function compared with controls who never had COVID-19.NEW & NOTEWORTHY This study was the first to investigate the persistent effects of COVID-19 on vascular function in otherwise healthy young adults. We demonstrated that peripheral macrovascular and microvascular vasodilation was significantly blunted in young adults still symptomatic from COVID-19 beyond the acute phase (>4 wk from diagnosis), whereas those who become asymptomatic have similar vascular function compared with controls who never had COVID-19. In contrast, cerebral vascular function and central arterial stiffness were unaffected irrespective of COVID-19 symptomology.

COVID 19 disease independently predicted endothelial dysfunction measured by flow-mediated dilatation.

The systemic effects of COVID-19 disease are still largely uncertain and needs to be scrutinized with further trials. Endothelial dysfunction (ED) is responsible for the majority of adverse cardiovascular events. Flow-mediated dilation (FMD) is easily obtainable method to assess ED accurately. It is aimed to evaluate ED by measuring FMD following COVID-19 disease. Patients diagnosed with COVID-19 disease were recruited to the hospital two month after the discharge. Sex and age-matched healthy subjects were determined as the control group. Blood samples and FMD measurements were obtained from each participant. All subjects were divided into two groups according to the presence of ED determined by FMD measurements. These two groups were compared in terms of demographic features and the presence of recovered COVID-19 disease. A total of 92 subjects consisting of 59 without ED and 33 with ED were included in the study. ED (+) group was older (p = 0.015) and more likely to have hypertension (p = 0.044) and COVID-19 rate was higher in ED (+) group (p = 0.009). While neutrophil count (p = 0.047) and CRP (p = 0.036) were higher, eGFR (p = 0.044) was lower in ED (+) group. In the backward multivariable regression analysis, COVID-19 disease [OR = 3.611, 95% CI 1.069-12.198, p = 0.039] and BMI [OR = 1.122, 95% CI 1.023-1.231, p = 0.015] were independent predictors of ED. COVID-19 disease may cause ED which is the major underlying factor of cardiovascular diseases. Furthermore, COVID-19 disease may deteriorate the existing cardiovascular disease course. Detecting ED in the early phase or preventing by new treatment modalities may improve short and long-term outcome.

Endothelial function provides early prognostic information in patients with COVID-19: A cohort study.

BACKGROUND: The prothrombotic phenotype and diffuse intravascular coagulation observed in COVID-19 reflect endothelial dysfunction, which is linked to blood flow delivery deficiencies and cardiovascular risk. Assessments of detect vascular deficiencies among newly diagnosed and hospitalized patients due to COVID-19 have yet to be determined. OBJECTIVE: To assess endothelial function characteristics in relation to length of hospitalization and mortality in patients diagnosed with COVID-19 and compare to patients without COVID-19. METHODS: A prospective observational study involving 180 patients with confirmed COVID-19 (COVID-19 group) or suspected and ruled out COVID-19 (Non-COVID-19 group). Clinical evaluation and flow mediated vasodilation (FMD) were performed between the first 24-48 h of hospitalization. Patients were followed until death or discharge. RESULTS: We evaluated 98 patients (COVID-19 group) and 82 (Non-COVID-19 group), COVID-19 group remained hospitalized longer and more deaths occurred compared to the Non-COVID-19 group (p = 0.01; and p < 0.01). Patients in COVID-19 group also had a significantly greater reduction in both FMDmm and FMD% (p < 0.01 in both). We found that absolute FMD≤0.26 mm and relative FMD≤3.43% were the ideal cutoff point to predict mortality and longer hospital stay. In Kaplan Meyer's analysis patients had a high probability of death within a period of up to 10 days of hospitalization. CONCLUSION: Patients hospitalized for COVID-19 present endothelial vascular dysfunction early, remained hospitalized longer and had a higher number of deaths, when compared with patients without COVID-19.

Microvascular Dysfunction in Patients with Critical Covid-19, a Pilot Study.

BACKGROUND: Endothelial and microvascular dysfunction may be a key pathogenic feature of severe COVID-19. The aim of this study was to investigate endothelial-dependent and endothelial-independent skin microvascular reactivity in patients with critical COVID-19. METHODS: Twelve patients with COVID-19 treated with non-invasive or invasive mechanical ventilation were included in the study. We investigated skin microvascular reactivity on 2 separate days during hospitalization (study day 1 and 2) and at least 3 months after disease onset (study day 3). Twelve controls with no confirmed or suspected COVID-19 infection during 2020 were also examined. Skin perfusion was investigated through Laser Speckle Contrast Imaging before and after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to determine the endothelial-dependent and the endothelial-independent vasodilation, respectively. RESULTS: Compared to controls, patients with critical COVID-19 had higher basal skin perfusion and reduced responses to endothelial-dependent (ACh, P = 0.002) and endothelial-independent (SNP, P = 0.01) vasodilator drugs on study day 1. In addition, the ACh/SNP ratio was significantly reduced in patients (0.50 ±â€Š0.36 vs. 0.91 ±â€Š0.49 in controls, P = 0.02). Three months after disease onset, surviving patients tended to have reduced ACh-mediated vasodilation compared to controls (P = 0.08). CONCLUSIONS: This small-sized pilot study demonstrates that critical COVID-19 infection is associated with microvascular impairment and, in particular, a markedly reduced endothelial function. Our results also suggest that microvascular function may not be fully recovered 3 months after disease onset.