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.

Association of health vulnerability with adverse outcomes in older people with COVID-19: a prospective cohort study.

OBJECTIVES: Health vulnerability is associated with a higher risk of mortality and functional decline in older people in the community. However, few studies have evaluated the role of the Vulnerable Elders Survey (VES-13) in predicting clinical outcomes of hospitalized patients. In the present study, we tested the ability of the VES-13 to predict mortality and the need for invasive mechanical ventilation in older people hospitalized with coronavirus disease 2019 (COVID-19). METHODS: This prospective cohort included 91 participants aged ≥60 years who were confirmed to have COVID-19. VES-13 was applied, and the demographic, clinical, and laboratory variables were collected within 72h of hospitalization. A Poisson generalized linear regression model with robust variance was used to estimate the relative risk of death and invasive mechanical ventilation. RESULTS: Of the total number of patients, 19 (21%) died and 15 (16%) required invasive mechanical ventilation. Regarding health vulnerability, 54 (59.4%) participants were classified as non-vulnerable, 30 (33%) as vulnerable, and 7 (7.6%) as extremely vulnerable. Patients classified as extremely vulnerable and male sex were strongly and independently associated with a higher relative risk of in-hospital mortality (p<0.05) and need for invasive mechanical ventilation (p<0.05). CONCLUSION: Elderly patients classified as extremely vulnerable had more unfavorable outcomes after hospitalization for COVID-19. These data highlight the importance of identifying health vulnerabilities in this population.

Adjunctive inspiratory muscle training for patients with COVID-19 (COVIDIMT): protocol for randomised controlled double-blind trial.

INTRODUCTION: A significant number of patients with COVID-19 may experience dyspnoea, anxiety, depression, pain, fatigue and physical impairment symptoms, raising the need for a multidisciplinary rehabilitation approach, especially for those with advanced age, obesity, comorbidities and organ failure. Traditional pulmonary rehabilitation (PR), including exercise training, psychosocial counselling and education, has been employed to improve pulmonary function, exercise capacity and quality of life in patients with COVID-19. However, the effects of inspiratory muscle training (IMT) in PR programmes remain unclear. This study aimed to determine whether the addition of a supervised IMT in a PR is more effective than PR itself in improving dyspnoea, health-related quality of life and exercise capacity in symptomatic patients with post-COVID-19. METHODS AND ANALYSIS: This parallel-group, assessor-blinded randomised controlled trial, powered for superiority, aimed to assess exercise capacity as the primary outcome. A total of 138 are being recruited at two PR centres in Brazil. Following baseline testing, participants will be randomised using concealed allocation, to receive either (1) standard PR with sham IMT or (2) standard PR added to IMT. Treatment effects or differences between the outcomes (at baseline, after 8 and 16 weeks, and after 6 months) of the study groups will be analysed using an ordinary two-way analysis of variance. ETHICS AND DISSEMINATION: This trial was approved by the Brazilian National Ethics Committee and obtained approval on 7 October 2020 (document number 4324069). The findings will be disseminated through publications in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT04595097.

Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle.

The study aimed to determine the levels of skeletal muscle angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19-65 years, weight: 56-137 kg, BMI: 23-44) and 69 women (age: 18-55 years, weight: 41-126 kg, BMI: 22-39) was analyzed in duplicate by western blot. VO2 max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2 max per kg of legs lean mass (VO2 max-LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (ß = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2 max-LLM had also predictive value (ß = 0.09). There was a significant fat % by VO2 max-LLM interaction, such that for subjects with low fat %, VO2 max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2 max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.