Cardiorespiratory abnormalities in ICU survivors of COVID-19 with postacute sequelae of SARS-CoV-2 infection are unrelated to invasive mechanical ventilation.

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) often leads to exertional intolerance and reduced exercise capacity, particularly in individuals previously admitted to an intensive care unit (ICU). However, the impact of invasive mechanical ventilation (IMV) on PASC-associated cardiorespiratory abnormalities during exercise remains poorly understood. This single-center, cross-sectional study aimed to gather knowledge on this topic. Fifty-two patients with PASC recruited ∼6 mo after ICU discharge were clustered based on their need for IMV (PASC + IMV, n = 27) or noninvasive support therapy (PASC + NIS, n = 25). Patients underwent pulmonary function and cardiopulmonary exercise testing (CPX) and were compared with a reference group (CONTROL, n = 19) comprising individuals of both sexes with similar age, comorbidities, and physical activity levels but without a history of COVID-19 illness. Individuals with PASC, irrespective of support therapy, presented with higher rates of cardiorespiratory abnormalities than CONTROL, especially dysfunctional breathing patterns, dynamic hyperinflation, reduced oxygen uptake and oxygen pulse, and blunted heart rate recovery (all P < 0.05). Only the rate of abnormal oxygen pulse was greater among PASC + IMV group than PASC + NIS group (P = 0.05). Mean estimates for all CPX variables were comparable between PASC + IMV and PASC + NIS groups (all P > 0.05). These findings indicate significant involvement of both central and peripheral factors, leading to exertional intolerance in individuals with PASC previously admitted to the ICU, regardless of their need for IMV.NEW & NOTEWORTHY We found cardiorespiratory abnormalities in ICU survivors of severe-to-critical COVID-19 with PASC to be independent of IMV need. Overall, both group of patients experienced dysfunctional breathing patterns, dynamic hyperinflation, lower oxygen uptake and oxygen pulse, and blunted heart rate responses to CPX. PASC seems to impact exertional tolerance and exercise capacity due to ventilatory inefficiency, impaired aerobic metabolism, and potential systolic and autonomic dysfunction, all of these irrespective of support therapy during ICU stay.

Effect of exercise training on the renin-angiotensin-aldosterone system: a meta-analysis.

Blood pressure (BP) management reduces the risk of cardiovascular disease (CVD). The renin-angiotensin-aldosterone system (RAAS) plays an important role in regulating and maintaining blood volume and pressure. This analysis aimed to investigate the effect of exercise training on plasma renin, angiotensin-II and aldosterone, epinephrine, norepinephrine, urinary sodium and potassium, BP and heart rate (HR). We systematically searched PubMed, Web of Science, and the Cochrane Library of Controlled Trials until 30 November 2022. The search strategy included RAAS key words in combination with exercise training terms and medical subject headings. Manual searching of reference lists from systematic reviews and eligible studies completed the search. A random effects meta-analysis model was used. Eighteen trials with a total of 803 participants were included. After exercise training, plasma angiotensin-II (SMD -0.71; 95% CI -1.24, -0.19; p = 0.008; n = 9 trials), aldosterone (SMD -0.37; 95% CI -0.65, -0.09; p = 0.009; n = 8 trials) and norepinephrine (SMD -0.82; 95% CI -1.18, -0.46; p < 0.001; n = 8 trials) were reduced. However, plasma renin activity, epinephrine, and 24-h urinary sodium and potassium excretion remained unchanged with exercise training. Systolic BP was reduced (MD -6.2 mmHg; 95% CI -9.9, -2.6; p = 0.001) as was diastolic BP (MD -4.5 mmHg; 95% CI -6.9, -2.1; p < 0.001) but not HR (MD -3.0 bpm; 95% CI -6.0, 0.4; p = 0.053). Exercise training may reduce some aspects of RAAS and sympathetic nervous system activity, and this explains some of the anti-hypertensive response.

Physiological responses during walking in men and women with intermittent claudication.

BACKGROUND: Miyasato et al. show that peak oxygen consumption, walking economy, anaerobic threshold, and cardiovascular responses (heart rate, blood pressure, and rate pressure product) during walking were similar between men and women with peripheral artery disease and intermittent claudication. There were no differences in the physiological responses to walking between men and women with intermittent claudication. Sex per se is not a factor that demands changes in walking prescription for patients with intermittent claudication. OBJECTIVE: Peak oxygen consumption (VO2peak), anaerobic threshold, walking economy, and cardiovascular responses during walking are used to guide and monitor walking training in patients with peripheral artery disease and intermittent claudication. Women with peripheral artery disease and intermittent claudication present greater impairments than men, and evaluating training markers according to sex for decisions regarding walking prescription in this population is important. This study aimed to compare VO2peak, walking economy, anaerobic threshold, and cardiovascular responses during walking in men and women with peripheral artery disease and intermittent claudication. METHODS: Forty patients (20 men and 20 women with similar baseline characteristics) underwent a cardiopulmonary treadmill test (3.2km/h and 2% increase in slope every 2 minutes until maximal leg pain). The VO2 and rate-pressure product were assessed. Data from men and women were compared using t-tests. RESULTS: There were no significant differences between men and women (VO2peak: 15.0±4.8 versus 13.9±2.9mL∙kg-1∙min-1, p=0.38; walking economy: 9.6±2.7 versus 8.4±1.6mL∙kg-1∙min-1, p=0.09; anaerobic threshold: 10.5±3.2 versus 10.5±2.2mL∙kg-1∙min-1, p=0.98; rate pressure product at 1st stage: 13,465± 2,910 versus 14,445±4,379bpm∙mmHg, p=0.41; and rate pressure product at anaerobic threshold:13,673±3,100 versus 16,390±5,870bpm∙mmHg, p=0.08 and rate pressure product at peak exercise: 21,253±6,141 versus 21,923±7,414bpm∙mmHg, p=0.76, respectively). CONCLUSION: Men and women with peripheral artery disease and similar baseline characteristics presented similar responses to walking, suggesting that decisions regarding walking prescription and monitoring can be made regardless of sex in this specific population.

Impact of Methyl-Donor Micronutrient Supplementation on DNA Methylation Patterns: A Systematic Review and Meta-Analysis of in vitro, Animal, and Human Studies.

BACKGROUND: DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation levels, and altered ingestion of folate, choline, betaine, B vitamins and methionine may impact genes both globally and at the level of promoter regions. Despite this, the role of methyl-donor micronutrient supplementation on DNA methylation profiles is currently unclear. OBJECTIVES: The aims of this systematic review and meta-analysis were to identify and synthesize the evidence about methyl-donor nutrient supplementation on DNA methylation. METHODS: A systematic literature search was performed in Medline, Embase, Scopus, and Web of Science databases with a combination of terms related to DNA methylation assessment, supplementation, and methyl-donor nutrients. Studies (in vitro, animal models, or human clinical trials) were included if DNA methylation levels after any kind of methyl-donor micronutrient supplementation or treatment was investigated. Studies were assessed for bias using Revised Cochrane risk-of-bias tool for randomized trials, risk-of-bias in Non-randomized Studies of Interventions or Systematic Review Centre for Laboratory Animal Experimentation tools. Data were extracted from studies measuring DNA methylation levels in any sample or tissue, following any kind of methyl-donor micronutrient supplementation or treatment. Separate random-effects meta-analyses were performed for animal model studies and human clinical trials that examined the effects of folic acid supplementation on DNA methylation. RESULTS: Fifty-seven studies were included in this systematic review: 18 human clinical trials, 35 in animal model, and 4 in vitro studies. Concerning overall risk of bias, most of the studies were classified as "high risk" or "some concerns." Meta-analysis with meta-regression from studies in animal models showed that folic acid dose significantly affected DNA methylation and that high and very high doses showed increases in DNA methylation when compared to low doses. However, meta-analysis of human clinical trials showed that folic acid supplementation did not promote significant changes in DNA methylation when compared to placebo. CONCLUSION: Folic acid supplementation may change global DNA methylation levels in animals supplemented with high, as compared to low, doses. Heterogeneity in studies and supplementation protocols make it difficult to establish clinical recommendations. However, these effects, even if small, might be of clinical importance in the management of patients with diseases related to DNA hypomethylation.

Effects of a 16-week home-based exercise training programme on health-related quality of life, functional capacity, and persistent symptoms in survivors of severe/critical COVID-19: a randomised controlled trial.

BACKGROUND: Long-lasting effects of COVID-19 may include cardiovascular, respiratory, skeletal muscle, metabolic, psychological disorders and persistent symptoms that can impair health-related quality of life (HRQoL). We investigated the effects of a home-based exercise training (HBET) programme on HRQoL and health-related outcomes in survivors of severe/critical COVID-19. METHODS: This was a single-centre, single-blinded, parallel-group, randomised controlled trial. Fifty survivors of severe/critical COVID-19 (5±1 months after intensive care unit discharge) were randomly allocated (1:1) to either a 3 times a week (~60-80 min/session), semi-supervised, individualised, HBET programme or standard of care (CONTROL). Changes in HRQoL were evaluated through the 36-Item Short-Form Health Survey, and physical component summary was predetermined as the primary outcome. Secondary outcomes included cardiorespiratory fitness, pulmonary function, functional capacity, body composition and persistent symptoms. Assessments were performed at baseline and after 16 weeks of intervention. Statistical analysis followed intention-to-treat principles. RESULTS: After the intervention, HBET showed greater HRQoL score than CONTROL in the physical component summary (estimated mean difference, EMD: 16.8 points; 95% CI 5.8 to 27.9; effect size, ES: 0.74), physical functioning (EMD: 22.5 points, 95% CI 6.1 to 42.9, ES: 0.83), general health (EMD: 17.4 points, 95% CI 1.8 to 33.1, ES: 0.73) and vitality (EMD: 15.1 points, 95% CI 0.2 to 30.1, ES: 0.49) domains. 30-second sit-to-stand (EMD: 2.38 reps, 95% CI 0.01 to 4.76, ES: 0.86), and muscle weakness and myalgia were also improved in HBET compared with CONTROL (p<0.05). No significant differences were seen in the remaining variables. There were no adverse events. CONCLUSION: HBET is an effective and safe intervention to improve physical domains of HRQoL, functional capacity and persistent symptoms in survivors of severe/critical COVID-19. TRIAL REGISTRATION NUMBER: NCT04615052.

Physiological responses during walking in men and women with intermittent claudication

ABSTRACT Objective Peak oxygen consumption (VO2peak), anaerobic threshold, walking economy, and cardiovascular responses during walking are used to guide and monitor walking training in patients with peripheral artery disease and intermittent claudication. Women with peripheral artery disease and intermittent claudication present greater impairments than men, and evaluating training markers according to sex for decisions regarding walking prescription in this population is important. This study aimed to compare VO2peak, walking economy, anaerobic threshold, and cardiovascular responses during walking in men and women with peripheral artery disease and intermittent claudication. Methods Forty patients (20 men and 20 women with similar baseline characteristics) underwent a cardiopulmonary treadmill test (3.2km/h and 2% increase in slope every 2 minutes until maximal leg pain). The VO2 and rate-pressure product were assessed. Data from men and women were compared using t-tests. Results There were no significant differences between men and women (VO2peak: 15.0±4.8 versus 13.9±2.9mL∙kg-1∙min-1, p=0.38; walking economy: 9.6±2.7 versus 8.4±1.6mL∙kg-1∙min-1, p=0.09; anaerobic threshold: 10.5±3.2 versus 10.5±2.2mL∙kg-1∙min-1, p=0.98; rate pressure product at 1st stage: 13,465± 2,910 versus 14,445±4,379bpm∙mmHg, p=0.41; and rate pressure product at anaerobic threshold:13,673±3,100 versus 16,390±5,870bpm∙mmHg, p=0.08 and rate pressure product at peak exercise: 21,253±6,141 versus 21,923±7,414bpm∙mmHg, p=0.76, respectively). Conclusion Men and women with peripheral artery disease and similar baseline characteristics presented similar responses to walking, suggesting that decisions regarding walking prescription and monitoring can be made regardless of sex in this specific population.

Oxygen uptake kinetics and chronotropic responses to exercise are impaired in survivors of severe COVID-19.

The post-acute phase of coronavirus disease 2019 (COVID-19) is often marked by several persistent symptoms and exertional intolerance, which compromise survivors' exercise capacity. This was a cross-sectional study aiming to investigate the impact of COVID-19 on oxygen uptake (V̇o2) kinetics and cardiopulmonary function in survivors of severe COVID-19 about 3-6 mo after intensive care unit (ICU) hospitalization. Thirty-five COVID-19 survivors previously admitted to ICU (5 ± 1 mo after hospital discharge) and 18 controls matched for sex, age, comorbidities, and physical activity level with no prior history of SARS-CoV-2 infection were recruited. Subjects were submitted to a maximum-graded cardiopulmonary exercise test (CPX) with an initial 3-min period of a constant, moderate-intensity walk (i.e., below ventilatory threshold, VT). V̇o2 kinetics was remarkably impaired in COVID-19 survivors as evidenced at the on-transient by an 85% (P = 0.008) and 28% (P = 0.001) greater oxygen deficit and mean response time (MRT), respectively. Furthermore, COVID-19 survivors showed an 11% longer (P = 0.046) half-time of recovery of V̇o2 (T1/2V̇o2) at the off-transient. CPX also revealed cardiopulmonary impairments following COVID-19. Peak oxygen uptake (V̇o2peak), percent-predicted V̇o2peak, and V̇o2 at the ventilatory threshold (V̇o2VT) were reduced by 17%, 17%, and 12% in COVID-19 survivors, respectively (all P < 0.05). None of the ventilatory parameters differed between groups (all P > 0.05). In addition, COVID-19 survivors also presented with blunted chronotropic responses (i.e., chronotropic index, maximum heart rate, and heart rate recovery; all P < 0.05). These findings suggest that COVID-19 negatively affects central (chronotropic) and peripheral (metabolic) factors that impair the rate at which V̇o2 is adjusted to changes in energy demands.NEW & NOTEWORTHY Our findings provide novel data regarding the impact of COVID-19 on submaximal and maximal cardiopulmonary responses to exercise. We showed that V̇o2 kinetics is significantly impaired at both the onset (on-transient) and the recovery phase (off-transient) of exercise in these patients. Furthermore, our results suggest that survivors of severe COVID-19 may have a higher metabolic demand at a walking pace. These findings may partly explain the exertional intolerance frequently observed following COVID-19.

Lifestyle Interventions and Weight Management in Systemic Lupus Erythematosus Patients: A Systematic Literature Review and Metanalysis.

Background: We aimed to identify and describe different types of lifestyle interventions primarily or secondarily focused on weight loss in SLE patients. Methods: A systematic search of controlled trials published until June 2021 that assigned adults patients after dietary or exercise intervention resulted in 248 studies initially screened. Results: Six studies with seven interventions (3 dietary and 4 exercise training programs) fulfilled the eligibility criteria and were included in the meta-analysis with a median of age 35.8 (31.3 to 49.0 years); median of BMI 26.6 (25.2 to 33.6 kg/m2). After six to twelve weeks of diet or exercise program, no differences were observed in body weight [-1.539 (-4.482 to 1.405) kg (CI 95%), p = 0.306]. Also, a subgroup analysis also revelated no body weight difference following dietary intervention [-3.561 (-9.604 to 2.481) kg (CI 95%), p = 0.248] or exercise intervention [-0.910 (-4.279 to 2.460) kg (CI 95%), p = 0.597]. Conclusion: The results showed that different protocols of exercise intervention or diets were not effective to reduce body weight in patients with SLE. However, only one of the selected trials had a specific study design and protocol focusing on weight loss management.

Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.

BACKGROUND: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1ß, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.

Home-Based Exercise Training During COVID-19 Pandemic in Post-Bariatric Patients: a Randomized Controlled Trial.

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No independent associations between physical activity and clinical outcomes among hospitalized patients with moderate to severe COVID-19.

BACKGROUND: Regular physical activity (PA) has been postulated to improve, or at least maintain, immunity across the life span. However, the link between physical (in)activity and coronavirus disease 2019 (COVID-19) remains to be established. This small-scale prospective cohort study is nested within a randomized controlled trial aimed to investigate the possible associations between PA levels and clinical outcomes among hospitalized patients with moderate to severe COVID-19. METHODS: Hospitalized patients with COVID-19 (mean age: 54.9 years) were recruited from the Clinical Hospital of the School of Medicine of the University of Sao Paulo (a quaternary referral teaching hospital) and from Ibirapuera Field Hospital, both located in Sao Paulo, Brazil. PA level was assessed using the Baecke Questionnaire of Habitual Physical Activity. The primary outcome was hospital length of stay. The secondary outcomes were mortality, admission to the intensive care unit (ICU), and mechanical ventilation requirement. RESULTS: The median hospital length of stay was 7.0 ± 4.0 days, median ± IQR; 3.3% of patients died, 13.8% were admitted to the ICU, and 8.6% required mechanical ventilation. Adjusted linear regression models showed that PA indices were not associated with hospital length of stay (work index: ß = -0.57 (95% confidence interval (95%CI): -1.80 to 0.65), p = 0.355; sport index: ß = 0.43 (95%CI: -0.94 to 1.80), p = 0.536; leisure-time index: ß = 1.18 (95%CI: -0.22 to 2.59), p = 0.099; and total activity index: ß = 0.20 (95%CI: -0.48 to 0.87), p = 0.563). None of the PA indices were associated with mortality, admission to the ICU, or mechanical ventilation requirement (all p > 0.050). CONCLUSION: Among hospitalized patients with COVID-19, PA did not independently associate with hospital length of stay or any other clinically relevant outcomes. These findings should be interpreted as meaning that, among already hospitalized patients with more severe forms of COVID-19, being active is a potential protective factor likely outweighed by a cluster of comorbidities (e.g., type 2 diabetes, hypertension, weight excess) and older age, suggesting that the benefit of PA against the worsening of COVID-19 may vary across stages of the disease.

Post-exercise Hypotension Following a Single Bout of High Intensity Interval Exercise vs. a Single Bout of Moderate Intensity Continuous Exercise in Adults With or Without Hypertension: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Post-exercise hypotension (PEH) is an important tool in the daily management of patients with hypertension. Varying the exercise parameters is likely to change the blood pressure (BP) response following a bout of exercise. In recent years, high-intensity interval exercise (HIIE) has gained significant popularity in exercise-based prevention and rehabilitation of clinical populations. Yet, to date, it is not known whether a single session of HIIE maximizes PEH more than a bout of moderate-intensity continuous exercise (MICE). Objective: To compare the effect of HIIE vs. MICE on PEH by means of a systematic review and meta-analysis. Methods: A systematic search in the electronic databases MEDLINE, Embase, and SPORTDiscus was conducted from the earliest date available until February 24, 2020. Randomized clinical trials comparing the transient effect of a single bout of HIIE to MICE on office and/or ambulatory BP in humans (≥18 years) were included. Data were pooled using random effects models with summary data reported as weighted means and 95% confidence interval (CIs). Results: Data from 14 trials were included, involving 18 comparisons between HIIE and MICE and 276 (193 males) participants. The immediate effects, measured as office BP at 30- and 60-min post-exercise, was similar for a bout of HIIE and MICE (p > 0.05 for systolic and diastolic BP). However, HIIE elicited a more pronounced BP reduction than MICE [(-5.3 mmHg (-7.3 to -3.3)/ -1.63 mmHg (-3.00 to -0.26)] during the subsequent hours of ambulatory daytime monitoring. No differences were observed for ambulatory nighttime BP (p > 0.05). Conclusion: HIIE promoted a larger PEH than MICE on ambulatory daytime BP. However, the number of studies was low, patients were mostly young to middle-aged individuals, and only a few studies included patients with hypertension. Therefore, there is a need for studies that involve older individuals with hypertension and use ambulatory BP monitoring to confirm HIIE's superiority as a safe BP lowering intervention in today's clinical practice. Systematic Review Registration: PROSPERO (registration number: CRD42020171640).

Constraints of Weight Loss as a Marker of Bariatric Surgery Success: An Exploratory Study.

PURPOSE: The aim of this exploratory study was to investigate whether the degree of weight loss properly reflects improvements in cardiometabolic health among patients who underwent Roux-en-Y gastric bypass. METHODS: In this ancillary analysis from a clinical trial, patients were clustered into tertiles according to the magnitude of the percentage weight loss (1st tertile: "higher weight loss": -37.1 ± 5.8%; 2nd tertile: "moderate weight loss": -29.7 ± 1.4%; 3rd tertile: "lower weight loss": -24.2 ± 2.3%). Delta changes (9 months after surgery-baseline) in clustered cardiometabolic risk (i.e., blood pressure index, fasting glucose, high-density lipoprotein [HDL] and triglycerides [TG]), glycated hemoglobin (HbA1c), homeostasis model assessment (HOMA-IR), and C-reactive protein (CRP) were calculated. RESULTS: A total of 42 patients who had complete bodyweight data (age = 40 ± 8 year; BMI = 47.8 ± 7.1 kg/m2) were included. Surgery led to substantial weight loss (-37.9 ± 11.3 kg, P < 0,001), and clinically significant improvements in blood pressure index (-17.7 ± 8.2 mmHg, P < 0.001), fasting glucose (-36.6 ± 52.5 mg/dL, P < 0.001), HDL (9.4 ± 7.1 mg/dL, P < 0.001), TG (-35.8 ± 44.1 mg/dL P < 0,001), HbA1c (-1.2 ± 1.6%, P < 0.001), HOMA-IR (-4.7 ± 3.9 mg/dL, P < 0.001) and CRP (-8.5 ± 6.7 µg/mL P < 0.001). Comparisons across tertiles revealed no differences for cardiometabolic risk score, fasting glucose, HbAc1, HOMA-IR, blood pressure index, CRP, HDL, and TG (P > 0.05 for all). Individual variable analysis confirmed cardiometabolic improvements across the spectrum on weight-loss. There were no associations between weight loss and any dependent variable. CONCLUSION: Weight loss following bariatric surgery does not correlate with improvements in cardiovascular risk factors. These findings suggest that weight loss alone may be insufficient to assess the cardiometabolic success of bariatric surgery, and the search for alternate proxies that better predict surgery success are needed.

Influence of vitamin D status on hospital length of stay and prognosis in hospitalized patients with moderate to severe COVID-19: a multicenter prospective cohort study.

BACKGROUND: Vitamin D acts as a mediator in the immune system regulating antiviral mechanisms and inflammatory processes. Vitamin D insufficiency has been suggested as a potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although its impact on the prognosis of hospitalized patients with coronavirus disease 2019 (COVID-19) remains unclear. OBJECTIVE: This multicenter prospective cohort study was designed to investigate whether serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with hospital length of stay and prognosis in hospitalized patients with COVID-19. METHODS: Patients with moderate to severe COVID-19 (n = 220) were recruited from 2 hospitals in Sao Paulo, Brazil. Serum 25(OH)D concentrations were categorized as follows: <10 ng/mL, 10 to <20 ng/mL, 20 to <30 ng/mL, and ≥30 ng/mL, and <10 ng/mL and ≥10 ng/mL. The primary outcome was hospital length of stay and the secondary outcomes were the rate of patients who required invasive mechanical ventilation and mortality. RESULTS: There were no significant differences in hospital length of stay when the 4 25(OH)D categories were compared (P = 0.120). Patients exhibiting 25(OH)D <10 ng/mL showed a trend (P = 0.057) for longer hospital length of stay compared with those with 25(OH)D ≥10 ng/mL [9.0 d (95% CI: 6.4, 11.6 d) vs. 7.0 d (95% CI: 6.6, 7.4 d)]. The multivariable Cox proportional hazard models showed no significant associations between 25(OH)D and primary or secondary outcomes. CONCLUSIONS: Among hospitalized patients with moderate to severe COVID-19, those with severe 25(OH)D deficiency (<10 ng/mL) exhibited a trend for longer hospital length of stay compared with patients with higher 25(OH)D concentrations. This association was not significant in the multivariable Cox regression model. Prospective studies should test whether correcting severe 25(OH)D deficiency could improve the prognosis of patients with COVID-19.

Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.

Importance: The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear. Objective: To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19. Design, Setting, and Participants: This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. Interventions: Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 120) or placebo (n = 120). Main Outcomes and Measures: The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. Results: Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention. Conclusions and Relevance: Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04449718.

Influence of Adherence to Social Distancing Due to the COVID-19 Pandemic on Physical Activity Level in Post-bariatric Patients.

We assessed physical activity using accelerometers and a questionnaire in 33 post-bariatric patients who reported to be adherent (n = 15) or not (n = 18) to social distancing due to the COVID-19 pandemic. Patients adherent to social distancing spent more time in sedentary behavior (1.1 h/day, 0.1, 2.2; p = 0.045) and less time in moderate-to-vigorous physical activity (- 12.2 min/day, - 23.8, - 0.6; p = 0.040) vs. non-adherent ones. Bland-Altman analysis comparing objective and subjective physical activity estimates showed a bias for time spent in sedentary behavior and moderate-to-vigorous activity of 2.8 h/day and 8.5 min/day. In conclusion, post-bariatric patients who were adherent to social distancing measures were more inactive and sedentary than non-adherent ones. Strategies to increase physical activity in post-bariatric patients exposed to social distancing are necessary during the COVID-19 pandemic.

Twelve weeks of resistance training performed with different number of sets: Effects on maximal strength and resting blood pressure of individuals with hypertension.

Objective: This study aimed to verify the effect of resistance training performed with single (SET1) or three sets (SET3) on muscle strength and resting blood pressure (BP) of individuals with hypertension. BP was also assessed during knee extension exercise with submaximal load before and after training. Methods: Thirty-eight patients with hypertension were randomly assigned to a control group (CON: n = 12; 55.6 ± 3.2 years; 65.3 ± 9.3 kg; 163.5 ± 8.6 cm), SET1 group (n = 14; 58.1 ± 2.0 years; 65.4 ± 8.7 kg; 162.4 ± 11.1 cm) or SET3 group (n = 12; 57.9 ± 2.4 years; 66.3 ± 11.4 kg; 161.6 ± 7.5 cm). The training was conducted for 12 weeks (3 d.w-1; 4 exercises; 12-15 repetitions; moderate intensity). Results: No differences were found in pre-training values for BP and strength between groups. After training, SET3 showed lower values than CON for resting systolic (121.3 ± 8.0 vs 129.3 ± 10.3 mmHg; P = .01) and diastolic BP (73.5 ± 6.0 vs 79.5 ± 7.4 mmHg; P = .02). Muscle strength in bench-press and knee extension exercises increased in SET1 (48.1 ± 6.3 and 71.3 ± 12.2 kg, respectively) and SET3 (50.2 ± 7.8 and 75.2 ± 9.6 kg, respectively) in relation to CON (39.3 ± 5.1 and 62.4 ± 9.9 kg) (P < .01). BP during knee extension (70% of one maximal repetition) did not differ between groups either before or after training. Conclusion: Resistance training with a single set could be interesting when there is a need to increase muscle strength without necessarily reducing resting BP. On the other hand, the performance of three sets increased muscle strength and reduced BP at rest in individuals with hypertension.

Benefits of Home-Based Exercise Training Following Critical SARS-CoV-2 Infection: A Case Report.

In the current scenario, in which an elevated number of COVID-19 survivors present with severe physical deconditioning, exercise intolerance, persistent symptoms, and other post-acute consequences, effective rehabilitation strategies are of utmost relevance. In this study, we report for the first time the effect of home-based exercise training (HBET) in a survivor patient from critical COVID-19 illness. A 67-year-old woman who had critical COVID-19 disease [71 days of hospitalization, of which 49 days were in the intensive care unit (ICU) with invasive mechanical ventilation due to respiratory failure] underwent a 10-week HBET aiming to recovering overall physical condition. Before and after the intervention, we assessed cardiopulmonary parameters, skeletal muscle strength and functionality, fatigue severity, and self-reported persistent symptoms. At baseline (3 months after discharge), she presented with severe impairment in cardiorespiratory functional capacity (<50% age predicted VO2peak). After the intervention, remarkable improvements in VO2peak (from 10.61 to 15.48 mL·kg-1·min-1, Δ: 45.9%), oxygen uptake efficiency slope (OUES; from 1.0 to 1.3 L·min-1, Δ: 30.1%), HR/VO2 slope (from 92 to 52 bpm·L-1, Δ: -43.5%), the lowest VE/VCO2 ratio (from 35.4 to 32.9 L·min-1, Δ: -7.1%), and exertional dyspnea were observed. In addition, handgrip strength (from 22 to 27 kg, Δ: 22.7%), 30-s Sit-to-Stand (30-STS; from 14 to 16 repetitions, Δ:14.3%), Timed-Up-and-Go (TUG; from 8.25 to 7.01 s, Δ: -15%) performance and post-COVID functional status (PCFS) score (from 4 to 2) were also improved from baseline to post-intervention. Self-reported persistent symptoms were also improved, and Fatigue Severity Scale (FSS) score decreased (from 4 to 2.7) from baseline to post-intervention. This is the first evidence that a semi-supervised, HBET program may be safe and potentially effective in improving cardiorespiratory and physical functionality in COVID-19 survivors. Controlled studies are warranted to confirm these findings.

Cardiovascular Responses during and after Maximal Walking in Men and Women with Symptomatic Peripheral Artery Disease.

BACKGROUND: Walking is recommended for patients with peripheral arterial disease (PAD). It has been shown that patients with PAD present sharper increases in blood pressure (BP) and heart rate (HR) during maximal walking when compared with healthy subjects. Additionally, women with PAD present a worse physiological profile, and it is possible that they may present higher cardiovascular load during and after a bout of maximal walking than men. Thus, the objective of this study was to compare cardiovascular and autonomic responses during and after maximal walking between men and women with PAD and intermittent claudication (IC). METHODS: Forty patients with PAD and IC (20 men and 20 women) underwent, in random order, 2 sessions: control (standing on treadmill) and exercise (maximal treadmill walking test with Gardner's protocol). During the exercise, HR and BP were measured. Before and after the sessions, cardiovascular variables (BP HR, cardiac output, peripheral vascular resistance, and stroke volume) and autonomic modulation (HR and BP variabilities and baroreflex sensitivity) were assessed. In addition, an ambulatory BP monitoring was recorded after each session. RESULTS: Men and women presented similar maximal walking capacity. During the walking test, HR and systolic BP increased similarly in men and women. After the maximal walking, cardiovascular and autonomic responses did not differ between the genders. In addition, postintervention ambulatory BP parameters were also similar in men and women. Therefore, in men and women, maximal walking similarly reduced clinic systolic BP and stroke volume, and increased HR and total power of HR variability during the recovery period. CONCLUSIONS: Men and women with PAD and IC present similar cardiovascular and autonomic responses during and after maximal walking.