The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R):protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium

Introduction Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. Methods and analysis This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform (www.yourcovidrecovery.nhs.uk). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. Ethics and dissemination Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Article summary Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priorit

The role of adiposity and physical activity for protection and recovery from severe COVID-19

The role of adiposity and physical activity for protection and recovery from severe COVID-19</p

Supplementary information for Effect of replacing television viewing with different intensities of physical activity on COVID-19 mortality risk: Short communication from UK Biobank

Supplementary files for article Effect of replacing television viewing with different intensities of physical activity on COVID-19 mortality risk: Short communication from UK BiobankAims: This study aimed to examine the theoretical effects of replacing television (TV) viewing with different intensities of physical activity on COVID-19 mortality risk using isotemporal substitution models. Methods: The analytical sample was composed of 359,756 UK Biobank participants. TV viewing and physical activity were assessed by self-report. Logistic regressions adjusted for covariates were used to model the effects of substituting an hour a day of TV viewing with an hour of walking, moderate-intensity physical activity (MPA) or vigorous-intensity physical activity (VPA) on COVID-19 mortality risk. Results: From 16 March 2020 to 12 November 2021, there were 879 COVID-19 deaths in the analytical sample. Substituting an hour a day of TV viewing with an hour of walking was associated with a 17% lower risk of COVID-19 mortality (odds ratio (OR)=0.83, 95% confidence interval (CI) 0.74–0.92). In sex-stratified analyses, the same substitution was associated with a lower risk in both men (OR=0.85, 95% CI 0.74–0.96) and women (OR=0.78, 95% CI 0.65–0.95). However, replacing an hour a day of TV viewing with an hour of MPA was only associated with a lower risk in women (OR=0.80, 95% CI 0.65–0.98). Conclusions: Replacing TV viewing with walking was associated with a significant reduction in COVID-19 mortality risk. Public health authorities should consider promoting the replacement of TV viewing with walking as a protective strategy against COVID-19 mortality.</p

Effect of replacing television viewing with different intensities of physical activity on COVID-19 mortality risk: Short communication from UK Biobank

Aims: This study aimed to examine the theoretical effects of replacing television (TV) viewing with different intensities of physical activity on COVID-19 mortality risk using isotemporal substitution models. Methods: The analytical sample was composed of 359,756 UK Biobank participants. TV viewing and physical activity were assessed by self-report. Logistic regressions adjusted for covariates were used to model the effects of substituting an hour a day of TV viewing with an hour of walking, moderate-intensity physical activity (MPA) or vigorous-intensity physical activity (VPA) on COVID-19 mortality risk. Results: From 16 March 2020 to 12 November 2021, there were 879 COVID-19 deaths in the analytical sample. Substituting an hour a day of TV viewing with an hour of walking was associated with a 17% lower risk of COVID-19 mortality (odds ratio (OR)=0.83, 95% confidence interval (CI) 0.74–0.92). In sex-stratified analyses, the same substitution was associated with a lower risk in both men (OR=0.85, 95% CI 0.74–0.96) and women (OR=0.78, 95% CI 0.65–0.95). However, replacing an hour a day of TV viewing with an hour of MPA was only associated with a lower risk in women (OR=0.80, 95% CI 0.65–0.98). Conclusions: Replacing TV viewing with walking was associated with a significant reduction in COVID-19 mortality risk. Public health authorities should consider promoting the replacement of TV viewing with walking as a protective strategy against COVID-19 mortality.</p

The joint associations of physical activity and TV viewing time with COVID-19 mortality: an analysis of UK Biobank

We used logistic regression to investigate the joint associations of physical activity level (high: ≥3000 MET-min/week, moderate: ≥600 MET-min/week, low: not meeting either criteria) and TV viewing time (low: ≤1 h/day, moderate: 2-3 h/day, high: ≥4 h/day) with COVID-19 mortality risk in UK Biobank. Additional models were performed with adjustment for body mass index (BMI) and waist circumference. Within the 373, 523 included participants, there were 940 COVID-19 deaths between 16 March 2020 and 12 November 2021. Compared to highly active individuals with a low TV viewing time, highly active individuals with a high TV viewing time were at significantly higher risk of COVID-19 mortality (odds ratio = 1.54, 95% confidence interval = 1.11-2.15). However, the greatest risk was observed for the combination of a low physical activity level and a high TV viewing time (2.29, 1.63-3.21). After adjusting for either BMI or waist circumference, only this latter combination remained at a significantly higher risk, although the effect estimate was attenuated by 43% and 48%, respectively. In sum, a high TV viewing time may be a risk factor for COVID-19 mortality even amongst highly active individuals. Higher adiposity appears to partly explain the elevated risk associated with a low physical activity level and a high TV viewing time.</p

Television viewing time, overweight, obesity and severe COVID-19: a brief report from UK Biobank

Background: Overweight and obesity are well-established risk factors for COVID-19 severity; however, less is known about the role of sedentary behaviours such as TV viewing. The purpose of this brief report was to determine whether lower TV viewing time may mitigate the risk of severe COVID19 in individuals with excess weight. Methods: We analysed 329 751 UK Biobank participants to investigate the independent and combined associations of BMI and self-reported TV viewing time with odds of severe COVID-19 (inpatient COVID-19 or COVID-19 death). Results: Between March 16th and December 8th 2020, there were 1648 instances of severe COVID19. Per 1 unit (h/day) increase in TV viewing time, the odds of severe COVID-19 increased by 5% (adjusted odds ratio (OR) = 1.05, 95% confidence interval = 1.02–1.08). Compared to normal-weight individuals with low (≤1h/day) TV viewing time, the ORs for overweight individuals with low and high (≥4h/day) TV viewing time were 1.17 (0.89–1.55) and 1.66 (1.31–2.11), respectively. For individuals with obesity, the respective ORs for low and high TV viewing time were 2.18 (1.61–2.95) and 2.14 (1.69–2.73). Conclusion: Higher TV viewing time was associated with higher odds of severe COVID-19 independent of BMI and moderate-to-vigorous physical activity. Additionally, low TV viewing time may partly attenuate the elevated odds associated with overweight, but not obesity.</p

High grip strength attenuates risk of severe COVID-19 in males but not females with obesity: A short communication of prospective findings from UK Biobank

We examined the joint associations of BMI category and grip strength tertile with risk of severe COVID-19 (inpatient COVID-19 or COVID-19 mortality) in 327 500 UK Biobank participants. Compared to normal-weight males with high grip strength, the odds ratio (95 % confidence interval) for males with obesity with low grip strength was 2.39 (1.59–3.60), but 1.52 (0.98–2.35) for males with obesity with a high grip strength. A higher grip strength did not appear to be associated with lower risk of severe COVID-19 in females. Muscle mass and strength development should be considered as a means to reduce risk of severe COVID-19 for males with obesity

Adipose inflammation: South Asian ethnicity and central obesity are independently associated with higher immune cell recruitment to adipose‐specific media: A pilot study in men

Abstract A South Asian (SA) cardiovascular phenomenon exists whereby SAs have excess burden of cardiovascular disease (CVD) despite having low prevalence of recognized CVD risk factors. The aim of the current study was to determine whether perturbations in monocyte biology contribute to this phenomenon via higher circulating cell numbers, a more pro‐inflammatory phenotype, and higher transmigration and adhesion. Adhesion is linked to vascular inflammation whereas transmigration is linked to tissue inflammation. SA men with (N = 10; SAs with central obesity [CO‐SA]) and without (N = 10; lean SA [LE‐SA]) central obesity, plus White European counterparts (N = 10; white Europeans with central obesity [CO‐WE], N = 10; lean white Europeans [LE‐WE]) participated. An ex vivo assay mimicking blood flow dynamics coupled to flow cytometry determined the adhesion and transmigration of monocyte subsets toward chemokine‐rich media cultured from pre‐adipocytes (absolute responses). Migration and adhesion were also standardized for differences in numbers of circulating monocytes between participants (relative responses). Metabolic and inflammatory markers were assessed. SAs had higher absolute (but not relative) adhesion and migration of monocytes than WEs. Central obesity was associated with higher absolute and relative adhesion and migration of monocytes. SAs had higher concentrations of all monocyte subsets compared with WEs coinciding with adverse cardiovascular‐inflammatory profiles. LE‐SAs had similar monocyte concentrations, transmigration, and adhesion compared with CO‐WEs, corresponding with similar cardiovascular‐inflammatory profiles. The study provides novel evidence for higher monocyte counts associated with higher transmigration and adhesion in SA compared with WE men. Importantly, similar monocyte biology and cardiovascular‐inflammatory profiles were seen in LE‐SAs compared with CO‐WEs, which may contribute to the higher risk of CVD at lower body mass index experienced by SAs

Adipose inflammation: South Asian ethnicity and central obesity are independently associated with higher immune cell recruitment to adipose‐specific media: a pilot study in men

A South Asian (SA) cardiovascular phenomenon exists whereby SAs have excess burden of cardiovascular disease (CVD) despite having low prevalence of recognized CVD risk factors. The aim of the current study was to determine whether perturbations in monocyte biology contribute to this phenomenon via higher circulating cell numbers, a more pro‐inflammatory phenotype, and higher transmigration and adhesion. Adhesion is linked to vascular inflammation whereas transmigration is linked to tissue inflammation. SA men with (N = 10; SAs with central obesity [CO‐SA]) and without (N = 10; lean SA [LE‐SA]) central obesity, plus White European counterparts (N = 10; white Europeans with central obesity [CO‐WE], N = 10; lean white Europeans [LE‐WE]) participated. An ex vivo assay mimicking blood flow dynamics coupled to flow cytometry determined the adhesion and transmigration of monocyte subsets toward chemokine‐rich media cultured from pre‐adipocytes (absolute responses). Migration and adhesion were also standardized for differences in numbers of circulating monocytes between participants (relative responses). Metabolic and inflammatory markers were assessed. SAs had higher absolute (but not relative) adhesion and migration of monocytes than WEs. Central obesity was associated with higher absolute and relative adhesion and migration of monocytes. SAs had higher concentrations of all monocyte subsets compared with WEs coinciding with adverse cardiovascular‐inflammatory profiles. LE‐SAs had similar monocyte concentrations, transmigration, and adhesion compared with CO‐WEs, corresponding with similar cardiovascular‐inflammatory profiles. The study provides novel evidence for higher monocyte counts associated with higher transmigration and adhesion in SA compared with WE men. Importantly, similar monocyte biology and cardiovascular‐inflammatory profiles were seen in LE‐SAs compared with CO‐WEs, which may contribute to the higher risk of CVD at lower body mass index experienced by SAs.</p

Inactivity and obesity: consequences for macrophage-mediated inflammation and the development of cardiometabolic disease

Obesity and dyslipidaemia are strongly associated with the development of cardiometabolic diseases including cardiovascular disease, stroke, type 2 diabetes, insulin resistance and non-alcoholic fatty liver disease. While these conditions are preventable, they are leading causes of mortality globally. There is now overwhelming clinical and experimental evidence that these conditions are driven by chronic systemic inflammation, with a growing body of data suggesting that this can be regulated by increasing levels of physical activity and reducing sedentary time. In this review we address the role of macrophage-mediated inflammation on the development of cardiometabolic diseases in individuals with overweight and obesity and how reducing sedentary behaviour and increasing physical activity appears to lessen these proinflammatory processes, reducing the risk of developing cardiometabolic diseases. While loss of subcutaneous and visceral fat mass is important for reducing chronic systemic inflammation, the mediating effects of increasing physical activity levels and lowering sedentary time on the development of inflamed adipose tissue also occur independently of changes in adiposity. The message that weight-loss is not necessary for the benefits of physical activity in lowering chronic inflammation and improving health should encourage those for whom losing weight is difficult. Additionally, while the health benefits of meeting the recommended physical activity guidelines are clear, simply moving more appears to lower chronic systemic inflammation. Reducing sitting time and increasing light physical activity may therefore provide an alternative, more approachable manner for some with overweight and obesity to become more active, reduce chronic inflammation and improve cardiometabolic health.</p