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.

Acute Muscle Mass Loss Predicts Long-Term Fatigue, Myalgia, and Health Care Costs in COVID-19 Survivors.

OBJECTIVE: We examined the impact of loss of skeletal muscle mass in post-acute sequelae of SARS-CoV-2 infection, hospital readmission rate, self-perception of health, and health care costs in a cohort of COVID-19 survivors. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: Tertiary Clinical Hospital. Eighty COVID-19 survivors age 59 ± 14 years were prospectively assessed. METHODS: Handgrip strength and vastus lateralis muscle cross-sectional area were evaluated at hospital admission, discharge, and 6 months after discharge. Post-acute sequelae of SARS-CoV-2 were evaluated 6 months after discharge (main outcome). Also, health care costs, hospital readmission rate, and self-perception of health were evaluated 2 and 6 months after hospital discharge. To examine whether the magnitude of muscle mass loss impacts the outcomes, we ranked patients according to relative vastus lateralis muscle cross-sectional area reduction during hospital stay into either "high muscle loss" (-18 ± 11%) or "low muscle loss" (-4 ± 2%) group, based on median values. RESULTS: High muscle loss group showed greater prevalence of fatigue (76% vs 46%, P = .0337) and myalgia (66% vs 36%, P = .0388), and lower muscle mass (-8% vs 3%, P < .0001) than low muscle loss group 6 months after discharge. No between-group difference was observed for hospital readmission and self-perceived health (P > .05). High muscle loss group demonstrated greater total COVID-19-related health care costs 2 ($77,283.87 vs. $3057.14, P = .0223, respectively) and 6 months ($90,001.35 vs $12, 913.27, P = .0210, respectively) after discharge vs low muscle loss group. Muscle mass loss was shown to be a predictor of total COVID-19-related health care costs at 2 (adjusted ß = $10, 070.81, P < .0001) and 6 months after discharge (adjusted ß = $9885.63, P < .0001). CONCLUSIONS AND IMPLICATIONS: COVID-19 survivors experiencing high muscle mass loss during hospital stay fail to fully recover muscle health. In addition, greater muscle loss was associated with a higher frequency of post-acute sequelae of SARS-CoV-2 and greater total COVID-19-related health care costs 2 and 6 months after discharge. Altogether, these data suggest that the loss of muscle mass resulting from COVID-19 hospitalization may incur in an economical burden to health care systems.

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.

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.

Muscle strength and muscle mass as predictors of hospital length of stay in patients with moderate to severe COVID-19: a prospective observational study

Abstract Background Strength and muscle mass are predictors of relevant clinical outcomes in critically ill patients, but in hospitalized patients with COVID-19, it remains to be determined. In this prospective observational study, we investigated whether muscle strength or muscle mass are predictive of hospital length of stay (LOS) in patients with moderate to severe COVID-19 patients. Methods We evaluated prospectively 196 patients at hospital admission for muscle mass and strength. Ten patients did not test positive for SARS-CoV-2 during hospitalization and were excluded from the analyses. Results The sample comprised patients of both sexes (50% male) with a mean age (SD) of 59 (±15) years, body mass index of 29.5 (±6.9) kg/m2. The prevalence of current smoking patients was 24.7%, and more prevalent coexisting conditions were hypertension (67.7%), obesity (40.9%), and type 2 diabetes (36.0%). Mean (SD) LOS was 8.6 days (7.7);17.0% of the patients required intensive care;3.8% used invasive mechanical ventilation;and 6.6% died during the hospitalization period. The crude hazard ratio (HR) for LOS was greatest for handgrip strength comparing the strongest versus other patients (1.47 [95% CI: 1.07?2.03;P = 0.019]). Evidence of an association between increased handgrip strength and shorter hospital stay was also identified when handgrip strength was standardized according to the sex-specific mean and standard deviation (1.23 [95% CI: 1.06?1.43;P = 0.007]). Mean LOS was shorter for the strongest patients (7.5 ± 6.1 days) versus others (9.2 ± 8.4 days). Evidence of associations were also present for vastus lateralis cross-sectional area. The crude HR identified shorter hospital stay for patients with greater sex-specific standardized values (1.20 [95% CI: 1.03?1.39;P = 0.016]). Evidence was also obtained associating longer hospital stays for patients with the lowest values for vastus lateralis cross-sectional area (0.63 [95% CI: 0.46?0.88;P = 0.006). Mean LOS for the patients with the lowest muscle cross-sectional area was longer (10.8 ± 8.8 days) versus others (7.7 ± 7.2 days). The magnitude of associations for handgrip strength and vastus lateralis cross-sectional area remained consistent and statistically significant after adjusting for other covariates. Conclusions Muscle strength and mass assessed upon hospital admission are predictors of LOS in patients with moderate to severe COVID-19, which stresses the value of muscle health in prognosis of this disease.