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.

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.

Lower-Body Resistance Training Reduces Interleukin-1ß and Transforming Growth Factor-ß1 Levels and Fatigue and Increases Physical Performance in Breast Cancer Survivors.

ABSTRACT: Martins, FM, Santagnello, SB, de Oliveira Junior, GN, de Sousa, JdFR, Michelin, MA, Nomelini, RS, Murta, EFC, and Orsatti, FL. Lower-body resistance training reduces interleukin-1ß and transforming growth factor-ß1 levels and fatigue and increases physical performance in breast cancer survivors. J Strength Cond Res 37(2): 439-451, 2023-This article ascertains whether resistance training (RT) improves inflammatory markers, fatigue (sensations and fatigability), and physical performance in breast cancer survivors (BCS) and investigates whether the changes in the inflammatory markers, fatigue, and physical performance are associated with each other. Volunteers were randomly divided into 2 groups: control group (n = 11) and RT group (n = 11). Resistance training (3 sets of 8-12 repetitions with 80% 1 repetition maximum (1RM) on 4 exercises-leg extension, leg curl, 45° leg press, and calf raise) was performed 3 times a week for 12 weeks. Self-reported fatigue (SRF), fatigability (critical torque [CT] and W prime [W']), muscle strength, and circulating inflammatory markers were assessed using the Brief Fatigue Inventory, iDXA, 1RM test, protocol of 60 maximal voluntary isometric contractions, and enzyme-linked immunosorbent assay, respectively. Resistance training reduced interleukin (IL)-1ß, transforming growth factor (TGF)-ß1, and SRF score and increased muscle strength, 6-minute walk test (6MWT), CT, and W'. In the RT group, the changes in SRF were positively associated with the changes in IL-1ß. The changes in muscle strength were associated with the changes in CT and W', and the changes in the 6MWT were associated with the changes in CT, W', muscle strength, and SRF. Resistance training improved fatigue and physical performance and reduced IL-1ß, and TGF-ß1 in BCS. Although improvement in fatigability seems to be dependent on the increase in muscle strength, improvement in the sensation of fatigue seems to be dependent on the reduction in IL-1ß after RT. Increase in physical performance seems to be dependent on improvement in muscle strength and fatigue.

Post-acute sequelae of SARS-CoV-2 associates with physical inactivity in a cohort of COVID-19 survivors.

The aim of this study was to determine whether Post-acute Sequelae of SARS-CoV-2 Infection (PASC) are associated with physical inactivity in COVID-19 survivors. This is a cohort study of COVID-19 survivors discharged from a tertiary hospital in Sao Paulo, Brazil. Patients admitted as inpatients due to laboratory-confirmed COVID-19 between March and August 2020 were consecutively invited for a follow-up in-person visit 6 to 11 months after hospitalization. Ten symptoms of PASC were assessed using standardized scales. Physical activity was assessed by questionnaire and participants were classified according to WHO Guidelines. 614 patients were analyzed (age: 56 ± 13 years; 53% male). Frequency of physical inactivity in patients exhibiting none, at least 1, 1-4, and 5 or more symptoms of PASC was 51%, 62%, 58%, and 71%, respectively. Adjusted models showed that patients with one or more persistent PASC symptoms have greater odds of being physically inactive than those without any persistent symptoms (OR: 1.57 [95% CI 1.04-2.39], P = 0.032). Dyspnea (OR: 2.22 [1.50-3.33], P < 0.001), fatigue (OR: 2.01 [1.40-2.90], P < 0.001), insomnia (OR: 1.69 [1.16-2.49], P = 0.007), post-traumatic stress (OR: 1.53 [1.05-2.23], P = 0.028), and severe muscle/joint pain (OR: 1.53 [95% CI 1.08-2.17], P = 0.011) were associated with greater odds of being physically inactive. This study suggests that PASC is associated with physical inactivity, which itself may be considered as a persistent symptom among COVID-19 survivors. This may help in the early identification of patients who could benefit from additional interventions tailored to combat inactivity (even after treatment of PASC), with potential beneficial impacts on overall morbidity/mortality and health systems worldwide.

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.

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

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.

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

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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.

Resistance training-induced improvement in exercise tolerance is not dependent on muscle mass gain in post-menopausal women.

Menopause transition may impair muscle function, decreasing exercise tolerance. The torque-duration relationship (hyperbolic curve) forms a practical framework within which exercise tolerance may be explored. In this regard, resistance training (RT) increases the curvature constant of this relationship (W'). Muscle hypertrophy and strength gains have been suggested as possible mediators of RT-induced improvement in W', however, it is unclear what the main mediator is. Higher-volume RT (HV-RT), beyond that recommended by RT-guidelines (i.e. three sets per exercise), may promote greater hypertrophy, but not higher strength gains. Hence, this study aimed to investigate whether greater hypertrophy in HV-RT maximises W' gain when compared to LVRT in postmenopausal women (PW). Fifty-eight PW were randomised to the control group (CTRL), HV-RT (six sets per exercise) or LV-RT (three sets per exercise). They underwent a 12-week RT program and were assessed for W', thigh lean body mass (TLBM) and maximal isometric voluntary contraction (MIVC). The TLBM gain was higher (P < 0.001) in the HV-RT (9.4%) than LV-RT (3.7%). However, both HV-RT and LV-RT similarly increased MIVC (9.7% vs. 16.5%, P = 0.063) and W' (26.4% vs. 34.6% P = 0.163). Additionally, the changes in W' were associated with the changes in TLBM (31%, P = 0.003) and MIVC (52%, P= <0.001). However, when the changes in TLBM and MIVC were inserted into the predictive model, only the MIVC (33%, P = 0.002) was a predictor of W'. Thus, although HV-RT promoted greater hypertrophy than LV-RT, HV-RT does not seem to maximise W' in PW.

Improvements in muscle strength, power, and size and self-reported fatigue as mediators of the effect of resistance exercise on physical performance breast cancer survivor women: a randomized controlled trial.

PURPOSE: To gain more knowledge about the mechanism (i.e., mediators) of resistance exercise (RE)-induced improvements in physical performance (PP), we seek to investigate whether improvements in muscle strength (MS), muscle power (MP), and lean body mass (LBM) and (or) self-reported fatigue (SRF) are mediators of the effect of RE on PP in breast cancer survivor women (BCSW). METHODS: The volunteers were randomly divided into two groups: control group (CT; n = 9) and resistance exercise (RE; n = 11). The RE protocol consisted of three sets in each exercise (leg extension, leg curl, 45° leg press, and calf raise), between 8 and 12 repetitions per set, with an estimated load of 80% of one-repetition maximum (1RM), and three times a week on non-consecutive days for 12 weeks. The CT group performed only stretching exercises twice a week. SRF, maximal muscle power (Pmax), MP, LBM, and PP were assessed using the Brief Fatigue Inventory Questionnaire; 1RM test; isoinertial dynamometer; DXA; and walking speed, sit-to-stand (STS), and timed up and go (TUG) test, respectively. RESULTS: Following 12 weeks, the RE group reduced SRF and increased MP, Pmax, LBM, and performance in all tests (walking speed, STS, and TUG) when compared with the CT group. There were significant associations of the changes in LBM, MS, Pmax, and SRF with changes in physical performance tests only in the RE group. CONCLUSION: Our findings suggest that improvements in LBM, MS, MP, and self-reported fatigue mediate the effect of resistance exercise on physical performance in BCSW.