Decreased physical performance despite objective and subjective maximal exhaustion in post-COVID-19 individuals with fatigue.

INTRODUCTION: Fatigue is a common symptom in post-COVID-19 patients. Individuals with fatigue often perform less well compared to healthy peers or without fatigue. It is not yet clear to what extent fatigue is related to the inability to reach maximum exhaustion during physical exercise. METHODS: A symptom-based questionnaire based on the Carruthers guidelines (2003) was used for reporting the presence of fatigue and further symptoms related to COVID-19 from 85 participants (60.0% male, 33.5 ± 11.9 years). Cardiopulmonary exercise testing (CPET) and lactate measurement at the end of the test were conducted. Objective and subjective exhaustion criteria according to Wasserman of physically active individuals with fatigue (FS) were compared to those without fatigue (NFS). RESULTS: Differences between FS and NFS were found in Peak V̇O2/BM (p < 0.001) and Max Power/BM (p < 0.001). FS were more likely to suffer from further persistent symptoms (p < 0.05). The exhaustion criterion Max. lactate was reached significantly more often by NFS individuals. CONCLUSION: Although the aerobic performance (Max Power/BM) and the metabolic rate (Peak V̇O2/BM and Max. lactate) of FS were lower compared to NFS, they were equally able to reach objective exhaustion criteria. The decreased number of FS who reached the lactate criteria and the decreased V̇O2 peak indicates a change in metabolism. Other persistent post-COVID-19 symptoms besides fatigue may also impair performance, trainability and the ability to reach objective exhaustion. Trial registration Trial registration: DRKS00023717; date of registration: 15.06.2021 (retrospectively registered).

Left Ventricular Global Longitudinal Strain as a Parameter of Mild Myocardial Dysfunction in Athletes after COVID-19.

Whether symptoms during COVID-19 contribute to impaired left ventricular (LV) function remains unclear. We determine LV global longitudinal strain (GLS) between athletes with a positive COVID-19 test (PCAt) and healthy control athletes (CON) and relate it to symptoms during COVID-19. GLS is determined in four-, two-, and three-chamber views and assessed offline by a blinded investigator in 88 PCAt (35% women) (training at least three times per week/>20 MET) and 52 CONs from the national or state squad (38% women) at a median of two months after COVID-19. The results show that the GLS is significantly lower (GLS -18.53 ± 1.94% vs. -19.94 ± 1.42%, p < 0.001) and diastolic function significantly reduces (E/A 1.54 ± 0.52 vs. 1.66 ± 0.43, p = 0.020; E/E'l 5.74 ± 1.74 vs. 5.22 ± 1.36, p = 0.024) in PCAt. There is no association between GLS and symptoms like resting or exertional dyspnea, palpitations, chest pain or increased resting heart rate. However, there is a trend toward a lower GLS in PCAt with subjectively perceived performance limitation (p =0.054). A significantly lower GLS and diastolic function in PCAt compared with healthy peers may indicate mild myocardial dysfunction after COVID-19. However, the changes are within the normal range, so that clinical relevance is questionable. Further studies on the effect of lower GLS on performance parameters are necessary.

Strain Echocardiography in Acute COVID-19 and Post-COVID Syndrome: More than Just a Snapshot.

Speckle-tracking echocardiography (STE) has become an established, widely available diagnostic method in the past few years, making its value clear in cases of COVID-19 and the further course of the disease, including post-COVID syndrome. Since the beginning of the pandemic, many studies have been published on the use of STE in this condition, enabling, on the one hand, a better understanding of myocardial involvement in COVID-19 and, on the other, a better identification of risk to patients, although some questions remain unanswered in regard to specific pathomechanisms, especially in post-COVID patients. This review takes a closer look at current findings and potential future developments by summarising the extant data on the use of STE, with a focus on left and right ventricular longitudinal strain.

Monitoring of strength, inflammation and muscle function in allogenic stem-cell transplantation patients - a pilot study for novel biomarker and risk stratification determination.

Background: Low aerobic capacity is associated with an increased mortality risk in allogenic stem-cell transplantation (alloSCT) patients, but currently used risk scores in the pre-transplantation workup are still underestimating physical activity as a prognostic factor. Aim: To examine the physical condition, muscle function, blood inflammation and training adherence of alloSCT patients during inpatient time to identify potential biomarkers associated with development of myopathy and sarcopenia. Methods: Patients undergoing alloSCT were examined at four time points (T0: before alloSCT; Tha: hospital admission; T1: engraftment; T2: inpatient discharge). T0 included cardiopulmonary performance, body composition, grip and knee strength, motor skill tests (One-leg stand/Tinetti/Chair-rising), blood sampling (blood cell profiling and inflammation targets (Kynurenin/high sensitivity C-reactive Protein (hsCRP)/Tumor necrosis factor alpha (TNF-alpha)/Musclin/Galectin-3) and quality of life, state of health, fatigue, muscle weakness and physical activity by questionnaires (IPAQ/BSA/SARC-F/Fatigue). At T1 and T2, blood samples, grip strength and motor skill tests were repeated. Glucocorticoid dose and daily physical activity were documented during inpatient stay. Results: 26 of 35 included patients (4 females; age 55.58 ± 12.32 years; BMI 24.70 ± 3.27 kg/m2; VO2peak 16.55 ± 4.06 ml/min/kg) could proceed to alloSCT. Grip strength and Tinetti decreased from T0 until T2, no difference in Chair-rising test, One-leg and Tandem stand. All patients engrafted after 24.9 days ± 3.9 days. HsCRP and Kynurenine increased from T0 to T1, decreased at T2. TNF-alpha (T0vsT2/T1vsT2) and Musclin (T0vsT1) decreased. At T2, Galectin-3 was higher compared to T0/T1. Correlation analysis of grip strength and inflammatory markers revealed a positive correlation with TNF-alpha at T2. 50% of patients documented physical activity and questionnaire and reported a 50%-reduction of daily endurance and strength training between T1 to T2. Conclusion: Allogeneic stem-cell transplantation is associated with immune system vulnerability due to conditioning, increased inflammation and fatigue, and loss of muscle strength and function. In addition to hsCRP, Kynurenine seems to be a reliable biomarker to monitor acute and regenerative inflammation status of alloSCT patients, while Musclin and Galectin-3 may be added to physiological assessment regarding myopathy and sarcopenia. Grip strength and daily activity level should be documented by professionals to identify risk patients early and support them with optimal (exercise) therapy.

Recovery of performance and persistent symptoms in athletes after COVID-19.

INTRODUCTION: After the acute Sars-CoV-2-infection, some athletes suffer from persistent, performance-impairing symptoms, although the course of the disease is often mild to moderate. The relation between cardiopulmonary performance and persistent symptoms after the acute period is still unclear. In addition, information about the development of this relationship is lacking. OBJECTIVE: To assess the prevalence of persistent symptoms over time and their association with the performance capability of athletes. METHODS: We conducted two cardiopulmonary exercise tests (CPET) in a three months interval with 60 athletes (age: 35.2±12.1 years, 56.7% male) after infection with Sars-CoV-2 (t0: study inclusion; t1: three months post t0). At each examination, athletes were asked about their persistent symptoms. To evaluate the change of Peak VO2/BM (Body Mass) between the time before infection and the first examination, the VO2/BM (predVO2) before infection was predicted based on anthropometric data and exercise history of the athletes. For data analysis, athletes were grouped according to their symptom status (symptom-free, SF; persistent symptoms, PS) and its progression from the first to the second examination 1) SF-SF, 2) PS-SF and 3) PS-PS. RESULTS: Comparing the SF and PS groups at t0, significant differences for Max Power/BM, Max Power/lbm (lean body mass), Peak VO2, Peak VO2/BM, Peak VO2/lbm, Peak VO2/HR, Peak VE, Peak Vt and VE/VCO2-Slope were observed. Regarding the progression over three months, an increase in Max Power/BM was shown in SF-SF and PS-SF (tendency). Max Power/lbm increased in SF-SF and PS-PS (tendency). A decrease of VE/VCO2-Slope in PS-PS was found. CONCLUSION: COVID-19 led to a decline in performance that was greater in PS than in SF. Additionally, PS had decreased ventilatory parameters compared to SF. Furthermore, an improvement over time was observed in some CPET parameters and a partial recovery was observed judging by the decrease in various symptoms.

Two-year follow-up after a six-week high-intensity training intervention study with breast cancer patients: physiological, psychological and immunological differences.

PURPOSE: Previously we demonstrated the feasibility of a six-week-long combination of high-intensity interval endurance and strength training (HIT/HIRT) for women with nonmetastatic breast cancer leading to improvements in psychological well-being and performance. Now we report results of a 24-month follow-up. METHODS: Previous intervention (IG, n = 10; 58.7 ± 8.4yrs) and control group (CG, n = 9; 58.8 ± 6.6yrs) were asked for follow-up examinations 12 (T12) and 24 months (T24) after cessation of the supervised training (POST). Medical history, mental well-being, performance and immunological variables were analyzed with respect to intervention start (PRE). RESULTS: IG maximum oxygen consumption (⩒O2peak) 12%-improved POST (p = 0.05) and declined to baseline values T24, while CG ⩒O2peak increased 12% T24 (p = 0.01). IG strength (1RM) increased 31% POST (p < 0.001) and remained above baseline level T24 (p = 0.003), whereas CG 1RM slightly improved T24 (+19%, p = 0.034). IG Anxiety and Depression decreased POST and did not change until T24. IG C-reactive protein decreased POST and increased to pre-exercise levels T24. CG immunological/inflammatory/life quality markers did not change. CONCLUSIONS: Six weeks of HIT/HIRT by breast cancer patients can induce similar beneficial effects like two years of convalescence, but outcomes were unstable and showed a fast backslide in aerobic capacity, activity level and in pro-inflammatory state within 12 months.IMPLICATIONS FOR REHABILITATIONHigh-intensity interval endurance and strength training (HIT/HIRT) for female breast cancer patients was shown to improve psychological well-being and performance, but long-term effects/adherence are unknown.Significant backslides in aerobic capacity, activity level as well as in the pro-inflammatory response after one and two years are observed and should be monitored.Continuous supervision and/or support of breast cancer patients before, during, and after medical care due to poor training adherence when voluntarily executed is recommended.

The ELSA trial: single versus combinatory effects of non-prohibited beta-2 agonists on skeletal muscle metabolism, cardio-pulmonary function and endurance performance-study protocol for a randomized 4-way balanced cross-over trial.

BACKGROUND: Asthma and/or airway hyper-responsiveness (AHR) are common in elite endurance athletes with a high prevalence rate of beta-2 adrenoreceptor (beta-2) agonists use. Nevertheless, there are data on dose-dependent ergogenic effects of beta-2 agonists suggesting increased muscle strength, endurance and neuromuscular performance. Therefore, most beta-2 agonists belong to the World Anti Doping Agency (WADA) list of prohibited substances and it is tempting to speculate that illegitimate use of beta-2 agonists might be a common practice to boost performance in competitive sports. It is currently unknown whether or not inhaled beta-2 agonists enhance performance by stimulatory effects in skeletal and cardiac muscle. METHODS: The ELSA trial is a double-blinded, placebo-controlled, randomized, balanced, four-way cross-over study. Study participants (n=24, 12 ♀, 12 ♂) complete four study arms (i.e. periods with treatment A, placebo; B, salbutamol; C, formoterol; D, formoterol + salbutamol) in random order after an initial preliminary testing session. Participants inhale the study medication 20 min before the 10-min time trial (TT; exercise performance test), where participants cycle 10 min at the highest possible workload. Cardiac output is measured continuously. A skeletal muscle biopsy is collected 3 h after the TT. Study endpoints include measures of skeletal muscle expression of nuclear receptors, hormones and cytokine levels, urinary and plasma concentrations of salbutamol and formoterol, circulating cardiac markers, cardiopulmonary function and exercise performance (average power and peak power during the TT). Blood and urine are collected and respiratory testing is performed 24 h post TT. This clinical trial evaluates the potential performance-enhancing effects of non-prohibited, not medically indicated inhaled short- and long-acting beta-2 agonists on skeletal muscle gene expression, endocrine regulation, cardiac biomarkers, cardiopulmonary function and acute endurance exercise performance. These data will be used by WADA to adapt the annually published list of prohibited substances (WADA 2021) and will be published in scientific journals. TRIAL REGISTRATION: The trial is registered at the European Clinical Trials Database (Eudra CT) with the number: 2015-005598-19 as well as at the German register for clinical studies (DRKS number 00010574 ).

Sarcopenia Screening Allows Identifying High-Risk Patients for Allogenic Stem Cell Transplantation.

Allogenic stem cell transplantation (aSCT) is the only potentially curative treatment for high-risk hematological diseases. Despite advancements in supportive measures, aSCT outcome is still affected by considerable transplant-related mortality. We implemented a new sarcopenia assessment prior to aSCT to evaluate its predictive capability for all-cause and non-relapse mortality. Therefore all patients initially scheduled for aSCT within a 25-month period were screened during pre-transplantation-routine for muscle mass, grip strength, and aerobic capacity (AC) by measuring peak oxygen uptake (VO2peak). Patients were assigned to one of five groups adapted according current sarcopenia guidelines. Primary endpoints were all-cause and non-relapse mortality within a follow up time of up to 12 months. A total of 178 patients were included and rated as normal (n = 48), impaired aerobic capacity (n = 56), pre-sarcopenic (n = 26), sarcopenic (n = 27), and severe sarcopenic (n = 22) without significant age-differences between groups. Patients presenting with sarcopenia showed a significant three-fold increase in all-cause and non-relapse mortality compared to patients with normal screening results. AC showed to be the strongest single predictor with a more than two-fold increase of mortality for low AC. We conclude that risk stratification based on combination of muscle mass, grip strength, and AC allowed identifying a subgroup with increased risk for complications in patients undergoing aSCT.

Differences in V˙O2max Measurements Between Breath-by-Breath and Mixing-Chamber Mode in the COSMED K5.

PURPOSE: Automated metabolic analyzers are frequently utilized to measure maximal oxygen consumption (V˙O2max). However, in portable devices, the results may be influenced by the analyzer's technological approach, being either breath-by-breath (BBB) or dynamic micro mixing chamber mode (DMC). The portable metabolic analyzer K5 (COSMED, Rome, Italy) provides both technologies within one device, and the authors aimed to evaluate differences in V˙O2max between modes in endurance athletes. METHODS: Sixteen trained male participants performed an incremental test to voluntary exhaustion on a cycle ergometer, while ventilation and gas exchange were measured by 2 structurally identical COSMED K5 metabolic analyzers synchronously, one operating in BBB and the other in DMC mode. Except for the flow signal, which was measured by 1 sensor and transmitted to both devices, the devices operated independently. V˙O2max was defined as the highest 30-second average. RESULTS: V˙O2max and V˙CO2@V˙O2max were significantly lower in BBB compared with DMC mode (-4.44% and -2.71%), with effect sizes being large to moderate (ES, Cohen d = 0.82 and 1.87). Small differences were obtained for respiratory frequency (0.94%, ES = 0.36), minute ventilation (0.29%, ES = 0.20), and respiratory exchange ratio (1.74%, ES = 0.57). CONCLUSION: V˙O2max was substantially lower in BBB than in DMC mode. Considering previous studies that also indicated lower V˙O2 values in BBB at high intensities and a superior validity of the K5 in DMC mode, the authors conclude that the DMC mode should be selected to measure V˙O2max in athletes.

Inter- and intra-unit reliability of the COSMED K5: Implications for multicentric and longitudinal testing.

PURPOSE: To evaluate the intra-unit (RELINTRA) and inter-unit reliability (RELINTER) of two structurally identical units of the metabolic analyser K5 (COSMED, Rome, Italy) that allows to utilize either breath-by-breath (BBB) or dynamic mixing chamber (DMC) technology. METHODS: Identical flow- and gas-signals were transmitted to both K5s that always operated simultaneously either in BBB- or DMC-mode. To assess RELINTRA and RELINTER, a metabolic simulator was applied to simulate four graded levels of respiration. RELINTRA and RELINTER were expressed as typical error (TE%) and Intraclass Correlation Coefficient (ICC). To assess also inter-unit differences via natural respiratory signals, 12 male athletes performed one incremental bike step test each in BBB- and DMC-mode. Inter-unit differences within biological testing were expressed as percentages. RESULTS: In BBB, TE% of RELINTRA ranged 0.30-0.67 vs. RELINTER 0.16-1.39 and ICC ranged 0.57-1.00 vs. 0.09-1.00. In DMC, TE% of RELINTRA ranged 0.38-0.90 vs. RELINTER 0.03-0.86 and ICC ranged 0.22-1.00 vs. 0.52-1.00. Mean inter-unit differences ranged -2.30-2.20% (Cohen's ds (ds) 0.13-1.52) for BBB- and -0.55-0.61% (ds 0.00-0.65) for DMC-mode, respectively. Inter-unit differences for [Formula: see text] and RER were significant (p < 0.05) at each step. CONCLUSION: Two structurally identical K5-units demonstrated accurate RELINTRA with TE < 2.0% and similar RELINTER during metabolic simulation. During biological testing, inter-unit differences for [Formula: see text] and RER in BBB-mode were higher than 2% with partially large ES in BBB. Hence, the K5 should be allocated personally wherever possible. Otherwise, e.g. in multicenter studies, a decrease in total reliability needs to be considered especially when the BBB-mode is applied.

Beneficial Molecular Adaptations In BRCA-Mutation Carriers By Combined HIT/HIRT Intervention: Results From A Pilot Study.

: Based on growing evidence that breast cancer (BRCA) also plays a pivotal role in the regulation of skeletal muscle metabolism and the response to anti-oxidative stress, we examined the influence of regular exercise in human BRCA mutation carriers on their BRCA1 gene/protein expression and inflammatory/oxidative response. Sixteen BRCA-mutation carriers were assigned to an intervention (IG) or control group (CG). IG received a combination of high-intensity interval endurance (HIT) and strength training (HIRT) for six weeks, whereas CG received a low-intensity activity program. Before (T0) and at the end of the intervention (T1), muscle biopsy, physiological performance, blood withdrawal and anthropometry were obtained. Parameters included: Muscle BRCA1 gene/protein expression, inflammatory/oxidative stress, anti-oxidative capacity, peak oxygen capacity (VO2peak) and 1-repetition maximum (1-RM) at six different training machines. VO2peak and 1-RM of IG were increased at T1 compared to T0, whereas CG performance, physiological and molecular parameters remained unchanged. IG showed increased BRCA1 protein concentration as well as anti-oxidative capacity, whereas gene expression was unaltered. IG inflammatory and oxidative damage did not differ between time points. Combined HIT/HIRT increases aerobic and strength performance of BRCA-mutation carriers with up regulated BRCA1 protein expression and improved anti-oxidative status without showing an increased inflammatory response.

Objectively-Measured Light-Intensity Physical Activity and Risk of Cancer Mortality: A Meta-analysis of Prospective Cohort Studies.

BACKGROUND: The impact of light-intensity physical activity (LPA) in preventing cancer mortality has been questioned. To address this concern, the present meta-analysis aimed to quantify the association between objectively-measured LPA and risk of cancer mortality. METHODS: We conducted a systematic literature search in PubMed and Scopus to January 2020. Prospective cohort studies reporting the association between objectively-measured LPA using activity monitors (e.g., accelerometers) and risk of cancer mortality in the general population were included. The summary hazard ratios (HR) per 30 min/day of LPA and 95% confidence intervals (CI) were obtained using a random-effects model. Dose-response analysis was used to plot their relationship. RESULTS: Five prospective cohort studies were included, in which the definition of LPA based on accelerometer readings was mainly set within 100 to 2,100 counts/min. The summary HR for cancer mortality per 30 min/day of LPA was 0.86 (95% CI, 0.79-0.95; I 2 < 1%), and the association between LPA and risk reduction in cancer mortality was linearly shaped (P nonlinearity = 0.72). LPA exhibited a comparable magnitude of risk reduction in cancer mortality of moderate-to-vigorous physical activity regardless of equal time-length (0.87 per 30 min/day vs. 0.94 per 30 min/day, P interaction = 0.46) or equal amount (0.74 vs. 0.94 per 150 metabolic equivalents-min/day, P interaction = 0.11). Furthermore, replacing sedentary time by LPA of 30 min/day decreased the risk of cancer mortality by 9%. CONCLUSIONS: Objectively-measured LPA conferred benefits in decreasing the risk of cancer mortality. IMPACT: LPA should be considered in physical activity guidelines to decrease the risk of cancer mortality.

The COSMED K5 in Breath-by-Breath and Mixing Chamber Mode at Low to High Intensities.

PURPOSE: The portable metabolic analyzer COSMED K5 (Rome, Italy) allows for switching between breath-by-breath (BBB) and dynamic micro-mixing chamber (DMC) modes. This study aimed to evaluate the reliability and validity of the K5 in BBB and DMC at low, moderate, and high metabolic rates. METHODS: Two K5 simultaneously operated in BBB or DMC, whereas (i) a metabolic simulator (MS) produced four different metabolic rates (repeated eight times), and (ii) 12 endurance-trained participants performed bike exercise at 30%, 40%, 50%, and 85% of their individual power output at V˙O2max (repeated three times). K5 data were compared with predicted simulated values and consecutive Douglas bag measurements. RESULTS: Reliability did not differ significantly between BBB and DMC, whereas the typical error and intraclass correlation coefficients for oxygen uptake (V˙O2), carbon dioxide output (V˙CO2), and minute ventilation (V˙E) ranged from 0.27% to 6.18% and from 0.32 to 1.00 within four metabolic rates, respectively. Validity indicated by mean differences ranged between 0.61% and -2.05% for V˙O2, 2.99% to -11.04% for V˙CO2, and 0.93% to -6.76% for V˙E compared with MS and Douglas bag at low to moderate metabolic rates and was generally similar for MS and bike exercise. At high rates, mean differences for V˙O2 amounted to -4.63% to -7.27% in BBB and -0.38% to -3.81% in DMC, indicating a significantly larger difference of BBB at the highest metabolic rate. CONCLUSION: The K5 demonstrated accurate to acceptable reliability in BBB and DMC at all metabolic rates. Validity was accurate at low and moderate metabolic rates. At high metabolic rates, BBB underestimated V˙O2, whereas DMC showed superior validity. To test endurance athletes at high workloads, the DMC mode is recommended.