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.

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To test whether high circulating insulin concentrations influence the transport of β-alanine into skeletal muscle at either saturating or subsaturating β-alanine concentrations, we conducted two experiments whereby β-alanine and insulin concentrations were controlled. In experiment 1, 12 men received supraphysiological amounts of β-alanine intravenously (0.11 g·kg−1·min−1 for 150 min), with or without insulin infusion. β-Alanine and carnosine were measured in muscle before and 30 min after infusion. Blood samples were taken throughout the infusion protocol for plasma insulin and β-alanine analyses. β-Alanine content in 24-h urine was assessed. In experiment 2, six men ingested typical doses of β-alanine (10 mg/kg) before insulin infusion or no infusion. β-Alanine was assessed in muscle before and 120 min following ingestion. In experiment 1, no differences between conditions were shown for plasma β-alanine, muscle β-alanine, muscle carnosine and urinary β-alanine concentrations (all P > 0.05). In experiment 2, no differences between conditions were shown for plasma β-alanine or muscle β-alanine concentrations (all P > 0.05). Hyperinsulinemia did not increase β-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the Vmax of β-alanine transporter TauT nor when it was below saturation. These results suggest that increasing insulin concentration is not necessary to maximize β-alanine transport into muscle following β-alanine intake.

The post-acute phase of 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 (VO2) kinetics and cardiopulmonary function in survivors of severe COVID-19 three to six months after intensive care unit (ICU) hospitalization. Thirty-five COVID-19 survivors previously admitted to ICU (5±1 months 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 maximal graded cardiopulmonary exercise test (CPX) with an initial 3-minute period of a constant, moderate-intensity walk (i.e., below ventilatory threshold, VT). VO2 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 a 11% longer (P=0.046) half-time of recovery of VO2 (T1/2VO2) at the off-transient. CPX also revealed cardiopulmonary impairments following COVID-19. VO2peak, percent-predicted VO2peak and VO2VT 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). Additionally, 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 VO2 is adjusted to changes in energy demands.

Creatine has been considered an effective ergogenic aid for several decades; it can help athletes engaged in a variety of sports and obtain performance gains. Creatine supplementation increases muscle creatine stores; several factors have been identified that may modify the intramuscular increase and subsequent performance benefits, including baseline muscle Cr content, type II muscle fibre content and size, habitual dietary intake of Cr, aging, and exercise. Timing of creatine supplementation in relation to exercise has recently been proposed as an important consideration to optimise muscle loading and performance gains, although current consensus is lacking regarding the ideal ingestion time. Research has shifted towards comparing creatine supplementation strategies pre-, during-, or post-exercise. Emerging evidence suggests greater benefits when creatine is consumed after exercise compared to pre-exercise, although methodological limitations currently preclude solid conclusions. Furthermore, physiological and mechanistic data are lacking, in regard to claims that the timing of creatine supplementation around exercise moderates gains in muscle creatine and exercise performance. This review discusses novel scientific evidence on the timing of creatine intake, the possible mechanisms that may be involved, and whether the timing of creatine supplementation around exercise is truly a real concern.

Importance: Strength and muscle mass are predictors of relevant clinical outcomes in critically ill patients, but in hospitalized patients with COVID-19 remains to be determined. Objective: To investigate whether muscle strength or muscle mass are predictive of hospital length of stay (LOS) in patients with moderate to severe COVID-19. Design: Prospective observational study. Setting: Clinical Hospital of the School of Medicine of the University of Sao Paulo. Participants: One hundred ninety-six patients were evaluated. Ten patients did not test positive for SARS-CoV-2 during hospitalization and were excluded from the analyses. The sample comprised patients of both sexes (50% male) with a mean age (SD) of 59 (SD = 15) years, body mass index of 29.5 (SD = 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. Main outcome: The outcome was LOS, defined as time from hospital admission to medical discharge. Results: The crude Hazard Ratio (HR) for LOS was greatest for handgrip strength comparing the strongest vs. other patients (1.54 [95%CI: 1.12 to 2.12; p = 0.008]). 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 to 1.19; p = 0.008]). The magnitude of these associations remained consistent and statistically significant after adjusting for other covariates. Mean LOS was shorter for the strongest patients (7.5 , SD = 6.1 days) vs. others (9.2, SD = 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 (1.17 [95%CI: 1.01 to 1.36; p = 0.037]); however, we found increased uncertainty in the estimate with the addition of other covariates (1.18 [95%CI: 0.97 to 1.43; p = 0.092]). Evidence was also obtained associating longer hospital stays for patients with the lowest values for vastus lateralis cross-sectional area (0.69 [95%CI: 0.50 to 0.95; p = 0.025). Mean LOS for the patients with the lowest muscle cross-sectional area was longer (10.8, SD = 8.8 days) vs. others (7.7, SD = 7.2 days). Conclusions and Relevance: 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.

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 (&lt;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.

Higher daily protein intake, with an emphasis on leucine content, is thought to mitigate age-related anabolic resistance, potentially counteracting age-related morphological and functional declines. The present study investigated potential associations between total daily leucine intake and dependent variables, including quadriceps muscle cross-sectional area (CSA) and maximum dynamic muscle strength (1-RM) in a cohort of healthy free-living older individuals of both sexes (n = 67; 34/33 men/women). Participants performed three 24 h dietary recalls and underwent a magnetic resonance imaging exam followed by 1-RM tests. Our results demonstrate moderate associations between total daily leucine and both quadriceps CSA (r = 0.42; p = 0.004) and 1-RM (r = 0.45; p = 0.001). Furthermore, our exploratory biphasic linear regression analyses, adjusted for sex, age, and protein intake relative to body weight, revealed a plateau for daily leucine intake and muscle mass and muscle strength (~7.6–8.0 g·day−1) in older adults. In conclusion, we demonstrated that total daily leucine intake is associated with muscle mass and strength in healthy older individuals and this association remains after controlling for multiple factors, including overall protein intake. Furthermore, our breakpoint analysis revealed non-linearities and a potential threshold for habitual leucine intake, which may help guide future research on the effects of chronic leucine intake in age-related muscle loss.