Influence of Manual Diaphragm Release Technique Combined with Inspiratory Muscle Training on Selected Persistent Symptoms in Men with Post-Covid-19 Syndrome: A Randomized Controlled Trial.

OBJECTIVE: To determine whether the addition of manual diaphragm release to an inspiratory muscle training programme is more  effective than inspiratory muscle training alone in reducing blood pressure, dyspnoea, fatigue, and aerobic performance capacity in men with post-COVID-19 syndrome. DESIGN: A prospective, randomized-controlled trial. SETTING: Chest Disease Department, Outpatient Clinic, Cairo University, Egypt. PARTICIPANTS: Fifty-two men with post-COVID-19 syndrome were allocated randomly to the study and control groups. INTERVENTION: The study group underwent diaphragm release plus inspiratory muscle training, whereas the control group received inspiratory muscle training only. OUTCOME MEASURES: All patients were assessed with the following measures at baseline and 6 weeks postintervention: maximum static inspiratory pressure for inspiratory muscle strength, peripheral arterial blood pressure, Modified Medical Research Council scale for dyspnoea, Fatigue Severity Scale, serum lactate level, and 6-min walk test distance for aerobic performance. RESULTS: All outcome measures showed a significant improvement in favour of the study group (p < 0.001) over the control group. However, maximum static inspiratory pressure increased significantly, by 48.17% (p < 0.001) in the study group with no significant change in the control group. CONCLUSION: Addition of manual diaphragm release to an inspiratory muscle training programme potentiates the role of inspiratory muscle training in the management of men with symptomatic post-COVID-19 syndrome.

The Effects of COVID-19 on Skeletal Muscles, Muscle Fatigue and Rehabilitation Programs Outcomes.

Background and Objectives: Consequences due to infection with SARS-CoV-2 virus can have a direct impact on skeletal muscle, due to the fact that both cardiac and skeletal muscle tissue show robust ACE2(angiotensin-converting enzyme 2) expression, suggesting a potential susceptibility to SARS-CoV-2 infection in both types of tissues. From the articles analyzed we concluded that the musculoskeletal damage is firstly produced by the inflammatory effects, cytokine storm and muscle catabolism. However, myopathy, polyneuropathy and therapies such as corticoids were also considered important factors in muscle fatigue and functional incapacity. Pulmonary rehabilitation programs and early mobilization had a highly contribution during the acute phase and post-illness recovery process and helped patients to reduce dyspnea, increase the capacity of physical effort, overcome psychological disorders and improved the quality of their life. Materials and Methods: We have included in this review 33 articles that contain data on muscle damage following SARS-CoV-2 infection. We used the following keywords to search for articles: SARS-CoV-2, COVID-19, muscle weakness, muscle disease, muscle fatigue, neurological disorders. As a search strategy we used PubMed, Cochrane Database of Systematic Reviews; Database of Abstracts of Reviews of Effects and Health Technology Assessment Database to collect the information. We also have chosen the most recent articles published in the last 5 years. Conclusions: Muscular damage, as well as the decrease in the quality of life, are often a consequence of severe SARS-CoV-2 infection through: systemic inflammation, corticotherapy, prolonged bed rest and other unknown factors. Pulmonary rehabilitation programs and early mobilization had a highly contribution during the acute phase and post-illness recovery process and helped patients to reduce dyspnea, increase the capacity of physical effort, overcome psychological disorders and improve the quality of their life.

Muscle fatigability and post-acute COVID-19 syndrome: A case study.

The acute phase of COVID-19 has been well studied, however with increasing post-acute COVID-19 syndrome, much is unknown about its long-term effects. A common symptom in both the acute and post-acute phases has been fatigue, assessed predominantly qualitatively. Here we present a case study objectively assessing neuromuscular fatiguability in a young male (27 year, 1.85 m, 78 kg) who continues to experience COVID-19 related fatigue and cognitive dysfunction, including other symptoms, 12+ months post-infection. Prior to infection, he was part of a neuromuscular study forming the basis of our pre-COVID-19 results. The study was repeated 12 months post-COVID-19 infection. Muscle strength, endurance, torque steadiness, voluntary activation, twitch properties, electromyography, and compound muscle action potential were obtained and compared pre- and post-COVID-19. All measurements were done using a dorsiflexion dynamometer in which the participant also was asked to produce a one-minute fatiguing maximal voluntary contraction. Muscle strength, voluntary activation, and fatigability (slope of torque) showed no meaningful differences, suggesting intrinsic neuromuscular properties are not affected. However, torque steadiness was impaired three-fold in the post- compared with pre-COVID-19 test. The participant also reported a higher level of perceived exertion subjectively and a continued complaint of fatigue. These findings indicate that muscle fatiguability in post-acute COVID-19 syndrome may not be a limitation of the muscle and its activation, but a perceptual disconnect caused by cognitive impairments relating to physical efforts. This case report suggests the potential value of larger studies designed to assess these features in post-acute COVID-19 syndrome.

COVID-19 disease in professional football players: symptoms and impact on pulmonary function and metabolic power during matches.

This study aimed at: (1) Reporting COVID-19 symptoms and duration in professional football players; (2) comparing players' pulmonary function before and after COVID-19; (3) comparing players' metabolic power (Pmet ) before and after COVID-19. Thirteen male players (Age: 23.9 ± 4.0 years, V̇O2peak : 49.7 ± 4.0 mL/kg/min) underwent a medical screening and performed a running incremental step test and a spirometry test after COVID-19. Spirometric data were compared with the ones collected at the beginning of the same season. Players' mean Pmet of the 10 matches played before COVID-19 was compared with mean Pmet of the 10 matches played after COVID-19. Players completed a questionnaire on COVID-19 symptoms and duration 6 months following the disease. COVID-19 positivity lasted on average 15 ± 5 days. "General fatigue" and "muscle fatigue" symptoms were reported by all players during COVID-19 and persisted for 77% (general fatigue) and 54% (muscle fatigue) of the players for 37 ± 28 and 38 ± 29 days after the disease, respectively. No significant changes in spirometric measurements were found after COVID-19, even though some impairments at the individual level were observed. Conversely, a linear mixed-effects model analysis showed a significant reduction of Pmet (-4.1 ± 3.5%) following COVID-19 (t = -2.686, p < 0.05). "General fatigue" and "muscle fatigue" symptoms may persist for several weeks following COVID-19 in professional football players and should be considered for a safer return to sport. Players' capacity to compete at high intensities might be compromised after COVID-19.

STIM1 and ORAI1 mutations leading to tubular aggregate myopathies are sensitive to the Store-operated Ca2+-entry modulators CIC-37 and CIC-39.

Gain-of-function mutations on STIM1 and ORAI1 genes are responsible for an increased store-operated calcium entry, and underlie the characteristic symptoms of three overlapping ultra-rare genetic disorders (i.e tubular aggregate myopathy, Stormorken syndrome, York platelet syndrome) that can be grouped as tubular aggregate myopathies. These mutations lead to a wide spectrum of defects, which usually include muscle weakness and cramps. Negative modulators of store-operated Ca2+-entry targeting wild-type STIM1 and ORAI1 have entered clinical trials for a different array of disorders, including pancreatitis, COVID-19, cancer, and autoimmune disorders and, while efficacy data is awaited, safety data indicates tolerability of this STIM1/ORAI1 mutations are amenable to pharmacological intervention. If this were so, given that there are no approved treatments or clinical trials ongoing for these rare disorders, it could be envisaged that these agents could also rehabilitate tubular aggregate myopathy patients. In the present contribution we characterized the Ca2+-entry patterns induced by eleven STIM1 and three ORAI1 mutations in heterologous systems or in patient-derived cells, i.e. fibroblasts and myotubes, and evaluated the effect of CIC-37 and CIC-39, two novel store-operated calcium entry modulators. Our data show that all STIM1 and ORAI1 gain-of-function mutations tested, with the possible exception of the R304Q STIM1 mutation, are amenable to inhibition, albeit with slightly different sensitivities, paving the way to the development of SOCE modulators in tubular aggregate myopathies.

Molecular Mechanisms of Muscle Fatigue.

Muscle fatigue (MF) declines the capacity of muscles to complete a task over time at a constant load. MF is usually short-lasting, reversible, and is experienced as a feeling of tiredness or lack of energy. The leading causes of short-lasting fatigue are related to overtraining, undertraining/deconditioning, or physical injury. Conversely, MF can be persistent and more serious when associated with pathological states or following chronic exposure to certain medication or toxic composites. In conjunction with chronic fatigue, the muscle feels floppy, and the force generated by muscles is always low, causing the individual to feel frail constantly. The leading cause underpinning the development of chronic fatigue is related to muscle wasting mediated by aging, immobilization, insulin resistance (through high-fat dietary intake or pharmacologically mediated Peroxisome Proliferator-Activated Receptor (PPAR) agonism), diseases associated with systemic inflammation (arthritis, sepsis, infections, trauma, cardiovascular and respiratory disorders (heart failure, chronic obstructive pulmonary disease (COPD))), chronic kidney failure, muscle dystrophies, muscle myopathies, multiple sclerosis, and, more recently, coronavirus disease 2019 (COVID-19). The primary outcome of displaying chronic muscle fatigue is a poor quality of life. This type of fatigue represents a significant daily challenge for those affected and for the national health authorities through the financial burden attached to patient support. Although the origin of chronic fatigue is multifactorial, the MF in illness conditions is intrinsically linked to the occurrence of muscle loss. The sequence of events leading to chronic fatigue can be schematically denoted as: trigger (genetic or pathological) -> molecular outcome within the muscle cell -> muscle wasting -> loss of muscle function -> occurrence of chronic muscle fatigue. The present review will only highlight and discuss current knowledge on the molecular mechanisms that contribute to the upregulation of muscle wasting, thereby helping us understand how we could prevent or treat this debilitating condition.