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.

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.