Much of the spotlight for coronavirus disease 2019 (COVID-19) is on the acute symptoms and recovery. However, many recovered patients face persistent physical, cognitive, and psychological symptoms well past the acute phase. Of these symptoms, fatigue is one of the most persistent and debilitating. In this “perspective article,” we define fatigue as the decrease in physical and/or mental performance that results from changes in central, psychological, and/or peripheral factors due to the COVID-19 disease and propose a model to explain potential factors contributing to post-COVID-19 fatigue. According to our model, fatigue is dependent on conditional and physiological factors. Conditional dependency comprises the task, environment, and physical and mental capacity of individuals, while physiological factors include central, psychological, and peripheral aspects. This model provides a framework for clinicians and researchers. However, future research is needed to validate our proposed model and elucidate all mechanisms of fatigue due to COVID-19.

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The primary purpose of this study was to determine the influence of load compliance on time to failure during sustained isometric contractions performed with the elbow flexor muscles at four submaximal target forces. Subjects pulled against a rigid restraint during the force task and maintained a constant elbow angle, while supporting an equivalent inertial load during the position task. Each task was sustained for as long as possible. Twenty-one healthy adults (23 ± 6 yr; 11 men) participated in the study. The maximal voluntary contraction (MVC) force was similar (P = 0.95) before the subjects performed the force and position tasks at each of the four target forces: 20, 30, 45, and 60% of MVC force. The time to task failure was longer for the force tasks (576 ± 80 and 325 ± 70 s) than for the position tasks (299 ± 77 and 168 ± 35 s) at target forces of 20 and 30% (P < 0.001), but was similar for the force tasks (178 ± 35 and 86 ± 14 s) and the position tasks (132 ± 29 and 87 ± 14 s) at target forces of 45 and 60% (P > 0.19). The briefer times to failure for the position task at the lower forces were accompanied by greater rates of increase in elbow flexor muscle activity, mean arterial pressure, heart rate, and rating of perceived exertion. There was no difference in the estimates of external mechanical work at any target force. The dominant mechanisms limiting time to failure of sustained isometric contractions with the elbow flexor muscles appear to change at target forces between 30 and 45% MVC, with load compliance being a significant factor at lower forces only.

To identify the underlying physiological mechanisms for the difference in the time to failure for two types of fatiguing contractions, 20 subjects performed force and position tasks with the elbow flexor muscles at a comparable net muscle torque for a similar duration. Prior to terminating each task, blood flow was occluded to estimate the relative amount of feedback transmitted by small-diameter afferents to the spinal cord. Mean arterial pressure at the conclusion of the fatiguing contraction increased similarly for the two tasks (force: 119% +/- 14%; position: 114% +/- 15%). However, the final values for the electromyographic activity for the elbow flexor muscles (26% +/- 14% and 21% +/- 11%, respectively; P < 0.05), and the increase in the fluctuations in acceleration and force (225% +/- 152% and 154% +/- 53%, respectively; P < 0.05) in the sagittal plane, were significantly greater during the position task compared with the force task. These results suggest a different balance in the excitatory and inhibitory inputs to the spinal motor neurons for the two tasks, which has implications for the design of work tasks and exercise prescription in rehabilitation.

Time to failure and electromyogram activity were measured during two types of sustained submaximal contractions with the elbow flexors that required each subject to exert the same net muscle torque with the forearm in two different postures. Twenty men performed the tasks, either by maintaining a constant force while pushing against a force transducer (force task), or by supporting an equivalent load while maintaining a constant elbow angle (position task). The time to failure for the position task with the elbow flexed at 1.57 rad and the forearm horizontal was less than that for the force task (5.2 +/- 2.6 and 8.8 +/- 3.6 min, P = 0.003), whereas it was similar when the forearm was vertical (7.9 +/- 4.1 and 7.8 +/- 4.5 min, P = 0.995). The activity of the rotator cuff muscles was greater during the position tasks (25.1 +/- 10.1% maximal voluntary contraction) compared with the force tasks (15.2 +/- 5.4% maximal voluntary contraction, P < 0.001) in both forearm postures. However, the rates of increase in electromyogram of the accessory muscles and mean arterial pressure were greater for the position task only when the forearm was horizontal (P < 0.05), whereas it was similar for the elbow flexors. These findings indicate that forearm posture influences the difference in the time to failure for the two fatiguing contractions. When there was a difference between the two tasks, the task with the briefer time to failure involved greater rates of increase in accessory muscle activity and mean arterial pressure.

The study compared positron emission tomography/computed tomography (PET/CT) of [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]-FDG) uptake by skeletal muscles and the amount of muscle activity as indicated by surface electromyographic (EMG) recordings when young and old men performed fatiguing isometric contractions that required either force or position control. EMG signals were recorded from thigh muscles of six young men (26 ± 6 yr) and six old men (77 ± 6 yr) during fatiguing contractions with the knee extensors. PET/CT scans were performed immediately after task failure. Glucose uptake in 24 leg muscles, quantified as standardized uptake values, was greater for the old men after the force task and differed across tasks for the young men (force, 0.64 ± 0.3 g/ml; position, 0.73 ± 0.3 g/ml), but not the old men (force, 0.84 ± 0.3 g/ml; position, 0.79 ± 0.26 g/ml) (age × task interaction; P < 0.001). In contrast, the rate of increase in EMG amplitude for the agonist muscles was greater for the young men during the two contractions and there was no difference for either group of subjects in the rate of increase in EMG amplitude across the two tasks. The imaging estimates of glucose uptake indicated age- and task-dependent differences in the spatial distribution of [(18)F]-FDG uptake by skeletal muscles during fatiguing contractions. The findings demonstrate that PET/CT imaging of [(18)F]-FDG uptake, but not surface EMG recordings, detected the modulation of muscle activity across the fatiguing tasks by the young men but not the old men.

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Twenty subjects participated in four experiments designed to compare time to task failure and motor-unit recruitment threshold during contractions sustained at 15% of maximum as the elbow flexor muscles either supported an inertial load (position task) or exerted an equivalent constant torque against a rigid restraint (force task). Subcutaneous branched bipolar electrodes were used to record single motor unit activity from the biceps brachii muscle during ramp contractions performed before and at 50 and 90% of the time to failure for the position task during both fatiguing contractions. The time to task failure was briefer for the position task than for the force task (P=0.0002). Thirty and 29 motor units were isolated during the force and position tasks, respectively. The recruitment threshold declined by 48 and 30% (P=0.0001) during the position task for motor units with an initial recruitment threshold below and above the target force, respectively, whereas no significant change in recruitment threshold was observed during the force task. Changes in recruitment threshold were associated with a decrease in the mean discharge rate (-16%), an increase in discharge rate variability (+40%), and a prolongation of the first two interspike intervals (+29 and +13%). These data indicate that there were faster changes in motor unit recruitment and rate coding during the position task than the force task despite a similar net muscle torque during both tasks. Moreover, the results suggest that the differential synaptic input observed during the position task influences most of the motor unit pool.