Objectives People living with long COVID describe a high symptom burden, and a more detailed assessment is needed to inform rehabilitation recommendations. The objectives were to use validated questionnaires to measure the severity of fatigue and compare this with normative data and thresholds for clinical relevance in other diseases; measure and describe the impact of postexertional malaise (PEM); and assess symptoms of dysfunctional breathing, self-reported physical activity, and health-related quality of life. Methods This was an observational study with a cross-sectional survey design (data collection from February 2021 to April 2021). Eligible participants were adults experiencing persistent symptoms due to COVID-19 that did not predate the confirmed or suspected infection. Questionnaires included the Functional Assessment of Chronic Illness Therapy–Fatigue Scale (FACIT-F) and the DePaul Symptom Questionnaire–Post-Exertional Malaise. Results After data cleaning, 213 participants were included in the analysis. The total FACIT-F score was 18 (SD = 10) (where the score can range from 0 to 52 and a lower score indicates more severe fatigue), and 71.4% were experiencing chronic fatigue. Postexertional symptom exacerbation affected most participants, and 58.7% met the PEM scoring thresholds used in people living with myalgic encephalomyelitis/chronic fatigue syndrome. Conclusion Long COVID is characterized by chronic fatigue that is clinically relevant and at least as severe as fatigue in several other clinical conditions. PEM is a significant challenge for this patient group. Because of the potential for setbacks and deteriorated function following overexertion, fatigue and postexertional symptom exacerbation must be monitored and reported in clinical practice and in studies involving interventions for people with long COVID. Impact Physical therapists working with people with long COVID should measure and validate the patient’s experience. Postexertional symptom exacerbation must be considered, and rehabilitation needs to be carefully designed based on individual presentation. Beneficial interventions might first ensure symptom stabilization via pacing, a self-management strategy for the activity that helps minimize postexertional malaise.

Aims We asked whether acclimatisation to chronic hypoxia (CH) attenuates the level of supraspinal fatigue that is observed after locomotor exercise in acute hypoxia (AH). Methods Seven recreationally-active participants performed identical bouts of constant-load cycling (131±39W, 10.1±1.4min) on three occasions: 1) in normoxia (N, PIO2, 147.1mmHg); 2) in AH (FIO2, 0.105; PIO2, 73.8mmHg); 3) after 14 days in CH (5,260m; PIO2, 75.7mmHg). Throughout trials, prefrontal-cortex tissue oxygenation and middle cerebral artery blood velocity (MCAV) were assessed using near-infrared-spectroscopy and transcranial Doppler sonography. Pre- and post-exercise twitch responses to femoral nerve stimulation and transcranial magnetic stimulation were obtained to assess neuromuscular and corticospinal function. Results In AH, prefrontal oxygenation declined at rest (Δ7±5%) and end-exercise (Δ26±13) (P<0.01); the degree of deoxygenation in AH was greater than N and CH (P<0.05). The cerebral O2 delivery index (MCAv×CaO2) was 19±14% lower during the final minute of exercise in AH compared to N (P=0.013) and 20±12% lower compared to CH (P=0.040). Maximum voluntary and potentiated twitch force were decreased below baseline after exercise in AH and CH, but not N. Cortical voluntary activation decreased below baseline after exercise in AH (Δ11%, P=0.014), but not CH (Δ6%, P=0.174) or N (Δ4%, P=0.298). A twofold greater increase in motor evoked potential amplitude was evident after exercise in CH compared to AH and N. Conclusion These data indicate that exacerbated supraspinal fatigue after exercise in AH is attenuated after 14 days of acclimatisation to altitude. The reduced development of supraspinal fatigue in CH may have been attributable to increased corticospinal excitability, consequent to an increased cerebral O2 delivery.

The development of muscle fatigue is oxygen (O2)-delivery sensitive [arterial O2 content (CaO2) × limb blood flow (QL)]. Locomotor exercise in acute hypoxia (AH) is, compared with sea level (SL), associated with reduced CaO2 and exaggerated inspiratory muscle work (Winsp), which impairs QL, both of which exacerbate fatigue individually by compromising O2 delivery. Since chronic hypoxia (CH) normalizes CaO2 but exacerbates Winsp, we investigated the consequences of a 14-day exposure to high altitude on exercise-induced locomotor muscle fatigue. Eight subjects performed the identical constant-load cycling exercise (138 ± 14 W; 11 ± 1 min) at SL (partial pressure of inspired O2, 147.1 ± 0.5 Torr), in AH (73.8 ± 0.2 Torr), and in CH (75.7 ± 0.1 Torr). Peripheral fatigue was expressed as pre- to postexercise percent reduction in electrically evoked potentiated quadriceps twitch force (ΔQtw,pot). Central fatigue was expressed as the exercise-induced percent decrease in voluntary muscle activation (ΔVA). Resting CaO2 at SL and CH was similar, but CaO2 in AH was lower compared with SL and CH (17.3 ± 0.5, 19.3 ± 0.7, 20.3 ± 1.3 ml O2/dl, respectively). Winsp during exercise increased with acclimatization (SL: 387 ± 36, AH: 503 ± 53, CH: 608 ± 67 cmH2O·s(-1)·min(-1); P < 0.01). Exercise at SL did not induce central or peripheral fatigue. ΔQtw,pot was significant but similar in AH and CH (21 ± 2% and 19 ± 3%; P = 0.24). ΔVA was significant in both hypoxic conditions but smaller in CH vs. AH (4 ± 1% vs. 8 ± 2%; P < 0.05). In conclusion, acclimatization to severe altitude does not attenuate the substantial impact of hypoxia on the development of peripheral fatigue. In contrast, acclimatization attenuates, but does not eliminate, the exacerbation of central fatigue associated with exercise in severe AH.

Purpose To outline how hypoxia profoundly affects neuronal functionality and thus compromise exercise-performance. Methods Investigations using electroencephalography (EEG) and transcranial magnetic stimulation (TMS) detecting neuronal changes at rest and those studying fatiguing effects on whole-body exercise performance in acute (AH) and chronic hypoxia (CH) were evaluated. Results At rest during very early hypoxia (<1-h), slowing of cerebral neuronal activity is evident despite no change in corticospinal excitability. As time in hypoxia progresses (3-h), increased corticospinal excitability becomes evident; however, changes in neuronal activity are unknown. Prolonged exposure (3–5 d) causes a respiratory alkalosis which modulates Na+ channels, potentially explaining reduced neuronal excitability. Locomotor exercise in AH exacerbates the development of peripheral-fatigue; as the severity of hypoxia increases, mechanisms of peripheral-fatigue become less dominant and CNS hypoxia becomes the predominant factor. The greatest central-fatigue in AH occurs when SaO2 is ≤75%, a level that coincides with increasing impairments in neuronal activity. CH does not improve the level of peripheral-fatigue observed in AH; however, it attenuates the development of central-fatigue paralleling increases in cerebral O2 availability and corticospinal excitability. Conclusions The attenuated development of central-fatigue in CH might explain, the improvements in locomotor exercise-performance commonly observed after acclimatisation to high altitude.