Neural dysregulation in post-COVID fatigue

Abstract

Following infection from SARS-CoV-2, a substantial minority of people develop lingering after-effects known as ‘long COVID’. Fatigue is a common complaint with substantial impact on daily life, but the neural mechanisms behind post-COVID fatigue remain unclear. We recruited 37 volunteers with self-reported fatigue after a mild COVID infection and carried out a battery of behavioural and neurophysiological tests assessing the central, peripheral and autonomic nervous systems. In comparison to age and sex matched volunteers without fatigue (n = 52), we show underactivity in specific cortical circuits, dysregulation of autonomic function, and myopathic change in skeletal muscle. Cluster analysis revealed no sub-groupings, suggesting post-COVID fatigue is a single entity with individual variation, rather than a small number of distinct syndromes. Based on our analysis we were also able to exclude dysregulation in sensory feedback circuits and descending neuromodulatory control. These abnormalities on objective tests may aid in the development of novel approaches for disease monitoring.

Recovery of neurophysiological measures in post-COVID fatigue: a 12-month longitudinal follow-up study

“…In a previous study 12 in long COVID after non-severe SARS-CoV-2 infection, where there had been no requirement for acute hospital in-patient care, we demonstrated changes in muscle physiology. In addition, we found reduced responsiveness in some of the neural circuitry governing cortical excitability, and a rise in the resting heart rate probably indicating an altered balance between sympathetic and parasympathetic systems.…”

Recovery of Neurophysiological Measures in Post-COVID Fatigue – a 12-month Longitudinal Follow-up Study

“…In our previous study 13 , we provided evidence that measures of the central (intracortical facilitation, TMS_ICF), peripheral (peripheral fatigue, TI_PeriphFatigue) and autonomic (mean heart rate, Mean_HR and peripheral oxygen saturation, SaO2) nervous systems were different between people with pCF compared to sex-and age-matched controls. However, these findings could not infer causation; measures could have been different prior to the infection (and thus conferred an increased likelihood of developing pCF) or the abnormal measures could be a consequence of the infection (and hence might be useful as a biomarker for tracking changes in fatigue).…”

“…In a previous study 13 we demonstrated changes in muscle physiology in long COVID after non-severe SARS-CoV-2 infection, where there had been no requirement for acute hospital in-patient care. These changes might explain some of the symptoms of fatigue described by patients.…”

“…Our previous publication 13 employed 35 non-invasive behavioural and neurophysiological tests to assess specific circuits within the central, peripheral and autonomic nervous systems. In this longitudinal follow up study, we used only the sub-set of these tests which were significantly different between people with pCF and controls in our original paper.…”

“…The twitch interpolation procedure allows assessment of an individual's ability to activate a muscle maximally voluntarily; in this study, we also measured changes after a sustained (fatiguing) contraction 14 . The protocol followed previous work from this laboratory 15 and was identical to that used in Baker, et al 13 . Subjects sat with their dominant arm and forearm strapped into a dynamometer to measure torque about the elbow; the shoulder was flexed, and the elbow at a right angle, so that the upper arm was horizontal and the forearm vertical.…”