Neural Dysregulation in Post-COVID Fatigue

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 indicate novel avenues for principled therapeutic intervention, and could act as fast and reliable biomarkers for diagnosing and monitoring the progression of fatigue over time.