Evidence of Accumulating Neurophysiologic Dysfunction in Persistent Post-COVID Fatigue

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Abstract A major consequence of the COVID-19 pandemic has been the emergence of post-COVID syndrome (PCS), and more specifically, post-COVID fatigue (pCF), with an estimated prevalence of ∼2%. We previously showed that, compared to healthy controls, people with pCF exhibit changes in muscle physiology, cortical circuitry, and autonomic function. Here we present results from a cohort of people with pCF (N=145), between 12 weeks and 45 months post-infection. We report self-perception of fatigue; objective measures of cortical circuits via transcranial magnetic stimulation and reaction time tasks; peripheral muscle fatigue; and autonomic function such as heart rate variability. Those with pCF persisting >200 days had significantly more fatigue and showed increased cortical excitability, slower reaction times and increased peripheral muscle fatigue compared to those with <200 days of pCF . In pCF, if there is no spontaneous recovery, fatigue worsens, and patients continue to accumulate significant neurophysiologic abnormalities.

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