Unraveling the Neural Mechanisms Behind Post-COVID Fatigue

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaway

  • This study revealed that people with post-COVID fatigue (pCF) have underactivity in certain cortical circuits, dysregulation of autonomic function, and myopathic alterations in skeletal muscles.

Why This Matters

  • Persistent fatigue following SARS-CoV-2 infection can make everyday actions become laborious, negatively affecting quality of life and productivity.

  • A better understanding of the underlying neural mechanisms may pave the way for future medical interventions and serve as biomarkers for diagnosing and monitoring pCF.

Study Design

  • The study included a total of 37 volunteers with self-reported pCF following SARS-CoV-2 infection who had not required hospitalization and 52 control volunteers who were matched according to age and sex.

  • All participants made a laboratory visit 6 to 26 weeks after diagnosis.

  • Researchers ran a battery of behavioral and neurophysiologic tests to evaluate the central, peripheral, and autonomic nervous systems.

Key Results

  • Participants with pCF had an increased level of peripheral fatigue (48.5 ± 5.3% in pCF, vs 67.1 ± 3.6% in controls; P < .0033), suggesting that pCF results in metabolic changes in muscle fibers leading to reduced force output after prolonged activity.

  • Intracortical facilitation was significantly lower in participants with pCF (conditioned motor evoked potential relative to unconditioned, 170.6 ± 13% in pCF, vs 258.3 ± 19.7% in controls; P < .001), suggesting reduced cortical excitability.

  • Increased resting heart rate was identified in those with pCF relative to the control cohort (74.8 ± 1.9 vs 67.7 ± 3.6 beats/min; P < .0017).

  • Participants with pCF had a significant decrease in blood oxygen saturation (95.3 ± 1.9% in pCF, vs 97.2 ± 1.5% in controls; P = .00002)

  • Cluster analysis demonstrated that measures could not be subgrouped, indicating that each one captures a separate dimension of dysregulation in pCF.


  • The small sample size restricted the statistical power of some analyses.


  • This study was funded by the Medical Research Council (UKRI).

  • The authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Neural Dysregulation in Post-Covid Fatigue,” written by Anne ME Baker, Faculty of Medical Sciences, Newcastle University, UK, and colleagues, published on MedRxiv.org and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.

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