Germann et al. (2025)
- Authors: Maria Germann, Natalie J. Maffitt, Olivia A. Burton, Amn Ashhad, Anne M.E. Baker, Boubker Zaaimi, Wan-Fai Ng, Demetris S. Soteropoulos, Stuart N. Baker, Mark R. Baker
- Institutes: Newcastle University, Newcastle upon Tyne, United Kingdom, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
- Publisher: medRxiv
- Link: DOI
Summary
This research provides objective evidence that post-COVID fatigue is a progressive condition where physiological abnormalities in the brain and muscles accumulate over time. Rather than showing slow recovery, patients who do not improve within the first few months appear to develop worsening neurophysiological dysfunction. This validates patient reports of increasing disability and highlights the need for clinical interventions that target these measurable changes in the nervous system early in the disease course.
What was researched?
The study investigated whether the neurophysiological abnormalities seen in post-COVID fatigue resolve over time or progress as the condition becomes chronic.
Why was it researched?
While early studies identified changes in brain and muscle function in Long COVID, it was unclear if these represented a static injury or a dynamic, worsening process in patients who fail to recover spontaneously.
How was it researched?
Researchers analyzed a cohort of 145 patients with post-COVID fatigue between 12 weeks and 45 months post-infection using transcranial magnetic stimulation (TMS), reaction time tasks, peripheral muscle fatigue tests, and heart rate variability measurements.
What has been found?
Patients with fatigue persisting longer than 200 days showed significantly higher fatigue scores, increased cortical excitability, slower reaction times, and greater peripheral muscle fatigue compared to those with shorter durations. The findings indicate that in the absence of recovery, physiological dysfunction in cortical circuits and muscles continues to accumulate and worsen over several years.
Discussion
The study is limited by its cross-sectional design, though the broad range of post-infection times allows for a clear observation of disease progression. The results suggest that the ‘brain fog’ and physical exhaustion experienced by patients have a measurable, worsening biological basis in the central and peripheral nervous systems.
Conclusion & Future Work
Persistent post-COVID fatigue involves an accumulation of neurophysiologic dysfunction rather than a simple failure to recover. These findings emphasize the importance of early diagnosis and the development of treatments to halt this progressive neurophysiological decline.