Evidence of clinical and brain recovery in post-COVID-19 condition: a three-year follow-up study, 2025, Dadsena

[Dolphin]

Free full text:

https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcaf366/8262587

Evidence of clinical and brain recovery in post-COVID-19 condition: a three-year follow-up study​

Ravi Dadsena, PhD, Sophie Wetz, Anna Hofmann, MD, PhD, Ana Sofia Costa, PhD, Sandro Romanzetti, PhD, Stella Andrea Lischewski, MD, PhD, Christina Krockauer, MD, PhD, Carolin Balloff, PhD, Ferdinand Binkofski, MD, PhD, Jörg B Schulz, MD, PhD,
Kathrin Reetz, MD, PhD, Julia Walders, MD, PhD
Brain Communications, fcaf366, https://doi.org/10.1093/braincomms/fcaf366
Published:

23 September 2025
Article history

Abstract​

Fatigue and cognitive dysfunction linked to persistent brain changes have been reported for up to two years after COVID-19. In this study, we followed the clinical, neuroimaging and fluid biomarker trajectories over three years post SARS-CoV-2 infection to evaluate potential signs and underlying factors of brain recovery.

We conducted a monocentric, longitudinal study using resting-state functional and structural T1-weighted magnetic resonance imaging data from 51 patients with Post-COVID-19 Condition (mean age 50 years, 33 female) collected at a mean time of 6, 23 and 38 months after COVID-19 infection. The trajectory of brain changes was compared to 23 age- and sex-matched healthy controls (mean age 37 years, 13 female) with similar time intervals between brain scans and analysed in relation to clinical, neuropsychological and fluid biomarkers including interleukins and neurodestruction markers at all timepoints. In addition, hand grip strength to evaluate muscular fatigue, was assessed at the final follow-up visit.

Self-reported fatigue improved over time but was still moderate on average three years after COVID-19 infection, while measures of hand grip strength and cognitive performance were largely unaffected. We found a significant increase of both lateral ventricles (∼8%) and the third (∼6%) ventricle accompanied by a structural volume reduction in adjacent areas including the thalamus, pallidum, caudate nucleus and putamen. An increased neuronal activation pattern was widespread and pronounced in these areas. The brainstem no longer exhibited volume loss as reported in our pervious study, but enhanced functional connectivity. Laboratory markers including interleukins and neuronal injury markers remained within the normal reference ranges across all study timepoints.

Our study revealed an overall slow but evident clinical improvement, including improved fatigue, regular muscular strength and recovery as well as normal cognitive function without signs of systemic inflammation three years after COVID-19. Clinical improvement is reflected by a pattern of brain recovery along periventricular regions. This pattern is characterized by structural stabilization and increased connectivity starting in the brainstem as well as efficient neuronal recruitment and increased activation in the basal ganglia, with no evidence of neuronal injury. These results highlight the positive long-term recovery trajectory in post-COVID patients.

 

[Dolphin]

 

[rvallee]

Our study revealed an overall slow but evident clinical improvement

This remains a huge problem. I have significantly improved over the last 3 years. Ups and downs, but the difference is actually very significant. Still fully disabled. Still can't do shit. Still can't think or do normal things. I still have a horrible quality of, well, existence, because I don't consider my situation to qualify as living. I'm actually more miserable as a result, because although my brain fog isn't that much better, I feel more conscious and aware, and have to face how total the destruction of my life has been those past 17 years.

Millions are still disabled, and as much as physicians love to point out that there is no permanent damage, losing years of life to illness is as permanent as it gets. You never get back this time, and you still lose all the things that broke along the way. Especially when it's long enough that it makes you pass having a career and children and other things you can't ever get back.

Plus, to speak of improvement when assessing the impairment is very flawed to begin with is not as straightforward as what they are used to deal with, broken bones and other things where improvement is fully linear, barring some incident. Overall this is a very bleak picture, all made worse by the fact that medicine absolutely does not respect any of this, still leaves everyone to deal with the consequences without any support.

 

[Utsikt]

Just wait until they are on the receiving end of the disability and disease. Then it suddenly can’t be treated soon enough.

Not to mention that covid is an ongoing problem because barely anyone are concerned with attempting to reduce the amount of infections. So even if the individuals gradually improve with time, the overall burden of society doesn’t decrease. It just becomes the new normal.

 

[Peter T]

The paper said:
Our study revealed an overall slow but evident clinical improvement

This also does not consider the possibility of subsequent deterioration.

With my ME I was steadily improving over the first few years, but now with subsequent relapses my cognitive skills are much deteriorated, for example for the first fifteen years I was still able to read between four and six books a week, however for the last ten years it takes me on average a year to read just one book so it has to be something that I very much want to read.