Protocol Neurobiological basis and risk factors of .. fatigue and concentration problems after COVID-19: ..prospective case–control study, 2023, Verveen et al

Sly Saint · Jul 1, 2023

Abstract
Introduction The risk factors for persistent fatigue and cognitive complaints after infection with SARS-CoV-2 and the underlying pathophysiology are largely unknown. Both clinical factors and cognitive-behavioural factors have been suggested to play a role in the perpetuation of complaints. A neurobiological aetiology, such as neuroinflammation, could be the underlying pathophysiological mechanism for persisting complaints.

To unravel factors associated with persisting complaints, VeCosCO will compare individuals with and without persistent fatigue and cognitive complaints >3 months after infection with SARS-CoV-2. The study consists of two work packages. The first work package aims to (1) investigate the relation between persisting complaints and neuropsychological functioning; (2) determine risk factors and at-risk phenotypes for the development of persistent fatigue and cognitive complaints, including the presence of postexertional malaise and (3) describe consequences of persistent complaints on quality of life, healthcare consumption and physical functioning. The second work package aims to (1) determine the presence of neuroinflammation with [18F]DPA-714 whole-body positron emission tomography (PET) scans in patients with persisting complaints and (2) explore the relationship between (neuro)inflammation and brain structure and functioning measured with MRI.

https://bmjopen.bmj.com/content/13/6/e072611

Methods and analysis This is a prospective case–control study in participants with and without persistent fatigue and cognitive complaints, >3 months after laboratory-confirmed SARS-CoV-2 infection. Participants will be mainly included from existing COVID-19 cohorts in the Netherlands covering the full spectrum of COVID-19 acute disease severity. Primary outcomes are neuropsychological functioning, postexertional malaise, neuroinflammation measured using [18F]DPA-714 PET, and brain functioning and structure using (f)MRI.

Ethics and dissemination Work package 1 (NL79575.018.21) and 2 (NL77033.029.21) were approved by the medical ethical review board of the Amsterdam University Medical Centers (The Netherlands). Informed consent is required prior to participation in the study. Results of this study will be submitted for publication in peer-reviewed journals and shared with the key population.

https://bmjopen.bmj.com/content/13/6/e072611

EndME · Jul 1, 2023

A year ago a small, yet significant in what it found, preprint emerged from this study https://www.s4me.info/threads/prepr...n-on-18f-dpa-714-pet-2022-visser-et-al.27980/.

Unfortunately, it seems results didn't hold up at a larger scale https://ntr.nl/site/tekst/Informatie+post-covid/163.

One of the co-authors is Dr. CBT Hans Knoop so I will have to carefully read through what is happening.

Sean · Jul 2, 2023

Both clinical factors and cognitive-behavioural factors have been suggested to play a role in the perpetuation of complaints.

Decades on and they are still stuck at the suggested/possible/promising phase.

And gotta love the passive 'have been suggested' framing. Yeah, by people like you, Knoop. And it was stronger than merely suggested.

They are using some decent objective measures, and acknowledge the existence of PEM, though how they measure that will be critical.

Trish · Jul 3, 2023

EndME said: ↑

Unfortunately, it seems results didn't hold up at a larger scale https://ntr.nl/site/tekst/Informatie+post-covid/163.
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Some quotes:

In the Focus episodes about post-COVID, a number of scientific studies are featured. Below you will find more information about these studies per episode and a number of frequently asked questions will be answered.

For more information about post-COVID in general, please visit the C-support website .
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Episode 1
The CO-FLOW research, Merel Hellemons, Erasmus MC

What is the CO-FLOW study?
CO-FLOW is a study of the physical, psychological and cognitive recovery and the quality of the aftercare process after an infection with COVID-19 in patients who have been admitted to a hospital in the Rotterdam-Rijnmond/Delft region. The research was made possible by ZonMw's COVID-19 Care and Prevention Program ( COVID-19 Follow-up care paths and Long-term Outcomes Within the Dutch health care system: a combined rehabilitation, pulmonary, and intensive care perspective (CO- FLOW study) ZonMw Projects) and a start-up grant from Erasmus MC, Rijndam Rehabilitation and Care Institution Laurens. The study started in July 2020 and all participants have now been followed for 2 years. All collected data is currently being analyzed and the results will then be published. In the coming years, annual questionnaires will also be used to gain more insight into the longer-term recovery.
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Our results up to 1 year after hospital discharge show that most recovery takes place in the first 6 months, both for physical and mental recovery. In addition, we see that a large proportion of the participants experience persistent complaints 1 year after hospital discharge. The most common complaints are: reduced condition (82%), fatigue (65%), muscle weakness (57%) and concentration and memory problems (54%).
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What has been further researched in the field of the immune system within CO-FLOW?
In a sub-study of CO-FLOW we looked at dysregulation of the immune system in relation to persistent fatigue and other post-COVID complaints (IMMUNO-FATIGUE Study). This shows that there is extensive chronic dysregulation of the immune system in post-COVID after hospitalization, but that there is no clear relationship with fatigue specifically. The results of this research have been submitted for publication and are currently being quality-assessed by peers.
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Episode 2
The muscle research, Rob Wüst, VU Amsterdam

What does the muscle test entail?
The muscle research that VU University Amsterdam is conducting in collaboration with the Amsterdam UMC focuses on a better understanding of muscle-related complaints and post-exertional malaise (PEM) in patients with post-COVID. Last year, 25 post-COVID patients and 25 healthy people participated in this. The initial results have been submitted to a scientific journal for peer review, and will be shared when there is more clarity.

What is Post-Exertional Malaise?
Post-exertional malaise (PEM) is the worsening of complaints that occur about one to two days after physical or mental exertion and that can last for weeks to months. PEM also occurs in other post-viral infections and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). PEM is an important limiting factor, as a result of which patients with post-COVID are often unable to work (fully) and are also severely limited in their functioning in other areas. Due to the occurrence of PEM, some forms of rehabilitation and physiotherapy are counterproductive to the recovery of these patients.
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Episode 2
The brain research, Nelleke Tolboom, UMC Utrecht and Denise Visser, Amsterdam UMC

What does brain research entail?
Some of the patients who have experienced a COVID-19 infection keep complaints such as fatigue complaints and complaints of the ability to think. These complaints can still be present months after the infection and can severely limit people in their functioning. The exact cause of these complaints is still unknown, but inflammatory processes in the brain may play a role. Inflammatory processes in the brain can be visualized by making a PET scan with the substance [18F]DPA-714 .
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EndME · Jul 3, 2023

Overall Merel Hellemons makes a great impression on me. It's great to see that Hellemons was part of the recent evaluation of the Knoop CBT for Long-Covid trial https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciad399/7210772.

It's very dissapointing to see that the clinical collaborators of Rob Wüst, who himself has always made an excellent impression on me and repeatedly does so, van Vugt and Appelman are part of this disastrous CBT trial. I can only hope that this was due to them somehow being part of the general selection process of patients without having anything to do with the trial.

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Protocol Neurobiological basis and risk factors of .. fatigue and concentration problems after COVID-19: ..prospective case–control study, 2023, Verveen et al

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