Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: ..., 2022, Fleischer et al

Full titles: Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: Findings from a Prospective Observational Cohort Study in 171 Patients

Abstract

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs. Reports of persistent or newly emergent symptoms, including those related to the nervous system, have increased over the course of the pandemic, leading to the introduction of post-COVID-19 syndrome. However, this novel syndrome is still ill-defined and structured objectification of complaints is scarce. Therefore, we performed a prospective observational cohort study to better define and validate subjective neurological disturbances in patients with post-COVID-19 syndrome.

Methods
A total of 171 patients fulfilling the post-COVID-19 WHO Delphi consensus criteria underwent a comprehensive neurological diagnostic work-up including neurovascular, electrophysiological, and blood analysis. In addition, magnetic resonance imaging (MRI) and lumbar puncture were conducted in subgroups of patients. Furthermore, patients underwent neuropsychological, psychosomatic, and fatigue assessment.

Results
Patients were predominantly female, middle-aged, and had incurred mostly mild-to-moderate acute COVID-19. The most frequent post-COVID-19 complaints included fatigue, difficulties in concentration, and memory deficits. In most patients (85.8%), in-depth neurological assessment yielded no pathological findings. In 97.7% of the cases, either no diagnosis other than post COVID-19 syndrome, or no diagnosis likely related to preceding acute COVID-19 could be established. Sensory or motor complaints were more often associated with a neurological diagnosis other than post-COVID-19 syndrome. Previous psychiatric conditions were identified as a risk factor for developing post-COVID-19 syndrome. We found high somatization scores in our patient group that correlated with cognitive deficits and the extent of fatigue.

Conclusions
Albeit frequently reported by patients, objectifiable affection of the nervous system is rare in post-COVID-19 syndrome. Instead, elevated levels of somatization point towards a pathogenesis potentially involving psychosomatic factors. However, thorough neurological assessment is important in this patient group in order to not miss neurological diseases other than post-COVID-19.


Key Summary Points

Why carry out this study?
To validate subjective neurological complaints in patients with post-COVID-19 by applying a comprehensive neuro-psychiatric diagnostic workup.

What was learned from the study?
The nervous system is rarely affected in patients with post-COVID-19 syndrome.
Psychosomatic factors probably contribute to the pathogenesis of post-COVID-19 syndrome.
Patients presenting with post-COVID-19 should be thoroughly assessed in order to not miss other diagnoses.

Open access, https://link.springer.com/article/10.1007/s40120-022-00395-z

 

I had to reread the last sentence 2 or 3 times until my ME brain realized that it is not actually "Patients pretending..."

 

Alright, let's tear this paper apart. These scientists are dead wrong in their conclusion that LC is psychosomatic. Their study has multiple fatal flaws. Their argument rests on several shaky pillars:

• The tests we did are normal, so there's nothing wrong with you.
• If you're bothered by certain symptoms, they're definitely psychosomatic.
  
• If you had a psychiatric disorder before LC, you're more likely to have symptoms, proving it's psychosomatic.

First, they did the wrong tests and looked at the wrong symptoms. They did no autonomic testing, and no 2-day CPETs. No tests for small fiber neuropathy. Second, they only looked at fatigue, an incredibly non-specific symptom. Nothing about exercise intolerance or PEM.

Second, their conclusion that patients have high levels of somaticization is fatally flawed. How do they rate somaticization? The PHQ-15--see a copy here. It asks how much people are bothered by certain symptoms. PwLC are likely to have many of these symtoms--such as palpitations, GI problems, and fatigue--and are likely to be highly distressed because their symptoms are severely disabling, new, and uncertain in prognosis. I cannot see any way that these scores won't be sky-high in chronically ill people.

Third, they argued that LC is psychosomatic because people with pre-existing psychiatric disorders are more likely to complain of cognitive symptoms. This so absurd I'm not even sure how to respond to this. People with psychiatric disorders are more likely to have psychiatric symptoms? To me, that's a tautology from which no conclusions can be drawn. It doesn't seem like they specifically tried to separate pre vs post-Covid symptoms in this group. But even if you consider the change in symptoms, outcomes after in insult to the brain could be worse for people with pre-existing psychiatric conditions. Why? Because people with mental conditions have less reserve capacity. (I've experienced this firsthand as an autistic pwME.)

 

I believe Kleinschnitz is known to be a long Covid and ME/CFS minimizer in that he has appeared in German newspapers to promote the idea that both conditions are psychosomatic.

 

And I am Russel's teapot.

Honestly, though, is the average physician scientifically illiterate? Most seem only able to execute scripts, simply do not understand how science works at all. Reminds me of engineers, especially the hubris. The entire profession seems to be shackled by what's in textbooks, there is no ability to discover new things anymore. If it's not in textbooks already it just doesn't exist. Borderline reaching theology.

The difference between memorizing stuff other people figured out and figuring out new things is basically the whole difficulty. Lots of people understand relativity, likely none of them could have come up with it.

 

In an earlier media article about this study the number of 20% psychiatric pre-existing conditions was mentioned.
20% corresponds to the average population or is even slightly below. A percentage is missing in the abstract.

 

I just read this interview. It's really terrible...

https://www.google.nl/amp/s/www1.wd...orona-behandlung-psychologisch-100.amp?espv=1

 

Since it's so rare for physicians to openly criticize their peers on this issue:

https://twitter.com/user/status/1567521449669279747


The 2nd tweet basically answers itself, it's this research that leads to chronically ill people to fight for help and recognition. It's simply the position of people like this dude that it's how it should be, he is definitely not conflicted with the suffering he is causing.

 

Disappointing that the authors are so focused on their psychosomatic hypothesis because the main finding of this study seems to be that a neurological investigation is indicated in patients with Long Covid, even those who initially had relatively mild COVID-19.

The paper states: "For the total cohort, 20.5% of participants received a neurological diagnosis apart from post-COVID19, of which 18.2% were not associated with COVID-19." Unfortunately the paper does not represent clear data on how important those diagnoses were in explaining the patients symptoms and disability. For some it might have been a common diagnosis like restless leg syndrome or migraine. But there were also patients in whom multiple sclerosis or "EBV meningitis" was detected. The authors conclude: "thorough neurological assessment is important in this patient group in order to not miss neurological diseases other than post-COVID-19" but this is overshadowed by all their overstatements regarding a psychosomatic explanation.

Let's have a look at the arguments for a psychosomatic aetiology. The authors seem to provide 2. First they write in the abstract: "Previous psychiatric conditions were identified as a risk factor for developing post-COVID-19 syndrome." This is a bit strange because they did not have a control group or collected data from patients before they got sick, so not sure how they could determine that psychiatric conditions were a risk factor. Retrospectively they found that 19% of the cohort had previous psychiatric preconditions (mostly depression). Not sure if one can say that this is exceptionally large. In comparison, 28.3% of the cohort had a previous cardiovascular condition and 29% previous neurological conditions. So it wasn't like psychiatric conditions stood out in any way. Patients with a previous history of psychiatric conditions were more likely to report fatigue, psychiatric symptoms and difficulties in concentration but I don't think this says much about it being a risk factor.

The second argument is this: "We found high somatization scores in our patient group that correlated with cognitive deficits and the extent of fatigue". But as usual they simply used a questionable questionnaire: the Patient Health Questionnaire Somatic Symptom Severity Scale (PHQ-15). As you can see below, it simply asks about various symptoms without providing any clue that these might be psychosomatic or not. One could have just as easily created a "multiple sclerosis questionnaire" with vague symptoms like fatigue, concentration difficulties, constipation etc and claim that the survey showed patients had MS. Frankly, it is a bit embarrassing that tools like these are used in scientific studies.

 

For those who understand German. An article by Christiana Berndt who takes a critical look at the study as well.

 

The PHQ-15 questionnaire proves nothing. It has the scientific validity of the same questionnaire being used to prove alien abductions and their weird experiments. Prove to me that it wasn't aliens that caused all this post-Covid-19 stuff, and ME, and every other disease we do not fully understand! Shades of Russel's teapot! (Thanks @rvallee I had forgotten that one.)

On Russell's teapot, the discussion is about the existence of a small teapot in space. It cannot be detected with any means at our disposal, hence its unfalsifiable. Should it be taken seriously?

Either it exists or it does not. As an absolute fact we can say nothing.

As a matter of probability it reveals people's assumptions and belief systems if they assert some particular probability. For the record, I do not believe in a teapot in space, nor do I disbelieve, but I assert that from all we know it is so improbable it reaches the level of absurdity, barring some freak event we know nothing of. If I were a billionaire space trickster I might well launch a teapot as a joke.

Psychosomatic disease is an obvious truth if you substitute the body affecting the brain, and vice versa, and leave out mind. Its simply saying that brain and body are connected, well, duh!

Psychogenic disease is an extreme hypothesis still waiting for any proof at all, even tenuous proof. Well, lets look at some of the extreme views you need to consider it an established fact.

First, mind exists. No study proves that. Its an hypothesis. If you substitute brain function it makes a bit more sense, but the ability to make dubious conclusions becomes a little harder.

Second, mind causes disease. This is a point in contention in all these claims, again unproven.

Third, every other possibility can be ignored. This is the closed world assumption in computer science, and in reasoning its a major source of error. It especially ignores the unknown unknowns.

I am deeply concerned that this the field of psychogenic medicine is a house built of assumptions, each unproven, where each new layer is built on the previous layer, and never examined to see if its stable. The glue holding the house up is made of dogmatism, zombie science, and ignorance.

Everything in science should be falsifiable. If it isn't its not science. Its pseudoscience. Any medical position should be scientific, and hence falsifiable. If it isn't it should not be in medicine. Its undesirable but not unexpected that there are positions in medicine that are not proven and not falsified, but still falsifiable. That makes it a scientific work in progress. Its unacceptable to just assume that unproven things where we are unsure of their probability can be used to reliably infer other things.

No conclusion can be drawn from this study aside that the tests used were not able to determine what is going wrong. As pointed out earlier the failure to use tests that might have a high probability of finding abnormalities (such as 2 day CPET but also thousands more) just shows how limited the standard neurological approach currently is. It says more about the limitations of current neurological practice than it says about the psychogenic status of patients.

 

Response Letter to Vink et al. ‘Neurological Study Does Not Provide Any Evidence that Long COVID is Psychosomatic’

"The authors allege that our study would have labelled all patients with post-COVID-19 syndrome as ‘psychosomatic’ since the neurological workup was normal. Unfortunately, however, this claim is a misrepresentation of our conclusions. Rather, we suggested that psychosomatic factors should be taken into account since we were widely unable to objectify neurological impairment in our cohort. We regard this approach as state-of-the-art in modern medicine. It is best medical practice and in line with current guidelines—including post-COVID-19 guidelines [3]—to consider psychological and social factors in disease states without obvious organ damage. Even further, physicians would be acting negligently and potentially withholding patients from effective therapies, such as psychotherapy, if psychosomatic origin was not taken into account under such a constellation. The authors summarize their view as ‘absence of evidence is no evidence of absence’. This rather general statement does not add anything specific to the current debate but in fact could be directed to any scientific finding. We have not claimed causality from our data and are fully aware of the fact that it is never possible to finally ‘prove’ absence of a specific condition."

Open access, https://link.springer.com/article/10.1007/s40120-022-00424-x

 

This alone derails much of what they are saying. You can make a symptom list, but going from that to inferred psychosomatic (actually psychogenic) disease is a failure of reason. You can pose it as an hypothesis, but in more than a century of studies there is yet no study that proves the existence of any psychogenic disease. Uncritically accepting hypothesis as fact, or even probable, is deeply problematic.

The alternative seems to be that "psychosomatic" is of no clinical value. Its too broad a description. Its like saying "medical condition" or one of the broad categories of symptoms like pain or fatigue. Its not enough for saying anything other than in the broadest terms.

 

He has established an open peer review site as a GitHub repository, OPeerR.

Responses to this article are in this folder. This includes supplementary comments on statistical issues in this paper (mostly to do with rounding it seems).

There is another folder for a related 2024 paper, which I will post on the relevant thread.