News from the Visegrád Countries - Czech Republic, Poland, Slovakia and Hungary

Just a bunch of unrelated long covid research news from Hungary that I've collected in the past couple of weeks.

1. The University of Debrecen receives roughly a billion forints from the Ministry of Innovation and Technology National Research Development and Innovation Fund to study the full disease spectrum of covid, including long-term sequelae. This uni was the first one to set up a long covid clinic in the country. They are going to build an epidemiological database based on the data of 700 people with long covid, 7000 people who had covid but recovered and 150 000 people who were vaccinated against covid and who they already have in their database. It will start with a retrospective analysis and longitudinal prospective studies will be built on it (clinical, immunological, socioeconomic, quality of life). They would like to identify risk factors and be able to choose more effective medication.

However, it looks like they are focusing on symptoms in connection with the lungs and heart. There is a lot of confusion about long covid here and most doctors seem to think it means those identifiable organic problems. However, they mention they want to study post-covid arrhythmias and I know that some doctors know about POTS at that clinic, so POTS may have a chance in these studies. (POTS seems to have a tiny bit better acceptance here than ME/CFS, I hear about it from cardiologists at these long covid conferences from time to time. However, I've never actually seen a LC patient with a POTS diagnosis in real life here, so this recognition is probably still rare.)

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2. An upcoming event: Young Pediatricians' 20th Conference. It has a few abstracts (PDF) on long covid in children and it is important, since Péter Krivácsy and Attila Szabó are the two doctors from Semmelweis University who managed to get funding from the Academy of Sciences for their research (long-term followup of children with LC) and this must be that.

Google translate:

Neurological and psychiatric symptoms of childhood long COVID syndrome
Transylvanian-Great Blanka1, Garai Réka1, Herczeg Vivien1, Kelemen Judit1, Péter Krivácsy1, Kovács Fanni1, Máthé Anna1, Takács Johanna2, Winter Bálint1, Seifert Lilla1, Eszter Zsáry1, Attila Szabó1
1 SE I. Sz Pediatric Clinic,
2 SE Faculty of Health Sciences

Objective. Childhood long COVID syndrome (LCS) poses another challenge to pediatricians worldwide.
The aim of our research was to learn about LCS, as accurate knowledge is essential to develop specific case definitions and guidelines to ensure adequate clinical care. LCS is defined as symptoms occurring 4 weeks or more after acute COVID-19 infection or symptoms remaining from an acute infection. The complaints that occur are very heterogeneous and can often affect several organ systems, so it is advisable to examine the affected organ groups separately for a more accurate understanding.

The exact pathomechanism of the development of neurological symptoms is currently unproven, and four theories are known. It has been suggested that the complaints may be due in part to impaired blood-brain barrier protective function due to endothelial dysfunction and to ischemic processes caused by micro-hemorrhages and thrombi. In addition, the direct destructive effect of the virus is known, as the ACE2 receptor is found in large numbers on astroglia. The virus is able to enter the central nervous system through the bublus olfactorium or the damaged blood-brain barrier.

The inflammatory response elicited by viral infection, characterized by leukocyte infiltration and other neuroimmunological processes, also plays a role in the development of symptoms. In addition, the pathomechanism may be due to a metabolic disorder caused by hypometabolism due to infection of other organs. The origin of psychiatric symptoms is also questionable, as it is difficult to determine which stem from the physiopathology of SARS-CoV-2 infection and which are from the psychological effects of the disease exacerbated by restrictive measures taken due to the pandemic.

Methods. In the course of our observational study, we collected data from the Department of Pediatrics No. 24 of March 20, 2021 and May 26, 2021. medical records of all LCS patients published between Descriptive analyzes were performed that summarized the patients ’medical history, clinical picture, and the studies performed and their results.

Results. In the study of 97 children so far, the average duration of symptoms was 4 months, affecting an average of 6 of the 10 major organ systems. Prolonged fatigue and the frequency of various mental complaints such as anxiety and altered mood were alarmingly high. A total of 71 children reported at least minor deterioration in quality of life. Neurological complaints such as headache, persistent fatigue, insecurity / dizziness were experienced by 82 children, of whom neurological examinations were different from physiological in only 9%, but trigeminal cephalalgia also occurred in one case. 73% of children reported having a mental illness during their illness. In 29 cases, specialist consultation was required, resulting in 16 new preliminary diagnoses, including major depression and anxiety.

Conclusions. In our research, we found a deterioration in the quality of life of the majority of children. The incidence of various neurological and mental complaints was alarmingly high. Evidence-based pediatric guidelines could help establish the most effective course of investigation and treatment. Separating the organic and psychological backgrounds of neurological complaints is a particular challenge.
Within psychiatric symptoms, further clarification is needed to determine which of these symptoms stem from the physiopathology of SARS-CoV-2 infection and which are from the psychological effects of the disease, which have been exacerbated by pandemic restrictions. Well-structured control studies are needed to establish evidence-based patient care. We are already planning such research with our research team in the future.
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Long COVID: Illness or Life Situation? Analysis of symptoms and quality of life in children studied for longCOVID syndrome in a control group

Eszter Zsáry, Fanni Kovács, Vivien Herczeg, Réka Garai, Bálint Tél, Andrea Pálmay, Nikolett Ténai, Anna Máthé, Péter Krivácsy,
Attila Szabó
Semmelweis University 1st Department of Pediatrics

Introduction. Long COVID syndrome is a condition in which new or persistent symptoms appear 4 or more weeks after an acute COVID-19 infection. Long COVID syndrome can affect both adults and children and has extremely diverse symptoms, many of which are difficult to objectify. Exclusionary diagnosis, so the investigation may be lengthy, and evidence-based causal therapy is not currently available.

Objective. The aim was to compare the results of the study of sick children arriving at the Long COVID outpatient clinic at the No. 1 Pediatric Clinic with a healthy control group.

Methods. Based on our preliminary results, we examined a total of 112 patients (42 males, 70 females) and 18 control children (11 males, 7 females) between September 2021 and February 2022. The control group consisted of volunteer children who had either not been infected with COVID-19 or had not had a prolonged symptom associated with the infection for 1 month since the acute infection. The mean age of the patients was 12 years and that of the control group was 13 years. The children and their parents completed a WHO-approved questionnaire asking them about a total of 50 symptoms, as well as time spent working and studying and self-sufficiency. In addition, a 12-question quality of life questionnaire was included in the study. In this scale on a scale of 0-4, they were assessed for the burden on them by different life situations (sports, community activities, etc.). The higher the value, the worse the function, and a maximum of 48 points could be collected.

Results. Symptoms were grouped by organ system during evaluation. Patients in each symptom group reported more complaints than healthy children.

The exception to this is the psychiatric symptom group, where 67% of patients and 77% of the control group had complaints, mostly anxiety, discomfort, and disinterest. It should be noted that 79% of our patients, while 56% of healthy volunteers reported at least one neurological symptom (eg, less sleep, forgetfulness, persistent headache, dizziness, etc.), and 47% of the patients and 22% of the control group reported gastrointestinal symptoms (eg diarrhea, abdominal pain, tightness, etc.).

Time spent working and studying was reduced in 19% of cases among patients and 5% in children in the control group. Self-sufficiency was impaired in 17% of patients due to their health status, while it did not change in the control group. In the quality of life questionnaire, patients scored an average of 15 points, compared with an average of 8 points in the control group. It is important to note that the standard deviation of the scores achieved by the patients was much larger (12) than that of the control group (4). 15% of patients achieved a score greater than 24 points, meaning that their quality of life deteriorated by more than 50%.

Conclusions. In summary, some of the patients' complaints with a more subjective judgment were observed in the control group, with a similar proportion. Deterioration in quality of life was also present not only in patients but also in healthy subjects, but to a lesser extent.
We consider it important to increase the number of items by involving more patients and volunteers, and to expand our study with the results of physical and laboratory tests. Our research will contribute to a clearer distinction between the somatic and psychological components of complaints caused by long COVID syndrome and the effects of external factors in the future, thus providing adequate therapeutic assistance to our patients.
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3. Andy posted this study a few weeks ago: The associations of long-COVID symptoms, clinical characteristics and affective psychological constructs in a non-hospitalized cohort, 2022, Ocsovszky
And I commented that one of the listed authors, Béla Merkely, rector of Semmelweis University might be the new person responsible for healthcare in Hungary. The good news is that it didn't happen, another person (I know very little about) got that position. Phew. This is important because Ádám Kósa MEP is going to talk to this person about adapting the NICE guideline in Hungary and about the fact that people with ME/CFS are practically just ignored here.

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4. There was a Hungarian article about this study: A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings, 2022, Sneller et al, titled NO EVIDENCE HAS BEEN FOUND FOR LONG COVID SYNDROME, BUT SYMPTOMS MAY AFFECT ANXIETY WOMEN THE MOST

The first half of the article is as terrible as it sounds, however, the second half was pretty good, basically explaining why this may not actually be the case, quoting other examples from medicine, talking about how women are taken less seriously in medicine and mentioning a few studies that did find something in connection with covid (cognition, brain scans). I thought it was pretty good clickbait actually. It was published in a popular science-tech-economics kind of magazine.

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5. I've checked the Medical Research Council's website again and they approved this study:

Title: Measuring the quality of life of Post COVID / Long COVID patients in a non-interventional questionnaire clinical trial and comparing them with population reference values
Applicant: Semmelweis University
Supervisor: Dr. Zoltán Vokó and Dr. András Inotai

These people work for the Center for Health Technology Assessment at Semmelweis University.
 
A longer, in-depth article about one of the upcoming studies in connection with long covid that got funding from the Hungarian Academy of Sciences. This one:

- Effect of post-COVID-19 status on cerebral blood flow reactivity in physically active and inactive adults. Recognizing the role of sports in prevention / rehabilitation (Ákos Koller, Semmelweis University)

The people involved: Professor Ákos Koller, head of the Microcirculation Laboratories at the Faculty of General Medicine of the Semmelweis University and the Hungarian University of Physical Education and Sports, and Johanna Takács, a psychologist and sports psychologist, assistant professor at the Faculty of Health Sciences at Semmelweis University

Some excerpts with Google translate:

“Because there is currently no animal model and time is running out due to patient suffering, we aimed to look at the effects of Covid-19 on the brain in humans in a noninvasive way (without wounding). We are wondering what kind of cerebrovascular and mental-cognitive problems we find in people who have been infected, the scale of the symptoms and how much they can be related to the severity of the disease, ”added Ákos Koller.

The research team also aims to measure the rate of blood flow in one of the middle cerebral arteries in two groups, an athlete and a physically inactive person who had undergone Covid-19. This is done in collaboration with the SE Department of Neurology, where Róbert Debreczeni, associate professor, is a major expert in measuring cerebral blood flow, the so-called transcranial Doppler ultrasound, which measures the rate of blood flow through the forehead.

Athletes are found with the involvement of the Hungarian University of Physical Education and Sports Science, while the SE Faculty of Health Sciences can involve similar non-athletic subjects in the experiment. Having 25-25 participants in each group would already provide a good foundation. They also want to examine older people.

If the blood circulation in the brain is well regulated, parts of the brain can take out as much blood as they need. However, if the cerebral circulation is not well regulated, some parts do not get enough blood, and when the blood pressure changes, the cerebral blood supply can fluctuate between extreme values, which the patient experiences as a headache, tension and weakness.

We know how healthy cerebral circulation responds. We want to see what's going on with someone who's been through Covidon. We believe that the difference will be seen in the fact that fit individuals have had an easier time with Covid disease. Obviously there are glaring, rare cases, but in general it can be said that whoever trains bears better

Said Ákos Koller.

By the reactivity of cerebral blood flow indicated in the title of the project they mean that they trigger various stimuli. For example, they squeeze a blood vessel, release the pressure, and watch the rate of blood flow change. In a good case, the blood moves quickly and normal circulation is restored. “From this we can deduce how the more distant vascular sections behave,” he added.


Another method is to inhale a small amount of carbon dioxide (as much as it does harm), of course, and look at how the brain’s bloodstream responds. They also monitor how the blood flows after handshake exercises. If the nerve and muscle connections work well, an increase in flow will occur. These and other tests map possible changes in the regulation of cerebral circulation in long-Covid cases.

Circulatory tests are complemented by analysis of mental and psychic abilities and see if there is a correlation with the quality of regulation of cerebral blood flow.

Where cerebral circulation is not well regulated, mental symptoms are typically more common. For example, it changes with aging, traumatic injuries, and often its unsatisfactory functioning is also responsible for mental problems such as cognitive impairment in old age.

For this, standard neurocognitive, neuropsychological tests are used, which are primarily used to measure attention, memory, and executive functions. Based on all this, the effect of long-Covid can be expected to be demonstrated.

(...)

When asked how specific the virus is, it also causes mental and psychiatric symptoms, the answer was that it occurs in many diseases, especially if it lasts for a long time, but it may not be as severe as with Covid-19.

Johanna Takács noted that the virus itself did not cause mental symptoms such as depression or anxiety. They tend to occur after recovery, depending on how severe the disease was. Neurocognitive symptoms that affect attention and memory are specifically observed in post-Covid states.

This suggests that the virus has affected the central nervous system, the peripheral nervous system. "However, the exact mechanism for this is still in question," he said.

Johanna Takács said it already appears that the post-acute Covid condition is relatively common, but not a significant number of people still have symptoms months later: research affects about ten percent of those infected. Patients with neurological symptoms such as cerebral fog or altered mental status were present in one-third of those with neurological symptoms.

Headaches and other brain diseases also occur in one-third. “It shows that there is a temporary disorder in the normal functioning of the brain, which experience has shown is mainly a problem of attention and memory,” he noted.

(...)

Their research aims to once again draw attention to the importance of everyday sports. In their view, sports education should start as early as kindergarten to get children used to physical activity.

Ákos Koller said that sport also helps the post-Covid symptom, for example, because it has a very complex effect.

Sport builds a self-confidence, decision-making ability, pain tolerance. It strengthens the nervous system, mental abilities, that is, it helps the body into the body in many places. It makes you healthier, stronger. Anyone who sports usually bears the difficulties better and helps a lot with depression

He explained.
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Wyva said:
A longer, in-depth article about one of the upcoming studies in connection with long covid that got funding from the Hungarian Academy of Sciences. This one:

- Effect of post-COVID-19 status on cerebral blood flow reactivity in physically active and inactive adults. Recognizing the role of sports in prevention / rehabilitation (Ákos Koller, Semmelweis University)

The people involved: Professor Ákos Koller, head of the Microcirculation Laboratories at the Faculty of General Medicine of the Semmelweis University and the Hungarian University of Physical Education and Sports, and Johanna Takács, a psychologist and sports psychologist, assistant professor at the Faculty of Health Sciences at Semmelweis University

Some excerpts with Google translate:
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Interesting, but does this read as though the researchers are coming at the topic with a number of preconceptions that will get in the way of asking the right questions?
 
Peter Trewhitt said:
Interesting, but does this read as though the researchers are coming at the topic with a number of preconceptions that will get in the way of asking the right questions?
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I also get that impression a bit.

As for fit people: There are plenty of young, previously very athletic covid long haulers in my group who are literally going crazy right now because they can't return to their workouts due to PEM (clearly delayed PEM with a wide range of symptoms). They all join my group and ask about how they could get rid of this, what's the way out, when and how can they really return to sports? They tend to expect there must be some trick somewhere, somehow. Then the other previously super-sporty people in the group (often long haulers themselves who have been ill for longer) tell them not to even think about doing any such thing for a while, because even when they thought they were finally well enough they still weren't and relapsed again.
 
Wyva said:
There are plenty of young, previously very athletic covid long haulers in my group who are literally going crazy right now because they can't return to their workouts due to PEM
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I think this is an important issue, you also see it with young ME suffers too. For many people in Western Culture exercise is part of their sense of identity and going to the gym significant for their self worth and a significant leisure activity. I suspect some people need the right support to cope with reducing their activity.
 
An abstract for a presentation at the Congess of the Hungarian Society of Nuclear Medicine, titled Examination and follow-up of COVID-19 disease by brain PET / CT examination. It is about a study that seems to confirm the changes in the brain scans after covid, reported elsewhere, but they also mention a limiting factor. Google translate:

Lili Száraz1, Sándor Czibor2, Judit Simon3, Emese Zsarnóczay3, Júlia Fanni Kiss2, Brigitta Dombai4, Veronika Müller4, Pál Maurovich-Horvat3, Tamás Györke2
1Semmelweis University, Faculty of Medicine, Budapest
2Semmelweis University, Department of Medical Imaging, Department of Nuclear Medicine, Budapest
3Semmelweis University, Department of Medical Imaging, Department of Radiology, Budapest
4Semmelweis University, Department of Pulmonology, Budapest

Introduction: COVID-19 is a respiratory infection caused by the SARS-CoV-2 virus with multisystemic inflammatory symptoms. In the assessment of central nervous system symptoms, PET / CT may provide additional information on late complications as a functional imaging study. The aim of our study was to evaluate brain FDG-PET / CT scans in active coronavirus-infected patients at the Department of Nuclear Medicine, Department of Medical Imaging, Semmelweis University, and to compare the results with their three-month control studies.

Material and method: Patients in our single-center, prospective study underwent brain PET / CT scans at the active infestation stage and three months later. The image material was evaluated using GE Cortex ID software, which compares the metabolic activity of different cortical regions to a normal database. From the results thus obtained, the Z-score values were used for the analysis. The values of each brain area were summed and categorized according to retained and decreased function by designating different Z-score intersections (-2; -1.5; -1). The present study included 36 patients (14 women, 22 men) with a mean age of 52 years (range, 42 to 75 years).

Results: Diffuse, significant cortical hypometabolism was observed in the majority of patients on the images taken during the infectious phase, with a large rate of normalization (observed in more than 90% of patients along the Z-score cut-off point) in the control images. The most common areas of residual hypometabolism were the medial prefrontal and temporal regions and the anterior cingulum, respectively, with the lowest rate of normalization.

Conclusion: The residual cortical hypometabolic abnormalities observed in the cohort studied correlate with the scientific reports on the subject, so COVID-19 is likely to have long-term residual hypometabolic symptoms in the brain, specifically in the olfactory center, orbitofrontal areas. However, a limiting factor in the research is that patients have already received corticosteroid therapy at the time of first admission, which may explain diffuse hypometabolism, and we do not have PET data on their pre-COVID-19 brain function.
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An abstract from the International Conference on Sports Science, coming from the Hungarian Defense Forces Medical Center, Aeromedical and Military Aptitude Research and Treatment Institute. Data based on 47 divers and parachuters with a median age of 36.

Effects of COVID-19 infection on physical performance

ABSTRACT

  • Guth-Orji Ágnes - Doctoral School of Military Engineering, University of Public Service, Budapest, Hungary; Hungarian Defense Forces Medical Center, Aeromedical and Military Aptitude Research and Treatment Institute, Kecskemét, Hungary
  • Csókási Krisztina - Personality and Health Psychology Department, Institute of Psychology, University of Pécs, Pécs, Hungary


Background: COVID-19 infection, besides many other consequences, might have an impact on physical performance and strength even in healthy sportsmen. Cardiotoxic complication can be a threat long after the infection therefore time of returning to training is an important question. It is widely known that returning to training after COVID-19 infection must be careful and gradual, but sport medicine specialists need practical tools to make a medically safe decision regarding the timing of going back to physical activity and work. The aim of the present study was to determine the effects of COVID-19 symptoms on post infection physical performance.

Methods: In our research we have analyzed the data of 47 divers and parachuters (age: 36,43 ± 9,52 years, with average BMI of 26,59 ± 2,44 kg/m²) physical performance with a modified Bruce treadmill protocol after an average of 66,91 days following COVID-19 diagnosis. The ‘Bruce protocol’ is performed on treadmill with standard workload by stages, setting the speed and the elevation starting with 2,7 km/h and 10% inclination in the 1st stage. For non-athletes each stage is 3 minutes, for athletes each load stage is usually 1 minute. For patients after COVID-19 infection we focused on moderate and more gradual increase of workload to ensure a longer warm up and medically well-monitored reaction to work load. Therefore in our modified Bruce protocol we used 2 minutes stages and the 1st stage was divided into 3 stages, 2,7 km/h with 0% inclination in stage 0, than 2,7 km/h with 5% inclination in stage ½ and then reach the 2,7 km/h speed with 10% inclination of the standard Bruce protocol stage 1. After this, the workload in the following stages were according to the standard Bruce protocol. The test included the continuous monitoring of pulse, blood pressure, ECG, blood oxygen level with a peripheral pulse oximeter and physical performance in term of metabolic equivalent (MET). Self-reported data on symptoms (fatigue, fever, loss of smell or taste perception, and cough) during COVID-19 infection were collected also.

Results: Maximum level of physical performance (MET) was negatively associated with pulse reaction in each stage of workload (r= -0,374 - -0,706; p<0,01). Fever and loss of smell or taste perception were not associated with maximum MET, pulse reaction, blood pressure or changes in systolic and diastolic blood pressure. Cough was significantly related to pulse rates in stage 3 and stage 4 (p<0,05), participants reporting cough during COVID-19 infection had significantly lower pulse rates in the last two stages of examination. Fatigue was significantly associated (p<0,05) to the % of the age-adjusted vitamax pulse in stage 0, stage ½, stage 2, and to pulse rate in stage ½ (fatigue had marginally significant effect on pulse rates in stage 0, stage 1, stage 2, and on the % of the age-adjusted vitamax pulse in stage 1). Nevertheless, cough and fatigue had no effect on maximum MET, blood pressure and changes in systolic and diastolic blood pressure during the test. Participants having a chronic disease had significantly higher pulse rates in stage 0, stage ½ and stage 1, and marginally lower maximum MET. Having a chronic disease was significantly associated with having fever during COVID-19 infection (p<0,05), but not with other symptoms.

Discussion: Our preliminary data suggest that among the typical symptoms of COVID-19 infection, fever or loss of taste and smell do not have significant effect on physical performance after approximately 2 months following the infection. Opposingly, the presence of subjective complain of fatigue and cough may have a significant impact on physical performance at the same time interval. Moreover it seems that this modified Bruce treadmill protocol is a safe way to measure the physical condition and may help to determine the date of safely returning to training or help to define the level of rehabilitation in case of more severe COVID-19 infection in gradual training programs.
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I've found a 25-minute long presentation from Dr Guth-Orji (from my previous post) on YouTube on the effects of covid on aviation safety.

She talks a lot about the various sequelae of covid and that it should be taken very seriously because almost every one of these can effect a pilot's abilities to fly safely. She mentioned various medical post-covid problems and symptoms, even problems with the eyes etc, so it was quite detailed. However, she didn't mention ME/CFS or PEM at all (only chronic fatigue as the most common symptom). She empasized that mental health issues are also present, I think she said something like 30% of the patients have some mental health issue and 30% of those is newly diagnosed and that this can happen in mild or asymptomatic cases too. So this was quite disappointing, because I expected military/aviation research to be more thorough about this due to the safety issues.

One thing that was new to me (which may not be new to others, I don't know) is that in military aviation (and this applies to divers and parachuters too) if you catch covid, you are not allowed to fly (dive etc) for at least 30 days at all. Afterwards you have to go through a complete medical checkup to see if you are fit for the job. She said in civil aviation this is nowhere near as strict, which is an issue.
 
Not much, just a couple of long covid studies that got ethical approval recently in Hungary:

Google translate:

Title: Detection of eye movement disorders in dizzy patients after Covid-19 infection and analysis of the data with artificial intelligence
Applicant: MMS One Zrt.
Study leader: Dr. Tamás T. László

(The applicant is an IT development company, the doctor seems to be an otorhinolaryngologist from the local university hospital)
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Title: Measurement of the quality of life of Post COVID/Long COVID patients in the framework of a non-interventional questionnaire clinical study and their comparison with population reference values
Applicant: Semmelweis University
Study leader: Dr. Zoltán Vokó and Dr. András Inotai

(They work at the Center for Health Technology Assessment at Semmelweis University, and are not psychiatrists.)
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Title: Identification of biomarkers using multiomic methods in post-COVID syndrome
Applicant: National Institute of Early Pulmonology
Research supervisor: Dr. Balázs Döme

(This is pulmonology though and whenever I hear their experts talk about long covid here (at the Academy's symposium etc), they only talk about how it affects mostly older people who were hospitalized, so it may not be "our" long covid.)
 
I think I've mentioned it a couple of times that it is really rare here that anyone mentions ME/CFS at all in any context (and they don't mean simply chronic fatigue by it). We aren't really actively chased by psychiatrists here so much, we are just simply ignored usually and everyone is severely uninformed about the existence of the disease. So now I've found a review article from last September (which has been listed in the Academy's repository only now). It is from the journal Orvosi Hetilap ("Medical Weekly"), the oldest medical journal in Hungary, first published in 1857.

Immunological phenomena related to infections: the importance of the gray zone, 2021, Zóka et al

Fortunately they also provided an English abstract:

Summary. Immunologic phenomena related to infections are well known to be truly heterogeneous, both regarding their etiology and the clinical picture. Overlapping symptoms and incomplete presentations are not seldom, which often constitute diagnostic challenge. Certain, optional complications of infectious diseases led to the creation of the focal infection theory more than a century ago, although only on the basis of assumptions derived from elusive and naive theories.

However, an expanding body of evidence ever since did underline the impact of previous and persistent infections on the immunologic, metabolic and endocrine homeostasis. Besides briefly touching the well-defined diseases, as well as the outdated theories of this field, we aim to provide an overview of the grey zone of infection-related immunologic phenomena, the existence of which is biologically well established, however, their true significance on an individual basis remains uncertain. Orv Hetil. 2021; 162(38): 1526–1532.
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It is behind a paywall and was written by three infectologists/microbiologists. I checked the references and while most of them were about certain infections and their connections with various well-defined medical conditions, the last few references were these:

  • 50
    Rasa S, Nora-Krukle Z, Henning N, et al. Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Transl Med. 2018; 16: 268.

  • 51
    Lande A, Fluge Ø, Strand EB, et al. Human leukocyte antigen alleles associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Sci Rep. 2020; 10: 5267.

  • 52
    Curriu M, Carrillo J, Massanella M, et al. Screening NK-, B- and T-cell phenotype and function in patients suffering from chronic fatigue syndrome. J Transl Med. 2013; 11: 68.

  • 53
    Montoya JG, Holmes TH, Anderson JN, et al. Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proc Natl Acad Sci USA 2017; 114: E7150–E7158.
(I also found a Wessely one though but far before these in the list:
11 Wessely S. Surgery for the treatment of psychiatric illness: the need to test untested theories. J R Soc Med. 2009; 102: 445–451.)

So now I'm planning to buy the article to read those probably two sentences about ME/CFS at the very end. (I need to set up a Paypal account to do so and I think I'll just need to start a whole new day to be able to do that...)
 
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I've bought the article: most of it was about other, much better defined medical conditions and one paragraph was about ME/CFS. (The Wessely quote was about something unrelated.)

It only said that basically due to the association with HLA alleles and certain measurable immunological differences (T-cells, NK cells, serum cytokine patterns) a consensus has been formed about an autoimmune origin. (Well, I'm not quite sure about this.)

It also said that despite this, no biomarker suitable for diagnostics has been identified. This may mean that a central part of the pathogenesis has not been found yet, but they think it is much more likely that the condition is due to some complex imbalance problem.

There are various infections involved, viral, bacterial, etc, also these pathogens can be there temporarily or for a longer time or even persist forever in the body. There is not enough data to see if these different pathogens create different changes immunologically or they have different risk factors.

And then in the conclusion it says that these particular issues supported by little or weak evidence might lead to misdiagnosis (they mean overdiagnosis here), but that cannot be a sufficient argument for ignoring them. Also mentions that in cases of people with hard-to-define symptoms, subclinical infections and immunological conditions but with incomplete symptoms should not be ignored. Then in the very end the article says that if, while keeping medical evidence in mind, we (=doctors) can also incorporate a spectrum-level view about medical conditions with an infectious or immunological background into our thinking and we can also draw the patient's attention to these associations, then maybe several psychiatric diagnoses can be avoided and the patient won't become a "crux medicorum" in our eyes. Or that patients won't end up feeling they are not understood and look for unevidenced health services outside of evidence-based medicine.
 
An abstract published in Ideggyógyászati Szemle Proceedings (Clinical Neuroscience Proceedings) by neurologists at the Hungarian National Institute of Mental Health, Neurology and Neurosurgery. This is the Google translated version:

Post-Covid syndrome autonomic nervous system abnormalities
Danuta SZIRMA1, Orsolya GYÖRFI1, Anita KAMONDI1

Introduction: Based on literature data, residual neurocognitive symptoms can be detected in approximately 80% of cases after a Covid illness. Some of these symptoms can be associated with damage to the autonomic nervous system (for example, blurred vision, palpitations, dry eyes). The damaging effect of the infection on the nervous system is explained by several possible mechanisms, so the virus-induced cytokine storm, the damaging effect of direct viral spread and the immune-mediated autoimmune mechanism also arise. The exact localization of the autonomic nervous system abnormalities and the degree of involvement are not known.

Methods: The aim of our study was to measure the involvement of the peripheral autonomic nervous system in patients with SARS-CoV-2 infection and to compare the data with the results of the physical neurological examination. During our research, we examined 35 (21 women, 14 men, average age: 39 ± 7 years) patients with SARS-CoV-2 infection and temporary or permanent neurocognitive and/or autonomic nervous system symptoms. After a detailed physical neurological examination, a Quantitative Sudomotor Axon Reflex Test (QSART) and sudomotor sympathetic skin response (SSR) tests were performed to assess the functioning of the peripheral autonomic nervous system with the Vitalscan SudoCheck+ device. Heart rate variability (HRV) was also determined using a WIWE device.

Results: No focal neurological symptoms were found in any of the patients. Among the autonomic nervous system tests, the SSR measurement proved to be the most sensitive in the studied population: a discrepancy was found in 8/35 patients (23%). In five patients, we obtained results indicating a moderate level of damage (bioelectrical skin conductivity: 43.6–59.4 µS, normal range: 60–100 µS), and in 4 patients, severe damage (bioelectrical skin conductivity: 24.3–39.5 µS).

During the examination of the sudomotor axon reflex, a borderline pathological response was found in 24/35 patients (67%).

During the one-minute HRV measurement, we followed the standard deviation of the heart rate variability (SDNN) and the square root of the mean square of the RR intervals (RMSSD). Abnormally low values were measured in two patients (SDNN: 18–23 ms; normal range: >100 ms, RMSSD: 13–14 ms; normal range: 15–63 ms).

Conclusion: During our autonomic nervous system examination, we confirmed a peripheral autonomic nervous system disorder in approximately 20% of the test subjects. This rate is higher than before the Covid-19 epidemic in the average population of the same age group; to verify this, we plan to compare the data with a control group (without SARS-CoV-2 infection).
 
An interview with Dr Ádám Dénes about covid and its effects on the brain. His field is neurobiology/neuroimmunology and he is one of the people who received a grant from the Hungarian Academy of Sciences to research long covid. He is investigating the role of microglia at the Institute of Experimental Medicine (and his paper is supposed to get published soon).

The interview is quite lengthy, the negatives are: no mention of ME/CFS or PEM and he also talks about the benefits of exercise (mostly in general for similar neurological conditions).

Translated with DeepL (and its mistakes edited by me - hopefully I didn't miss any):

Your results will be published soon. What have you found?

We found severe inflammation in the brain tissue of people who died of coronavirus, and in severe infections, many areas of the brain were affected. So-called microglial cells, which are the main regulators of inflammatory processes in the brain, appear to show a high degree of inflammatory upregulation in response to infection.

What do we know about microglial cells and what is their role?

Glial cells play an important role in the brain, essentially surrounding and serving nerve cells. Microglial cells also perform the function of the immune system of the brain.

They have a protective role in stroke and other brain injuries: they act as a kind of conductor, helping nerve cells to regenerate.
If they malfunction, this changes the condition of the nerve cells and the blood flow to the brain. They are also maintainers, responsible for regulating the amount of synapses at the end of nerve cell extensions, meaning they also play a big role in the formation of new neural connections. This means that if they malfunction, the storage of new memories in our brain is altered, among other things. We have seen that, as a result of the coronavirus infection, some of the glial cells have become severely inflamed, some have lost their normal function and some have died.

What are the possible consequences?

The inflammation associated with Covid-19 can develop in many places in the blood vessels, in the ventricles or in the brain stem. Anatomically, it reaches the olfactory bulb area and the brain nerves more quickly and easily, which is why many people experience loss of taste and smell. Otherwise, it seems almost random which functions are affected in a patient, influenced by many factors that are not yet known. Since inflammation also affects the blood vessels, it has quite extensive consequences for the brain through disruption of the blood supply.

Many areas of the brain are affected, and the extent of this can vary greatly from patient to patient, so the symptoms can be varied.
The disease state that develops is also influenced by the person's medical history. For example, pre-existing vascular diseases such as diabetes, hypertension, atherosclerosis, high blood lipid levels, may not only aggravate the acute disease, but also seem to increase the inflammatory state of blood vessels and microglial cells in the brain. So chronic disease has an impact on the neurological consequences of acute and post-Covid. And in the long term, nerve cells, their fibres and synapses may be damaged due to the amplification of inflammatory processes and dysfunction of brain glial cells.

But the nerve cells themselves are not initially damaged in this process. If detected early, can we prevent such a condition from becoming permanent with permanent damage to the nerve cells?

The biggest problem is that however early we detect this pathology in a patient, unfortunately we don't really know how to treat it. This is also an important issue in other chronic diseases, where the problem is the same, because in the course of these diseases we also see inflammation in the body and inflammatory changes in the brain.

But will we be able to manage this problem over time?

We need at least two factors. We would need imaging or biomarkers that can be easily measured in the blood to show brain lesions in a patient in time, before symptoms appear. Some of these are available today, but are very expensive and too complex for mass application. Even if this changes over time, we currently have no tools to address the problems. We would need to be able to influence inflammatory and degenerative processes to prevent permanent neurological damage - unfortunately there are not many effective procedures or therapies for this.

Can't anti-inflammatory drugs help?

The problem is that traditional drugs such as steroids work by always reducing the production of some inflammatory substance, but in doing so they shift the balance of other substances that also regulate inflammatory processes. It has long been known that in neurological diseases their effects are contradictory. In some patients, for example, steroids may work for a while, but in the long term they are more harmful than helpful. Precisely because it is not the inflammation itself that should be reduced, but the regulation of these inflammatory processes that should be pulled back on an even, good track. Also, in the case of Covid, there is an immune response going on in the meantime to inhibit the infection, so care must also be taken not to reduce this by reducing inflammation. There is currently no holy grail that meets these criteria.

Are there statistics on what proportion of infected people are affected by post-Covid neurological symptoms?

It depends on the variant, the course of the waves, the transmission, the population itself, and the general health of the infected. We know that in more than half of cases, some neurological symptoms are experienced in the acute phase. These include dizziness, headache, loss of taste and smell, memory loss, and in more severe cases - and fortunately much less frequently - seizures or coma. Autonomic nervous system disorders also affect a significant proportion of patients, from sweating, visual disturbances and circulatory problems to skin and muscle symptoms, as these nerve bundles can also be damaged. Another question is what percentage of these symptoms persist once a patient has recovered.

Is there a correlation between the severity of the disease and the onset of post-Covid symptoms?

Post-Covid, which causes neurological symptoms, is not related to the severity of the acute illness, sometimes after banal symptoms a person may struggle with neurological symptoms for many months.

Sometimes a child who has barely felt the infection can suffer from headaches, memory problems or behavioural problems for a year afterwards.
One of the reasons for this may be that, even though the body has an effective defence against the virus, these inflammatory processes affecting many organs are triggered. In addition, although omicron seems to cause much less severe disease, and therefore lower mortality, post-Covid syndrome appears to occur at almost the same rate in this variant. In addition, it also appears that in both acute and post-Covid disease, brain involvement may cause symptoms that appear to be related to respiration or circulation, when in fact it is not only the respiratory system or the heart that is affected, but also the brain centres that control these functions that become inflamed, disrupting their normal functioning.

Is this why patients whose lungs were apparently not in such bad shape suddenly collapsed?

Yes, it is possible, and the same is true for some circulatory disorders. If this type of neurological inflammation persists over a long period of time, it will eventually affect the whole body, because, for example, the blood supply and function of many organs is impaired by a general circulatory or autonomic nervous system dysfunction.

Will the neurological symptoms subside in the long term?

Yes, fortunately most of them improve. And there is also the possibility of regeneration, if there is no permanent nerve damage to the brain areas, there is a chance that the nervous system can rebuild some of its networks because of its plasticity. We just can't shorten that period yet and in many cases regeneration is incomplete.

Should we expect that even if these processes end, they will increase the risk of developing dementia, and that we may face such an effect decades later?

This is an intensively researched area at the moment and we do not yet have a precise answer. If inflammatory or degenerative changes are taking place in the nervous system, this in itself may have an impact on long-term neurological function. But it may be that within this, specifically, Covid-generated processes will stimulate some forms of dementia, while showing no link with other diseases. Of course, the consequences will also depend on the type of chronic disease a particular patient has, how old they are, their lifestyle, etc. However, it is likely that Covid and post-Covid will be a major risk factor for dementia.

But it will be many years before we will see this for sure. And then we haven't even mentioned that not only the inflammation but also the virus itself may be present in brain tissue for up to months in some patients. That can again push this inflammatory response ahead of itself, so there's going to be an even longer term run-off. There is very little clinical data on this at present, as we have few methods to detect the virus in living human brain tissue.

Does vaccination really help to combat post-Covid?

It certainly helps to prevent the disease, especially the severe course, but also the long-lasting symptoms.

Some patients with existing post-Covid symptoms also improve after vaccination.
This may be due to the fact that after the acute inflammation caused by the vaccine, regulatory immune processes are triggered that help to control the inflammatory processes that have been triggered and may help regeneration.

Another study has also found that various chronic inflammatory diseases, such as diabetes, also alter the function of glial cells, leading to the development of mental illness. What can someone with a chronic illness do to prevent this?

Altered glial cell function can be a pathogenic factor in a wide variety of diseases. In the development of depression, for example, you can see that levels of certain inflammatory factors are elevated - not to the same extent as in an ongoing infectious disease, but if these factors are present at lower levels for years, it slowly re-tunes the brain.

These processes can also be linked to mental illnesses such as schizophrenia. Unfortunately, there are currently no good solutions to prevent them. What is certain, however, is that lifestyle and maintaining physical and mental activity are very important in preventing and slowing down almost all types of neurodegeneration or depression. Unfortunately, the mechanisms of neurodegenerative changes are still poorly understood, and in some cases mental decline can be more effectively controlled by exercise than by drugs.

But this does not mean, of course, that effective drugs are not needed. Let us hope that significant progress will be made in this area in the near future.


Translated with www.DeepL.com/Translator (free version)
Click to expand...
 
I'm trying to catch up with things a bit. I didn't even really check Facebook when I was on my break for health reasons so I missed this very sad post from the Czech ME/CFS patient organization from August.

Translation:

Hello everyone.
This suspends the activities of the Club of Patients with ME/CFS indefinitely. Unfortunately we are all too sick to do anything. We did everything we could, but it didn’t lead to any improvement in the situation. Over the last few months our activities have basically stopped for health reasons.
The website will remain available.
Huge https://me-cfs.eu/oznameni-klubu-pacientu-s-me-cfs-o.../
Best wishes , jan choutka
Click to expand...

Here is the Google translated version of their full announcement.

If you remember, Jan Choutka is a Czech pwME who tried to get the NICE guideline implemented locally, without success despite his efforts. He met too much resistance (you can read a bit more about it here). I also remember he published a paper about post-viral syndromes in Nature with Iwasaki etc.
 
That's very sad. It's worth clicking through on the link in Wyva's post to read a bit more about how close the advocates got to getting a new clinical guideline, and then the dashing of that hope. I wonder if there is anything any of the European organisations can do to help? Although probably the Czech advocates need to rest now, and recover their health, and they would be needed to work out a new plan forward.

My thoughts are with these advocates including Mr Choutka.
 
I was asked by the editor-in-chief of the health website InforMed to write an up-to-date article on ME/CFS. InforMed is a smaller health news website written by doctors for patients (but it definitely has some traffic because the "ask a doctor" section seems pretty busy with questions). It is also quite old, started more than 20 years ago and in general is seen as a reliable health website as it is operated by doctors themselves.

So here is my article, translated to English with Google translate:
What we know today about chronic fatigue syndrome

And here is the original Hungarian version: https://www.informed.hu/betegsegek/...a-kronikus-faradtsag-szindromarol-246732.html

The Google translation might sound a bit weird, as always. I tried to be as conservative in my statements and as close to what my sources say as possible, in order to show a high degree of credibility. The editor-in-chief asked about me after publishing the article, so I hope that the fact that I am a patient will be alright and the article will remain regardless (this info about me is openly available on my website, I'm not hiding anything).
 
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