Unexplained post-acute infection syndromes, 2021, Choutka, Iwasaki, Hornig et al

[rvallee]

Full title: Unexplained post-acute infection syndromes
Authors: Jan Choutka, Viraj Jansari, Mady Hornig & Akiko Iwasaki
Published: Nature, 18 May 2022


Abstract

SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine. The relatively similar symptom profiles of individual PAISs, irrespective of the infectious agent, as well as the overlap of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggest the potential involvement of a common etiopathogenesis. In this Review, we summarize what is known about unexplained PAISs, provide context for post-acute sequelae of SARS-CoV-2 infection (PASC), and delineate the need for basic biomedical research into the underlying mechanisms behind this group of enigmatic chronic illnesses.

https://www.nature.com/articles/s41591-022-01810-6

 

[duncan]

merged thread

A couple of the authors' names got my attention, so I skimmed this. I honed in on their Lyme analysis. I personally would give that a "D" grade, but I'm sicker than typical these days so perhaps I'm being too harsh. I cannot speak to the strength of the rest.

 

[duncan]

Always nice to see some of these authors, but imho crappy Lyme coverage. I'm not sure what that says about the integrity of the rest of the piece. Maybe nothing. Also, I bring a bias to bear in that if I think someone's Lyme position is suspect, that reflects often on how I regard other musings they might offer - which clearly is not fair.

 

[Wyva]

If the first author's, Jan Choutka's name sounds unfamiliar: He is (I think) the chairman of the Czech ME/CFS Association. Recently I shared his posts in the Visegrád countries thread, where he explained that they wanted the Czech Republic to adapt the NICE guidelines and the process to develop a guideline was first approved but later was stopped by the Medical Association without a warning.

 

[Andy]

If the first author's, Jan Choutka's name sounds unfamiliar: He is (I think) the chairman of the Czech ME/CFS Association. Recently I shared his posts in the Visegrád countries group, where he explained that they wanted the Czech Republic to adapt the NICE guidelines and the process to develop a guideline was first approved but later was stopped by the Medical Association without a warning.

 

[cassava7]

This is a thorough epidemiological overview of post-infectious illnesses, which I believe could be shared with scientists and clinicians interested in a crash course.

The article is balanced in that it presents what is definitively known — post-infectious illness is not new, neither uncommon, and cannot be ignored — while acknowledging the methodological issues of the studies they cite. The authors’ insistence on the fact that these issues stem from the lack of research, funding and interest in the medical field is appreciable.

The discussion on post-Ebola, post-dengue, post-chikunguya and post-West Nile virus syndromes was especially interesting to me as I was aware of some of the studies on these illnesses but had not been able to look into them. As for EBV, all the studies that we know of in the ME community are all cited.

Importantly, as far as they could, the authors mentioned for each post-infectious illness the prevalence of ME/CFS in cohorts where this was reported (although older criteria were used), including years after disease onset, for example for Q-fever fatigue syndrome.

The section on etiology and pathophysiology is lacking, but I understand that the focus of the authors was to give a broad overview of some hypotheses (i.e. limit themselves to short tentative explanations) rather than a detailed breakdown of the common symptoms that they refer to, such as PEM, orthostatic intolerance, cognitive impairment and fatigue, where they would cite the more rigorous, larger and/or replicated findings on these symptoms.

The section on limitations and methodological issues includes those listed above, and can be summarized as: 1) more basic biomedical research is needed and 2) research cohorts should be well characterized, i.e. constituted of patients with an identified infectious trigger and meeting modern criteria for ME/CFS.

Jan Choutka is a fantastic advocate for ME/CFS patients in the Czech Republic and I am glad that he was able to lead this work. From my perspective, he usually has a critical view on ME/CFS research, and it is reflected in the article (it was required for this work to be of good quality). I am also glad to see that Prof Awasaki’s claimed commitment to post-infectious illness research was not limited to vain words.

It is quite an achievement for a ME/CFS patient to have an article published in Nature. The tide is turning, perhaps. Or seemingly.

Edit: Prof Awasaki has shared the main points of the review in a Twitter thread.

 

[InitialConditions]

I quite like the term post-acute infection syndromes, as opposed to post-viral or post-infection syndome/fatigue. The former leaves open the possibility that the virus/microbe is still active or present in the body.

 

[Mithriel]

The list of similar symptoms and the general thrust seemed to echo what this forum has been saying for years; that ME is a disease which is the end point of different infections. Even traumatic onsets may be a change from mild disease to a more obvious one caused by a common place infection.

In effect they are using PAIS instead of ME/CFS as the generic term where ME from the epidemics and localised outbreaks is one of many causes - a position I am happy with - and dropping the psychology led CFS so there is a less muddled focus.

It also leaves room for post viral syndromes to be the prolonged fatigue after infection that resolves after a time which is a concept we really need in medicine.

 

[chrisb]

he former leaves open the possibility that the virus/microbe is still active or present in the body.

But the term Post viral was always ambiguous. Perhaps deliberately so. It was often interpreted as meaning post viral infection, leaving uncertain whether or not the virus had been cleared.

 

[ME/CFS Skeptic]

Looks like a very useful overview.

I like that it mentions the major limitations of the current studies because a lot of the prospective studies didn't accurately measure ME/CFS or reported a prevalence rate of 20% in the control group.

It has a modest conclusion and mostly signals that there are many post-infectious syndromes that have many parallels and require further study.

 

[Jonathan Edwards]

The review brings together some useful background clinical and epidemiological information. The section on pathogenesis is pedestrian and I think unrealistic, but it is the received dogma it seems.

An interesting point is that they quote ms as a potential model for autoimmunity due to cross-reactivity. It may turn out that this is one of the very few autoimmune diseases where a specific antigen is a trigger for this reason. But equally the model does not seem to work for PAIS or ME/CFS where the symptom pattern seems to be the same irrespective of inciting antigens. If PAIS or ME/CFS were due to cross reactivity we would either expect them to be restricted to one organism or to show quite different symptoms and signs according to the respective cross reacting antigen. So I think the new information on MS tends to go against any analogy with PAIS. MS is very specific in pathology, even if the symptoms vary with the myelinated area damaged.

 

[DokaGirl]

Thank you to these authors for their look at the big picture. Compartmentalized and linear thinking has seriously delayed advancement in diagnosis and treatment of PAIS.

The author's say the common understanding of the outcome of viral illness is that the patient either recovers or dies. No in between. This seemed to be the view put forth early on with COVID reporting.

These researchers ask us to consider diseases with a middle-ground outcome. Neither recovery, nor death, but much suffering.

Perhaps there is another disease, long accepted as organic, that may have a viral cause. That was the thinking decades ago with hypothyroidism. Now the autoimmune disease Hashimoto's is said to cause hypothyroidism. But what triggers the autoimmune response?

It is tragic that narrow thinking has kept medical science from seeing that viruses and other biological agents may be the cause of very many diseases we are yet to fully understand.

 

[LarsSG]

But equally the model does not seem to work for PAIS or ME/CFS where the symptom pattern seems to be the same irrespective of inciting antigens.

My impression is that ME symptoms vary quite considerably. It would be interesting to study to see if people with suspected post-EBV infection ME onset, for instance, are at all different from a group with a different suspected onset. It might be very hard to separate two groups in this way, but maybe it would lead to something interesting. Has anyone studied this in a systematic way?

I suspect you most likely wouldn't find anything, mostly because it would be very difficult to separate the patients with any certainty, but patient reports of symptoms vary so much that it doesn't seem that off the wall to think you might.

Even for those with Long Covid of the kind that seems quite similar to ME, there does seem to be a somewhat different set of symptoms than you'd typically see with ME. Perhaps that means Long Covid is distinct from ME, perhaps it means LC is a type of ME that differs somewhat because the trigger was coronavirus instead of some other agent. Similarly, the Royal Free outbreak symptoms sound quite different from what many of us now have, similarly for Akureyri and other outbreaks that coincided with polio. To my mind, this adds up to at least a suggestion that ME might be different if associated with different infectious agents.

 

[Jonathan Edwards]

Even for those with Long Covid of the kind that seems quite similar to ME, there does seem to be a somewhat different set of symptoms than you'd typically see with ME. Perhaps that means Long Covid is distinct from ME, perhaps it means LC is a type of ME that differs somewhat because the trigger was coronavirus instead of some other agent. Similarly, the Royal Free outbreak symptoms sound quite different from what many of us now have, similarly for Akureyri and other outbreaks that coincided with polio. To my mind, this adds up to at least a suggestion that ME might be different if associated with different infectious agents.

I think one has to separate out the features that occur as part of sa specific acute illness and which may persist as markers of damage from that specific illness. That would include loss of taste and respiratory problems from lung damage for Covid and neurological signs possibly suggestive of encephalomyelitis for whatever the RFH virus was.

Contrast that with Guillain Barré syndrome following trivial gut or respiratory infection or with MS as a potential PAIS for EBV due to autoimmunity. The post-acute illness bears no relation to the presentation of the acute infection.

I think there has been a huge confusion between the acute 'ME' illness at the Royal Free, which generated the name, and what we now call ME, which a small proportion of the original sufferers were left with.

 

[chrisb]

I think there has been a huge confusion between the acute 'ME' illness at the Royal Free, which generated the name, and what we now call ME, which a small proportion of the original sufferers were left with.

Still, as it is now almost 70 years since the original work and attempts to conceptualise the problem are still having the utmost difficulty, it is remarkable that Ramsey and co made the advances which they did. Given the opposition.

EDIT also, I'm not sure about the "small proportion". It depends what is meant by small. McEvedy's findings seem wholly unreliable. It is not clear at what time he got round to analysing his data. It was certainly after the 1970 publication. I recall that in the 1980 there were a fairly substantia number of members of the MEA who had been affected. That was partly why Ramsey instituted a survey in about 1986. I still have the half completed form.

 

[DigitalDrifter]

I recall that in the 1980 there were a fairly substantia number of members of the MEA who had been affected.

Simon says those were just Neurasthenia patients who didn't want to accept the stigma of mental health.

 

[chrisb]

That is the problem with ME.

It is like a game of "Simon says".

A statement cano nly be considered true if introduced by "Simon says..."

 

[janice]

My impression is that ME symptoms vary quite considerably. It would be interesting to study to see if people with suspected post-EBV infection ME onset, for instance, are at all different from a group with a different suspected onset. It might be very hard to separate two groups in this way, but maybe it would lead to something interesting. Has anyone studied this in a systematic way?

I suspect you most likely wouldn't find anything, mostly because it would be very difficult to separate the patients with any certainty, but patient reports of symptoms vary so much that it doesn't seem that off the wall to think you might.

Even for those with Long Covid of the kind that seems quite similar to ME, there does seem to be a somewhat different set of symptoms than you'd typically see with ME. Perhaps that means Long Covid is distinct from ME, perhaps it means LC is a type of ME that differs somewhat because the trigger was coronavirus instead of some other agent. Similarly, the Royal Free outbreak symptoms sound quite different from what many of us now have, similarly for Akureyri and other outbreaks that coincided with polio. To my mind, this adds up to at least a suggestion that ME might be different if associated with different infectious agents.

I wonder if NHS records of NHS lab results showing EBV/ glandular fever could be used to do a longitudinal study of those patient records to see what the long term health outcomes have been. Has there ever been such a study?
I’m thinking similar to US army longitudinal study of EBV/MS with 10 million subjects. Surely the NHS patient records could top that number and hence give fantastic statistical power to the results.

 

[rvallee]

I wonder if NHS records of NHS lab results showing EBV/ glandular fever could be used to do a longitudinal study of those patient records to see what the long term health outcomes have been. Has there ever been such a study?
I’m thinking similar to US army longitudinal study of EBV/MS with 10 million subjects. Surely the NHS patient records could top that number and hence give fantastic statistical power to the results.

I doubt those records would be useful. They are missing too much data and are too inaccurate.

Military records, though, like used for the MS study, potentially very useful. Militaries care very much about combat readiness, they don't train troops then not care whether they are functional or not. New funding opportunities have opened up for this in the US, it would be very appropriate to use it here.

 

[bobbler]

I doubt those records would be useful. They are missing too much data and are too inaccurate.

Military records, though, like used for the MS study, potentially very useful. Militaries care very much about combat readiness, they don't train troops then not care whether they are functional or not. New funding opportunities have opened up for this in the US, it would be very appropriate to use it here.

Indeed - I had it and GP misdiagnosed several times and then when accurately diagnosed by seeing the right person who had ENT experience (that's EBV, are you sure shouldn't I have a test? NO.. it's DEFINTELY EBV you can have a test but that is just for the sake of it when you are already so ill) I was encouraged not to have a blood test and the diagnosis conveniently hidden in notes - when I asked for it to be put back on there as a history note and watched one GP type it in then it would be conveniently 'disappeared' the next time I saw it.

I always get confused when there were claims of NHS data being some goldmine. IT people know that data you get out is only as good as what you put in. And whether it is in the interests of the person doing the 'inputting' to have it in there completely influences what people 'have'. Is bad data worse than no data? probably/almost certainly (if you are overlooking and not doing a very intelligent attempt to flag what will be causing and therefore hidden by gaps and why they would occur)...

But yes if theoretically we didn't have the leeway and other issues so that it had to be accurate and diagnoses weren't tail wags dog then science and medicine would almost certainly be further along and doing this? Which is annoying in itself