IACFSME 2022 Virtual Medical Conference: Day 3 Presentations: 29 July (9 am to 4.40 pm EDT)

Continuation of notes from the @s4me_info twitter thread.

This post is a copy of notes made during the July 29 session Immunology of long COVID presented by Akiko Iwasaki.

=== start of comments ===

Iwasaki started with general info on Long Covid. The percentage of symptomatic patients goes down after infection, she explained, but it doesn’t go down to zero. It plateaus.

We need to understand why some people fail to recover.

She also highlighted the problem that there is no universal way to define Long Covid leading to variations in studies and making it difficult to give one number of how many people are affected

Iwasaki talked about the results of a mouse model of mild COVID.

They wanted to know if a mild respiratory infection could affect the brain.

They found that several cytokines were elevated including in the cerebrospinal fluid weeks after the mild COVID infection.

They also found reactive microglia in the brains of the mice which is interesting because they also found this in autopsies of people with a positive test for Sars-Cov-2 (some of these didn't have any COVID symptoms)

One of the elevated cytokines they found in the CSF of the mice is called CCL11.

This cytokine was also found to be elevated in the blood of long COVID patients with brain fog (not in those without brain fog)

Iwasaki concluded that infection of the central nervous system (CNS) is not required to induce significant CNS pathology.

Long COVID might be caused by circulating cytokines that impact the brain in a chronic matter because of epigenetic regulation of the microglia.

Lastly, Iwasaki also presented yet unpublished data from the Mount-Sinai Yale study (MY-Long Covid Study).

This study very extensive testing in patients with long covid, patients with covid who recovered and two groups of healthy controls up to 110 days post-infection.

Long COVID patients had increased B cell activation and increased exhausted T cells.

They also had increased anti-SARS-CoV-2 antibodies, even after controlling for vaccine doses.

There was also reactivation of some herpes-viruses (EBV).

The most striking finding, however, were decreased cortisol levels in long covid patients. They were only about half of controls and also predicted the severity of Long Covid.

Iwasaki said she hopes to extend these analyses to ME/CFS as she thinks there are many parallels and overlaps between Long Covid and ME/CFS.

=== end of comments ===
 
Continuation of notes from the @s4me_info twitter thread.

This post is a copy of notes made during the July 29 session at 1:40 PM and covers presentations by three speakers: Ali Boolani, Liisa Selin, and Deborah Duricka.

=== start of comments ===

The next speaker is Ali Boolani (Clarkson University). His team looked at electronic medical records of patients with a PCR-confirmed diagnosis of COVID-19 from multiple hospitals.

In total they had data on 60.000 patients.

They then looked at how many of these patients got a post-COVID ME/CFS diagnosis.

This turned out to be the case for approximately 8500 patients or around 14%.

Boolani highlighted several limitations to this data.

Not all diagnostic codes were entered correctly and when they looked at some of the records, important things were missed.

The limitations became clear when they looked at predictors of ME/CFS diagnosis.

Being older, male and Caucasian increased the odds of a ME/CFS diagnosis and classification accuracy for machine learning models was low.

Boolani briefly suggested that this could mean that getting a registered ME/CFS diagnosis is subjective: that some people are more likely to receive one than others (regardless of medical condition).

The next presentation is by Liisa Selin (University of Massachusetts) on CD8 T cell over-activation and exhaustion.

Selin says they are seeing similar immune abnormalities in Long Covid as in ME/CFS.

She thinks that Inspiritol (a new patented 5-compound drug) has potential as treatment because it has various immune-modulating effects.

The last presentation before the break is from Deborah Duricka (Neurovision Inc) on how "Stellate Ganglion Block" might help to improve symptoms of Long Covid.

She has previously reported a retrospective case series on this.

A stellate ganglion block is an injection of local anesthetic to block the sympathetic nerves in the neck.

Duricka says she is new to the field of ME/CFS but that she noted that stellate ganglion block improved symptoms in Long Covid patients.

The sample size, however, was limited to 11.

That's the end of tweeting for today.

=== end of comments ===
 
Iwasaki's presentation" said:
The most striking finding, however, were decreased cortisol levels in long covid patients. They were only about half of controls and also predicted the severity of Long Covid.
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I'm skeptical about this. Cortisol changes could be a result of a change in lifestyle that happens when you are sick. The people in this sample had been sick for a while, and so there had been lots of time for lifestyles to change.

Cort's report said:
This wasn’t one of those studies focused on patients who had had long-COVID for 1 month or 3 months. With the average time since infection averaging 410 days, long COVID had had ample time to settle in and do its work. These patients came the closest we’ve seen yet to approximating an ME/CFS patient.
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If you don't have to rush to get up in the morning and deal with a busy workday, your body probably doesn't need the same level of cortisol than if you do. It would be a waste of energy producing lots of cortisol in a body having a very quiet life with few interactions or unexpected events. Data in studies supposedly showing low cortisol in ME/CFS that I have seen always show a wide range and a large amount of overlap with healthy controls.

Edit: re variation in cortisol depending on life demands
Effect of increase in cortisol level due to stress in healthy young individuals on dynamic and static balance scores
The mean cortisol level was found to increase approximately 9 times in stressful periods compared with that in relaxed periods.
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From Cort Johnson:
The Hugely Predictive Factor for Long COVID...is also found in ME/CFS and Fibromyalgia: the IACFS/ME Conference II

Yale immunologist Akiko Iwasaki swept into the keynote session of the IACFS/ME with some never-before-revealed findings.

She couldn't have chosen a better place. The "hugely predictive" factor for long COVID she found - low cortisol - as well as the EBV reactivation and T-cell exhaustion she also found - have all shown up in ME/CFS as well.

Find out more in

The Hugely Predictive Factor for Long COVID...is also found in ME/CFS and Fibromyalgia: the IACFS/ME Conference II
https://www.healthrising.org/blog/2...ng-covid-factor-chronic-fatigue-fibromyalgia/

Iwasaki is interested in doing a similar ME/CFS study but doesn’t have funding for it.
:(
 
ahimsa said:
Continuation of notes from the @s4me_info twitter thread.

The next speaker is Ali Boolani (Clarkson University). His team looked at electronic medical records of patients with a PCR-confirmed diagnosis of COVID-19 from multiple hospitals.

In total they had data on 60.000 patients.

They then looked at how many of these patients got a post-COVID ME/CFS diagnosis.

This turned out to be the case for approximately 8500 patients or around 14%.
Click to expand...

That's very informative, if unfortunate. 14% of one particular cohort. I wish we knew more about this population--hospitalized, non-hospitalized, either, how long they were sick, how age/sex are skewed, etc. Unfortunately, I couldn't find anything about this study online. It must not have been published yet, but I'm guessing it'd be a significant paper, so hopefully he plans to publish it. The fact they used existing diagnoses isn't ideal, but allows them to cast a wider net than looking for diagnoses themselves. I believe we discussed a LC study that used EHR data before, and several people commented that the prevalence of different symptoms seemed very low and skewed towards "concrete" ailments, hinting at potential biases around what was actually diagnosed.
 
Hutan said:
Bacteria are hosts to viral parasites, phages. Where bacteria are scarce and difficult to find, the presence of phages can provide a way to determine whether the host bacteria are present.

Chronic borreliosis can have an onset and ongoing symptoms that overlap clinically with ME/CFS.

Dr De Meirler's team has been looking at the presence of Borrelia species phages in ME/CFS using the qPCR technique. There are 20 different species of Borrelia, grouped into 3 types:
Lyme
Miyamotoi (a group with just the one species in it)
Relapsing fever

Recently a test has been developed that is provided by RED labs working with a Belgian university. The approach is to do one pass to see if any of the phages associated with borrelia types are present, then if they are, to do another test to identify the species of the Borrelia.

A study began in July 2019 with 130 ME/CFS patients (meeting Fukuda and ICC criteria); 90 healthy controls. Dutch and Belgian people
8 ml of venous blood is analysed with the Phelix Page Borrelia qPCR
Sensitivity is 100%; specificity is greater than 90%

106/130 people with ME/CFS were found to be positive for phage borrelia
93 for miyamotoi
13 for relapsing fever species
2 for miyamotoi + relapsing fever
1 - I didn't get that - Lyme?

18/90 controls were positive
10 for miyamotoi
3 for relapsing fever
2 for miyamotoi +relapsing fever
...

Presence of lyme was 0.8% in ME/CFS versus none in controls
Presence of miyamotoi was 72% in ME/CFS versus 11% in controls

Miyamotoi is a Borrelia species first isolated in Japan but found all over the world. It is still poorly understood. It was first found in humans in Russia in 2011. It can be transmitted direct from human to human, no need for the tick vector. There is a lot of intra-species variation, creating the possibility of some varieties being more pathogenic to humans than some others.

Dr Meirleir believes that it is a prime candidate to be a major one of the chronic infections that underlie ME/CFS. He thinks it needs further study.

Questions: why are the phages found in healthy people? Miyamotoi doesn't need ticks for transmission, so a history of tick bite isn't necessary. There is variation in miyamotoi, with some subspecies perhaps less pathogenic, and host-species interactions.

Can this finding be extrapolated beyond the sample population? Yes, people from all over the world have been tested and miyamotoi has been found.
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I do not believe that DeMeirleir made mention as of whether he has conflicts of interests or not. I am not sure whether he has shares, owns or is an associate of Red Labs, which has a lab both in Belgium and conveniently in Reno Nevada where he works too. Red Labs' website does not disclose who owns the company and who is on their board of directors.

He mentions that the patients that he sees come from all around the world. But in itself it still represents a self-selection- I did not review the methods of this study he presented and whether patients studied only came from his office. (though your notes @Hutan mentioned Dutch and Belgian patients)

I could not help but notice the next presentations which were difficult case presentations, at one point there was a poll question asking what what the patient's diagnosis, and of all the responses, 1% (probably 1 answer) said the patient had Lyme disease, when the correct answer (or the most probably) was Long-Covid.

So I am taking his study with a grain of salt.
 
Merged thread - This article refers to this talk:
Phage borrelia qPCR in ME/CFS patients
Kenny L. De Meirleir
Whittemore Peterson Institute/ University of Nevada, Reno/ Himmunitas Foundation, USA & Belgium
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__________________

Could a Major Chronic Infection be Underlying ME/CFS? The IACFS/ME Conference Pt. V
https://www.healthrising.org/blog/2022/10/18/borrelia-miyamotoi-chronic-fatigue-syndrome/
The fifth in a series of blogs reporting on the 2022 IACFS/ME Conference focuses on an intriguing possibility: that heretofore unknown infection is present in most people with chronic fatigue syndrome (ME/CFS).

Talk about a jaw-dropping statement. With the exception of Dr. Chia’s work on enteroviruses and Ariza’s work on the Epstein-Barr virus, most researchers have pretty much given up on finding “the chronic infection” underlying ME/CFS. Repeated failures to find evidence of a pathogen have led to the conclusion that while ME/CFS can be triggered by a variety of infection, the pathogen is likely long gone. With the emergence of long COVID, though, the idea of viral persistence has caught hold and the question is back – could a persistent pathogen or bits of a pathogen be causing ME/CFS?
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Health Rising blogpost about a very out-there hypothesis.
 
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The infection 'must be gone' idea never chimed with me. I think there are many possible candidates that could be contenders. The symptoms of ME are all symptoms of an ongoing infection(s).

Long term antimicrobial therapy got me pretty near functional (N=1, so not meaningful really;)) and this it pretty much the only approach that I have seen others improve. Others not.

I doubt very much any medical or research group would test in a rct the type of treatment that I received. Little openness to it or curiosity. That'll change I think only with a decent test showing ongoing infections.
 
Ron Davis

25:47 Now the other thing that we decided to do in this project is to test some of the ideas that patients have had, are they right or not. So I've heard a lot from patients that "Oh I keep getting viral infections . . .I get them all the time, it's really my real problem . . . I'm very susceptible to viral infections". And I ask them what virus do you think you're getting? "Oh I'm sure it's HHv7 or it's another herpes virus and that's what caused my illness in the first place". So we decided to actually test this and we had to develop a technology to really do it and to do what I thought was correct.

28:24 The results of that is basically there aren't virus infections that are different from healthy controls. A few people do have them but healthy controls have more in this small study, so it makes me suspicious that in fact they don't have viral infections. They have something else going on that feels like a virus infection and a lot of inflammation things things will make you feel like that. Most of these viruses probably, by themselves, don't really do anything by themselves. It's not to their advantage to give a signal to the body that they're there. The body is the one that does the signaling that there's something wrong. And I think if you have that signal like inflammation it may feel like a viral infection. The only reason I'm stressing that point is that if it's most likely you don't have a viral infection you shouldn't be taking antivirals probably, because they're probably not that healthy for you. And the reason they're probably not that healthy is that the antivirals generally target the synthesis of the DNA from the virus and it works because it's a very primitive
 
Joan Crawford said:
The infection 'must be gone' idea never chimed with me. I think there are many possible candidates that could be contenders. The symptoms of ME are all symptoms of an ongoing infection(s).

Long term antimicrobial therapy got me pretty near functional (N=1, so not meaningful really;)) and this it pretty much the only approach that I have seen others improve. Others not.

I doubt very much any medical or research group would test in a rct the type of treatment that I received. Little openness to it or curiosity. That'll change I think only with a decent test showing ongoing infections.
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Likewise, treating bacterial infections improves me for a period. If I can get my immune system to go on the march I improve. No doubt I have bacteria in my kidneys from the urine dipstick tests but whether its the cause of the problem or just a side show I have no idea. I think persistent bacterial infection is likely. Chris Ponting was suggesting LPS in the blood of ME/CFS patients caused clotting, if that is right then its bacteria and its a question of where and how to treat it given antibiotics have done nothing for me.
 
Mij said:
And I think if you have that signal like inflammation it may feel like a viral infection.
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I definitely agree with that. I think many of PWME's symptoms are perceptions of feelings without the physical/chemical abnormalities that typically cause them. It probably only takes one misfiring neuron to produce the perception of lethargy, or pain in some part of the body, or some other such symptom.
 
We know of a few bacterial and parasite infections that persist in the face of treatment, and that are commonly failed by diagnostics. Borrelia comes to mind, as do bartonella and babesiosis.

For at least a portion of ME/CFS patients. persistent unresolved infection should remain on the table.
 
BrightCandle said:
If I can get my immune system to go on the march I improve.
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It's possible that's why the Covid jabs make me feel great. Also, if I get a bad cold, I'm seized with the energy to clean the whole house the day before I start streaming, croaking, and hacking.

I remember reading somewhere that it's a histamine surge that causes the sudden spurt of energy, but admittedly this was years ago and it might not have been an especially reliable source.
 
duncan said:
For at least a portion of ME/CFS patients. persistent unresolved infection should remain on the table.
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As a cause of ME, or just as something that worsens existing ME? I suppose there could be some cases where a persistent infection could keep a patient in the ME state whereas they would otherwise be able to switch their ME off, but I think that would be a fairly tiny percentage of PWME. Aside from those few possible cases, I'd say that PWME should be tested extra-well for persistent infections, which could result in a reduction of ME severity, but that it's not a priority for ME research.
 
Creekside said:
As a cause of ME, or just as something that worsens existing ME?
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Technically speaking, both.

Creekside said:
Aside from those few possible cases, I'd say that PWME should be tested extra-well for persistent infections, which could result in a reduction of ME severity, but that it's not a priority for ME research.
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A couple things to unpack here.

First, testing extra-well for persistent infections is just not really a thing with some pathogens, including many borrelia species and bartonella strains (ever been around a cat?). Babesiosis is no cake-walk either. And if you assume some pathogens hide out in tissues or are intracellular or have some enhanced capacity at immune evasion, there's a lot more candidates to consider as diagnostic nightmares.

Second, I hope we can define more precisely what ME/CFS is before we try to claim we have the inside track on how to prioritize research. We might have preferences or inclinations, but that's not the same thing, is it. Right now we just afix an ME/CFS label to anyone who shares a cluster of symptoms. That clustering could ALL be pathogen-based, or none of it could be pathogen-based (e.g. immune dysfunction) , or some mix of the two. We don't know yet. So I would personally be reluctant to say what should be a higher priority.
 
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