Is Apheresis an effective treatment for Long Covid and ME?

[SWAlexander]

I have known I had very thick blood and I couldn't complete home blood tests using lancets since 2016 if not earlier. I have ever since the condition developed and I can't get close to that much blood out of a lancet prick as that women, one to two drops is about the limit of it. I thought this was a well known aspect of the condition so presumably someone has researched into this before now?

I know for sure I have thick blood for a long time.
In 2016 my PICC line was blocked every day and had to be washed/blown out. This was not a very pleasant experience and I survived it only by taking mint before the procedure.
Last year in the hospital my IV dripline stopped because of clogged up arteries.
The interesting part is, no doctor paid attention or cared.

 

[junkcrap50]

#LongCovid sticky blood. (Content warning: trying - and failing - to squeeze a drop of blood from my finger)

I have known I had very thick blood and I couldn't complete home blood tests using lancets since 2016 if not earlier. I have ever since the condition developed and I can't get close to that much blood out of a lancet prick as that women, one to two drops is about the limit of it. I thought this was a well known aspect of the condition so presumably someone has researched into this before now?

Wow. I too can't get any blood out of a finger prick test. Only like 2 drops but with a lot of effort and squeezing finger. Huh.

 

[MonkeyMan]

He said he might be coming to see Dr William Weir who runs an ME clinic in my home.

Sounds like he's given up on the HELP apheresis curing him, then?

 

[Countrygirl]

Sounds like he's given up on the HELP apheresis curing him, then?

NO! He reserved an appointment in case it didn't help/cure. This was arranged BEFORE he went to Germany.

 

[SNT Gatchaman]

From a 2017 Q&A with Janet Dafoe:

IN the video, at the 2.20 mark, Ron talks about using a filter on serum to see if filtered serum still produces the impedance effect that characterises mecfs. He says most of the effect disappears from using the filter. That suggests the target molecule, hypothesiesd to be causing the trouble, is a big one that has been caught in the filter. "probably a protein." and not likely to be a metabolite. (I'm catching the inference here that metabolites are smaller.)

Big = larger than 10,000 molecular weight. Proteins, protein groups or antibodies (including autoantibodies). Amino acids are smaller, around 300 molecular weight.

People previously have commented that plasmapheresis (the standard form) has not helped them. In Ron's experiment he filtered particles larger than a certain size and this reduced "most of the effect". I wonder if smaller particles (that weren't filtered by Ron's size gating), might be captured/excluded by the HELP apheresis technique.

It may be that the forms as imaged in the Pretorius paper a few posts above are the larger ones, in which case there may be a sizeable component of smaller particles causing pathology.

The question I have: is the abnormal amyloid protein responsible for the impedance effect. I think it is.

I'm sure they're on this, but blood pre and post HELP apheresis needs to be assessed by Ron's impedance device (nano-needle).

• Detection of Alzheimer's disease amyloid-beta plaque deposition by deep brain impedance profiling
• Deciphering the Disaggregation Mechanism of Amyloid Beta Aggregate by 4-(2-Hydroxyethyl)-1-Piperazinepropanesulfonic Acid Using Electrochemical Impedance Spectroscopy

 

[SNT Gatchaman]

Here's what I think is going in this disease:

• Ron Davis found "something in the blood" that was reasonably large (< cell size, but > molecule).
• He found abnormal impedance in the blood of ME/CFS patients
• Filtering plasma by size removed most but not all of the abnormal impedance effect
• Transferring ME plasma to normal (mice) induces ME/fibromyalgia type symptomatology
• Resia Pretorius found serum amyloid (SAA4) - 17.5 x control level in the microclots
• Amyloid is formed of abnormal beta-pleated sheets which cause abnormal impedance
• Amyloid tends to induce further protein misfolding

So...

ME and long COVID are the same disease, both an amyloid pathology that affects the blood and causes coagulation, immune and inflammatory derangement centred at the micro-circulation level.

Downstream symptoms are all secondary (haemodynamic, neuroinflammation, gut wall permeability). There is an element of the SARS-CoV-2 virus that kicks this amyloid formation process off (and I think we can guess what element that will be). Other viruses and insults can presumably kick-start the amyloid formation also.

If the amyloid burden becomes sufficiently high in some people it is unable to be controlled and self-perpetuates.

 

[andyguitar]

ME and long COVID are the same disease, both an amyloid pathology that affects the blood and causes coagulation, immune and inflammatory derangement centred at the micro-circulation level.

But there must be something else going on here. Not everyone gets long covid or ME (after an infection).Patients medical history might provide a clue to what makes them susceptible.

Other viruses and insults can presumably kick-start the amyloid formation also.

That maybe the case but the question for me is how come people can spend years of their being infected with a range of pathogens and not get me/cfs and then one day they do?

 

[SNT Gatchaman]

But there must be something else going on here. Not everyone gets long covid or ME (after an infection).

Absolutely. That might be genetic variation in the ability to clear the amyloid/micro-clot aggregates. We also know that there are sex differences at the blood vessel level. Perhaps in order to propagate beyond the body's ability to handle, they are privileged in (for example) smaller-than-average diameter capillaries.

This could explain why children have a higher recovery rate, starting with smaller capillaries and then out-growing the imbalance and allowing the fibrinolysis balance to normalise and clear.

That maybe the case but the question for me is how come people can spend years of their being infected with a range of pathogens and not get me/cfs and then one day they do?

May be dependent on the particular pathogen having the ability to form the abnormal amyloid, and doing it in sufficient numbers to overcome the body's ability to handle in any given infection event. Maybe a step-wise immune perturbation, following sufficient viral infections (e.g. starting with EBV).

Recovering the ability to clear the micro-clots might explain the stories of some people's recovery being slow, slow, slow and then rapid. Perhaps this is the bi-stable state OMF were theorising, rather than a metabolic trap in neurons.

We know that acute COVID causes very abnormal thrombosis events in the severely affected (multi-organ). The evidence at the start of the pandemic also showed that initial "dose" of the virus was important. Unprotected healthcare workers exposed to large inhalational loads did badly.

COVID also had this unusual behaviour where people looked to be recovering and then rapidly deteriorated. I wonder if that's a clue too.

It just seems to me that there might be acute and chronic forms of this pathology. Severe SARS 1/2/ MERS / Ebola etc disease might be "acute fatal ME".

 

[andyguitar]

That might be genetic variation in the ability to clear the amyloid/micro-clot aggregates.

COVID also had this unusual behaviour where people looked to be recovering and then rapidly deteriorated. I wonder if that's a clue too.

Or maybe a simple behavioural difference ie when some people get ill they try to "push through it" and make matters worse.

 

[junkcrap50]

From a 2017 Q&A with Janet Dafoe:
People previously have commented that plasmapheresis (the standard form) has not helped them. In Ron's experiment he filtered particles larger than a certain size and this reduced "most of the effect". I wonder if smaller particles (that weren't filtered by Ron's size gating), might be captured/excluded by the HELP apheresis technique.

Whoa that's news to me that filtration partially worked. I always read and thought that it did not, which helped make the particle size very small about an exosome size. I'm surprised more wasn't made and discussed about filtration working. If it could be used and applied clinically, even if it had partial or temporary benefit, then it could provide tremendous relief all patients, especially the severe. I'm surprised more news wasn't made about filtration possibilities as the result of this finding.

 

[EtherSpin]

What I can tell you is that Pretorius said that if it’s chronic (LC) it’s too late and normal anticoagulants don’t help (like heparin shots). Amy said that it is to extrapolate to ME. So I think that wouldn’t be successful. I will talk to Jaeger again. She seems to be very interested in my case (EV infection and trajectory). I will try everything to get this apharesis. Otherwise last resort is Valcyte and we all know how dangerous this try would be.

Thank you for the reply, I appreciate it. Hope you don't mind a further query.
Didn't Khan have what we'd term chronic or "Long" COVID ? Or did he have very acute onset and then get treatment expeditiously?
What's EV infection sorry?
HUGE fingers crossed you get to try the treatment man.
Apologies in advance for my lack of context here

 

[SNT Gatchaman]

Given the possibility that larger aggregate amyloid / beta-sheet proteins found within micro-clots, and digested by circulating PBMC/monocytes could be the explanation for the nano-needle impedance findings in ME —

Gosh, I hope it's possible to quickly test recovering/recovered acute COVID and 6, 9, 12 month long COVID blood for similar impedance findings and of course look for micro-clots in long-term ME.

It seems to me that this is deserving of some of that $1.15B NIH grant...

@Janet Dafoe if I may. (Hello from NZ ! )

 

[Mary]

I wonder if exactly how "sticky" one's blood was would correlate with the severity of ME/CFS? e.g., I'm considered moderate - I can do 3-1/2 - 4 hours of light activity a day - if I do more, I crash the next day like clockwork. I don't have brain fog or severe POTS, though my immune system is definitely impaired - I get sick a LOT. And on blood draws etc., my blood hasn't shown any evidence of "stickiness". Though it very well could have it to some degree.

So I'm wondering if someone with severe ME/CFS would have much stickier blood - maybe?

 

[SNT Gatchaman]

COVID also had this unusual behaviour where people looked to be recovering and then rapidly deteriorated. I wonder if that's a clue too.

Or maybe a simple behavioural difference ie when some people get ill they try to "push through it" and make matters worse.

Sorry, I wasn't clear with that post. I was thinking more of the severe acute cases. Those extubated and out of ICU in a step-down ward or those not yet intubated and in an HDU or general ward. There was always this story of them starting to look really quite good and then crashing (ICU style, not ME style) precipitously 3-6 days later.

Remember when Boris Johnson was in ICU but not ventilated (probably on non-invasive support). They were watching him like a hawk for a few days.

Progressive pulmonary capillary damage? The ICU docs always said the disease was "weird" and wasn't behaving "normally".

 

[Shanti1]

Here's an issue I don't get: OK Covid folks have micro clots. They have not been ill that long, comparatively. But folks with ME have been ill for years and years and years. and blood does regenerate and so does tissue. So, do they too have micro clots? After 10-15 years of illness. Then the question becomes: what is driving the body to make these micro clots, assuming this thesis is correct. Some initial virus? Still not having left body? or what? Any help with this appreciated. Thanks.

There is much to investigate prompted by the micro-clot finding in LC patients that could be relevant to ME. Getting rid of the clots safely sounds like priority 1 though: initially mechanically, then maybe pharmaceutically.

ME and long COVID are the same disease, both an amyloid pathology that affects the blood and causes coagulation, immune and inflammatory derangement centred at the micro-circulation level.

When considering all the info in this thread, I see similarities between Long-COVID and ME/CFS, but also places where they differ and my read is that persistent micro-clots may be a difference. I base this on the reported finding that Long-COVID patents have low SvO2, presumably due to microclots. In contrast, ME/CFS patients have normal SvO2 at rest and HIGH SvO2 during exercise (see earlier studies posted).

So in one condition, we have the inability to extract oxygen (ME/CFS) and in the other we have hyper-extraction of oxygen due to poor tissue perfusion secondary to micro-clots (Long-COVID). Based on these findings, how can the same pathology be occurring?

In addition, the SARS-COV-2 is very tightly linked with severe clotting pathology while viruses like EBV, HHV-6 and Enteroviruses are not known to cause this type of severe clotting with active infection.

The low ESR found in ME/CFS also points away from clotting as the primary pathology as you would typically find a high ESR in hypercoagulation syndromes.

I think it is more likely the in ME/CFS we are seeing some hypercoagulation due to inflammation and autoantibodies associated with a variation of anti-phospholipid syndrome. However, if it were clotting alone causing the issue, I think we would see a low SvO2, and we don't.

This makes me think we are also seeing dysautonomia impacting the capillary blood flow (as described in the paper posted by @Pyrrhus earlier), mitochondrial dysfunction (causing inability to utilize oxygen), and possibly poor release of O2 from RBC due to their altered deformability. All of these factors would be consistent with the high SvO2 (low oxygen extraction) which has been observed.

This isn't to say that HELP Apheresis wouldn't be useful, perhaps even greatly so, but in my opinion, it would be for other reasons than the type of micro-clot occurring in Long-COVID.

 

[Countrygirl]

Thank you for the reply, I appreciate it. Hope you don't mind a further query.
Didn't Khan have what we'd term chronic or "Long" COVID ? Or did he have very acute onset and then get treatment expeditiously?
What's EV infection sorry?
HUGE fingers crossed you get to try the treatment man.
Apologies in advance for my lack of context here

Asad had LC and then a diagnosis of ME.

 

[SNT Gatchaman]

When considering all the info in this thread, I see similarities between Long-COVID and ME/CFS, but also places where they differ and my read is that persistent micro-clots may be a difference. I base this on the reported finding that Long-COVID patents have low SvO2, presumably due to microclots. In contrast, ME/CFS patients have normal SvO2 at rest and HIGH SvO2 during exercise (see earlier studies posted).

Yes, I think we need to ensure that those low and high SvO2 findings is correct. I know I had an extremely low value when I first presented and that Asad Khan was not quite as low at his (I think) 12 month mark. I want to re-check mine next week...

If it's true that long-term ME have normalised or high SvO2, then that could indicate the difference between "early-phase" ME and "late-phase" ME. The micro-circulation is dynamic and as more of the capillary bed gets compromised, short AV shunts might form, allowing RBCs to bypass and so not get held up and over de-oxygenated. The anaerobic-favouring metabolic pathways may de-oxygenate less also.

If this is all true, I don't know what the implication is for long-term / severe patients, but it's entirely possible that on resolution of that underlying pathological process, the micro-circulation could recover, along with the metabolic pathways. (The metabolism may need assistance).

See for example Systemic microvascular shunting through hyperdynamic capillaries after acute physiological disturbances following cardiopulmonary bypass.

 

[wabi-sabi]

So is there a safe way to anticoagulate yourself at home?

 

[wabi-sabi]

And how does the microclot hypothesis fit in with some of Dr. Systrom's work where he's looking at people with small fiber neuropathy? Didn't he think there was some problem with neuro regulation of vasodilation that was causing the oxygen extraction problems? Are we thinking that the small fiber neuropathy is somehow caused by the microclot or that there are two different mechanisms of impaired oxygenation and then all the same downstream problems?

https://journal.chestnet.org/article/S0012-3692(21)00256-7/fulltext

 

[SNT Gatchaman]

So is there a safe way to anticoagulate yourself at home?

That sounds dangerous! And I don't think that is the answer. You have to get rid of the micro-clots and they are resistant to normal processes (probably even when anti-coagulated). It's not just that they're "clots" it's that the clots contain protected inflammatory mediators that cause endothelial, platelet and blood cell dysfunction.

Mechanical removal via this technique looks like it's redressing the imbalance in many patients. Anecdotally many are looking significantly better. We don't yet know if it holds up long term.

Ultimately less mechanical and more pharmaceutical would be ideal.