Is Apheresis an effective treatment for Long Covid and ME?

[Akasha]

This one is cheaper and probably enough as well. The other one had a discount a couple of weeks ago...

Josh found sth very interesting. RBC clotting in a crash but normal when at baseline.
He has 200 patients in his study now.
Pics shared with permission:

Is he collecting the blood in sodium citrate tubes? If you don't use an anticoagulant, blood will look like this quite fast on a microscope.

 

[Martin aka paused||M.E.]

Is he collecting the blood in sodium citrate tubes?

Good question. But as the healthy controls look normal and so do the patients at baseline I doubt a technical failure with blood processing

 

[ljimbo423]

Have researchers found what the inflammatory agents are in these micrclots? Could Lipopolysaccharides (LPS) be an inflammatory agent trapped in these microclots found?

Several studies have found higher levels of LPS in the blood of ME/CFS patients compared to controls. The levels of LPS in the blood of those of us with ME/CFS might be even higher than what's been found, if many of them are trapped in these microclots.

I haven't read the whole paper but this does sound intriguing-

Capture of Lipopolysaccharide (Endotoxin) by the Blood Clot: A Comparative Study

Abstract
In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot) and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus.

Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument.

Here we show that, in addition to these passive functions in immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus, and both the platelet thrombus and the fibrin clot of mammals (human, mouse) operate to capture lipopolysaccharide (LPS, endotoxin).

The lipid A core of LPS is the principal agent of gram-negative septicemia, which is responsible for more than 100,000 human deaths annually in the United States and is similarly toxic to arthropods.

Quantification using the Limulus Amebocyte Lysate (LAL) test shows that clots capture significant quantities of LPS and fluorescent-labeled LPS can be seen by microscopy to decorate the clot fibrils.

Thrombi generated in the living mouse accumulate LPS in vivo. It is suggested that capture of LPS released from gram-negative bacteria entrapped by the blood clot operates to protect against the disease that might be caused by its systemic dispersal.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080192

 

[Akasha]

Good question. But as the healthy controls look normal and so do the patients at baseline I doubt a technical failure with blood processing

It would be great to try to replicate these findings. Please keep me updated if you find out how to obtain the sample and prepare the slide.

 

[junkcrap50]

Have researchers found what the inflammatory agents are in these micrclots? Could Lipopolysaccharides (LPS) be an inflammatory agent trapped in these microclots found?

Yes, they have looked into what was inside the microclots in Pretorius's paper: https://cardiab.biomedcentral.com/articles/10.1186/s12933-021-01359-7

We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID-19 and Long COVID/PASC, versus the equivalent volume of fully digested fluid of the control samples and T2DM. Of particular interest was a substantial increase in α(2)-antiplasmin (α2AP), various fibrinogen chains, as well as Serum Amyloid A (SAA) that were trapped in the solubilized fibrinolytic-resistant pellet deposits.

 

[SWAlexander]

Long COVID: The long-term health effects of COVID-19 Published Friday, 17 December, 2021

• Long COVID is a complex condition, presenting several symptoms and affecting multiple organs and systems.
• There is uncertainty about the prevalence of Long COVID symptoms in adults and children following infection. The Office for National Statistics estimates that around 1.2 million people in the UK (including around 77,000 children aged 2-16 and around 134,000 people between 17 and 25 years old) are experiencing self-reported Long COVID.
• According to the National Institute for Clinical Excellence, risk factors for Long COVID in adults include female sex, having poor pre-pandemic health and poor general health, suffering from asthma and being overweight or obese. Risk factors in children include allergies, asthma, eczema and one or more pre-existing conditions.
• There is emerging evidence on the impact of vaccination on Long COVID in adults, with vaccinations reducing the risk of developing many Long COVID symptoms.
• There are ongoing challenges for the medical profession in diagnosis and treatment. Many of these are still in their infancy. More time is needed to understand how long the condition lasts.
• Key unknowns include the role of different variants in causing Long COVID, the effects of vaccinations and boosters, and management of cases in the long term.
• Priorities for research include a better understanding of suitable interventions, prevalence in different groups (including children) and biological mechanisms.

https://post.parliament.uk/long-covid-the-long-term-health-effects-of-covid-19/

 

[GlassCannonLife]

Can anyone remind me why we are seeing low venous oxygen saturation with microclots??

I can't remember and it doesn't seem to make sense - wouldn't impaired capillary function and gas exchange result in increased venous oxygenation (less going into tissues.?). Unless this is a lung capillary bed effect.?? In which case arterial would be also low?

 

[Rufous McKinney]

my understanding is we have alot of oxygen left in our venous blood...

 

[GlassCannonLife]

my understanding is we have alot of oxygen left in our venous blood...

Hm I don't think so, I have the theoretical manuscript from @Aguirre-Chang where he mentions it being low being an issue, and I thought I remembered people saying things about it here (but it was in November and I'm super crashed atm and can't read over the whole thread).

 

[GlassCannonLife]

Also, has anyone followed this paper from Pretorius with any success? My GP is happy to give it a shot but I thought I'd check!

 

[mitoMAN]

Can anyone remind me why we are seeing low venous oxygen saturation with microclots??

I can't remember and it doesn't seem to make sense - wouldn't impaired capillary function and gas exchange result in increased venous oxygenation (less going into tissues.?). Unless this is a lung capillary bed effect.?? In which case arterial would be also low?

Actually Long Covid Studies found high venous oxygen which points to low extraction. Systrom did a great study on it:
https://www.healthrising.org/blog/2021/11/19/heart-failure-muscles-long-covid-chronic-fatigue/

• Increased oxygen saturation found in the venous blood – cinched the former finding. Since the veins direct the blood back to the heart after it has gone through the muscles, the blood oxygen levels of the venous blood should be much reduced. The higher levels of blood oxygen found in the veins of the long-COVID patients indicated their muscles were not taking normal amounts of it up. Because the mitochondria use oxygen to produce ATP they weren’t able to produce as much energy.
  
  
• High blood oxygen levels at the moment of peak exertion – indicated that the lungs were delivering sufficient amounts of oxygen to the blood but the oxygen was not getting taken up in normal amounts by the muscles.

 

[GlassCannonLife]

Actually Long Covid Studies found high venous oxygen which points to low extraction. Systrom did a great study on it:
https://www.healthrising.org/blog/2021/11/19/heart-failure-muscles-long-covid-chronic-fatigue/

• Increased oxygen saturation found in the venous blood – cinched the former finding. Since the veins direct the blood back to the heart after it has gone through the muscles, the blood oxygen levels of the venous blood should be much reduced. The higher levels of blood oxygen found in the veins of the long-COVID patients indicated their muscles were not taking normal amounts of it up. Because the mitochondria use oxygen to produce ATP they weren’t able to produce as much energy.
  
  
• High blood oxygen levels at the moment of peak exertion – indicated that the lungs were delivering sufficient amounts of oxygen to the blood but the oxygen was not getting taken up in normal amounts by the muscles.

Hmm interesting. Then what am I talking about? I don't think I'm misremembering as there was the whole thread by aguirre-chang about it etc..? Can you recall at all or you weren't in that discussion?

 

[Shanti1]

@GlassCannonLife My recollection from past posts on this thread was that Dr. Asad Khan reported that his SpVO2 was very low and there was a great deal of discussion on low SpVO2 resulting from blood passing too slowly through the microcirculation, causing the tissues to need to hyper extract O2 and all of this being tied into micro-clots. Later, there were discussions that people with Long-COVID may have high or low SpVO2, but I don't recall if there were any studies at that point posted on Long-COVID and SpVO2. Studies in people with ME/CFS tend to show high SpVO2, especially after exercise, indicating low oxygen extraction.

 

[GlassCannonLife]

@GlassCannonLife My recollection from past posts on this thread was that Dr. Asad Khan reported that his SpVO2 was very low and there was a great deal of discussion on low SpVO2 resulting from blood passing too slowly through the microcirculation, causing the tissues to need to hyper extract O2 and all of this being tied into micro-clots. Later, there were discussions that people with Long-COVID may have high or low SpVO2, but I don't recall if there were any studies at that point posted on Long-COVID and SpVO2. Studies in people with ME/CFS tend to show high SpVO2, especially after exercise, indicating low oxygen extraction.

Ah ok that's interesting thank you. I just had blood gases done in the depth of my crash at the hospital and had low venous pO2, O2 Saturation and oxygenated Hb, so I was wondering if it could be some covid mechanism.

I had had blood gases done 2 years ago in the ER when I had crashed badly also (much less bad than this time though), and those were in range but also right near the bottom (eg 63 when range is 60-85, vs 51 this time).

Seems like my ME is consistently like this..? I wonder if it could be clotting issues.

 

[SNT Gatchaman]

I think abnormally high and abnormally low SvO2 has been seen. Not sure if this represents the phase of the illness, but at the least it suggests disruption of tissue oxygenation, with both hypo- and hyper-extraction.

For myself, I've had exceptionally low readings. Remember these are peripheral readings, so not the definitive measurements you would get from sampling the pulmonary artery. I've had readings of 22%, 46% and 15%. (My intensive care colleagues were astonished that I was upright and walking.)

Don't know whether it's due to variations in red cell shape / deformability. The RBC bi-concave disc is optimised for surface area to volume to allow gas transfer, so we might be seeing reduced ability to extract at times (and metabolic compensations to anaerobic pathways); and then recovery of RBCs and tissue hyper-extraction to feed the chronically O2 starved tissues as they revert their metabolism toward normal.

Another possibility I was considering is regional variation. Say the microvasculature was compromised by, for example, microclots, but that this was only taking effect in limb muscles, gut or brain. Anaerobic metabolism would generate lactate. This needs to be cleared and the liver (perhaps favoured by its rich/dual blood supply) is less compromised and able to pay back the debt. But that payback is ATP-inefficient and so ultimately more O2 is used than in healthy people. See Cori cycle.

 

[Shanti1]

Ah ok that's interesting thank you. I just had blood gases done in the depth of my crash at the hospital and had low venous pO2, O2 Saturation and oxygenated Hb, so I was wondering if it could be some covid mechanism.

So if your arterial O2 saturation was low, that will lead to low SpVO2 (since there wasn't good oxygenation to begin with) and usually indicates a problem getting O2 in the lungs. Low O2 saturation is, of course, a COVID hallmark and can even happen in asymptomatic COVID. How low was your Oxygen saturation?

 

[GlassCannonLife]

Ah cool, thanks @SNT Gatchaman. I haven't had arterial readings taken ever, just venous blood from a cannulated arm. The doctors didn't comment on it being out of range though, not sure why. I guess because there's nothing they can do and don't want to make note of abnormalities they don't treat..?

@Shanti1 thanks, my COVID symptoms (aside from the horrible ME crashing) were very minimal, and I only had the barest trace of a cough by that stage. Oxygen saturation (spo2 from finger) was very good / normal..

 

[SNT Gatchaman]

The doctors didn't comment on it being out of range though, not sure why. I guess because there's nothing they can do and don't want to make note of abnormalities they don't treat..?

Yes, that was my experience with my initial reading in hospital (the 22% one). It isn't listed as out-of-range because there isn't a range given. This is because it's usually used in the ICU / critical emergency setting and neither you or I "looked sick". It's likely dismissed as a spurious reading that is inconsistent with the overall patient picture - and, as you say, nothing they can do. For me my O2 sats were perfectly normal so supplemental O2 was irrelevant.

I would like to see this measurement investigated further and its significance promoted. It would be interesting to do a retrospective study of the machine samples and see how many were significantly ("unfeasibly") low. Remember, in the ICU setting of heterogeneously critically ill patients central or mixed SvO2 of <50% had 57% in-hospital mortality [study].

 

[GlassCannonLife]

Yes, that was my experience with my initial reading in hospital (the 22% one). It isn't listed as out-of-range because there isn't a range given. This is because it's usually used in the ICU / critical emergency setting and neither you or I "looked sick". It's likely dismissed as a spurious reading that is inconsistent with the overall patient picture - and, as you say, nothing they can do. For me my O2 sats were perfectly normal so supplemental O2 was irrelevant.

I would like to see this measurement investigated further and its significance promoted. It would be interesting to do a retrospective study of the machine samples and see how many were significantly ("unfeasibly") low. Remember, in the ICU setting of heterogeneously critically ill patients central or mixed SvO2 of <50% had 57% in-hospital mortality [study].

Damn, that statistic seems like it warrants investigation doesn't it.

I was described as looking "pale" at least? Haha

 

[Shanti1]

thanks, my COVID symptoms (aside from the horrible ME crashing) were very minimal, and I only had the barest trace of a cough by that stage. Oxygen saturation (spo2 from finger) was very good / normal..

Thanks for clarifying. Since you had a peripheral draw for the SvO2, the ranges that are used for SvO2 as measured from a PIC line in the ICU aren't the same. As @SNT Gatchaman mentioned, there isn't an established range. Still, 51 is quite low. Here is a post with a study looking at peripheral SvO2 readings compared with central readings.

https://forums.phoenixrising.me/thr...-long-covid-and-me.85939/page-11#post-2373891

But the bottom line from the above post is:

A peripheral SpVO2 will typically read lower than a SmVO2 or ScVO2, however, any reading below 55% on SpVO2 is highly predictive of a low ScVO2