The micro-clot finding in Long Covid — implications for the possible aetiology of ME/CFS

Don’t know about Chris but Prof Akiko Iwasaki at Yale just met with Pretorius a week ago and seems to be impressed. She is saying the visible clumps are activated platelets — is that the same as microclots?

https://twitter.com/user/status/1589762087597019137

 

More images.. https://twitter.com/user/status/1590621694577631233

 

No, platelet clumps are something quite different from the claimed amyloid-containing clots, although the two might stick together.

I am not that impressed by Dr Iwasaki's habit of doing research by Twitter before she actually has results. I don't see serious scientists doing that. Her reviews of Long Covid have been pretty simplistic, consisting mostly of old hat notions anyone could have tacked together.

 

I am actually quite dismayed that an academic should splash patient samples on Twitter like this in relation to work that as far as I know is still to be replicated by anyone independent and which is very likely to be over interpreted by patients and parents.

Dr Iwasaki says: 'Activated platelet stained with anti-CD62P antibody are evident just looking through the eyepiece'

But hang on a minute - this is an extraordinarily naive statement to make isn't it? Looking through an eyepiece of a microscope is how you see stained cells - there isn't another way. And if someone has carefully picked a nice example for you to look at it may well look very impressive to someone unfamiliar with this sort of science. But for someone who knows how to evaluate stained cells it seems a pretty stupid thing to say.

 

I take it to mean that a simple microscope is all it takes, no need for fancy expensive equipment like imaging machines or electron microscopes that have months of queued work everyone is fighting for.

Can't say for the rest but that statement is clear to me. Any solution that requires manufacturing and deploying specialized machines will be a very hard sell, whereas microscopes are available at every single lab in the world. It's definitely a good feature, I'd even say it's a necessary feature, that nothing will be deployed to help us unless it's trivially easy to use in a clinical setting.

 

Except that this is a fluorescence microscope, which is a specialised piece of equipment that requires expertise to set up and use meaningfully and the main work involved is good quality staining that avoids false positive results. All Dr Iwasaki had to do was to look through a hole but some other people had been doing some quite complicated things beforehand, including finding a nice bit to look at, and also making sure the staining was not just artefact.

And even if fluorescence microscopes are standard for immunology departments why is it that there are stories going around that to perform these clot studies you have to buy a special set up from Dr Pretorius for maybe a quarter of a million dollars?

None of it makes sense to me and nor does it to any of the haematologists I have asked about it.

 

I think the intent was to say the posted picture was obtained just through the eyepiece.

https://twitter.com/user/status/1590044610474442753

 

She said 'just looking through'. A camera does not look through!

I find here comments extremely naive.

 

Dr Iwasaki should be explaining to laseerlaubnis that the professors in Germany are not doubting that some coloured lumps can be found in prepared specimens on slides. They are doubting that there are any clots actually in the people who provided the blood. And they may well be right.

 

I think that's the point: a proper mounted image capture device would record the image proximal to / instead of the eyepiece (as far as I understand). She's just showing a reasonably good image (for Twitter purposes) snapped by iPhone through the eyepiece (eyePhone?!?).

Newer phone cameras are so good that there are purpose-built adaptors for this, which she may have used.



https://www.ilabcam.com/

 

I really cannot see what it has to do with her comment!

She was saying that they taught her how to see the clots and wow all you have to do is look down the mike and there they are -

just like all you have to do to see Uri Geller's bent spoons is to look, and there they are... They must be real. And of course they are real and really bent, but that misses out rather a lot of the story...

 

Apologies for forgetting the punch line but I recall a friend describing a scientist/academic who was really high profile during a food "scare" in uncomplimentary terms --- news hog [EDIT - ? or some such]--- that scientist/academic did get a multimillion £ grant --- maybe that's all part of the "system" ?

 

100% agree re microclots. We don't know what they mean or if they mean anything at all, and we don't know if they're in vivo or simply an artifact of hypercoagulability or handling. Even if real they're likely downstream of what's actually going on.

I read her tweet as: they had been showing her techniques to demonstrate micro-clots (artifact-prone, in vitro as they are) and activated platelets. She didn't post any images of micro-clots. She did post the image of a cluster of activated platelets in whole blood, stained by anti-CD62p (P-selectin).

I also posted here Fereshteh Jahanbani's comment on this in relation to her team's recent ME/CFS publication.

 

https://www.youtube.com/watch?v=uDbwNFBz7Y8

Recent Sheffield ME & Fibro talk.
Prof Pretorius and Dr Caroline Dalton (Sheffield Hallam)

Felt overwhelmed by first talk by RP, too fast and detailed.

Second talk by CD was interesting and easier to follow. She seemed to understand pwME, raising good queries but unfortunately couldn’t get the acronym MECFS right.

What caught my attention was the last few comments on trials with ME patients and measuring microclots over a period of time to see if crashes correlate. If I heard right CD has a machine that optically quantifies microclots that she’s used in another disease (Parkinson’s?).

I think that this is referring to the LC/ME trial funded by PatientLed for RP plus three people/groups in UK (Liverpool/Manchester/Sheffield Hallam)

Only watched once and not the q&a yet. Posting for information only.

 

I listened to most of Caroline Dalton. Her results look fairly negative. Certainly no clear separation between patients and controls. Also, her pictures again just look like bits of artefact - I still do not see how they can have been in the live patient if the sample was centrifuged.

She said that the microclots were bigger and there were more of them but the picture only shows one on each frame as far as I can see. I don't think pictures like this can be interpreted usefully other than to show what the numbers are referring to.

There was also no discussion of methodological issues in her presentation that I picked up.

At least someone is trying to replicate - but so far it isn't looking as if the finding is consistent enough to be of clinical use.

 

I haven't seen references to this. do you have any more details?

 

Sorry, it came up on one of the threads at least once - maybe Tweets. I don't remember where but I do remember a figure of that sort being mentioned.

Caroline Dalton mentions that she already had equipment that would do the job, so presumably it requires more than a standard lab fluorescence microscope system with image analysis software. I have no idea how much that costs these days but I would guess more like tens of thousands. So it seems Pretorius is making use of some specialised technology.

My memory is that she has a commercial interest in such things but again, I cannot quote precise sources.

 

Yes I think that is correct. See comments starting here. It's not clear whether that's an overt attempt at profiting, vs simply commercially protecting the IP either through or from her university. Dr Beate Jaeger stated that she pays a license fee to RP, but that may be nominal/modest - we don't have details. The quarter of a million figure presumably relates to the cost of the fluorescent microscope, purchased from one of the usual vendors.

 

https://twitter.com/user/status/1636081250359279617

 

"Resolved" is not the same as "improved", so I hope that the preprint does not equate the two things as equal as well.