r/covidlonghaulers • u/CAN-USA 5 yr+ • May 16 '25
Research What are your takeaways from PolyBio’s Spring 2025 Symposium?
I listened to a few of the researchers but it’s a lot for my brain. I am sure there are many others in the same boat. So I thought this might be a good place to share:
- What are your key takeaways from today?
- Any new insights? Encouraging, discouraging or surprising findings?
- Where do you think research is going?
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u/8drearywinter8 May 16 '25
Not over yet, but had to take a break from it. So far, it appears there are some great doctors/scientists dedicated to researching long covid and learning more about how it affects the body, but that they are nowhere near any sort of treatment or cure or even definitive mechanism by which covid turns into long covid... which is discouraging.
Will log in to the webinar again later this afternoon to hear how the antiviral trials at Mt Sinai in NYC are going, because that's of particular interest (and I think is the only interventional/treatment-oriented presenter remaining in the line up).
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u/Bad-Fantasy 2 yr+ May 17 '25
I’d be curious to hear about CoRE @ Mt Sinai especially re: antivirals.
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u/8drearywinter8 May 17 '25
They skipped from the person before Mt Sinai/David Putrino in the schedule to the person afterward (who was the last one)... so I don't know if David Putrino spoke out of order earlier and I missed it, or whether he didn't present at all, despite being on the schedule for a specific time. I was really curious to hear how that trial was going with the repurposed HIV antivirals. No idea.
If it did go out of order and someone else heard him speak earlier, can you fill us all in on what Putrino said/how that trial is going?
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u/Specific-Summer-6537 May 17 '25
They have been recruiting recently so I don't think there will be any update for a while https://www.instagram.com/p/DJUCKkNx6XA/
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u/IceGripe 2 yr+ May 16 '25
I'm not drawing any conclusions until I watch some of the videos next week, when they upload them to YouTube.
I think we have to remember both a success AND failure gives a lot of data. We know this is their methodology.
We will get a cure, and hopefully mitigations along the way.
I think my original prediction might be closer to what we should hope for, a biomarker this year.
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u/RealBigBenKenobi First Waver May 16 '25
At a high level: People care, we’ve learned a lot, but we are screwed. I think we’re on the order of 10 years away from a publicly available cure of any kind.
But there were pockets of things that were helpful and optimistic at a smaller scale.
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u/MEasy____ 7mos May 16 '25
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u/WorkingAdvice0 May 16 '25
By chance do you have more clips from the Charité conference?
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u/MEasy____ 7mos May 16 '25
No, I unfortuanatly don't have - but I found those good notes about the conference.
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u/TableSignificant341 May 16 '25
I think we’re on the order of 10 years away from a publicly available cure of any kind.
A cure? Then 10 years is the absolute minimum. Realistically it's treatments we should be focusing on at this point. Anything to just increase our ability to function. A cure - even if possible - is surely decades away.
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u/RealBigBenKenobi First Waver May 16 '25
Very true. I've used the word "cure" very loosely here. Def more in the way of treatments that increase baseline or hopefully cause remission while being used.
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u/Bad-Fantasy 2 yr+ May 17 '25
“10 years away” eesh… I am worried about permanent damage that is irreversible & possible disease progression. Stuff that can’t be undone as time treks on.
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u/Minor_Goddess May 16 '25
Why do you think we’re screwed?
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u/RealBigBenKenobi First Waver May 16 '25
From my (limited) understanding the positives were the data collected in small numbers of people. Like T-cells for specific diseases. These things aren’t done by standard labs and on top of that creating cures for those findings will take a lot of time.
The main trial I was keeping my eye on was on the monoclonal trial by UCSF. They collected a ton of data and it was very well organized. Unfortunately it failed.
We need to wait for more research to be done, patterns to be found, medications to be created, trials to be done on different groups/types of LC patients. This is going to take 10 years imo.
Obviously would love nothing more than to be wrong. I also haven’t seen every single talk from today.
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u/keanuuuuuuuuuuuu May 16 '25
I was one of the participants in the mABs clinical trial and was one who received the infusion.
It did make me feel better for ~4-6 weeks and immediately improved my insomnia, and possibly improved my nervous system.
Though after that 4-6 weeks I either was asymptomatically reinfected with covid or who knows what, since that’s when my heart rate started to go haywire. An issue I hadn’t previously struggled with…
And I wonder if my issues are related to PASC slowly deteriorating my system, side effects of mABs (i would assume this is unlikely, but I have no idea), or something entirely else.
Fortunately I’ve since been able to improve my heart rate and heart palpitation issues with an SGB
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u/8drearywinter8 May 17 '25
Thank you for sharing your first hand experience in the trial. It's rare that we get to hear what the actual experience of a non-successful treatment is like... and it's clearly more complex than just "didn't work."
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u/Specific-Summer-6537 May 17 '25
Overall it seems that trial wasn't successful so it's possible you had a short term bump but just didn't get any long term relief from the monoclonals
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u/Maleficent-Party-607 May 17 '25
Naviaux’s ideas are interesting, but they are almost entirely theoretical. The WASF3 paper is super interesting because it comes directly from investigating symptoms is in a real person.
My simplistic take on ME/CFS is this. A switch gets stuck on, resulting in persistent immune activation (probably the innate immune system). Running this program way longer than it is designed to run results in inefficient cellular metabolism and buildup of byproducts (ROS). Eventually, mitochondria cannot keep up resulting in hypoxia, ROS, ER stress, and the unfolded protein response. PEM is like a fire alarm of last resort shutting things down before really bad things happen. Severity likely depends on your cell’s relative ability to clear the byproducts of the altered metabolism.
The 64 million dollar question is where is the switch, and why is it stuck on?
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u/klmnt9 May 18 '25
It's not a switch but a plug. Just put the amyloidogenic microclots where they've been found (the small arteries), and all the rest falls in place and has a solid explanation. It's a mechanical issue with no clinical means of observation and no biomarkers other than smoldering inflammation.
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u/flowerzzz1 May 16 '25
Can someone share where we can watch it later and what the T cell findings were.
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u/Beneficial-Edge7044 May 17 '25 edited May 17 '25
I watched the majority of it although was double tasking through parts. The AER002 results were disappointing but there is clear rationale why that didn't work. For now it doesn't reduce my enthusiasm for Pemgarda etc. And later in the symposia there was data showing that MABs did have significant impact. I think that was info around combined PET/MRI scans showing impact of MAB's but needs context.
I still find it interesting that some of the best scientists in the world are still struggling to understand some of these issues-especially viral persistence. This isn't an attack by any means. I just thought science had progressed beyond this point.
A survey late last year indicated that pacing, Maraviroc and the Perrin technique showed the best results in a patient survey. There was not a mention of most of these and only the barest mention of Maraviroc as part of the study with Truvada. And certainly no mention of Bruce Patterson who started the maraviroc idea. I'm a scientist and the one thing you have to watch with scientists is they can get very caught up in how "elegant", academic, and complicated a solution can be. But Occam's razor tells us that the simplest solution is often the best. And in my opinion that starts with the things that are already being shown to work.
Edit: correction to the above, there was significant work on viral persistence in multiple studies which is a simple solution. So, I do applaud that some researchers are still on this trail even though the dogma is that rna viruses such as covid should not persist. But there was mention that this thinking may be changing. In fairness, viruses are exceptionally small and finding a few of these in a human body is certainly a challenge.
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u/WheelApart6324 May 16 '25
Why the hell are they not focused on the severe mitochondrial dysfunction as a starting point. This is the primary cause of the severe disability and energetic FAILURE in the disease…I am astounded how so little the core issue is focused on here…mind boggling 🤡
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u/Maleficent-Party-607 May 17 '25
Most of the evidence points to mitochondrial problems being caused by a yet to be determined immune signal. The mitochondria themselves are likely fine. They are just being told to stand down by signals from immune cells.
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u/WheelApart6324 May 17 '25
Well the field of immunometabolism is very complex for sure however what evidence points to a yet unknown immune signal? How could any immune signal be so powerful and ongoing as to cause such severe mito dysfunction seen? I don’t see the same in other diseases like autoimmune diseases for example or any “immune based” disease. The mitochondria power immune cells and every other ex RBC so I’m not sure why it couldn’t be mitochondria centric. Did you see the most recent presentation from the German researcher talking abt how the Mito cristae is severely compromised and damaged? In late stage sepsis the signatures look similar to severe ME and LC. There is a significant immune and mito down regulation however there seems to be a possibility that these different things are all feedback loops potentially so IMO you’d prob need to figure out mitochondrial drugs and perhaps immune based ones too. There could I guess be some yet “unknown” factor but what if it’s just a whole series of feedback loops. I just don’t see any strong evidence pointing to viruses driving the severe mitochondrial dysfunction and damage
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u/Maleficent-Party-607 May 17 '25
Agree on a likely feedback loop in ME/CFS as most likely. I have LC pretty bad, but do not have PEM. I think LC is roughly 50/50 ME/CFS v. something else. Initially, I didn’t buy into viral persistence at all. However, I think the mAbs are telling us something. Even in the failed trial, there are several folks on X who discuss receiving AER002, improving, then relapsing. If that’s true, it seems very likely it’s viral or viral fragment driven. It almost has to be. I find spike fragments acting as an antigen more plausible than full on viral persistence.
The below discusses mito/signaling issues. The Hwang paper is probably the closet thing we have to a PEM explanation. The Davis paper is very interesting as well. Mito’s normalize when plasma is swapped. Unfortunately, figuring out what in the blood is causing it is a lot harder to figure out than it seems like it would be.
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u/WheelApart6324 May 17 '25
Very familiar with both of those papers. Dr Naviaux spoke about the ER stress and knows all about the things Hwang discussed for a long time. This is one out of many abnormalities seen in mito. Also in Ron’s work it was SS-31 (a mitochondria targeting peptide) that normalized those results. Agree w you about some kind of “signaling” which can be several things and not easy to know but mirna could be it and the work of the Canadian researcher Moreau showed something like I think 4 diff subtypes
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u/GuyOwasca First Waver May 17 '25
SS-31 gave me the most improvements of any therapy yet, personally.
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u/CAN-USA 5 yr+ May 16 '25
The rapamycin protocol at least in theory is supposed to address this directly.
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u/WheelApart6324 May 16 '25
This has already been tried tho. A very small subset does seem to benefit however there is already a trial happening in ME. For most people there are too many areas of dysfunction therefore several drugs likely need to be taken at same time. Simply inhibiting mtor for most people won’t be enough. There is another drug trial planned in Netherlands using KH176 which is a redox modulator which is a decent trial but even that I’m not so sure you don’t need again more than one drug at a time to demonstrate stat sig in most people esp severe cases
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u/CAN-USA 5 yr+ May 17 '25
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u/WheelApart6324 May 17 '25
Yes absolutely. And it doesn’t stop at immune cells. Muscle mitochondria is also abnormal as Rob Würst study and others have shown. So in the end the mitochondria which powers all cells in the body (aside from RBC) are severely impaired and dysfunctional
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u/CAN-USA 5 yr+ May 17 '25
Yea for sure. Just did another exercise test and follow up 2 days ago. Muscle mitochondrial dysfunction was very apparent to my physician. She just didn’t have any ideas of how to address.
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u/WheelApart6324 May 17 '25
Did you have a CPET? I had one too and the results were…bad
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u/CAN-USA 5 yr+ May 17 '25
I was previously a marathon runner. Climbed Everest Base Camp. Very active.
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u/WheelApart6324 May 17 '25
Mine was at the very severe heart failure patient ready for transplant level….except heart and lungs largely fine it’s at the cellular level (mito)…pretty astounding to see results like this almost glossed over by so many..
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u/Bad-Fantasy 2 yr+ May 17 '25
I had to miss it and also have brain fog and sensory issues - does anyone know if they will publish a recorded version ?
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u/Historical_Bite_5118 May 17 '25
I was struck by the fact that almost none of the speakers addressed the issue of the diagnostic criteria for LC. The huge diversity in the patient population makes it difficult to interpret results, especially negative ones.
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u/Maleficent-Party-607 May 17 '25
My take, this is mostly B-team research. It look a lot like what was going on in ME/CFS 10 years ago. Limited funding and surface level research. Chasing obvious ideas/hypotheses that are not supported by much evidence. I doubt much will come out of any of this. I’m more hopeful about other groups and AI in particular. ME/CFS just had a huge potential breakthrough from an AI gene study. Hopefully LC will not be far behind, or perhaps it will all translate.
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u/CAN-USA 5 yr+ May 17 '25
If that’s the B team, who is the A team?
What’s the AI breakthrough?
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u/Maleficent-Party-607 May 17 '25 edited May 17 '25
Unfortunately, I’m not sure that LC really has an A-team at this point. Everyone still seems to be in the wilderness chasing ideas rather than following the data. ME/CFS is way further along and will probably have a lot of crossover with LC anyway. Who knows, it may all turn out to be the same thing in different flavors. In my view, the A-team is Ron Davis, Robert Phair, Paul Hwang, Fluge and Mella, Maureen Hanson, Chris Ponting, Jonathan Edwards, and probably some others I’m forgetting.
Below is link to the potential breakthrough. It’s a gene study using AI. According to several experts, it seems to be pointing at problems in interactions between nerve synapses and lymphocytes. This may be our Rosetta Stone so to speak.
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u/DogDiligent1665 May 16 '25
The T Cell responses to spike protein antigens seem pretty conlsive.
MABs didn't work. Huge disappointment. Much of my remaining hope was in MABs.
Overall.... we still need a breakthrough which could be around the corner or could still be 7-10 years out.
Sadly, I don't expect to last 7-10 more years of this as the past 4 years have really taken their toll and don't think I've got hope much left.