PolyBio: New LongCOVID research launched by PolyBio’s global consortium of scientists

SNT Gatchaman

SNT Gatchaman

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Medford MA, February 22, 2024 – PolyBio Research Foundation, a global collaboration convening the world’s leading chronic disease scientists, today announced the second phase of its LongCovid Research Consortium (LCRC), including the distribution of $15M to fund scientific research, treatment innovation, and clinical trials for LongCOVID.

With its new phase of research initiatives, PolyBio adds preeminent scientists to its consortium, including Dr. Morgane Bomsel, Research Director at the Cochin Institute in Paris; Dr. Petter Brodin, Professor of Pediatric Immunology, Karolinska Institutet in Sweden and Imperial College London; and Dr. Chiara Giannarelli, Associate Professor in the Department of Medicine at NYU’s Grossman School of Medicine. These scientists boast decades of collective experience studying infectious and immune disease processes. Their participation expands the consortium‘s international reach, with the addition of research teams based in France, the UK, and Sweden to LCRC.
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In distributing its second round of funds, PolyBio will invest in deepening research on viral persistence in LongCOVID patients, including funding $2.1M at University of Pennsylvania and $1.3M at Sweden’s Karolinska Institutet to examine SARS-CoV-2 in the gut. “The gut appears to be a primary site of SARS-CoV-2 reservoirs in at least a subset of LongCOVID patients. Persistence of the virus in the gut is one of the biggest leads in the space,” says Dr. Sara Cherry, the John W. Eckman Professor of Medical Science in Pathology and Laboratory Medicine at the University of Pennsylvania, whose team is working to identify combinations of drugs that can eliminate virus in gut tissue.
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PolyBio will also fund scientists at UCSF to launch the world’s first program to collect comprehensive tissue samples – including from the bone marrow, lymph nodes, and the gut lining – from LongCOVID patients, providing an expansive view of viral persistence. Borrowing from research methods that were foundational to UCSF-driven breakthroughs in HIV research, the team will analyze samples for SARS-CoV-2. “The UCSF team contains people who helped make HIV/AIDS a treatable disease. These researchers rapidly pivoted into LongCOVID research at the outset of the pandemic, leveraging years of experience performing similar research on patients with HIV/AIDS,” says PolyBio President Proal. “It is incredible that the same expertise is now hyper-focused on solving LongCOVID.”
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They are also doing a trial of Lumbrokinase on ME/CFS, Long Covid and Long Lyme

Lumbrokinase LongCOVID & ME/CFS clinical trial - PolyBio Research Foundation

A clinical trial to test if the fibrinolytic enzyme Lumbrokinase improves symptoms and mitigates blood clotting issues or platelet hyperactivation in patients with LongCOVID, ME/CFS, & LongLyme disease. Small microclot deposits previously identified in LongCOVID and ME/CFS blood will be measured before and after treatment to determine if Lumbrokinase disrupts their formation.
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SARS-Cov-2 persistence and impact on long covid megakaryocytes & platelets looks interesting.

Morgane Bomsel, Dominique Salmon, Emilie Seyrat

The project will determine if replication-competent SARS-CoV-2 virus can be identified in the megakaryocytes (bone marrow-derived cells) and platelets of patients with Long COVID. The presence of viral particles (as measured via a microscope) and the infectivity of identified virus will be established. The project team is also performing a series of experiments to determine if Long COVID plasma contains 1) platelet micro-aggregates and circulating viral proteins such as spike 2) platelets with dysregulated energy metabolism 3) platelets with changes to gene activity profiles compared with platelets isolated from people without symptoms after COVID-19.
 
pooriepoor91 said:
They are also doing a trial of Lumbrokinase on ME/CFS, Long Covid and Long Lyme
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Taking nattokinase and lumbrokinase caused excessive bleeding in my case.

All my tests ruled out issues with hypercoagulability, hyperactivation of platelets, CD62P et 23 years ago. I had these tests done soon after reactivation of EBV and HHV6 relapse from taking immune modulators.
 
Key points from Steven Deeks at the PolyBio conference happening now:

1. LIINC Long Covid Clinical trials started/planned for 4 treatments
2. Same approach previous applied in understanding HIV and currently applied in Long Covid will be applied to funded ME research

Timothy Henrich at PolyBio conference describes the INTERRUPT-LC trial using an interleukin-15 (IL-15) receptor agonist approved for bladder cancer. The IL-15 receptor agonist (Anktiva) works by activating the body's natural killer and killer T-cell to clear viral reservoirs.

https://twitter.com/user/status/1791534765805310077
 
Yesterday there was a symposium by Polybio showing their latest work.

Both LC and ME/CFS but there is more focus on LC given recent funding so I put it there.

Here is a very extensive thread covering much of it (200+):
https://twitter.com/user/status/1791495605212336341
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And a shorter summary:
Finished the summary of the PolyBio conference.
Example of contents in the Google Doc.

The key points from Morgane Bomselt’s presentation are:

1. Research Focus:
- Morgane discussed the persistence of SARS-CoV-2 and its impact on long COVID, particularly focusing on megakaryocytes and platelets.

2. Background and Hypothesis:
- Previous research in the lab showed that viruses like HIV can persist in megakaryocytes and platelets, contributing to chronic infection.
- The hypothesis is that SARS-CoV-2 might similarly persist in megakaryocytes and platelets, forming replication-competent reservoirs that contribute to long COVID symptoms.

3. Megakaryocytes and Platelets in Acute COVID:
- In acute COVID-19, some individuals have detectable SARS-CoV-2 in their platelets and megakaryocytes.
- This presence is linked to worse outcomes in COVID-19.

4. Study Goals:
- To determine if SARS-CoV-2 persists in megakaryocytes and platelets in long COVID patients.
- To characterize the function and transcriptome of these cells in long COVID patients.
- To search for spike protein in the plasma and correlate with the presence of microclots.
- To evaluate tryptophan metabolism in relation to immune system modulation in long COVID.

5. Sample Collection and Analysis:
- Over 100 samples from long COVID patients have been collected, including plasma, platelets, and megakaryocytes.
- Comparisons are made with samples from COVID-recovered individuals and pre-COVID samples.

6. Initial Findings:
- Megakaryocytes in long COVID patients contain SARS-CoV-2 RNA and spike protein, indicative of viral replication.
- Platelets from long COVID patients also contain SARS-CoV-2 RNA and spike protein.
- Spike protein is detected in the plasma of a subset of long COVID patients, stratifying them into groups based on spike protein levels.

7. Implications:
- SARS-CoV-2 persistence in megakaryocytes and platelets suggests these cells may serve as viral reservoirs in long COVID patients.
- The presence of spike protein in plasma is associated with specific long COVID symptoms, particularly those related to cardiovascular and neurological issues.

8. Future Directions:
- Further analysis of the impact of SARS-CoV-2 persistence on megakaryocyte and platelet function.
- Exploration of the potential interaction between SARS-CoV-2 and other persistent viruses, such as herpesviruses.
- Investigating the broader implications of these findings for understanding long COVID pathogenesis and developing targeted treatments.

9. Acknowledgments:
- Collaboration with various institutions and researchers.
- Recognition of the contributions of team members and the support from funding sources, including the PolyBio Research Foundation.
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Summary document: https://docs.google.com/document/d/127j4WI5oAED4LRM0uy-a6RIRoYzhD61fGYc3bvlG64g/edit
https://twitter.com/user/status/1791919457083781147
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In my case it was because I didn't know about it.

Edit: Also it was the day after the Unite to Fight two day marathon conference, so I had no energy left to follow this one.

Also, not being on Twitter, I couldn't follow the posts there about it.

Will the talks be published on YouTube?
 
I'm not on Twitter and wasn't aware of this as upcoming. Plus we had UniteToFight 2024 which occupied attention. It's a good problem to have when major conferences are now colliding ! Personally I think viral persistence is an important hypothesis but it's not the only possibility - not least because there seem to be non-viral (eg Lyme) paths into the pathophenotype (although occult latent viruses could be relevant in those scenarios).

I am very interested in these megakaryocyte/blast findings - it could make a lot of sense for platelets to be dysfunctional due to their marrow-based (or even peripherally migrated) progenitors. There was a recent poster on this by Dominique Salmon / Morgane Bomsel's Paris team.
 
Andy said:
It was probably because people who noticed, or knew about, the event didn't post about it here, which could be for a variety of reasons.
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The downfall of Xitter is probably a big reason. It's often the only place to find out about it these days, and with fewer people to notice them. Although it's good that lots of summaries and videos get posted after, so missing it for a day or two isn't that big a deal. Sometimes I see something passing and assume someone else will post it here if I'm not really up for it at the moment, but if it doesn't happen I get around to creating a thread.

I don't remember seeing it announced before the day it was held, though. Some of this is probably with there being lots of news this week, from the United2fight conference and ME awareness week.
 
NelliePledge said:
Yeah people who use twitter as their only means to communicate need to adopt a different strategy with at least one other option.
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It probably was, but those are probably more direct/less available means, like subscribing to their newsletter, or maybe Facebook or other places. Not many places to get that kind of information. Same with OMF's symposiums, or the United2fight conference.

That's what made twitter unique. It used to be a place to get news from where journalists get some of their news.
 
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Amy Proal PhD intro 0:00
Petter Brodin MD PhD 10:21
Diane Griffin PhD 21:44
Kristin Ladell PhD speaking for David Price MD PhD 31:36
Morgane Bomsel PhD 40:03
Chiara Giannarelli MD PhD 52:37
Nicolas Huot PhD 1:02:16
Lael Yonker MD 1:15:11
Maayan Levy PhD 1:25:29
Michela Locci PhD 1:38:03
Steven Deeks MD 1:52:13
Tim Henrich MD MMSc 2:04:10
Resia Pretorius PhD 2:17:28
Gene Tan PhD 2:29:24
Nadia Roan PhD 2:39:39
Mark Painter PhD 2:51:49
Esen Sefik PhD 3:04:48
Rigel Chan PhD 3:17:30
Chris Dupont PhD 3:30:41
Victoria Cortes Bastos 3:42:27
Michael Peluso MD 3:52:39
Marcelo Freire DDS PhD 4:03:29
Sara Cherry PhD 4:16:33
Zian Tseng MD 4:28:36
David Putrino PhD 4:41:10
Mike VanElzakker PhD 4:53:14
Max Qian PhD 5:03:58
Matt Frank PhD 5:13:42
Ed Breitschwerdt PhD 5:26:31
Brent Harris MD PhD 5:40:55
 
https://www.meresearch.org.uk/project-update-from-dr-proal/

"Dr Amy Proal from PolyBio Research Foundation recently updated us on the progress of her project searching for viruses in tissue and nerve samples from people with ME/CFS. This project was funded by ME Research UK with the financial support of the Gordon Parish Charitable Trust.

The viruses most associated with ME/CFS (including polio-type enteroviruses and herpesviruses) can infect nerves and ‘hide’ in tissue, and may therefore remain in the body after an initial infection.

Dr Proal and her team (which also includes researchers at Berkeley National Laboratory and Harvard Medical School) are using new computer-based technologies to identify viruses in human tissue samples from people with ME/CFS and from healthy control subjects. They hope to clarify which of these viral species may contribute to the disease process in ME/CFS.

In addition to setting up and optimising the techniques being used, the researchers have been recruiting participants for the study, and have started collecting and processing the various tissue and nerve samples they require. Much of the analysis takes place in the next phase of the project, and we are looking forward to seeing those findings in due course.

Find out more about the project here"
 
I thought David Putrino's talk was interesting, so I had Claude.ai make a summary to share here:


Context
  • Long COVID and other complex chronic illnesses present over 200 symptoms affecting multiple organ systems
  • Traditional large-scale monotherapeutic trials are often ineffective due to the complexity and diversity of patient experiences

Three-Phase Clinical Trial Strategy

Phase 1: Rapid Interventional Trials
  • Sample size: 30-40 people per intervention arm
  • Deep phenotyping:
    • Conducted at baseline and end of intervention
    • Collaboration with Akiko Iwasaki's team
    • Focus areas: immune profiling, persistent pathogen levels, biomarkers of autonomic dysfunction
  • Objective: Identify biomarkers associated with drug response
  • Example:
    • Testing a broad-spectrum antiviral
    • Hypothetical finding: EBV titers bottoming out correlates with symptom improvement

Phase 2: Targeted Larger Trials
  • Recruitment based on Phase 1 results:
    • Select participants with biomarkers indicating likely positive response
  • Design: Larger-scale, placebo-controlled RCT of monotherapy
  • Primary goals:
    • Validate biomarkers identified in Phase 1
    • More effectively evaluate drug efficacy in a targeted population
  • Hypothesis: Significantly higher response rate compared to Phase 1

Phase 3: Adaptive Platform Trials
  • Focus: Testing multiple drug combinations
  • Design features:
    • Flexibility to adjust trial parameters based on ongoing results
    • Ability to test various intervention combinations simultaneously
  • Objective: Identify effective treatment combinations for specific patient phenotypes

Implementation at CORE (Center for Recovery from Complex Chronic Illnesses)
  • Multiple active interventional trials in progress or pending approval
  • Interventions being tested include:
    • Antivirals
    • Immunomodulators
    • Physical interventions (devices)

Key Strategy Elements
  • Start with smaller, deeply phenotyped trials to identify response predictors
  • Use these predictors to design more targeted, larger trials
  • Progress to adaptive trials testing combination therapies
  • Emphasis on understanding individual patient characteristics and their relation to treatment response
 
Lumbrokinase Long Covid & ME/CFS clinical trial
LINK

PolyBio is glad to be supporting the ME/CFS and Long Covid arms of this trial. If you are in the NYC area please check if you are eligible to participate! More info on the trial here:
https://twitter.com/user/status/1882496428431573376


Our lumbrokinase trial is recruiting patients. We are investigating the effect of a 6-week protocol of lumbrokinase

Individuals participating in the study must meet one of the following diagnoses: Long COVID, ME/CFS (pre-2020 diagnosis), Post-treatment Lyme Disease Syndrome. For more information, please reach out to coreresearch@mountsinai.org.
 
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