PolyBio Spring 2025 Symposium

https://bsky.app/profile/betsyladyzhets.bsky.social/post/3lpcj2jai3k2k

From Betsy Ladyshetz:

"Real bombshell of an update from Michael Peluso in this symposium: UCSF's highly-anticipated monoclonal antibody trial did not find the treatment helped alleviate Long COVID symptoms. He speculated that viral persistence may be a less promising avenue for LC than many have long hypothesized."
 
Live blog of the symposium from the Sick Times: https://thesicktimes.org/2025/05/16...symposium-on-long-covid-and-related-diseases/

Some snippets:
“Brain fog” is a common “nonspecific” symptom of many chronic diseases, including Long COVID, said Michael VanElzakker of Harvard Medical School. Through a series of high-tech neuroimaging techniques including those using magnetic resonance imaging (MRIs), his team found, in preliminary results,that both Long COVID and pre-COVID ME show changes to the brainstem. They specifically measured NAA, or N-Acetylaspartic acid, an amino acid derivative that plays an important role in neuronal health, where the vagus nerve connects to the central nervous system, he said.
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Hauitao Cheng of the Karolinska Institute then presented preliminary results from a detailed analysis of immune system markers in the gut. The study focused on people with Long COVID who have gastrointestinal symptoms, in comparison to people who were receiving colonoscopies for other reasons. Cheng and his colleagues identified a few differences between the Long COVID and control groups, including changes in T-cell and B-cell composition and chronic inflammation in the gut. Further analysis is underway.
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Michael Peluso from the University of California, San Francisco (UCSF) started this hour with a highly anticipated presentation, sharing results of his team’s monoclonal antibody (mAb) clinical trial. Unfortunately, the trial was unsuccessful: there was no difference in primary or secondary outcomes between people who received the mABs and those who received placebos.

Discussing this disappointing result, Peluso noted that the mAb his team tested — called AER002 — was out of date by the time they studied it, as it was developed for early pandemic-era variants. This was also a different drug from those used in prior case reports showing success with mAbs for treating Long COVID, he said. Peluso additionally noted that participants in this trial were not specifically screened for viral persistence, and may not have been the best people to test this type of drug.

Peluso speculated that viral persistence may be a less promising avenue for Long COVID treatment than many researchers and advocates have long hypothesized, but emphasized that he is “not discouraged.” He shared recommendations for further trials, adding, “I am confident that we are going to figure this out.”
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Next, Nadia Roan, also from UCSF, discussed other findings from the university’s LIINC cohort. Similar to John Wherry’s lab, this group analyzed specific T-cells that respond to SARS-CoV-2 and other viruses. They found that SARS-CoV-2-specific T-cells from Long COVID participants appear to be more exhausted and have other notable differences from similar T-cells in other people. Their results support both SARS-CoV-2 persisting and reactivating other viruses after acute infection. Up next, they’ll be collecting reproductive tissue samples from women with Long COVID.
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forestglip said:
"Real bombshell of an update from Michael Peluso in this symposium: UCSF's highly-anticipated monoclonal antibody trial did not find the treatment helped alleviate Long COVID symptoms. He speculated that viral persistence may be a less promising avenue for LC than many have long hypothesized."
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Utsikt said:
Has there ever been any real evidence for viral persistence?
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Sounds as if he may have got cold feet about his previous claims.
 
Utsikt said:
Has there ever been any real evidence for viral persistence?
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Isn't "viral persistence" more than one thing, though? For sure HIV, HHV-6 and shingles don't persist the same way, none can be found in most biological samples, and most wouldn't respond to most antiviral courses. If it were all that simple, AIDS would have been a breeze to treat: just run the antivirus, bro.
 
To me, this feels a little like the failed Rituximab trial. There are numerous credible N1s of LC patients cured with Pemgarda. There are several anecdotes out of UNC’a Long Covid Clinic alone. While I understand that N1s could be spurious (time heals, placebo, etc.), it just doesn’t feel that way in this case. The stories are similar when it works. Roughly 3-7 days of increased autonomic symptoms, then rapid improvement over the course of a week or so. Likewise, some people relapse at 1-3 months, which is in line with the half life.
 
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There was some speculation from Peluso's side on whether it was "just" the wrong drug. If there is viral persistence, I believe there could be something to that idea. It lost efficacy against SARS-CoV-2 variants in the end of 2022. Many of the patients enrolled had been (re)infected after 2022. So if there were a viral reservoir, it is conceivable that taking this drug against older variants would fail.
 
On the other hand, in the opening talk from Amy Proal, she said something where out of reflex my first instinct was to doubt her.

She said we need new methods to be able to find tiny tiny minimal amounts of viral RNA/DNA/proteins more accurately. My response being "If you need to find those infinitesimally small traces of virus, can it really be the driving issue of disease?". Not saying my instinct is right, but that's what I thought.
 
If people with long covid are Really disappointed regarding the viral persistence avenue, why can US ME orgs , who in my opinion have supported the long covid first Approach , not get how unserved those with long term ME have felt by being told by the nih to just accept a funding freeze, resources and focus going on to the long covid cohort onky etc , with a lot of focus on a virus and early stage research not directly connected to or beneficial to the M.E community?, Afaics there's little research going on concurrently to understand what viruses may be implicated in m,e if the viral persistence path holds up etc and they're already saying that some pwLC may be too long ill to best benefit from this approach even if it works very early stage. It's unacceptable for m.e to have been placed on the back burner or waiting for indirect spin offs. We are as deserving as MS of our own research program meeting our own needs
 
Stuart79 said:
To me, this feels a little like the failed Rituximab trial. There are numerous credible N1s of LC patients cured with Pemgarda. There are several anecdotes out of UNC’a Long Covid Clinic alone. While I understand that N1s could be spurious (time heals, placebo, etc.), it just doesn’t feel that way in this case. The stories are similar when it works. Roughly 3-7 days of increased autonomic symptoms, then rapid improvement over the course of a week or so. Likewise, some people relapse at 1-3 months, which is in line with the half life.
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Are there any relevant publications on Pemgarda?
 
Cinders66 said:
why can US ME orgs , who in my opinion have supported the long covid first Approach , not get how unserved those with long term ME have felt by being told by the nih to just accept a funding freeze, resources and focus going on to the long covid cohort onky etc , with a lot of focus on a virus and early stage research not directly connected to or beneficial to the M.E community?
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Particularly as it may well turn out that the answers for LC actually come from ME/CFS research (including DecodeME and friends).
 
Pemgarda is a monoclonal antibody against certain COVID variants right? But it only works preventatively, you can’t take it after you’ve been exposed. (ie. it only works extracellularly not intracellularly).

So I don’t really see why people think it would help Long COVID even if long COVID = persistant virus.

I guess perhaps preventing reinfections improves recovery chances?
 
San Francisco Chronicle: '36 people with long COVID tested a potential treatment. Here’s what the study found'
On Friday, study leader Dr. Michael Peluso of UCSF revealed the results to fellow long COVID researchers.

“I’m sad to say we did not detect a significant difference” between those who got the drug and those who did not, said Peluso, who reported the disappointing outcome during a webinar sponsored by the PolyBio Research Foundation [...]
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The researchers found that some people improved in both groups — the 24 who received the monoclonal antibodies and the 12 who did not. Others saw no improvement.
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Alternatively, Peluso said in his presentation, “we think only a subset of people have viral persistence.” In future such studies, he said, researchers will need to confirm whether each participant has a biomarker of viral persistence.
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Another possibility in the current study is that the monoclonal antibodies had lost potency. Known as AER002, the drug was manufactured by Aerium Therapeutics in Boston and aimed at the version of the virus that attacked people before 2022, Peluso said.

“Or maybe a single dose just didn’t work,” he said. “Maybe multiple doses are needed.”
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“I was shocked,” said Shelley Hayden, the third person to be infused. “I think I said swear words.”

Hayden, a marketing executive from Oakland whose post-COVID symptoms forced her to stop working shortly after the pandemic began in 2020, had gotten a placebo.

“I was 100% sure I’d gotten the monoclonal,” she said, because she felt feverish afterward.

Also, she improved over the next three months, feeling more energetic and having fewer stomach problems. Even her post-COVID eye twitch seemed to lessen.

“But nothing went away entirely,” said Hayden, 57. “I’m not cured.”
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At UCSF, Peluso and Dr. Steven Deeks are planning three new studies through their long COVID research program, LIINC, for “Long-term Impact of Infection with Novel Coronavirus.”

One study will look at whether the rheumatoid arthritis drug, Baricitinib, can help long COVID patients who have cognitive dysfunction. Another, funded by the Department of Defense, will test Bezisterim, under development for neurological conditions. The third will see whether boosting the immune system can ease long COVID.
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Cinders66 said:
If people with long covid are Really disappointed regarding the viral persistence avenue, why can US ME orgs , who in my opinion have supported the long covid first Approach , not get how unserved those with long term ME have felt by being told by the nih to just accept a funding freeze, resources and focus going on to the long covid cohort onky etc , with a lot of focus on a virus and early stage research not directly connected to or beneficial to the M.E community?, Afaics there's little research going on concurrently to understand what viruses may be implicated in m,e if the viral persistence path holds up etc and they're already saying that some pwLC may be too long ill to best benefit from this approach even if it works very early stage. It's unacceptable for m.e to have been placed on the back burner or waiting for indirect spin offs. We are as deserving as MS of our own research program meeting our own needs
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Going for LC was still the right thing to do because it gave access to funds that ME/CFS alone doesn't. We have to work with dysfunctional systems as they are, not the ones that should exist in a sane world.

It hasn't paid up yet, but at least the area of LC research that gets the most resources is pretty explicitly about PEM, so it's very unlikely that a breakthrough there wouldn't work for us. This problem is just absurdly complex, seemingly more so than almost any other problem in medicine, and it's very likely that it will require applying a specific technology that either hasn't been applied to it yet, or not in the right way, or hasn't been developed yet.

I can't see any problem with taking a strategy to maximize the chances of solving this. But that's probably because I see no scenario in which LC is more or less solved that leaves us behind. IMO they are tied together at the hip, bone deep.
 
Two separate researchers highlighted CMV in Long Covid and ME/CFS.

This is the Viral-specific CD8+ T cell slide from Nadia Roan in Long Covid vs Recovered controls. Looking at the slide CMV seems to show a big difference.
https://twitter.com/user/status/1923526695790800923



And this is a slide from Victoria Cortes Bastos highlighting differences in cerebrospinal fluid for seropositivity to CMV vs seropositivity to SARS-COV2 and Parovirus B19 in ME/CFS
https://twitter.com/user/status/1923446665605702088
 
rvallee said:
Going for LC was still the right thing to do because it gave access to funds that ME/CFS alone doesn't. We have to work with dysfunctional systems as they are, not the ones that should exist in a sane world.

It hasn't paid up yet, but at least the area of LC research that gets the most resources is pretty explicitly about PEM, so it's very unlikely that a breakthrough there wouldn't work for us. This problem is just absurdly complex, seemingly more so than almost any other problem in medicine, and it's very likely that it will require applying a specific technology that either hasn't been applied to it yet, or not in the right way, or hasn't been developed yet.

I can't see any problem with taking a strategy to maximize the chances of solving this. But that's probably because I see no scenario in which LC is more or less solved that leaves us behind. IMO they are tied together at the hip, bone deep.
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I think long-term severe ME cses That developed through years of exertion from no diagnosis, until they now can’t move and don’t see improvemen , with a swine flu trigger from 2007 might require different research & treatments to people ill less than 4 years, safe guarded by #MEActions stop rest pace advice, with a sars C cause and sitting at around mild-moderate. And i think both groups shoud be studied alongside each other, with pwME, hanging in by thread, getting access to drug trials and meds as urgently. I have no issue with collaboration but we rolled over on the nih long-covid first policy, particularly allowing sheer numbers to be used to decide urgency.
 
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