No “easy home runs”: Early Long COVID trials of Paxlovid and monoclonal antibodies failed, but the treatments still have potential Sick Times

  • Three prominent clinical trials targeting viral persistence in Long COVID with short treatment courses have not found that the drugs under study, Paxlovid and a monoclonal antibody, led to improved health for participants.
  • Viral persistence, the hypothesis that SARS-CoV-2 or pieces of it continually replicate in the body and lead to chronic symptoms, has been a challenge to study.
  • In an ideal scenario, a trial would specifically recruit participants with viral persistence markers and then measure changes in those markers. This hasn’t been feasible in the studies done so far.
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That’s because they don’t have actual markers. Except for a very small proportion, viral persistence is just a very popular theory in the patient community and BioBS hype.
 
I feel a bit gaslit by this article. The researchers in the Long Covid space absolutely were saying that all patients had viral persistence and set these trials up in response. Not just these there were lots of trials setup across Europe as well on Paxlovid and a variety of other antivirals. Every single one of them failed. They didn't find that a sub group of patients improved despite their 35% of patients showed signs of viral persistence.

It was a guess and they threw many trials at the problem and ultimately found nothing useful. Even now a lot of people believe what needs to happen is another trial on a different monoclonal that targets Covid because this is the one that will finally do it because one or two patients recovered using it.

Its railroading the entire research process and wasting money. They need to focus on core pathology and find a real predictive biomarker that correlates with disease severity before they can make any practical progress, can't reliably do drug trials until you have an objective measure of the patients that we are fairly sure is measuring or proxy measuring the core pathology.

Whatever happened to Polybio's antibody tagging to find where the persistence infections are so they could be positively identified? All we really have is some pictures of T cell density in some rats infected with Covid and its driven this entire thing.
 
Jaybee00 said:
Further, I think the fact that there is a “long covid space” with their own set of researchers (e.g. Peluso) and own set of social media people/journalists is really problematic and counterproductive because it just reinvents the wheel.
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I'm hoping the inclusion of 9000 LC patients in SequenceME will help the two spheres coalesce somewhat. Although thats a couple years off and not funded yet as far as we know.
 
Jaybee00 said:
Further, I think the fact that there is a “long covid space” with their own set of researchers (e.g. Peluso) and own set of social media people/journalists is really problematic and counterproductive because it just reinvents the wheel.
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Yup. “Long COVID” is being territorialised as a dieaease. With little consideration that the vast majority of cases are COVID associated cases of already named things like ME/CFS, OI, Post-ICU syndrome, Multisystem Inflammatory syndrome etc.
 
V.R.T. said:
I'm hoping the inclusion of 9000 LC patients in SequenceME will help the two spheres coalesce somewhat. Although thats a couple years off and not funded yet as far as we know.
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It might now as well, it might show a clear genetic difference underpinning Long Covid derived ME verses unknown origin ME. We could do with a lot more studied and the groups of various things like those that suffered from EBV looked at and compared to Covid origin and various other types. There is every chance the signal gets a lot stronger for particular SNPs for different origins. Really need to get to higher numbers especially of the small sub groups that there weren't enough of to produce independent significance.
 
For what it’s worth, I have some positive first hand experience with LC and mAbs.

I’ve had relatively severe long covid (essentially home bound) without PEM for two years. My symptoms are primarily heavy neurological and cardio/circulatory. I had a Pemgarda infusion in mid-June ago. I’m not fully cured, but I am much improved. I began feeling dramatically better 48 hours post-infusion and then felt the best I’ve felt in two years for the first week. Since then, I’ve oscillated between feeling nearly normal and feeling around 50% better than pre-Pemgarda. I’m convinced enough that it works, and that the Pemgarda trial will be positive, that Invivyd (Pemgarda maker) is now my largest stock holding.

My take is that LC and ME/CFS are not the same thing, but COVID infection seems to be particularly good at triggering ME/CFS. For those that have LC without ME/CFS, Pemgarda seems to be effective for many.

I think they screwed up the AER002 mAb trial due to both the choice of mAb and the trial design. AER002 is a lower dose (approximately 50% of the Pemgarda dose), and does not have FC effector function. In terms of the trial design, they set the only endpoint at 90 days. Per patients in the study I found on X, several saw improvement, but relapsed before 90 days. Finally, it’s not clear that AER002 is effective against all strains.
 
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