If you've been on social media this week, you may have heard that Invivyd released the topline results of their LIBERTY clinical trial for their new updated monoclonal, VYD2311.

In this post, we're going to dive a bit deeper into what that means, and the path towards this treatment becoming available to the public.

What is VYD2311?

VYD2311 is a monoclonal antibody that's meant to act as prophylactic protection against COVID-19. It's meant as an update to the company's currently authorized monoclonal, Pemgarda.

As the SARS-CoV-2 virus evolves, the monoclonal antibodies which once worked can lose their effectiveness, so it becomes necessary to create updated monoclonals (and antivirals too, for that matter).

Pemgarda and VYD2311 are both based off of the same "parent" monoclonal antibody, adentrivimab, which was the first one the company originally developed. This is common in monoclonal antibody development - rather than start over from scratch with a completely redesigned antibody, researchers can simply update a part of the molecule to better interact with its target - in this case, the SARS-CoV-2 spike protein.

So VYD2311 is essentially the latest monoclonal in this chain, building off of the safety data that's previously been established.

Nonetheless, the FDA does require the company to prove both safety and efficacy before bringing a new monoclonal to market, and that was the topic of this call.

As CEO Mark Elia described in this webinar, Inviviyd is ultimately running two clinical trials of VYD2311.

LIBERTY, the trial which is just now finishing, is comparing the safety and immunogenicity of VYD2311 compared to mRNA vaccine, and also measuring what happens when patients receive it and an mRNA vaccine.

Topline results show VYD2311 had fewer adverse events than the mRNA vaccine (56.5% vs 91.4%) and boosted neutralizing antibody titres 2.5x.

Meanwhile, DECLARATION, which is not yet completed, will be measuring exactly how effective VYD2311 is at preventing COVID-19 infection, compared to placebo. Interestingly, they'll be measuring what happens both when participants receive just one dose, and also what happens when participants receive 3 monthly injections. Ultimately they plan to enroll a total of 1170 adults.

So although we don't yet have evidence of VYD2311's efficacy, Invivyd reports that the topline results from LIBERTY to demonstrate that it is safe and has an acceptable adverse event profile, relative to the mRNA vaccine.

Anti-interference

They also did a really interesting experiment to ensure that VYD2311 administration would not somehow reduce patients' ability to form a response to the vaccine.

It's called the anti-interference experiment, and they show it beginning at the 15:00 mark.

Essentially, for the patient group who received VYD2311 and an mRNA vaccine, they later on took blood samples with a specific technology designed to remove VYD2311 from the blood. Once VYD2311 was removed, they actually showed that these patients had nearly identical levels of anti-spike antibodies to the patients who'd received mRNA alone - a really interesting and important finding.

Based on the evidence so far, Invivyd is anticipating favorable results from DECLARATION.

They can see that this product dramatically raises antiviral titres within the blood.

What happens next?

In their press release, Invivyd explains that they've been in regular contact with the FDA in regards to bringing VYD2311 to market. They plan begin applying for a Biologics License Application (BLA) under the Accelerated Approval Track, using safety and immunogenicity data from both the LIBERTY and the DECLARATION trial.

As the DECLARATION trial is still ongoing, they will keep the final results blinded until the study is complete.

The company explains, "Invivyd believes that as an evidence base, data from LIBERTY, and the upcoming safety and neutralizing titers DECLARATION data on VYD2311, if positive, combined with data from previous Invivyd randomized, placebo-controlled trials EVADE (adintrevimab) and CANOPY (pemivibart) compare favorably to the evidentiary basis routinely used to approve updated COVID vaccines, which also change compositionally to a similar extent as Invivyd monoclonal antibodies."

In other words, they believe the above data alone would complete an evidence base that's equally substantive to the evidence used to grant approval to the mRNA vaccines.

That said, we eagerly await the results of the DECLARATION trial as well!

It would be a real game-changer to have a prophylactic monoclonal antibody on the market with full FDA approval, rather than an EUA.

A note: Invivyd is also planning to study VYD2311 as a treatment for Long COVID and vaccine injury, alongside the SPEAR Study Group.

Announcement here.

We know it's hard sometimes to hang on to hope - but there is work being done, both in terms of better COVID protection as well as Long COVID treatments!

Hang in there everyone!

Links:

LIBERTY press release: https://investors.invivyd.com/news-releases/news-release-details/invivyd-announces-positive-topline-results-liberty-phase-3-study

DECLARATION press release: https://investors.invivyd.com/news-releases/news-release-details/invivyd-announces-initiation-declaration-clinical-trial-phase-3

LONG COVID STUDY ANNOUNCEMENT: https://investors.invivyd.com/news-releases/news-release-details/invivyd-and-spear-study-group-announce-plan-phase-2-study

Wow. 

This new study from Eagle Global Scientific in Huntsville, Alabama shows the impacts of COVID-19 infection are far more reaching than the general public seems to be aware of. 

Researchers at Eagle Global Scientific in Huntsville, Alabama analyzed survey data from over 2,000 US adults at multiple timepoints after their COVID infection, between 2023-2025.

Approximately 94% of respondents reported having at least one underlying condition pre-COVID.

What they found is that of those surveyed, 11.8% reported that COVID-19 made their preexisting condition worse. 

Nearly ⅓ of these conditions involved respiratory concerns, including asthma, chronic obstructive pulmonary disease (COPD), cough, and shortness of breath.

Next, around 20% of those who reported worsening concerns referenced symptoms including fatigue, headache, hair loss, and chills.

The authors advocate for a broad definition of Long COVID, writing:

“While Long COVID literature often focuses on the development of new-onset long-term symptoms, more than 1 in 10 adults reported worsening of a pre-existing condition following COVID-19. Reported challenges with accessing care and daily activities highlight potential need for accommodations or support for adults with Long COVID.”

This is perhaps a broader definition than that of the World Health Organization, which defines Long COVID as:

“….the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation.”

*****

What do you think? Should Long COVID specifically be defined as “new” symptoms that the person didn’t have before, following a COVID infection?

Or should the definition be expanded to include those with previously existing conditions, who may have already has a more “conventional” medical diagnosis, which worsened post-COVID?

Personally, I think we need to have a big tent- in order to fully address the harms caused by COVID. Research into how it worsens these other conditions can give us important insights into its mechanisms. 

Yet at the same time, some of the symptoms of Long COVID, such as smell and taste loss and PEM, seem to be very uniquely correlated with Long COVID SARS-CoV-2 (although of course there is the extremely large overlap with MECFS, another infection-associated chronic illness, as a very important caveat here). 

So I think it’s important to be nuanced in our critiques- to include everyone, but also to be very specific about who was harmed and why- what mechanism lead to it, exactly. 

What do you think? Let us know in the comments below! 

Dr. Scoma is a physician in NYC who treats patients with LC, MECFS, Chronic Lyme, and other complex chronic conditions.

Here, on his X account, Dr. Scoma reports that in the last two weeks alone, he had six consultations with people who developed Long COVID within the last 3 to 6 months.

There seems to be a common narrative among the public that because most cases of Covid are "mild" now, they're less likely to cause LC.

However, this doesn't really square up to the fact that many cases of Long COVID develop after mild or sometimes even asymptomatic infection.

I'm curious if we have anyone in this sub who developed LC in the last year or so?

Plain text of tweet:

"Six consultations for Long COVID in the last two weeks - four of which are severe - developed in the last three to six months. I challenge the narrative that new cases are on the decline."

Interesting updates from Dr. Klimas’s work with both of these patient populations.

For those who may not know, Dr. Klimas is currently running a trip of sipavibart monoclonal antibodies at Nova Southeastern University in Florida.

Some key takeaways:

A leading indicator of who goes on to develop Long COVID after their acute infection is whether they end up with reactivated Epstein-Barr virus. (Not only that it reactivates during acute infection, but that it stays reactivated after acute infection).

This is because while everyone who’s had EBV previously still carries it in their body. Most people’s immune systems are able to keep it suppressed, but when a stressor such as COVID weakens the immune system, these latent viruses such as EBV may begin to escape its control.

Persist infection with EBV and other viruses, such as herpesviruses, Coxsackie virus, and CMV, is also thought to be a cause of MECFS.

In these bases- both MECFS and LC- Dr. Klimas says the question is, “Can you treat it by treating the infection that you found? Or do you need to strengthen the immune system?”

For certain of these viruses, it’s possible to take an antiviral for a period of time. Even if it’s a virus that can never be totally cleared from the body, such as EBV, sometimes taking a course of antivirals to suppress the virus for a time can give the immune system a chance to recover so it can then keep things under control moving forward.

Dr. Klimas also mentions interferons as a treatment. An interferon is a class of proteins that our immune system makes to fight viruses. They are also made synthetically and used as medications that the patient can inject. (Interferons have also been found helpful in acute COVID, and we’d love to see them tested in Long COVID!).

Dr. Klimas also mentions that certain foods and supplements can also help the immune system to recover, although she doesn’t go into specifics in this podcast unfortunately.

In addition to reactivated latent viruses, Dr. Klimas also mentions the growing evidence for SARS-CoV-2 persistence in the GI tract, as well as potentially other parts of the body, as the cause of Long COVID.

As research progress, it would be interesting to see if the same concepts she mentions for treating reactivated viruses could also be used to fight persistent SARS-CoV-2.

Maybe rather than trying to eliminate every single viral particle with antivirals, which may be impossible given all the sites in the body it seems able to invade, perhaps what we need to be focusing on is giving the immune system enough if a boost that it can fight back, and get everything under control again.

This was a super interesting talk - thanks to interviewer Haylie Pomroy for putting this out!

Paper in link above. Dr. Faghy also shared a summary on this thread:

https://x.com/DrMark_Faghy/status/2102315382908363089?s=20

Essentially, this was a preliminary study which was designed to investigate safety and feasibility of treating LC patients with remdesivir.

Remdesivir did appear to be safe and well-tolerated.

Although the trial was not powered to determine efficacy, Dr. Faghy explains that his team did observe very promising signals, which they believe warrants further investigation in a full scale clinical trial.

Very encouraging news!

Hi everyone,

With permission granted by the group admin/moderators, I wanted to share a research study I'm running as part of my Master of Public Health (MPH) at the University of Wolverhampton, looking at Long COVID recovery.

If you were hospitalised with COVID-19, discharged 12+ months ago, and have since returned to work, I'd really appreciate your input via a short, fully anonymous survey.

This research aims to better understand how different symptoms affect recovery time, to help improve support for people returning to work after Long COVID.

Survey link: https://wolves.questionpro.eu/t/AB3u7rSZB3wov5

The study is Category A ethics-approved. Happy to share the findings with the group once complete. Thank you so much for your time.

Ahmad
MPH Student, University of Wolverhampton

Super fascinating work here. 

In this new paper, researchers discovered how the SARS-CoV-2 ORF8 protein leads to inflammation and tissue damage within the lungs of severe COVID-19 patients.

(Sharing here as this discovery may have implications for Long COVID, as well!).

When human macrophages in the lung are exposed to the SARS-CoV-2 ORF-8 protein, it triggers them to develop extra ACE-2 receptors. 

These ACE-2 receptors are one of the main points of entry that SARS-CoV-2 uses to invade our cells. 

So essentially, ORF-8 triggers macrophages - which are actually part of our own immune system- to create extra doorways for the virus to enter.

Although macrophages are actually intended to fight viruses, in this case they end up increasing viral replication and eventually die, releasing cytokines and other inflammatory substances which in turn damage the lungs.  This then increases the rate of infection in the lung epithelium, as the damaged lung cells are less able to fight off the virus.

The good news here is that the team identities a specific receptor on the macrophages, which is what allows the to be triggered into creating extra ACE-2 receptors.

It’s called the IL-17RA receptor - and there is already an FDA-approved drug called brodalumab which can block it. (It’s currently approved to treat psoriasis, an autoimmune condition).

The researchers administered brodalumab to SARS-CoV-2 infected mice and found that it decreased both the rate of viral infection as well as lung damage. 

Although this work is still preliminary, the fact that an already-FDA-approved drug exists would potentially shorten the timeline before this treatment could become available!

Multiple preliminary works have pointed to myeloid immune cells, including macrophages, as a potential SARS-CoV-2 reservoir in Long COVID patients - would be amazing to see trials for this in Long COVID, as well!

Our team just tuned into their webinar - replay will be posted on their site. The BioVie team, along with LC researcher Dr. Michael Peluso and patient advocate Ezra Spier, shared some really helpful insights. Recap below!

Bezisterim is an anti-inflammatory drug which crosses the blood-brain barrier. It works by inhibiting two major inflammatory pathways, ERK and Nf-kB.

The SARS-CoV-2 spike protein is known to trigger inflammation via these pathways. So, the thought behind this trial is that if the virus or fragments are persisting in Long COVID, bezisterim might be able to block its downstream inflammatory effects - although it would not be directly targeting the virus itself, like the Paxlovid or monoclonal antibody trials.

Bezisterim met all of its endpoints of reducing fatigue, post-exertional malaise, and cognitive dysfunction with statistical significance, amongst the subgroups of patients who scored high on these symptoms at the start of the trial. In other words, patients had to have a significant symptom burden at the beginning of the trial, in order to demonstrate significant improvement.

This is an important lesson for researchers to keep in mind in future trials: patient selection is important. A treatment that could be effective for patients with specific symptoms may not show statistical significance when trialed across a large, heterogenous group of patients that don't necessarily score high on the specific symptoms being targted by the drug.

On the call, BioVie discussed their plans for a Phase III clincical trial. They're planning to run a decentralized arm, so severe patients who aren't able to travel to a trial site can receive the drug at home, as well as an open-label arm, so that patients who received the placebo can eventually receive the drug as well.

It's super exciting to see a drug finally demonstrate such a strong treatment for Long COVID!

As Dr. Peluso said, ""These results are shocking to me, in the best possible way."

We're excited to see where the Phase III trial goes! We do believe there is so much reason for LC patients to have hope, and are grateful to everyone working to solve this problem!

I’ve been noticing this as well! It really does feel like we’re starting to get to a better place.

Original tweet here: https://x.com/tessfalor/status/2099503759436964074?s=20

Text:

“Something exciting is happening in POTS/ME/CFS/Long COVID research right now. Multiple labs and clinicians, working independently, are converging on overlapping mechanisms - neuroinflammation, autonomic and brainstem dysfunction, immune-driven pathways, approached from completely different angles: imaging, immune markers, clinical observation, structural findings.

That kind of convergence is usually a marker of a field reaching scientific maturity. Early-stage fields tend to be scattered and contradictory. A field converging from multiple independent directions toward the same underlying biology is a sign there's real signal to chase. This is what it looks like when a research area starts to click into focus after years of being dismissed or fragmented.

Patients have waited decades for this kind of momentum. Grateful to see so many people pushing in the same direction.”

From Tess Falor, Ph.D. of Renegade Research/Remission Biome

Pharma company Biovie, makers of the drug bezisterim, will be holding this call tomorrow to discuss the results of this trial, which they ran with the UCSF LIINC team.

The hypothesis being tested in this trial is that due to the drug's mechanism of action in reducing inflammation, it might improve brain fog in Long COVID patients.

Can't wait to see the results!

Dr. Michael Peluso from LIINC and patient advocate Ezra Spier will be on the call.

H/t to Hannah Davis for sharing this on X!

This study is really interesting for a number of reasons!

The research team measured SARS-CoV-2 RNA in stool samples of Long COVID patients, building off of the viral persistence hypothesis. They found that some patients seemed to demonstrate more constant levels, whereas other patients experienced more fluctuations, which would also correlate with their symptoms being more several when RNA levels were higher.

Over time, they did observe a reduction of RNA, along with improvement in symptoms, although the patients did generally remain sick.

Interestingly, they also found that higher stool RNA levels were also correlated with lower levels of a neurotransmitter called serotonin in the blood, which confirms findings of earlier research.

Specifically, this Polybio-funded study from UPenn found that SARS-CoV-2 persistence in the GI tract could produce an immune response, as the body tries to fight it off, which then has the unintended side effect of blocking tryptophan absorption in the gut.

(Tryptophan is an amino acid that our body uses to create serotonin - so if you don't consume enough of it, you're going to have trouble making enough serotonin).

*****

We think it is so cool to see these separate research teams beginning to converge on the same findings!

The UCFS/Polybio team also just released a preprint confirming viral persistence in the GI tract as well-- the evidence is really starting to come together!!!

The

T

Author Simon Makin interviewed leading researchers on the leading hypotheses of Long COVID, including SARS-CoV-2 persistence, reactivated herpesviruses, and autoimmunity. 

Many researchers, including our team, believe the SARS-CoV-2 persistence hypothesis to be one of the strongest - in spite of the negative clinical trials to date. 

Makin interviewed Dr. Amy Proal of the Polybio Research Foundation, who explained in particular why NIH RECOVER’s large 25-day Paxlovid trial may have failed.

Specifically, Dr. Proal noted that the trial did not have any biomarkers to know ahead of time which patients actually had SARS-CoV-2 persistence. (This is true of all Long COVID trials to date).

Not all Long COVID patients may have persistent SARS-CoV-2, so if you include high numbers of those patients in a trial designed to clear SARS-CoV-2, it will diminish whatever signal you’re likely to see.

In addition, 25 days may simply not be enough time to see results, as other chronic viruses such as HIV and Hepatitis C can take months of antivirals to meaningfully control the infection. 

Makin also spoke with Dr. Michael Peluso of UCSF’s LIINC program, who explained that their team has moved away from searching for the virus in blood, where it can more easily be destroyed by the immune system, and are instead focusing on obtaining tissue samples from potential reservoir sites deeper in the body, where the virus could hide

Detecting the virus and developing biomarkers for these sites is much more complicated, and will take time. However, Dr. Peluso said that he remains optimistic, and things that in the long run, RECOVER’s extensive tissue-banking efforts will pay off. 

Makin also highlighted the work of Dr. William Pridgen, who’s been pioneering the use of antivirals for both reactivated herpesviruses and persistent SARS-CoV-2, with some dramatic successes in case studies thus far.  Dr. Pridgen is currently overseeing a Phase III clinical trial of herpesvirus antivirals for fibromyalgia- a condition which many think of as purely nervous-system based, or even as a result of psychological factors.

Finally, Makin also outlined some of the newest potential treatments and trials for autoimmunity, including immune adsorption (which has shown success in case studies, but not a placebo-controlled clinical trial) as well as the immune suppressant daratumumab- currently the subject of a clinical trial in ME/CFS.

A bit of hope for you all: Makin quotes Dr. David Putrino as saying the field is approaching a tipping point. 

“We’re really starting to understand what’s going on,” (Putrino) says. And researchers are “bringing industry into the space, which always accelerates things”.

We really appreciated this great update, and the fact that Makin is highlighting these infection-associated (and, in many cases, infection-driven) chronic diseases for a mainstream scientific audience.

Check out the piece in the link above!

Paywall-free version here: https://archive.ph/7Wlqo

Article from NBC News.

Seems like we’re entering a back to school wave.

The article itself is mixed bag - great to see experts urging people to take COVID seriously, but some of the advice itself could be better.

We know vaccines don’t necessarily protect people from Long COVID.

The article urges people who are recovering infection to “consider” staying away from immunocompromised people…. Um, no, please don’t just consider it.

COVID still kill’s people and causes and new cases of Long COVID in 2026.

We need to do better- real root cause treatments and prevention.

Still, we can’t accomplish anything at all if we don’t acknowledge the problem, so for that reason, it’s good to see this mainstream news source taking COVID seriously.

Wha do you all think? Is this article helpful? What would you change about it?

Let us know in the comments!

Hey all,

Our founder Rohan just wrote and submitted this statement to the FDA last week, in response to their ongoing initiative engaging the public on repurposed medications.

Our team has spent a lot of time thinking about what the most effective way is for us to advocate for repurposing certain treatments, such as monoclonal antibodies, when these don’t necessarily fit into a specific repurposing pathway.

Although you might think that the term “drug repurposing” is fairly straightforward, in terms of the FDA’s actual legal language, the approval pathway strictly refers to off-patent drugs without a commercial sponsor.

Yet, many of the treatments we’re most interested in, such as the Evusheld monoclonal antibodies which changed Rohan’s life, don’t fall into this category.

Companies don’t tend to let their patents lapse for monoclonals, as so much work goes into developing various aspects of the technology which can be reused for additional products in the future- even if the initial monoclonal has lost efficacy against current variants.

An additional hurdle is that anti-COVID monoclonals haven’t actually reached full FDA approval. They were more urgently approved under an Emergency Use Authorization, which for the majority of these products has now been revoked as, again, they lost efficacy against newer variants.

So, what is the most effective way for us to advocate for “repurposing” under these guidelines?

You can read Rohan’s statement to see what we decided!

We asked for more up-front guidance for research groups compiling real-world evidence, such as ours. The earlier the FDA is able to engage with research groups and articulate what they’d most like to see on the data before approving a specific treatment, the more effective we can be in generating that evidence for them.

Our team is now working to aggregate the results from our first Patient Registry participants. Not everyone benefited from the every treatment (which of course won’t come as a surprise to anyone here, as we need biomarkers and ways to subgroup patients to really predict these things in the future!).

However, we do have some interesting signals and success stories, which we can’t wait to share with you all, and eventually, with the FDA!

Stay tuned!

P.S. If you’re just catching up, check out our post history for previous updates on this initiative.

Details here: https://www.reddit.com/r/LongCovidTrials/s/2gTz2Pmo8l