USA: The RECOVER Initiative - Long Covid research

Complete waste of time and resources, yet again.

But we know for a fact that the rehabilitation will be misrepresented. As will the pacing, as it's not a freaking treatment and should never be considered one.

It's not possible to have lower ambition than this.

 

Check out this presentation:
"Sayoni Das, PhD, SVP of Bioinformatics at PrecisionLife, Oxford, UK"
- UniteToFight2024*
From memory they identified genes related to sleep [i.e. from a (relatively small?) GWAS study - like DecodeME] - so possibly this led NIH to trial repurposing sleep medications?
If the above is correct (I'm not convinced!) then that would suggest that those who want drug trials now might see some progress post DecodeME (12 months time!)?


*https://unitetofight2024.world/program/

 

From X
https://twitter.com/user/status/1791431490158445053


Fun fact: *all* of the NIH-RECOVER studies involve a component of PEM but none of them involve objective measures of disease activity, and few protocols even mention it. The ones that do don’t have the most specific contemporary case definitions in place to adjudicate cases.

 

Trial by Error by David Tuller
Betsy Ladyshetz on Problems with NIH's RECOVER Initiative

Presentation:
Science journalist Betsy Ladyzhets, co-founder and co-editor of The Sick Times, has been covering the problemls with RECOVER, the $1.15 billion Long Covid initiative from the US National Institutes of Health. Ladyzhets recently wrote a new article about RECOVER, published in The Sick Times as well as STAT, based on documents she received from NIH through the Freedom of Information Act. We spoke the other day about what she found out.

 

The skepticism is unfortunately not only well-deserved, but far lower than it deserves to be. The dumpster fire that was the main paper of the ME/CFS study is only one of many large stains on the NIH.

 

As I didn’t see the recordings up yet, I shared a short thread on Twitter for any that would like to view in the meantime. This is probably duplicative, and mods feel free to delete or move as needed. Sharing if helpful to anyone.

Excerpts:

Koroshetz: “COVID is kind of a natural experiment to get at this problem…this is a once ever opportunity to study this condition..that’s really what our opportunity is here and we want to make the most of it (referring to ME/CFS).”

Koroshetz: “…the worry is we’re going to hit a plateau and end up with a lot of people with Myalgic Encephalomyelitis..”

Gibbons: “..NIAID has been studying ME/CFS for decades, or more, and yet we don’t have FDA-approved drugs for that…so there’s not been a lot of success in this post-infectious chronic condition space…quite frankly, the FDA was challenged with developing a regulatory pathway for biologics…”

Bertagnolli: “I could sit and make a list of 30 different, at least, potential therapeutics to pursue. The honest answer is, we don’t have an answer for you yet. Because, what is going to happen now is a very rapid and intense period of planning for how we strategize with the new resources we’ve received. We received $515 million now to move forward. The focus of that is to produce treatments for this disease. What the best strategy is to achieve that is going to be some intense focus over the next couple months. We’re taking this intense planning activity into the Office of the Director and we’re pulling out all the stops to come up with the smartest possible plan, knowing what we know today. The best possible way to use this new infusion of money we’ve gotten…we really do have a number of solid hypotheses now that can be pursed with clinical trials.”

An attendee asks the panel: “I’m just curious, about the history of ME/CFS…and what that teaches us?”

Koroshetz: “As Gary said, there’s no approved therapy for ME/CFS…the lessons from ME/CFS was, that you’re not going to fix the problem with a lot of small studies. You really need to collect a really well phenotyped cohort, collect the samples, and go at it in a very systemic fashion. We just came back from meetings with the NIAID consortium on ME/CFS…again, there’s lots of findings, but actually which one to put money on is difficult to know. RECOVER was really informed by ME/CFS research."

Bertagnolli: “I’d like to add one thing to that. I think another lesson learned from ME/CFS, is that we need to do better. We really need to do better for people with these chronic post-infectious syndromes. I think the community from people suffering from that disease feel like there hasn't been an urgency towards truly trying to solve that problem. Now that we have this opportunity, we don’t want to waste the opportunity to include them, and make sure that we understand how solve this for that entire community. I think that’s really critical.”

Gibbons: “I’d like to underscore, I think one of the opportunities of the additional funding we’ve been provided with, is to engage with some of those more comparatives studies, and understanding those overlaps. It may be an opportunity to take what we learn in Long COVID and hopefully inform those other post-infection chronic conditions like ME/CFS. I think that’s an opportunity we can do over these next few years with this additional capital."

Koroshetz: "The patients with ME/CFS are incredibly frustrated by the lack of interest by physicians with taking care of them...for years they've been fighting a perception that people don't think they have anything wrong with them...hopefully Long COVID has gotten rid of that…this is clearly an immune disorder, there’s no question about it.”

[Koroshetz then forgets the NASEM title for infectious-associated chronic conditions, asking "what did NASEM call it again?]

Hugh Auchincloss: "We do hope to have a major investigator and patient participation meeting by early in the Fall, to review directions going forward.”

An attendee asks Bertagnolli: "There's skepticism about RECOVER, I don't need to point out the articles. Monica, you're mentioning you put Office of Director into this, is there a new oversight of RECOVER, through the Office of Director? Perhaps speaking out of turn, there's a little bit more of a request for more transparency for how the funds are getting spent. I think it's fair to say."

Bertagnolli: “I’ve seen the list of really amazing manuscripts that will emerge over this summer, finally. I think people will start feeling much better about RECOVER, it’s first wave once the manuscripts really start flowing - and they are definitely coming. I think the other lesson is now - it is an infrastructure on a scale that has never happened before in research, ever. The reason for moving it into the OD, is to get everyone together to now take a look at everything we’ve learned and to come up with a strategy moving forward. RECOVER is not moving into the OD, I misspoke, what’s moving into the OD is this big planning activity. And why did I think that had to land in the OD? Because of how critically important this is as an initiative, that is doing things that we’ve never ever done before - and with the ability to engage with the broader community. Only planning..

I want to signal to the community. I think that’s also really important. We’re signaling to the community, that we built an amazing infrastructure and now we’re going to sit down and take a very deep look at what we’ve learned and then come up with a plan to go forward. And to be very transparent about that, and very clear about that. Frankly, we can be that way now because we’ve learned so much.”

 

A few more slides I noticed that seem relevant:

 

“Sore throat” and “Chills flushing sweats” not common in ME?

 

There's even more, menstrual changes, extreme thirst, shortness of breath, balance issues etc, symptoms you can read about even here on S4ME from people. These may not be covered well by the current literature though unfortunately.

 

Please NIH prove me wrong with your actions because the empty talk and 'wait and you'll see how hard we're working!' approach is just not doing it for me today.

 

'Pennington Biomedical researchers partner on award-winning Long Covid study’

'Executive Director Dr. John Kirwan of Pennington Biomedical collaborates with research colleagues across the nation to explore potential roots of Long COVID’

'Dr. John Kirwan is serving as a co-principal investigator on the Pathobiology in RECOVER of Metabolic and Immune Systems, or PROMIS, study. The study has been awarded more than $802,000 by the National Institutes of Health to identify potential causes of Long COVID.’

'Researchers from Pennington Biomedical, MaineHealth and the University of Kentucky are exploring the idea that COVID19 causes inflammation which stresses the immune systems to the point of triggering secondary complications such as fatigue, weakness, brain fog, and headaches among others. If proven, scientists can develop treatments to enhance immune function in patients with symptoms of Long COVID’

'Some of Dr. Kirwan’s other colleagues at Brigham and Women’s Hospital in Boston, Stanford University, and the University of Oregon will analyze blood and tissue samples to see if the virus is still present in patients with Long Covid. They will also find out whether the virus is generating substances that can prompt the immune system to cause fatigue, brain fog and other COVID symptoms.'

 

How to Fix $1.6 Billion Long COVID Program: Experts Weigh In
https://www.medscape.com/viewarticl...long-covid-program-experts-weigh-2024a1000bs4

When the National Institutes of Health (NIH) launched a $1 billion dollar research effort in 2021 focused on long COVID, hopes were high that it would lead to some answers for the mysterious riddle of the complex condition. Now, more than 3 years later and with total funding of about $1.6 billion, critics contend the federal government has little to show for its efforts.
...
[Al-Aly] argued that officials running the NIH program, known as the RECOVER Initiative, have been too defensive about the effort and not as open to helpful changes that would move it forward.
...
First Step: Improve Coordination
Improving coordination among researchers of long COVID is a great place to start, Al-Aly said. "We all want to move the ball forward, so let's put our heads together and do it," he said.

He recommended establishing an advisory board that includes the nation's top experts on long COVID. "Getting these people together in a room to discuss the best ways to allocate resources would help," he said.

Long COVID has proven to be distressingly similar to other post-viral syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome, according to a June 2023 article in the journal Frontiers of Medicine. Physicians who have worked on these conditions are also important resources for investigating the disease, he said. They shouldn't be on the sidelines. Many of those at the top of RECOVER aren't experts in these types of conditions, Al-Aly said.
...
Step Two: Move Beyond Symptom Management
Another overarching concern with RECOVER and with the condition as a whole is that researchers are still largely focused on symptom management rather than looking more deeply into the biological mechanisms driving this disease.
...
Step Three: More Clinical Trials
Another criticism of RECOVER is that it's heavy on observational studies, which make up 47% of the budget thus far rather than prospective clinical trials. Observational studies don't test potential treatments that could work for long COVID, rather, they follow participants on their current treatment regimen to see how they're fairing.
...
Step Four: Take the Focus Off 'Soft Therapies'
Additionally, McCone said NIH needs to take the focus off of what he called soft therapies, using things such as melatonin. Last month, the agency announced it would be testing the over-the-counter sleep supplement as a potential treatment for sleep disturbances due to long COVID. Other treatments, such as exercise therapy, have also been criticized by patients as not taking the condition seriously enough or being ineffective.

"We need pharmaceutical interventions that have a plausible mechanism for intervening with the pathophysiology of this disease," said McCone.

 

Merged thread

Medscape: How to Fix $1.6 Billion Long COVID Program: Experts Weigh In

This is an opinion piece regarding the long-Covid 1.6 billion investment in the US.

The 4 headlines are something that the ME field should also follow.

First Step: Improve Coordination

Step Two: Move Beyond Symptom Management

Step Three: More Clinical Trials

Step Four: Take the Focus Off 'Soft Therapies'


It's a short read, and you may need to have an account to access the article.
https://www.medscape.com/viewarticl...long-covid-program-experts-weigh-2024a1000bs4

 

That 47% on observational trials, around $500 million, was by far RECOVER's big mistake. The NIH essentially decided to give half of RECOVER's funding to an extraordinarily large observational trial with around 40,000 people. They collected so much data and collected it so badly that people in the know have said they will be shocked if anything useful comes out of that half a billion investment.

There's understandably been a lot of criticism on here towards the clinical trials - but those clinical trials represent just 13% of RECOVER's original budget, and they are far more focused than the observational trials, which frankly tells you a lot more about the observational trials than the clinical trials.

By contrast, RECOVER spent just $40 million of its funding on outside biomedical studies, which is in my opinion the greatest miss in the history of these illnesses - if that had been $400 million, you'd have actually for the first time created a large academic field. It also spent that $40 million really quite well all things considered. Which is where I differ from a lot of the Long Covid patient advocates - I completely agree with their emphasis on criticising the observational trials and the worst clinical trials, like the exercise one, but I think they should be calling for far more investment from RECOVER into fundamental research as opposed to further clinical trials at this stage.

 

[mods feel free to move to where most applicable]

"Lauren Stiles of Dysautonomia International on Her Story and What's Exciting Her Now'

"...NIH actually wrote back to us and said we're worried about calling it POTS because people might think it references marijuana.."

"They ignored most of our recommendations and really intentionally kept the patients in the dark. They would finalize the trial protocol, without even showing it to us, and then send it to us afterwards and tell everyone they got patient input on it."

"It was very clear that the patient engagement was for public relations purposes and it was not meant to be really meaningful. Now there are some researchers within RECOVER who were genuine in trying to get patient input included, but I would say at the highest levels of leadership that was not really a priority."

"From the very beginning, we and other groups advocated for people who had decades of experience in studying post-viral syndromes like POTS, like ME/CFS to be at the leadership level in RECOVER - not just to be on some side committee that had no real authority, but to actually be helping make the decisions on the study design and that was largely ignored. So when you give nearly two billion dollars to people who have no experience in post-viral syndromes don't be surprised if what you get is something that's disconnected from what the patients actually need."

Cort: "Adjusting, do you see any signs of that?"

Lauren: "Absolutely not. I see a defensive posture, I see defensiveness. I've been in meetings with Senator Sanders & the NIH Directors - all the Institute Directors involved in RECOVER, and it's just been excuses and defensiveness...not actually listening...even the researchers involved in RECOVER have raised concerns internally...it's also pretty awkward when you are on the study committees, to have to be the one criticizing it.."

"I don't see RECOVER changing the dynamic in any way. If anything, they're closing rank and putting out the defensive ranks..."

"I'll tell you what. They are more than 3 years into the study & autonomic testing has been recommending since the very first week of RECOVER..there was a committee..I was the only patient rep on the committee..we got the committee to vote in favor...they still haven't done any.."

"So now we're going to get data that doesn't mention anything about Autonomic Dysfunction."

"...why is NIH not empowering people who have any clue about post-viral syndromes to be part of the research teams, you know? so we were basically playing defensive editing..."

"we've asked the RECOVER autopsy study to capture the autonomic ganglia - that was my major contribution to RECOVER, that was demanding that they take autonomic ganglia and sensory ganglia samples from the autopsy study - and I did get that approved."