USA: NIH National Institutes of Health news

@Sean - I agree, which is why I wrote to NIHReform@mail.house.gov and first.opinion@statnews.com to clarify what is needed from this community's perspective (from my lens at least) from this agency. Hoping others will do the same too.

 

I am skeptical of the sincerity of this report, US Republicans have in plan to drastically reduce research funding if they could, but this criticism is surprisingly good. Although as pointed out above, jumping into trials is not a good thing, without a theoretical foundation or genuinely promising early results, they're pretty much completely wasted.

 

I’m skeptical too but surprised at the accuracy of the criticism, which to me indicates (to the leadership of this House Committee at least) that this issue of RECOVER is squarely on their radar.

Sent my testimony indicating that we need robust funding in this space, but highlighted where we could use help from their aims (a new IACCI Center restructure, help with transparency that would include meaningful patient engagement, etc.)

 

It's confusing - because clearly they see RECOVER as another stick to beat the NIH with, but their actual criticisms of RECOVER are very accurate as you say. Very difficult to work out what this means for Long Covid within the NIH. But the call for reorganisation is clearly bad news for the NIH.

 

Two possibilities:

a) One of the Republicans who attended the HELP hearing provided input here. I can’t remember which Republicans were at the hearing, but at least one of them has a close family member with Long Covid.

b) They lifted the paragraph on RECOVER from on of the Stat News articles because they saw RECOVER as another convenient way to bash the NIH

 

Neil Shapiro, Associate Director for Budget, NIH at ACD last week: "RECOVER Initiative has really been NIH's top priority in terms of advocating for a portion of those funds to be allocated by HHS for this type of research" (at 58:11)

Director Bertagnolli: "RECOVER. I want to touch on the program briefly because it is so important and so many people are counting on it. As you can see from this slide, we haven't been just sitting on our hands. RECOVER is one of world's largest and most diverse Long COVID cohorts and the only one that is deeply characterized. RECOVER has created a network of nearly 300 research sites...where hundreds of Long COVID researchers are working with nearly 90,000 participants.."

"Interventions not showing promise can be quickly terminated and the trials can quickly pivot to test new interventions as needed. In February, the project received an additional infusion of $515 million."

(starts at 27:18)

https://videocast.nih.gov/watch=54652

 

World Federation of Neurology: 'Neuro-ID Update [June '24]' by B. Jeanne Billioux, MD & Avindra Nath, MD

'For this Neuro-COVID-19 update, we review several recent articles on SARS-CoV-2 viral persistence, including Post-Acute Sequelae of COVID-19 (PASC), or Long-COVID'

'..the findings suggest that SARS-CoV-2 infection may lead to antigenic persistence in some patients, particularly those who were more ill, and may play a role in persistence of symptoms even in patients who were not ill enough to be hospitalised (Peluso 2024).'

'The concept of SARS-CoV-2 persistence and its association with PASC is quite intriguing, and an area of much-needed research, regarding both the nature of these potential viral reservoirs as well as in relationship to the treatment of PASC. Clinical trials are needed to stimulate the immune system or reverse immune exhaustion to see if this may help remove the viral remnants and alter the course of the illness.'

(Reading the tealeaves IMO, Nath [and Billioux of NINDS] makes another plea to his colleagues & to leadership to consider his clinical trial recommendations)

 

Just sharing from Day 2 of ACD last week now that the recording is up: https://videocast.nih.gov/watch=54654

(starts at around 1:03) Bertagnolli on RECOVER: "This is our interim progress, moving forward to a new stage of enhanced focus.."

Auchincloss: "About 17% of adults in this country have experienced Long COVID..it's a staggering number to realize..RECOVER was initiated in 2021 with the idea of understanding Long COVID and the long-term chronic illnesses associated with post-infection. From the very beginning we thought there would be overlap with this and the ME/CFS spectrum."

"The guiding principle from the beginning has to been engage the patients with representatives that are part of the process with developing scientific agenda and the research protocols. This has been true all the way through..."

Koroshetz: “I'm going to take actually a little bit of an objection to what was mentioned, that this is a new disease (Long COVID). I actually think this is an old disease, but we'll see. The reason for why I say that, is because NIAID, particularly Joe Breen, who was mentioned, and NINDS folks, have been working on Myalgic encephalomyelitis /chronic fatigue syndrome for a number of decades. And the symptoms that people with Long COVID have expressed say almost identical to what people with ME/CFS experience.

There are differences, not clear if the differences are related to the timeframes, most of the people with ME/CFS have been sick for years...with Long COVID people it's a year or two, or months. We'll have to see how that pans out. The neurologic symptoms, memory, word finding difficulties, concentration difficulties, executive functioning difficulties - these are the brain fog things that folks complain of and these also occur in ME/CFS."

"Now the big question - what is causing this problem? In ME/CFS, we've never been able to get to the bottom of it. However in ME/CFS, most of the evidence pointed to the fact that the condition started with what sounded like an infectious condition but people just never got better and it was impossible to figure this out because we would see people months or years after what the infection was.."

 

Koroshetz has been saying this since the beginning of the pandemic but this is such BS. They could have done prospective studies on EBV-triggered ME/CFS (or other strongly suspected infections). The Dubbo study did it, Leonard Jason did it, it is not rocket science and NIH has the money for such things. He is talking about it like they really wanted to do it, it was just "impossible". Give me a break...

 

STAT News: 'Readers respond to essays on long Covid...'

“NIH needs reform and restructuring, key Republicans committee chairs say,” by Cathy McMorris Rodgers and Robert B. Aderholt

"I agree with the authors that NIH needs reform. I was an athletic, otherwise healthy person who was struck down and disabled by long Covid in January 2022. For over two years, I’ve watched life pass me by as NIH has fumbled the $1.15 billion allocated to it by Congress to study and treat long Covid. This initiative, known as RECOVER, has failed to publish any research that furthers our understanding of the underlying cause of long Covid and the vast majority of clinical trials they’ve launched are for drugs that people have already tried and found unhelpful."

"Perhaps NIH would not have bungled the long Covid funding had it not completely ignored other post viral diseases, namely myalgic encephalomyelitis (ME) for the past 40 years. ME receives only $15 million a year — the most underfunded disease per patient burden at the NIH."

"NIH should reevaluate how it allocates funding to diseases and base allocations on objective patient burdens. HIV, a disease with treatments that allow people with it to live mostly normal lives, receives $3.3 billion annually through NIH. Meanwhile, ME patients are disabled, have no approved treatments, and suffer a higher patient burden. Covid long haulers are suffering the same fate, many struck down as first wavers in March of 2020 are still disabled and sick as ever over four years later. Despite this, there is still no yearly allocation for long Covid in NIH’s baseline budget, as funding has only ever come from one time appropriations. NIH should right-size funding for ME and long Covid and start taking these diseases seriously."

— John Bolecek, long Covid patient

 

STAT News: 'Can the National Institutes of Health navigate multiple storms and rebuild its bipartisan support?'

'..a bevy of challenges are spurring calls for reform on Capitol Hill that may be difficult for the agency to fend off..'

...the agency is finding itself navigating a perfect storm of challenges. These include:

-Lingering questions and concerns about the agency’s..research and activities related to SARS-CoV-2, the virus that causes Covid-19, including its handling of long Covid research."

'It will be tempting for those inside and outside of the NIH...to push back aggressively and dismiss calls for reform as being politically motivated. But doing so would fail to heed legitimate concerns and frustrations and miss opportunities for improvement."

 

2/27/24: 'NIAID's Jeanne Marrazzo'

Host: 'COVID has obviously been very much part of the research agenda in NIAID from the last four years. As you think forward, will there still be the Long COVID research agenda embedded into NIAID going into the future?'

Marrazzo: "I think there should be...it's always a matter of resources..and what we really need to focus on. People living with HIV also get Long COVID...Long COVID is a really big problem. It's pretty staggering. I think that whole post-viral infection, chronic infection, chronic inflammation situation is finally getting the look it deserves.

It's again where, yes we have NIAID, NHLBI, NINDS, but you know people live in one body and everything talks to each other- so, if there's anything good about the pandemic, many silver silver linings - but one of them really is to remind people that the virus wasn't over when it was "over", so many lingering things...I do think NIAID has to be front and center at the table with other people invested in this. The RECOVER cohort, NINDS - NIAID - NHLBI is a great start and a new model. I hope that it sets a precedent that continues to yield a lot of fruit."

 

After last week's LIINC / UCSF study, I wanted to go back and re-listen to this work from Jason Gale with Bloomberg: "How the Dead Are Helping the Living" from 10/25/2021 (and since I hadn't caught the 30-minute episode back then) and to then just to gauge how things have fared since (and was curious to analyze some of Nath’s hypotheses)

Features Walter Koroshetz (NINDS), Avindra Nath (NINDS), Steven Deeks (UCSF) & Daniel Chertow (NIH Clinical Center)

'By looking for clues among the deceased, Daniel Chertow aims to understand how to treat and prevent the disease in the living, including the lingering symptoms afflicting millions of Covid “long haulers.”

Excerpts:

“The condition is called long Covid, and Dan's research could help us understand how to better combat it. But science is an iterative process."

“..and in a reasonable portion of the population of survivors, long-term symptoms that are really distressing. Dan and his group are also trying to figure out how the virus and the body interact...Dan's research will not only help us understand what the causes are, but how to counter them.”

“Walter says it's this group of patients, the ones with unexplained fatigue, brain fog, weird heart palpitations and body aches and pains, who also represent the largest pool of patients who are persistently unwell as a result of the pandemic.”

Koroshetz: “Fatigue is a major problem. The long Covid symptoms consist of fatigue, trouble with memory, trouble with thinking quickly, executive function, trouble with sleep, pain syndromes, sometimes exercise intolerance. Those are the features of this syndrome that we don't have good explanations for at this point.”

“In some ways, the disease pattern many long Covid sufferers experience resembles mono or infectious mononucleosis...with infectious mononucleosis, there is another syndrome which you've probably heard about, called myalgic encephalomyelitis, chronic fatigue syndrome. And symptoms are very overlapping between what long Covid folks are complaining of and what happens in ME/CFS. It's just that ME/CFS has a six-month period.”

“Walter says researchers have been trying for years to figure out the causative driver of that longer-term illness after infectious mono.”

“Now with the 34 million people with Covid, it's a tremendous challenge now that we have to take up to try to figure that out. There is a greater chance that we're going to figure it out now because we have this opportunity to study so many people and to try and understand what differentiates those who get better quickly versus those who have these persistent symptoms. So the hope is that we can get some answers that would allow us to try different treatments to see what helps and then potentially also learn something about what causes ME/CFS as well.”

“This is Dr. Avi Nath. He's the clinical director at the NINDS...Avi says there could be two main driving forces behind the clinical manifestations. One is that the coronavirus manages to persist in the body somewhere, somehow, and that its lingering presence is damaging the body directly, or it's triggering an immune response that's causing the damage.”

“Another hypothesis is that the coronavirus has sent the immune system haywire, and it's this dysregulated immune response that's driving long Covid...I think there are all reasonable hypotheses, but they're not exclusive. They could be interrelated. Avi's been researching chronic fatigue for years, and now he's also trying to understand it, as well as other ailments in long Covid patients.”

Nath: “...but if you had a mild illness, perhaps you never mounted a strong enough immune response. You thought, oh, you know, I escaped this. But in reality, you never got rid of the virus...Avi says another possibility is that what's persisting are viral particles that may not be completely replicating, but are instead expressing some features of the virus.”

Nath: “Now what the body is going to see it as a foreign object is going to try to mount an immune response against it. So you get this chronic immune activation that persists in these individuals. But it's never good enough to get rid of it because they never got rid of it in the first place. But it's enough to start causing collateral damage. Avi sees the same pattern of immune activation and exhaustion in chronic fatigue or ME/CFS patients. They look very much like these long-haul Covid patients. And they have the similar problems. They usually start off with some viral infection, then they recover from it, and then this thing persists forever.”

“Steve Deeks from UCSF thinks the coronavirus might be leaving traces behind. It could be viral protein, strands of its genetic material, or even bits of antigen that the immune system responds to...we don't think it's virus replication, but I guess it could be virus that's replicating in target cells and tissues. We always thought that that was a potential reason for why this symptom persists."

“Steve says circumstantial evidence supports the concept that there's something persistent that's causing long Covid.”

“Deep in his lab, Dan Chertow and his team have amassed more than 10,000 autopsy specimens for meticulous study. Their analysis is beginning to yield some answers to the many questions around Long Covid and what causes it.”

“Dan says he expects this last bit of information shortly and then can finish a manuscript. But evidence pointing to the causes of long Covid are of little help to patients, unless the findings can yield ways to help them.”

 

The quotes from the interview sound very sensible and it's the same thing we've heard for years, but looking at the above quotes it seems like an interview talking place in an entirely different reality. If those running RECOVER believe in the above things why are they trialling exercise, light therapy and melatonin? Is that how you resolve viral persistence/autoimmunity/immune dysregulation/reaction of dormant viruses? I would say: For every complex problem there is an easy "solution" that is wrong.

 

That's where the disconnect for sure is @EndME. From everything I can gather, Koroshetz and Gibbons have probably the most power in the whole RECOVER Project (Marrazzo/Auchincloss after that, I'd wager).

If Koroshetz believes these 4 theories should be most likely, then I have no idea how he is allowing these clinical trials to be signed off (GET, light therapy, melatonin, video games). It makes little to no sense.

 

Time for an open letter to question him based on his own statements?

 

If someone wants to lead it, I’d be happy to send or also echo, but I fear we’d just get a canned “these trials are symptomatic treatments aimed at relief” response but we could still try, if someone wants to draft it up.

 

(stumbled on this as well, sharing just for sight)

Prognosis: Losing it: "Why COVID-19 Lingers" Jun 9, 2020 with Jason Gale of Bloomberg

“This is Dr. Avi Nath. He's a physician scientist with the NIH..Avi is clinical director of the NINDS and heads the section that looks at infections of the nervous system.”

“There are thousands of patients now complaining of the fact that they have persistent symptoms. The lingering symptoms that COVID patients experience are fairly broad. Avi is interested in brain fog, malaise, tiredness, symptoms reminiscent of myalgic encephalomyelitis or chronic fatigue syndrome, which he says is linked with a lot of viral infections..."

“These things are happening later in the course of the infection, suggesting that there's an immune component to it. So the virus goes down and the immune system gets hyperactive, and it can cause a variety of different types of neurological symptoms.”

“As unfortunate as these rare problems are, Avi says they represent an opportunity to learn how and why these post-viral syndromes occur, their biological pathways, so that we might be able to prevent them."

“..it's an unfortunate situation, but you can use it to your advantage to try and understand these diseases that we haven't been able to for a long, long time...The NIH has several research teams trying to unlock the secrets of these post-viral illnesses.”