Nature named Lisa McCorkell one of the top ten difference makers in science in 2022.
The NIH’s RECOVER Initiative is in a strange place. It’s gone through most of its $1.15 billion nest egg without producing anything of note and its critics abound.
It does have its supporters. Steven Deek at UCSF called RECOVER “a great success“, and other researchers at the 2023 Keystone Conference on long COVID sang its praises. Plus, it should be noted that NIH was forced to do something unprecedented with RECOVER when it tried to birth a new field of exploration almost overnight. That can’t have been easy and it invariably meant that a lot of people who knew nothing about post-infectious illnesses and neglected conditions like dysautonomia would end up in leadership positions.
Plus, studies are not produced overnight – even in the best of times, they take quite a bit of time to finish and get published. The ‘give RECOVER another year to show its chops’ theme, though, is starting to get a little old.
Without the 500 million dollar infusion RECOVER recently got from the Biden administration, RECOVER appears to have faced the almost unthinkable possibility of shutting its 80 clinical sites and research efforts.
Given how much the long-COVID and the ME/CFS and other post-infectious disease communities have been relying on the RECOVER Initiative to provide answers, I was eager to get Lisa McCorkell’s take on what’s going on over there.
THE GIST
- Main Takeaway – In its current iteration, the $1.15 billion RECOVER Initiative is not going to solve – or even come close to solving – long COVID.
- The NIH’s RECOVER Initiative is in a strange place. It’s gone through most of its $1.15 billion nest egg without producing anything significant of note and its critics abound. While it does have its supporters, without the 500 million dollar infusion RECOVER recently got, RECOVER appears to have faced the almost unthinkable possibility of shutting its 80 clinical sites and research efforts.
- Given how much the long-COVID and the ME/CFS and other post-infectious disease communities have been relying on the RECOVER Initiative to provide answers, I was eager to get Lisa McCorkell’s take on what’s going on over there.
- Lisa co-founded the Patient-Led Research Collaborative (PLRC) and sits on several RECOVER committees. The Nature journal named Lisa one of the top ten people who shaped science in 2022.
- I asked Lisa what she thought RECOVER’s strengths and weaknesses were.
- Sshe felt RECOVER’s strengths included its small extramural research effort, a fairly good job at enrollment, and having a long-term observational study. RECOVER’s weaknesses included putting so many of its resources into the observational study, not prioritizing what patients want to see in the clinical trials, and few, if any, resources devoted to hypothesis testing (other than the $40 million outlay in the beginning).
- I thought the RECOVER Initiative’s highest priority task would have been to create multiple biomarker-based research and clinical criteria for long COVID. Thus far, large pharmaceutical companies have mostly sat long COVID out, in part because they don’t have the good criteria they need to run their hugely expensive clinical trials. One could argue that the lack of a biomarker is the single greatest factor keeping long COVID from moving forward. So I asked her about that.
- Lisa said, “the way RECOVER was initially designed will probably not allow it to uncover abnormalities that could be used as a biomarker”. Whoa! A look at RECOVER’s protocols for its observational study indicated that she was right. RECOVER is spending most of its money on assessing factors that aren’t relevant to the biggest long-COVID subset – the ME/CFS-like subset.
- Except for a small amount of funding (@3%) RECOVER devoted to outside studies 2 1/2 years ago, RECOVER doesn’t appear to be doing the in-depth pathophysiological research needed to find biomarkers.
- Over time, RECOVER should be winnowing down and adding to its testing protocols as it learns what’s relevant and what’s not. Yet two and half years later, the testing protocols have remained set in stone. It seems inevitable that a great deal of funding will go to producing negative results.
- RECOVER also doesn’t appear interested in taking advantage of the rapid advances occurring in long-COVID research. It could be providing yearly funding opportunities, but it hasn’t funded any outside studies in the past 2 ½ years – it’s way behind the 8-ball there as well.
- Given what we know, it appears that RECOVER was always going to need much more money and time to fulfill its goals. A big question, though, is why, given the inability of the biggest long-COVID research effort on the planet to produce anything significant, anyone would want to give it more money.
- I had to ask a terrible question given how much hope had been invested in RECOVER, not just for long COVID but for diseases like ME/CFS. “Should RECOVER continue? Lisa – said she hoped it would – that there is value in continuing the observational research, but that she felt there needs to be changes. She was happy to see RECOVER get its recent $515 million lifeline but felt more patient involvement was needed in choosing the clinical trials, and that RECOVER should be engaged in more high risk-high reward research – and more pathobiology studies.
- Then came an incredible assertion given the RECOVER Initiative’s largesse: In its current state, she does not believe that RECOVER is going to lead to the solution for long COVID.
- With RECOVER soon to chew through its billion-dollar-plus wad without producing anything significant, some hard questions surely need to be asked. The office the Biden administration created almost a year ago (The Office of Long COVID Research and Practice) which has oversight authority on RECOVER and other programs, appears to be a paper tiger. Its website doesn’t list the Office’s director, its staff, the kind of oversight it’s doing, its progress reports, or even how to contact it.
- Citing many issues with long COVID’s long-term prospects (no long-term funding, lack of infrastructure support) and concerned how long the momentum long COVID has will last, in October, Lisa McCorkell and Michael Peluso (UCSF researcher) published an article, “Long COVID research risks losing momentum – we need a moonshot“, in Nature.
- The Moonshot Initiative asks for a billion dollars a year for ten years in funding from the NIH. Note that NIH spent 3.3 billion dollars this year on a disease (HIV/AIDS) that has effective treatments and afflicts about a third as many people as long COVID. The increase in funding the Office of AIDS Research at the NIH ($659 million) requested for next year is significantly more than the federal government is spending on long COVID this year.
The Lisa McCorkell Interview
(Lisa’s answers are in italics. Everything else is by me.)
“In its current state, I do not believe that RECOVER is going to lead to the solution for long COVID.” Lisa McCorkell
A person with long COVID, Lisa co-founded the Patient-Led Research Collaborative (PLRC). A patient representative who sits on the study design committee and a publication subcommittee, and has been a co-author of a few of RECOVER’s papers, Lisa has some insights into what’s going on in this immense initiative. Nature named Lisa one of the top ten people who shaped science in 2022.
The RECOVER Initiative’s strengths – observational trial, small amount of pathobiological funding; weaknesses – pretty much everything else (clinical trials, pathophysiology).
RECOVER’s Strengths and Weaknesses
I asked Lisa what she thought RECOVER’s weaknesses and strengths were.
- Strengths: She thought RECOVER’s strengths included its pathobiology studies and the extramural research RECOVER has funded. RECOVER has also done a fairly good job at enrollment. It was also a good idea to have a long-term observational study.
- Weaknesses: RECOVER’s weaknesses included putting so many of its resources into the observational study, not prioritizing what patients want to see in the clinical trials, and few, if any, resources devoted to hypothesis testing (other than the $40 million outlay in the beginning).
Research and Clinical Criteria (???)
I would have thought that RECOVER’s highest priority task would have been to create multiple biomarker-based research and clinical criteria for long COVID. Thus far, large pharmaceutical companies have mostly sat long COVID out, in part because they don’t have the good criteria they need to run their hugely expensive clinical trials. One could argue that the lack of a biomarker is the single greatest factor keeping long COVID from moving forward. I hadn’t seen anything from RECOVER on this critical task, though, and I asked Lisa about it.
Lisa said the National Academy of Sciences has been tasked with creating a “working definition” for long COVID for the US government. Lisa noted that RECOVER did take preliminary stab at identifying subsets that was published in the Journal of the American Medical Association.
A 2022 working definition that was developed emphasized that long-COVID contains different entities, each with different biological causes. Since then, two workshops and a questionnaire have been completed by various stakeholders. Three-quarters of the respondents (and 9 out of 10 patients, patient organizations, and/or caregivers) agreed that the definition should include “severe impacts on normal daily activities”. At some point (date undetermined), the Committee will produce a letter report that includes new definitions for long COVID.
THE RECOVER Study – That study assessed almost 10,000 people. Using only symptoms, it plucked out 3 ME/CFS-like subsets and one non-ME/CFS-like subset. Note how PEM and fatigue predominate in the ME/CFS-like subsets, which were broken down into brain-fogged and gut/dysautonomia subsets – which would likely be found in ME/CFS as well.
- Non-ME/CFS – loss of or change in smell or taste (100%)
- ME/CFS – fatigue/PEM – PEM (99%) and fatigue (84%)
- ME/CFS – Brain fog – brain fog (100%), PEM (99%), and fatigue (94%)
- ME/CFS – gut/dysautonomia – fatigue (94%), PEM (94%), dizziness (94%), brain fog (94%), GI (88%), and palpitations (86%).
This was a nice start and showed what RECOVER, with its large sample sizes, can produce, but we’re still stuck on symptom-based subsets and biological biomarkers are needed. It wasn’t until biological biomarkers were found in HIV that treatments showed up in spades.
- Check out “An Explosion in Therapeutics“
A Long-COVID Biomarker?
“… a biomarker, which is something we really need in the clinic to confirm diagnosis, provide an objective way to follow patients under treatment, and help develop effective treatments.” Eric Topol on long COVID
A biomarker that would galvanize the field and rapidly propel it forward would be, one would think, where RECOVER, with its immense resources and huge sample set, should shine – and perhaps one day it will – but not now. I asked Lisa why RECOVER hasn’t given us a biological biomarker yet.
Lisa said that the way RECOVER was initially designed will probably not allow it to uncover abnormalities that could be used as a biomarker.
That was a stunner. A look at the adult observational study protocols RECOVER’s spending the vast bulk of its funding on, though, suggests that unless something is going on we don’t know about, Lisa was right. The biggest long-COVID initiative isn’t even close to producing what is long COVID’s perhaps greatest need.
The latest observational study protocols (June 2023) suggest that if long COVID is like ME/CFS – and studies suggest that around half of long-COVID patients have something very similar to ME/CFS – the observational studies may simply be reinventing the wheel – and only a small portion of it, at that.
With regard to the ME/CFS-like subset, RECOVER appears to be reinventing the wheel – and not very much of it. (Image from Wikimedia Commons – Library of Congress)
Of the dozens of tests done, only perhaps the (limited) coagulation tests, the skin and muscle biopsies, the tilt table, gastric emptying, the CPET, an MRI, and lastly – the invasive exercise test which was added last year – appear to pertain to the ME/CFS-like group of long-COVID patients. The blood tests – our best chance to find a biomarker – seem likely to be completely unrevealing. The fact that so few ME/CFS relevant tests were included suggests that ME/CFS findings didn’t heavily inform RECOVER’s protocols.
Over time, as RECOVER understands what’s useful and what isn’t, it should be both winnowing down and adding to its testing protocols. One would hope it would know by now, for instance, what tests not to give its ME/CFS subset, yet two and half years later, the testing protocols have remained set in stone. The addition of the invasive exercise test in June of last year – as welcome as that is – is the only substantial change in RECOVER’s testing protocols that I could find. It seems inevitable that a great deal of funding will go to producing negative results.
It appears that RECOVER, in its current iteration, was never intended to dig deep into the pathophysiology of long COVID. While it did pour $37 million into outside pathophysiological studies, it’s rather damning that Lisa picked out this small slice of its funding (3.2%) for praise. One wonders how much we would know about long COVID, if instead of pouring $40 million into its pathophysiological studies, RECOVER had put $200 million into them?
RECOVER also doesn’t appear interested in taking advantage of the rapid advances occurring in long-COVID research. It could be providing yearly funding opportunities, but it hasn’t funded any outside studies in the past 2 ½ years – it’s way behind the 8-ball there as well.
RECOVER’s big ace in the hole is the massive blood, urine, and tissue samples it’s been collecting that could feed research into long-COVID pathophysiology for years. That will, of course, require RECOVER funding deep pathophysiological studies – something the Initiative has shown little interest in doing.
No one knows exactly what’s going on with RECOVER – and it would be very, very nice to be wrong about it – but one wonders if RECOVER’s creators expected it to be where it is now. One must conclude they probably did. Maybe their timeline was off a bit, but once RECOVER decided it would spend a very small amount of funding on pathophysiological studies, and the bulk of its money on huge but quite limited observational studies we were always going to end up here; RECOVER was always going to need much more money and time to fulfill its goals.
Maybe that was the plan. The problem is that RECOVER doesn’t look right now like it deserves that money. It appears to lack creativity and flexibility, and perhaps worst of all, it doesn’t appear to have paid much attention to the easiest part – getting up to date on the other post-infectious diseases. It looks more like the conservative NIH that people have complained about for years than a dynamic initiative that’s up to taking on long COVID.
Time will tell. Hopefully, RECOVER will surprise us yet.
A Terrible Question
It was a terrible question to ask: “Should RECOVER even continue?”
I asked Lisa a terrible question that I never thought I would ask. As an ME/CFS/FM patient who’d counted on RECOVER to blaze a path forward for my disease, this question came hard. I asked if she believed RECOVER should continue?
Lisa – said she hoped it would – that there is value in continuing the observational research but that she felt there needs to be changes. She was happy to see RECOVER get its recent $515 million lifeline but felt more patient involvement was needed in choosing the clinical trials, and that RECOVER should be engaged in more high risk-high reward research – and more pathobiology studies. In its current state, she does not believe that RECOVER is going to lead to the solution for long COVID.
That’s a pretty damning indictment of a long-COVID research effort that is magnitudes larger than any other. RECOVER’s conservative clinical trials were, with a few exceptions, disappointing and, at times, even a bit bizarre. RECOVER poured a ton of money into low-hanging fruit like cognitive retraining, a behavioral sleep (hypersomnia?) trial, and exercise.
With a minimum of funding, RECOVER could have designed a series of experimental trials that probed drug effectiveness and long-COVID pathophysiology. That’s the exciting, innovative approach one would have hoped RECOVER would have chosen. The answer to why RECOVER hasn’t chosen this pathway might tell us much about why RECOVER is where it is right now.
Oversight? What Oversight?
With RECOVER soon to chew through its billion-dollar-plus wad without producing anything significant, some hard questions surely need to be asked. It doesn’t appear that they are, however. In June 2023 (after quite a delay), the Biden administration created “The Office of Long COVID Research and Practice” which has oversight authority on RECOVER and other programs.
Eight months later, the office’s website consists of links to a bunch of federal reports – none produced by the Office or which have anything to do with it. Neither the Office’s director, its staff, the kind of oversight it’s doing, its progress reports, or even how to contact it have been produced. I had to find out who the Director was (Rachel Levine) using AI Copilot (lol). Secretary of Health and Human Services Xavier Becerra stated that the creation of the Office “solidifies this issue [of Long COVID] as an ongoing priority” of the Biden administration. Right now, it looks more like a paper tiger than anything else.
I’ve been told that the NIH doesn’t care what people outside the Institute think, but I wonder. It’s beholden to Congress for funding and it’s not the only game in town. Complaints about the NIH’s stodginess led to the creation of the Advanced Research Projects Agency for Health (ARPA-H), and other possibilities for long-COVID research (Congressionally Directed Research Funds – Department of Defense, the Biomedical Advanced Research and Development Authority (BARDA) have been discussed).
The RECOVER Initiative was the NIH’s opportunity to show it could rise to the occasion and creatively and effectively deal with a new disease. While the full RECOVER story has not been written it’s not looking good right now. Let’s hope for better news over the next year.
The Moonshot
The Long COVID Moonshot aims to provide a billion dollars a year for long COVID and other post-infectious diseases.
We were hoping that RECOVER, with its big bankroll, would light the way for long COVID and other post-infectious diseases. With those hopes fading, advocacy becomes ever more important. Advocacy is particularly critical given long COVID’s uniquely vulnerable situation. As a new disease, it doesn’t have the institutional infrastructure that will enable it to thrive. Absent effective advocacy that helps to build that infrastructure, long COVID risks slowly fading.
Concerned that the momentum long COVID has will not hold, last October, Lisa McCorkell and Michael Peluso (UCSF researcher) published an article, “Long COVID research risks losing momentum – we need a moonshot“, in Nature.
They presented long COVID as the best chance for researchers to “understand, and find treatments for, a chronic illness associated with an infectious disease”. They cited the uncoordinated nature of long-COVID research, the few clinical trials underway, the absence of long-term funding opportunities, and the desire among many to move on from anything COVID-related as reasons to be concerned about the long-term viability of the field.
Noting that long COVID is expected to cost the US economy over 3 trillion dollars over the next 5 years, that up to 2.5 million people in the U.S., and 24 million globally have ME/CFS, and up to 1.9 million people in the U.S. may have had post-treatment Lyme disease, they called for a long-COVID moonshot – a ten-year commitment from the US government to invest at least US$1 billion a year in long COVID and post-infectious disease research.
They also called for the creation of an NIH Office for Infection-Associated Chronic Conditions Research to coordinate research, establish research agendas, and have budgetary authority to fund work on all of these illnesses. (The Solve ME/CFS Initiative is involved in the creation of the NIH Office.)
A billion dollars a year may seem like a lot of money, but consider this: the NIH spent 3.3 billion dollars on a disease (HIV/AIDS) that has effective treatments and afflicts about a third as many people as long COVID. The Office of AIDS Research at the NIH requested a 20% increase in funding for HIV/AIDS this year. That requested increase alone ($659 million) is significantly more than the federal government is spending on long COVID this year.
Let no one think the NIH doesn’t have the money to fund a long-COVID moonshot. Whether it has the will or desire to do so is another matter.
To have successful clinical trials and get FDA votes for LongCovid treatments, diagnostic markers for both LongCovid and ME/CFS are required.
RECOVER’s weakness is not using the 2-Day CPET and 3 potential ME/CFS diagnostic tests: MicroRNAs, Raman Spectroscopy, and Electrical Impedance. MicroRNAs are the easiest to translate to clinical settings because there are already MicroRNA tests for other diseases.
The NIH thinks that ME/CFS is depression and by extension that Long Covid is too. We need to confront that and strike at it as soon as possible.
In 2019, the Nanoneedle (Electrical Impedance) could measure ME/CFS in a pilot study with 100% accuracy taking 200 measurements per second. It could have been harnessed to be used in LongCovid studies to measure the ME/CFS within LongCovid and uncover the variance from LongCovid but instead the NIH dismissed the Nanoneedle with Prejudice.
Years later, both ME/CFS and Depression are pursuing biomarkers with MicroRNAs and they don’t match, and are targeting different genes.
If you want treatments for LongCovid and ME/CFS in our lifetimes please fight for ME/CFS diagnostic biomarkers at every table.
5 studies can differentiate ME/CFS from MDD (Depression) and we should be fighting the NIH for what they have done rather than sitting on our hands.
Please.
Thanks Andrea – I hope the NIH doesn’t think ME/CFS is depression – but they are certainly funding it like its a nothing disease. Part of that is because funding at the NIH is so driven by researcher interest. That said, the NIH well knows how many people are suffering with ME/CFS and that it is not fulfilling its obligations to them. They need to help build this field with sustained support…and haven’t done that.
The most helpful thing for both these diseases would be, as you said, diagnostic biomarkers. They are what supercharged treatments for HIV. I agree with you -RECOVER and the NIH should be focusing on finding them. They are not easy to get to but they would clear up so much.
Thanks for the kind reply, Cort.
You can tell that NIH thinks ME/CFS is depression by multiple observations :
– The Nanoneedle was voted down because “ME/CFS is depression” by the NIH and they were asked not to reapply (which needs to be directly addressed politically at some point)
– “Sickness behavior” a hypothesis that Dr. Koroshetz and Dr. Koroshetz opened and closed with at the 2023 ME/CFS Conference is a MDD (Depression) hypothesis. The hypotheses featured in the roadmap and the conference like autoimmunity, viral reactivation, viral persistence, itaconate shunt, et cetera were invisible.
– Dr. Koroshetz opened his talk by discussing “perception” “interoception” and “are we in a good mood? Are we in a bad mood?” If you hear these particular words from anyone’s mouth or pen in regards to ME/CFS – run. It was not an opening from someone who even reads or listens to ME/CFS biomedical research.
– The opening and closing of the conference indicated to me at least that Depression/psychosomatic disorders are their hypothesis (without evidence) and I don’t think any amount of evidence is going to move that mountain. They have already made up their mind- it’s the only thing they care about buying or selling.
– I think the mountain that needs to be moved is the scientists and clinicians sitting at those voting tables.
– Using OMF resources to study microRNAs of both ME/CFS and Depression together is quite possibly our only way to do that.
– There are only 5 studies that I could find that differentiate ME/CFS from MDD and they suck. They are all Fukuda and other garbage definitions.
– So we need one that’s solid- 2-Day CPET – ICC/CCC – MicroRNAs – clinician-certified patients.
– Force them into a corner using the science they want, done our way.
– We need to prevent someone from bringing up the objection at the voting tables that matter. If we meet a goalpost, they will move it. We need to make sure our researchers are 3 goalposts ahead.
– We need to anticipate the objections to ME/CFS biomarkers, foresee the roadblocks, and help guide our researchers through them.
– We need to think about how our biomarkers will be cross-examined by non-experts, so-called experts with bad intentions, and a hostile audience with preconceived prejudices about ME/CFS that have no basis in fact.
– That’s how we beat them.
Dear Andrea,
Excellent summary and I think your attitude and approach is correct — we must be 3 steps ahead of their effforts to dismiss us and the science that supports us.
Thank you for those excellent observations following this wonderfully informative (as usual) article.
The aimless wandering in these study objectives and designs seems disingenuous. This sort of boondoggling with public money may be met with disapproval from unafflicted stakeholders concerned with expense, but the real risk is the furthering of the misconception that these diseases are unsolvable ‘because they must be predominantly psychosomatic illnesses’. Still, it looks like the numbers of people adding to the ranks of the unwell are growing, so maybe it’s a matter of reaching a critical mass that cannot be ignored in order to get the moonshot. The New York Times should be covering this.
this is one of those times I wish there was a ‘like’ button for the comments section. ::applause::
Thank you for a very well thought out analysis, Andrea!
I think we need the charter taken away from the organization which is 30 years into regulatory capture and therefore stuck in psychologizing ME/”CFS” and Long Covid.
I don’t think it’s possible to change the course of an organization which has been increasingly telling each other these are all psych for over 30 years.
Even if they got utterly humiliated by science proving physical causes. It would be denied and argued for decades.
I disagree. I don’t believe the NIH has ever funded a single psychological study on ME/CFS or a CBT/GET trial. While CBT/GET was getting millions of dollars of funding from the UK and the Netherlands it never got any interest here. The NIH continued funding its biological studies – and for all the NIH bashing we should remember that the NIH is still easily the biggest funder of biological research into ME/CFS.
I recently was on some committees for the ROADMAP and the NIH Conference – there was no discussion of psychological factors at all.
For all its faults the RECOVER program is almost completely biological as well. I believe its more a problem of researcher interest and the NIH being willing to support this disease so that it attracts the researchers it need to build a strong base. That’s why we’re going for a post-infectious disease institute there.
considering the lack of funding for ME/CFS for decades, the lack of proper direction to spend research money on identifying biomarkers and support possible diagnostics, while every NIH researcher knows these are the first essentials to come to solve a disease: could it be that the leaders of world do not want ME/CFS or Longcovid to be solved?
after all, the world economic forum declared that everyone would be ‘poor and happy in 2030’ and that’s what happens to all of us that develop ME/CFS-longcovid.
andrea, i completely agree with you. Can you furthermore give me the references of the 5 papers you refer to?
Wow. They could have accomplished FAR MORE by just divvying up their budget and giving it directly to the long covid patients to improve their lives with equipment and help.
When this initial funding was announced, I was fairly skeptical. I’ve seen so many promising “breakthroughs” amount to nothing. But to have a failure on the scale of the Recover initiative is absolutely gut punching. At 61, I no longer expect or even have hope of any true breakthrough in my lifetime.
I have immense anger at both the medical community & our government for the neglect & harm they’ve caused those of us with ME/CFS & related illnesses. I’m hoping younger people have a better outcome in their lifetimes.
Thank you for the enlightening article, Cort.
I can only hope – and I mean this sincerely – that this blog is wrong – and that RECOVER is engaged in things that we are not aware of. What I mean by that is that I still cannot believe that RECOVER has spent so much money to gain so little. I still have trouble fathoming that.
I am keeping up hope they’re more going on than we know and RECOVER is simply not telling us about it and I keep in mind that Dr. Stephen Deeks at UCSF – who is a very well respected researcher – called RECOVER “a great success”.
Let’s pray that he’s right.
If RECOVER is the failure you’re making it sound to be, what about initiatives in other healthcare systems? What’s going on with our European friends? Japan? Australia? Is there a reason we should feel so despondent just because this one area of US research is so abysmal?
There was an article in The Guardian newspaper “Long Covid”, you can look it up. It was published few days ago.
“Time to stop using term ‘long Covid’ as symptoms no worse than those after flu, Queensland’s chief health officer says
Researchers compared the symptoms and impairment of Covid and influenza patients a year after they tested positive”
Just to clarify, the QLD chief health officer said that long-covid rates were no worse than influenza post-viral complications. In other words, he believes there is no increased rate of ME/CFS after Covid compared to the rate of ME/CFS after the flu (and other viruses).
Part of his concern was to try to get people to not “overthink” their post-Covid symptoms and “worry” too much. I find that a strange argument. If you look at the rates of many diseases after an epidemic like the Spanish flu, many increase significantly (Parkinson’s as an example). Whether this increase is specific to the virus infection, or specific to the pandemic situation (vaccinations, mutations, reinfections etc.), doesn’t seem that relevant to me. You’re still may more likely to end up with ME/CFS whilst Covid is bouncing around than you were before 2020 (or 2019, depending on when and where you think it all started). Hopefully we aren’t still saying the same thing in ten years time.
RECOVER was unique in the huge funding given it -= $1.15 billion plus another $500 million given to it recently. No other project can touch that kind of funding but you’re right – there is a lot of research going on in Long COVID and the field is moving forward – no reason to be despondent about the field itself 🙂
This is a great question. Something I think we are all missing is the NIH is bogged down by government and slowness and lack of adaptability. That doesn’t mean all research or researchers are. There are lots of great scientists and doctors out there that I guarantee want to solve this as much as we do but lack the means to do it. It takes high cash infusion and pharma interest for there to be real breakthroughs that translate into treatment usually in my opinion. I don’t know what other countries are doing but they will have equally large proportions of people impacted by long COVID and maybe are doing more research than we know but on smaller scales. I look at the fact that the US is abysmal for FM research while Spain is constantly doing research on FM and coming out with publications on it.
Good point – lots of fibromyalgia research coming out of Spain – and that’s been going on for a long time.
“Hope” is not a scientific strategy to produce a biomarker.
How extremely disappointing. I’d be interested to see exactly how they spent all that money. Seems they’ve been paid very well to produce nothing substantial.
I would love to know their justifications for how they put this study together: why they’re following so many patients, how they chose their testing protocols, why they chose to put so little money into hypothesis testing and pathophysiology, how past post-infectious disease research informed the project, what their financial targets were…and did they really expect to end their 4 years of funding where they are now? They have 8 months before their funding was going to run out – and I don’t think they’ve produced one significant finding.
It looks bleak at this point but the RECOVER story is not over and I still have hope that there’s something we’re missing. Maybe in a year we’ll be ecstatic about it – I hope so.
Me too. Luckily though there are lots of other studies ongoing to fall back on. The UK decode ME study is due to publish the genetic results before August 2025 which I hope will shed some light, & then propel other studies on treatments. We are bound to find out SOMETHING definitive even if it’s not from the above organisation!
Is it maybe because there is no one person managing this or in charge and they weren’t equipped to do it on this large scale? I am just hazarding a guess but maybe it just gets messed up with red tape and paperwork and not sure how they actually make the final decisions. Were all the ideas submitted at once and agreed upon by people who have good knowledge of post-infectious diseases? I’d be interested to understand that process more so than understanding the money, it is really easy to burn through research dollars if the plan isn’t well laid out.
I don’t think we are going to find one biomarker for long COVID or even be so lucky to find a blood-based biomarker. We have yet to find that for ME/CFS or FM, and given that with all this research the medical community still can’t agree on what long COVID is and what the subsets of it are that is a long ways off. Same problems as we have in ME/CFS and FM. Without the biomarker as noted pharma will stay far away because it makes treatment trials really hard to have clear inclusion/exclusion criteria and without a clear picture of subsets and pathophysiology driving symptoms in the subset, how can you figure out what population would benefit most from a treatment? Throwing treatments at it will probably at best only work for small subsets of patients and so that may not show up as a positive signal in larger trials without honing down the subsets to an actionable target. So I think that the observational studies are really needed to better align on the subsets of patients. Because the symptoms diverge so much, you either are going to need a whole cocktail of treatments to deal with various symptoms, different cocktails for each subset, or you are going to need to find something early on/upstream in the pathophysiology cascade that can treat a broader swath of patients. But so far it seems like there is a million observational studies on all kinds of symptoms that can’t be fit into unifying cascade of pathophys events.
Well said!
Agree.
Agree and well said, Emily!
I have a thought on the “pathophysiology cascade.” I have thought for decades that it can only be understood seen from a novel fundamental disease model, just as the physicians debating miasmas before Pasteur simply couldn’t conceive of infectious disease. Yes, I can offer almost certainly wrong conjecture on what that would look like, and from that conjecture recently proposed (also almost certainly wrong) that PEM/PESE fits an autoimmune attack on the myoglobin (muscle) and neuroglobin (neuron) proteins which can only occur when their oxygen binding site is empty (exertion has occurred).
But what we really need is this century’s Pasteur, and to protect her from Semmelweis’ outcome.
It’s an election year and Biden is in a tough spot. People in Michigan are doing a good job pressuring him for cease fire in Palestine. Maybe patients in swing states could do the same and pressure the admin into creating the moonshot office/funding. There supposed to be tens of millions LC votes according to CDC, not counting friends and families.
Hi all,
This article nicely sums up the situation. I have inside information from NIH that the situation is worse than Cort states, not better. Dig down on those Pathophysiology studies and you will find that many SBIR projects funded with $40 million had nothing to do with Long COVID.
I was so distressed learning this in June 2022, I decided to take action. I applied to ARPA-H as a Program Manager with a $100 million Program proposal to specifically get FDA approved biomarkers for ME, LC, and other invisible illnesses such a depression and PTSD, and then Alzheimer’s and Parkinson’s as well. The Program would have leveraged PET and SPECT MRI as Jared Younger and others have done.
I spent almost 5 months full time on the proposal. I got no feedback except for, “it didn’t gain traction with our mission office”.
I watched every RECOVER webinar. I watched every one of the Roadmap presentations in each of the 8 webinars. I’m published in the medical literature, have an issued patent, and am a Program Management Professional, and won and successfully performed on a $225,000 National Science Foundation SBIR Grant. I live 17 miles from NIH and have worked there in Dr. David Goldstein’s lab (Dysautonomias and Parkinson’s). I’m an electrical engineer and really understand the physics of the nanoneedle and fully support it.
My congressman’s office, Rep. David Trone, did not get a response back from ARPA-H either.
FOIA anyone? I’ve personally pushed ARPA-H far enough. And I can reapply for PM with a new Program.
I’ve been sick for 18 years. I know what to do from a leadership perspective.
Could someone PLEASE give me ideas how I can get a leadership position with real money to spend on R&D and the authority to make sure the money goes where it’s intended to go?
And soon. Other offers are starting to come in for funding and/or jobs in unrelated positions. I need to start generating income.
At this point it’s ROI. I won’t keep throwing my time and energy into a black hole. Perhaps call it “effort preference”. I like to get stuff done.
I’m listening to all well-intentioned advice.
Wow…Sorry to hear all you went through but thanks for pushing! If ARPA-H is filled with people from NIH it’s no surprise they might be another dry hole. That is really bad news = and a FOIA sounds like a really good idea.
I just wanted to say thank you for trying. That was a very impressive effort.
I wish I was a billionaire so I could fund your proposal.
Wow, Cheryl,
That’s way more of your story than I’d heard before.
You’re right, that at this point a good understanding of who the people reviewing ARPA-H applications are, what the agenda of each is, and what kind of applications are being approved is the next step. I’m assuming that’s all opaque. I now get what you’re trying to do with FOIA.
Spending 5 months full time without income only to be told an opaque “no” seems off.
Anybody know any billionaires or foundations who would fund $5M projects?
Thank you everyone for your supportive comments.
Unlike NIH where $5million grants are common, at ARPA-H the budgets are 10x -20x that for Program Managers.
The PMs then issue requests for “performers” in the ranges closer to levels at NIH. Previously they did this via BAAs- Broad Agency Announcements but have since reconfigured the exact mechanism. Eva Garland Consulting has experience writing performer applications. They are not technically grants, but a faster/easier contractural vehicle.
I had asked for a budget of $100 million for my program. I learned a great deal about the people evaluating me. They either came from NIH or DARPA. I am happy to share my detailed knowledge about this one on one.
Basically, they have a mandate from President Biden to continue the Cancer Moonshot. If you follow the money, the Cancer Moonshot was funded by Congress from 2016-2023, at which time it stopped. The Cancer Moonshot contributed about $400 million annually to the National Cancer Institute’s annual budget of around $7billion. Those stats are easy to find.
ARPA-H had an initial annual budget of $1.5 billion. There are at least 4 programs at ARPA-H – at probably $100million each starting in 2023. So the math works out.
At the end of 2023 ARPA-H had 13 PMs. They plan to hire 7 more this year. PM terms are limited to 3 years with the possibility of an additional 3 years.
ARPA-H will be constantly hiring PMs. As at NIH, ARPA-H Programs are largely driven by the proposals they receive. If the programs relate to curing cancer, they have a much better chance at being selected. That is my observation.
I think the answer here is private money. I’m (was) a professional fundraiser who started and ran nonprofits for a living. We need control of our own funds as a patient-driven initiative because for the same “begging” effort to the govt (who then allocates the money but doesn’t spent it well), philanthropy could be funding worthwhile research directly. The ME/CFS orgs we have now do a great job in advocacy but I’ve been trying to lay out the foundation for a national patient-led charity like American Heart and other associations that would do just this. As a professional fundraiser I’m ready to go if anyone wants to connect directly and am speaking with a provider who’s willing to start a clinical trial for exhausted T cells if we can fund it.
“Millions missing” how about “Millions dupped”
If we don’t soon get out the hardball this could go on till the next millennium
It’s already been going on since the beggining of time
To me, this is a stalling of the progression of science
RESEARCH THE MICROBIOME ALREADY!! …
SHEEEEEEEESH!!
This is not only disappointing, it beggars belief. The % of Long Hailers with brain fog and ME/CFS symptoms is so significant one wonders how RECOVER managed to miss their importance— especially as it’s this cohort that will be affect economy and Society the most in the long term— through their inability to contribute to the economy and the extra burden of their care.
Governments were so quick to provide relief to those who couldn’t work during Covid. For those of us who did frontline work and
Hopefully the powers that be in government and all purse-string holders, will recognize that while RECOVER has not yet produced the results Long Haulers have been hoping for— it is more critical than ever to fund Long Covid research. We know what kind of research is needed now. We know it can’t wait. Let’s hope the failings identified here can be addressed ASAP. We know that great strides are being made by Long Covid specialists in repurposing medications and treatments and that they are desperately in need of ongoing funding to continue with clinical trials.
The loss of economic contributions by this cohort of long haulers is only going to grow as is their/our cost to society at large because they/ we are unable to contribute and work. It is maddening that governments have their heads in the sand around Long Covid. One hopes common sense would be all that is needed for the moonshot.
The fact that it does indeed beggar belief is why I’m hoping there’s something about RECOVER we don’t know!
There are a lot of ramifications if RECOVER fails to provide the goods. If$1.15 billion doesn’t buy you much why would you invest more into it? And if you do, why would you give it to the NIH? And if not them then who? The AHRQ is a possibility but they’re the new kids on the block.
If RECOVER does turn out to be a dog will the politicians be savvy enough to understand that it wasn’t because long COVID is impenetrable. The next year is going to tell us so much. RECOVER got its money in early 2021 I believe. It started enrolling in November of that year. I’m not sure when it enrolled everyone it wanted to, maybe around the end of 2022. Now in 2024 it’s time for the studies to start rolling out. Once they do we’ll really know what RECOVER is all about.
Thankfully there’s a lot more to long covid research than the USA. Some excellent, hopeful studies have recently come from Europe
Is it likely that there would be a biomarker, or even a group of biomarkers? People affected by LC are affected in so many ways, and the lists of symptoms identified so far is long. Would you really find much in common in the biomarkers of someone who got diabetes and someone who got orthostatic hypotension as their main LC diagnosis, for instance?
(Are all the extra cases of diabetes considered LC, or do they fall into another category, like increased risk factors from the acute infection?)
Are the sub-sets you listed all the sub-sets the study came up with, Cort?
Also, let’s suppose it’s auto-immune and researchers found an antibody or group of antibodies. What about seronegative cases? We really don’t understand how antibodies relate to disease yet.
All the aspects of LC are “hard” or “neglected” areas of medicine. And then, to make things worse, the researchers seem to have overlooked some of the good research we do have.
This is an open question: What was the purpose of RECOVER? Was it to collect as much data as possible? To sort of create a base for further research? So much of earlier research has been done on heterogenic diagnose criteria or whith to small study cohorts.
The absolutely first thing you do when creating a foundation is ofcourse observational studies. We can debate which observations that should be done. Then you proceed from there.
Are they doing the pbs-studies to be able to confirm or dismiss that strain of the science in the disease? “Let’s show once and for all that it doesn’t work!?” sort of?
If the RECOVER do not build that foundation we are still in scattered picture earlier research has produced?
Note also, there is research on “pure biological” reasons for what we today classify as psychological disorders/diseases. By the way what is the hen or the egg in “psychology”? That is another question, I know.
In Sweden our authorities dismiss alot of the research done on ME/CFS due to the small cohorts, to research done on cohorts with different criteria and research done but not replicated enough. That’s why I still think RECOVER is needed, as well as the other large studies now started on LC. If just establishing a large biobank connected with diagnose criterias and observations is accomplished, that is huge step forward.
I’m new to this, got diagnosed 2018, so maybe I’m just ignorant, blue eyes … And I do agree that advocating is nescesary to pull this RECOVER-Wagon further and into “some industrial plant” to build a product that can be used.
If this blog is correct – and we will see over time if it is – then RECOVER is both not building and building the foundation or base we need for further research. It’s not building it if it spent so much money on the very limited observational testing which will nnot tell us much about the ME/CFS-like cohort. I suspect it will be able to differentiate it from the other cohorts but by doing so it will not add much because the differentiating factors are already pretty much known.
It is building it in the way you described though – it has a HUGE biobank that can be mined for future studies.
It’s a lot of money to spend for just that though. Let’s hope there’s more about it than we know.
Thank you!
On first case, yes it would had been better with more extensive testing and specified testing for more data and to confirm – with a huge cohort – already done research (in to small cohorts).
On second case, yes that is the win so far … biobank.
Thank you Cort, for having this conversation and sharing it with us. This is important.
I have two observations:
FIrst, when I made my inputs to NIH NINDS ME/CFS crowdsourcing recently, in the stuff at the bottom of every Idea I recommended the same guideline:
50% of all resources should go to finding biomarkers and to repurposing (trialing) existing treatments, to do our best to get as many people as we can back on their feet as fast as we can
45% of all resources should go to pursuing research hypotheses, which is close enough to how money is spent today
5% of all resources should go to pure research, because we’re likely stuck until we find the novel disease mechanism which is blocking progress and which medicine hasn’t found in the 140 years since psychologizing the original “Neurasthenia”
I think those numbers should apply here.
Second, and bear with my narrative here (and this is very ugly)
When my father went to Washington DC in the late 1970s as his company’s new Director Government Relations, he knew he needed new skills fast and that DC is a very rough and tumble place. He drew on every contact in his Rolodex, our extended family, and every penny his expense account had to get the best training and mentoring he could. One of the most important things he learned was, “In Washington DC, nothing is as it appears. If you see something happen, figure out who benefits, and that’s who’s behind it, no matter how much it appears otherwise.”
I want to point something out (again). For lack of better statistics, we have about 5 million people disabled by ME/”CFS” in Europe and the west (of whom maybe 2 million are in the US), and in the last four years have accumulated another 5 million people disabled by Long Covid. Let’s talk about lifetime disability income. Every one of those cases is at least a million dollars (paid over decades, of course). That’s an exposure of about 5 trillion dollars for ME/CFS, and another 5 trillion dollars for LC. Even the national programs don’t have and can’t get that kind of money.
But more importantly, finding a biomarker, or even a treatment whose success could be used as a biomarker, would instantly bankrupt any private payer of disability income. This level of money is 100x the hurricanes which bankrupted much of the Florida property insurance industry. These folks have to be absolutely, existentially terrified of a biomarker.
So, back to RECOVER. By the principle my father learned almost 50 years ago, it’s guaranteed that the existentially terrified special interest had captured the viewpoint of people in the room setting RECOVER direction, and set that direction so as not to find a biomarker or a treatment in the short term. I know not just CDC has been in regulatory capture by that interest for over 30 years (the word “fatigue”, the term “chronic fatigue syndrome” are both evidence of that capture) but also the relevant parts of NIH have also been in regulatory capture as well (why do you think there are so many psychologizers, and psychologizers installed as PIs on key studies of ME/”CFS” and LC?).
I think we need the moonshot, it probably needs to go under ARPA-H management as soon as we figure out what way to head (but not before), and I think the psychologizers need to be explicitly excluded from the room, and as soon as someone shows their colors advocating the disability payers’ interests they get thrown out too. The moonshot is to get as many people back on their feet as fast as we can, from a physical illness we don’t yet understand how to think about.
Which also means we need this century’s Pasteur, and we need to protect her from Semmelweis’ fate.
I like your funding ideas! I think its very, very difficult for a disease like ME/CFS or fibromyalgia or IBS or even migraine – they’re all in the same boat – to hold sway in the NIH. A bias against these functionally disabling but hard to understand diseases that has built up over time. Despite the fact that they affect at least 10 million people, the NIH seems incapable or unwilling to do the work to build these fields. Whether its because institutionally they have difficulty doing that or what I don’t know but the NIH’s job is to support the health of the Americans – all Americans – and because its failing to do that it must change – or remain an organization that isn’t carrying out its mission and is failing a lot of people.
I agree with your general sentiments here, but I actually don’t think there is a conscious effort being made to block progress on biomarkers due to private insurance not wanting to pay disability. I think that because the NIH and government mechanisms are good enough at blocking progress themselves by layers of bureaucracy. Also, as we have seen in other cases private investment in research can spawn great breakthroughs that force a scientific acknowledgement. So even if we got a biomarker I guarantee insurers would still find a way to deny disability payments or somehow argue the biomarker isn’t establish or validated. Just like American healthcare insurance can deny whatever they want basically even if it is well validated and evidence based. So while it is definitely not in the insurers’ interest for progress to be made, they are probably just happy things are where they are rather than actively blocking.
HERE HERE!!!
Ignaz Semmelweis, for his theory on hand hygiene in preventing death of women in childbirth, was literally tossed aside, dying alone in a mental institution, a result of his health issues being first mistreated and then neglected.
Today, it is reported that in US hospitals, medical workers sanitize their hands well short of half the time they are supposed to, and more than half the time they do sanitize their hands, they do so improperly.
It appears we as a society are quite adept at pushing people aside and ignoring commonsense medical pursuits.
Are there any reasons why the NIH at some level on the chain of command might have sabotaged Recover on purpose?
I just don’t see it. The NIH has been under attack for its conservative ways, lack of results and overall stodginess for some time. It was given a lot of money by Congress to show that it was otherwise. If RECOVER fails, the NIH fails – with the potential consequence that Congress starts to lose faith with the NIH and looks elsewhere to give its money to.
Plus the researchers running RECOVER are spending years on this. If RECOVER fails, they fail and they get that stain on their reputation.
I think it was sign of desperation really that the Biden administration gave RECOVER $500 million more dollars. That suggests that they consider it too big to fail – that failure really can’t be contemplated on a project this big. That would suggest, though, that the Biden administration would look very carefully at what’s going right and what’s gone wrong with RECOVER and consider changing the leadership there. I haven’t heard that that is happening.
I just don’t see any reasons for anyone involved with RECOVER to want it to fail. This is a big program and they all need a win.
Please remember Francis Collins is out of NIH. He was the leadership for decades.
Dr. Monica Bertagnolli, an MD from National Cancer Institute, is the new Director as of May 15, 2023. One of her areas for investigation is “inflammation”.
Let’s be open to the possibility she could be a strong advocate for us.
Yes he is – but he was actually the first NIH Director who was a supporter. The Intramural study was apparently his idea and he got through the 3 ME/CFS research centers. After that he didn’t do anything other than to publicly support ME/CFS and long COVID at times. It was also his NIH which ignored long COVID until it got the RECOVER funds. Let’s hope a newer generation of NIH Directors does more. I wish the Director was from NINDS/NIAID – cancer gets tons of funding – but time will tell!
$1.65bn for a long-term observational study? What a joke.
“… The office the Biden administration created almost a year ago (The Office of Long COVID Research and Practice) which has oversight authority on RECOVER and other programs, appears to be a paper tiger. Its website doesn’t list the Office’s director, its staff, the kind of oversight it’s doing, its progress reports, or even how to contact it.”
Sounds like the Biden administration is simply throwing good money after bad. Nothing in this article inspires confidence in a meaningful outcome.
Thank you to everyone who has spent their time and limited energy advocating for solutions. I feel like we need a celebrity or a billionaire who has ME/CFS or Long Covid, or who has a close family member with the disease, who can be an advocate/funder and really get the public conversation going. I know this probably sounds simplistic, but I’m throwing it out there.
Additionally, those who are most affected by these horrible conditions often lack the energy to really put up a fight, but many of you are working so hard to make a difference, and I’m so thankful to all of you.
Thank you Cort for keeping us well informed.
I mean to me it’s obvious that they have no intention in doing anything other than pay themselves a billion dollars and then ask for more money. These frauds pushed dangerous vaccines on children who didn’t need them, and we expect them to care about this issue. All they care about it pushing vaccines. And avoiding accountability for the injuries they caused. Which is why I doubt any real answers will come out because they don’t care want to know the truth.