Growing Pains
Is RECOVER actually going to fund a large exercise study in long COVID?
The NIH’s RECOVER Initiative has not exactly been garnering a lot of praise. On the plus side, the NIH has clearly given the project a lot of thought and put together a program designed to produce meaningful results; i.e. results that stick. No more one-and-done studies, no loose ends – just a methodical rigorous approach to understanding long COVID that leaves us with answers. That’s the promise.
It hasn’t been as smooth as all that, though. It took the Initiative a year to start recruiting patients; for some reason, it strangely originally decided to study as many young patients as adults; the few studies that have been produced have been underwhelming in the extreme; and despite stating six or more months ago that it was going to start treatment studies, it’s begun a grand total of one.
Self-Imposed Injury
Let’s give RECOVER the benefit of the doubt and attribute the misfires to the growing pains that accompany any large initiative. Recently, though, a real head-scratcher has shown up. MEAction got the ball rolling when it reported last week that the RECOVER Initiative was moving forward with an exercise trial in long COVID. Rumors regarding an exercise trial have actually been floating around for a quite a while. In his book, “The Long Haul“, Ryan Prior reported that a $4 million “high-intensity interval” exercise trial had been greenlit but it wasn’t until MEAction reported it that it was clear that the trial was close to happening.
Talk about popping a balloon. The RECOVER Initiative has apparently seeded itself with ME/CFS experts. It says it’s listening to them and yet THIS happens, Interpreted one way, it’s basically potentially the worse news that the ME/CFS community could get: the RECOVER Initiative has gone biopsychosocial. (It almost certainly hasn’t but that’s going to be the interpretation). Another battle seemingly looms.
At the end of February, MEAction sent a detailed letter to the RECOVER Clinical Trials Steering Committee, reporting their concern that the trial would include people with the ME/CFS brand of long COVID. Citing the methodologically flawed PACE trial, and the years of problems it caused, as well as research studies indicating an impaired energy production process is present in ME/CFS, MEAction asked the NIH if they were accounting for the existence of post-exertional malaise (PEM) in their trial, requested that the trial exclude all patients with PEM, and that the particulars of the trial be made public.
Rachel Fairbank, the author of the Nature.com article, put a pin on the PEM question, when she noted that up to 60% of long-COVID patients could be categorized as having ME/CFS and that even more may experience PEM.
Of course, we have to remember that long COVID casts a wide net, and besides, a very prominent ME/CFS subset it also includes people with lung, kidney, and or heart problems and people who’ve been in intensive care and have become deconditioned from lack of activity. As MEAction acknowledged in their letter, other cohorts might benefit from exercise.
MEAction apparently has not gotten a response to its letter, but an article published in Nature.com, “Long COVID exercise trials proposed by NIH raise alarm“, ramped up the heat considerably. If RECOVER was able to at least temporarily blow off MEAction, they apparently felt they had to respond to the queries from a prominent scientific journal. They stated:
“the agency is working with patient representatives in shaping the exercise trial protocol”, and that they would include “inclusion and exclusion criteria to make sure that people who could be harmed by exercise will not be included in that platform trial”.
Is the RECOVER Initiative listening to people with long COVID and/or ME/CFS?
While the devil is in the details, that’s encouraging. What we don’t know and will probably never know is what effect MEAction’s and other advocacy efforts had on the makeup of the exercise trial. While RECOVER has incorporated ME/CFS experts and long-COVID patients into its decision-making process, it’s not clear how deeply embedded they are or how closely they are being listened to.
Ryan Prior reported that as of November 2021, RECOVER had failed to include patients and their experiences in a meaningful way. That surprised him given the important role that patients played in the last great new condition the NIH was faced with – HIV. One would have thought that the Initiative would have been eager to bring patients on board given how little it knew about long COVID- but not so.
Prior reported that the Body Politic urged the NIH to pay special attention to ME/CFS research. At least at that time, the group felt that the Initiative’s leadership only had “a shallow understanding in the field of post-viral research”, and was probably doomed to reinvent the wheel.
The RECOVER Initiative’s response to my questions asking whether it was employing exercise stressors to help advance its understanding of long COVID more quickly left me with a similar question. Time will tell, of course, what RECOVER will do – we still know very little about their studies, but the Initiative’s answers and its funding of studies that didn’t appear to involve exercise stressors did not seem to bode well.
Beyond that, it seems baffling that the NIH would choose an expensive exercise trial to be one of its first clinical trials. The benefits of exercise, of course, are well-known for people with lung or heart injuries. Breathing exercises can help with lung problems and interval training can help with heart issues. It seems more likely, though, that an exercise trial in long COVID would try to address the deconditioning that resulted from long hospital stays or from a lack of activity in the aftermath.
It’s not as if the medical world, though, doesn’t fully get that absent an ME/CFS-like condition, exercise is good for patients who’ve become deconditioned. That doesn’t require a $4 million study. One hopes that RECOVER is aware that given how vague the term ‘long COVID” is, the results of any exercise study, no matter how carefully the ME/CFS-like long COVID group is excluded, are going to be misconstrued as pertaining to all long COVID patients. Why risk that?
The ME/CFS community, of course had to deal with the fallout from exercise clinical trials for years. The entire history of graduated exercise therapy (GET) in ME/CFS was based on the proposition that people with ME/CFS had become deconditioned, and that once exercise resolved that, they would return to health. Despite the modest results of the cognitive behavioral (CBT) and graded exercise therapy (GET) trials, CBT and GET ended up subsuming the small ME/CFS clinical trial field.
Over time physiological studies poked holes in the deconditioning hypothesis. A large study emphatically showed that while deconditioning is present in ME/CFS, it did not impact the ability to produce energy; i.e. energy production was impaired whether a person was deconditioned or not.
Similarly, David Systrom’s invasive exercise studies showed that people with ME/CFS and/or long COVID exhibit the opposite results expected to occur with deconditioning. Workwell’s two-day exercise protocol definitively showed that exercise one day whacks ME/CFS patients’ ability to produce energy the next. Those kinds of specialized studies pointed to core problems in ME/CFS – something that graded exercise studies could never do.
Importantly, though, the results of one-day CPET studies can be misleading They often indicate that yes, deconditioning is present, leading the authors to propose exercise therapy as a fix. One long COVID study even asserted that the presence of deconditioning indicates that an “organic” condition is not present. A Scottish resistance exercise trial long-COVID study is underway.
Other studies that are more circumspect provide hope that the long-COVID field will not, in the end, have to reinvent the wheel regarding exercise. A University of California San Francisco review of 38 exercise studies published in the Journal of the American Medical Association (JAMA) concluded that deconditioning was common in long COVID but that so were “problems of oxygen extraction” – a key ME/CFS finding from David Systrom. It concluded that:
“Potential mechanisms for exertional intolerance other than deconditioning include altered autonomic function (eg, chronotropic incompetence, dysfunctional breathing), endothelial dysfunction, and muscular or mitochondrial pathology.”
Advocating against graded exercise therapy (GET) can be a bit tricky, though. Perhaps because perhaps many GET studies used the Oxford criteria, they do not, in general, show that harm has been done. A 2017 systematic review, for instance, found that “no evidence suggests that exercise therapy may worsen outcomes”. It may be better to ask, given the limited positive benefits that GET provides, whether it’s worth pursuing at all. That same review’s conclusion that people with ME/CFS “may feel less fatigued” isn’t likely to light a fire under patients or their advocates.
Charles McCone, a long-COVID patient working with the RECOVER Initiative, certainly isn’t excited about the promise of an exercise trial. He told Nature that he found it “baffling and discouraging” that the Initiative is spending money on an exercise trial. Noting that, “Dozens of drugs [for long COVID] have been identified as promising candidates that need immediate further study,” McCone delivered the kicker “Funding is limited”. (Note, though, that Nature reported that the RECOVER Initiative plans to spend $172 million on clinical trials.)
Herein lies the big question. Why spend $4 million on a study that’s pretty much guaranteed to produce modest results? This, after all, would not be a small study – it would be about half the size of the PACE trial in ME/CFS – still easily the largest study ever done on ME/CFS. (My second thought after hearing about the study was that the RECOVER Initiative had too much money… My first thought was “are they serious about long COVID?”; i.e. have they assessed the ME/CFS literature?). Lisa McCorkell, a co-founder of the Patient-Led Research Collaborative for long COVID asked, “Why?”, as well.
“In a world where there’s hundreds of things to trial, why are we choosing this one thing that we know has the potential to cause harm to a substantial portion of patients?”
The RECOVER Initiative, thus far, has one treatment trial underway. Is an exercise trial really going to be second? Is it really worth alienating the biggest long-COVID subset of patients – not to mention the entire ME/CFS community?
The ME/CFS community well knows how even modest results can get translated by journalists and doctors into conclusions that send research efforts, doctors’ protocols, and the public down tunnels with no cheese. Look at what’s happened with fibromyalgia. A few modest results have resulted in the fibromyalgia research field being virtually been overtaken by exercise studies. Dozens of fibromyalgia exercise studies have swamped that small field over the last year.
That won’t happen with the RECOVER Initiative – it’s simply too big but it literally couldn’t have found a better way to alienate its main clientele or attract more negative attention – something it surely doesn’t need – and may only be starting to get. Nature.com is not the only major media outlet digging into this. Stat News is also digging into the exercise trial – and that’s the really good news to come out of this: the media is watching…
Discouraging to see this approach come down the pike again.
It’s crazy – fecal transplants, low-dose naltrexone, biologics, vagus nerve stimulation, anti-coagulants, metformin, plasmapheresis, pentoxifylline and god knows what else – and THIS is what we’re talking right now. It’s just wild.
It will pass but if I was in charge of public relations for RECOVER I would be shaking my head. They could really use a win…
PACE 2 here we come! A big bung of funding. Mildly affected patients and results extrapolated to all. It’s a win win for the biopsychosocials
I almost panicked reading this. The vivid memory of a big PEM after running on a treadmill at the cardiologist’s office came back at once. Cort, you are a big voice for us, I hope your dismay – not sure of the proper wording here – will be heard
Quite the memory! Good for MEAction to draw attention to this study but I don’t think there’s any reason to panic. This is one study – if they end up doing it – out of hundreds that the RECOVER project will be doing.
I’m just kind of stunned that it’s happening at all. If RECOVER was worried that it was going to be accused of lacking in creativity and innovation – precisely the things the NIH is regularly accused of – they just put their foot squarely into it.
It’s almost laughable how bad they look and guess what – STAT News is probably going to take the next shot at this study.
I was an RN prior to to Covid (tested positive 4-20) and regularly put 15,000 steps on my phone at work. Post-covid, it took a year to walk a mile. Six months later, I went to three days a week because the exercise was all I got done in a day. Two years beyond that, I’m stuck at 1.5 miles. I can occasionally get to 2 miles on a good day. I can’t imagine participating in an exercise trial. It seems the self-selection of patients would skew the results. No one who is sane and affected physically would put themselves through that.
Good point Self-selection probably played a role in GET studies getting even the very modest outcomes that they did as well as the lack in reported harms.
I was turned down for the RECOVER project as a potential Long Covid case to study. I was told this was because my acute Covid had been too many months away from my on-going Long Covid! Huh? Anyhow, I was relieved as there were too many trips to make for the blood tests etc. and if I do something like that I get too tired for that day to do anything else. Thus, seeing this latest blip on their screen (with the exercise study) does not surprise me. I DO wish them luck in helping all of us however!
I hope that RECOVER realizes that they’re probably getting the cream of the crop as regards fitness. I don’t know if I’ve ever seen this issue expressed in studies but it’s got to be a real one.
Long COVID Justice released a petition about this study back in December – over 1700 people have endorsed and we still invite sign ons: https://actionnetwork.org/petitions/tell-nih
Thank you JD! Just signed.
Thanks for sharing the petition. Have signed and commented.
Signed
Thanks JD. Good work long COVID Justice! Just signed 🙂
Signed.
Signed
I signed this a while back and got a bunch of friends and family to sign as well. I’m so upset that they are going ahead with it in spite of all the feedback they have gotten. I think most folks with ME/CFS or long covid can figure out themselves how much activity they are able to do, and what is and isn’t working for them in terms of exercise. i have periods when modest walks are helpful and times when I can’t get off the couch or out of bed.
We’ll see what happens. Hopefully, the study doesn’t happen (is this what they want to spend their money on?) and if it does it will not include the ME/CFS subset. I’m looking forward to the STAT report on this…
Thank you for sharing. I signed and commented.
Just signed, thank you. I am one of the 25% and there’s no way I could do an exercise study. I used to go on day long hikes and now I am housebound, walking short distances between rooms is exhausting. The results are already severely skewed by testing people able to participate in an exercise study, not to mention dangerous and in my opinion highly unethical given what we know about the effects of PEM.
Hopefully the study will put the exercise theory to bed once and for all. Very sorry for the people involved
Something I wanted to share: I am trying out this new protocol for Brain Fog: Seems to be helping me at least 50 per cent. My brain fog and headaches have been pretty bad with Long Covid. So far no terrible side effects with this treatment! https://medicine.yale.edu/news-article/potential-new-treatment-for-brain-fog-in-long-covid-patients/
Thanks Trudy! Congratulations and continued good luck. We did a blog on Guanfacine back in December. Really nice to see these new options pop up!
https://www.healthrising.org/blog/2022/12/24/brain-fog-long-covid-chronic-fatigue-fibromyalgia/
Cort I must have missed that blog! Duh…. Brain fog…. Thanks for writing it! I will read now…
I saw a couple of articles on guanfacine and brain fog a short while ago and I copied one to show my doctor. She refused to prescribe it because she’d never heard of guanfacine. Well, a little later a friend diagnosed with ADHD told me she was on it. Under one name it is a non-stimulating ADHD drug and under another it is an alpha blocker for hypertension. Ha! I have borderline hypertension and my doc has been pressuring me to take medication for it. Next time I see her…
I always wonder how ME/CFS patients manage CPET tests….especially the 25%’ers.
I have been found with inflammation on my lungs in a FENO test but no asthma or obvious lung damage.
But my breathing is awful, day long for 6 years. So I was put down for a CPET, but now the physiologist and pulmonary consultant want to talk to me as they don’t think I’m fit enough….I’m mostly bedridden. Don’t know hat their plan B is but I DID wonder how it wouldn’t cause months long PEM!!!
To Jane: if I understand the test your doctor wants you to take, a CPET – or PET CT as it was called when I had it – was a completely passive imaging test and I had no PEM or side effects afterward. (My CFS doc won’t permit me to do any treadmill, etc, tests).
It is pure imaging, not functional imaging. The technician IV’d a small amount of contrast (nuclear) into my arm, I waited about an hour sitting up in a chair and reading while it circulated throughout my body, and then I lay down on a very comfortable table while the scanning machine slowly went from my head to about my knees. I zoned out.
I’d been nervous about the nuclear contrast, but cancer patients have these frequently to check to progress of treatment.
I was lucky to have no cancer, but the PET CT did explain the greater difficulty in my lungs – the bronchiectasis I had before Covid last May had gotten much worse.
This was very helpful in terms of informing the doctor for treatment and monitoring. No PEM at all.
Good luck.
Thank you Cameron
I had the test yr talking about last year as I’m having tummy issues and seem to have had every scan, CT and ….oscopy going. No cancer either.
No, this is a Cardio Pulmonary Exercise Test on a bike, hooked up to lung function measures. But thank you so much for replying xx
To Jane – Sorry I got the test names mixed up. But re the CPET you’re referring to, my cardiologist wanted me to have one of those a couple of years ago and my CFS doc said no. So my cardiologist came me a more passive version, where I sat the whole time and they injected nuclear contrast and then something to put my heart through the paces. Sometimes they then administer a substance to reverse the agent they use to simulate your own physical activity, and in my case, the doctor did. I had no adverse results from the test, although I’m always nervous about nuclear tests.
I wonder if they can give you the nuclear CPET instead of the traditional. I’d be as concerned as you are about the traditional CPET.
PS By the way, I came through with flying colors on the nuclear stress test. My cardiologist was amazed; my neurologist was also, and said I had “a runner’s heart.” Clearly all the fatigue, difficulty breathing, etc., was not coming from my heart. And I didn’t have to go through PEM or permanent worsening of ME/CFS to find that out.
PS Sorry, I seem to have gotten it wrong again! No one has tried to give me the bike test, but I wouldn’t take that either. My lung doctor has me do a “blowing” test for lung function and now I decline that as well, due to PEM (plus I don’t trust the accuracy of the readings). Once they did the cardio test and found my heart was functioning great, and the other tests that showed my lungs to be diseased, I figured they’d done enough testing and we knew enough. I’m currently looking into non-machine pulmonary PT preferably all sitting or lying down.
Thanks Cameron. I’ll discus it with the consultant. I….and they…are worried that I’m not fit enough to do it, and I don’t want to induce months of PEM. In the USA …I’m UK…they seem to have it to work out their exact Anaerobic Threshold. I was due to have it for inflammation seen in FENO test. We’ll see. Thank you for replying xx
I used to get something over 15-18,000 steps as a baker for a luxury hotel. Now, 16 months after my initial diagnosis with Covid, I can barely walk from my bed to the bathroom in my room. I’m using a walker and going to physical therapy. Muscle spasms, shooting nerve pain, my leg jerking on it’s own. It’s so discouraging to think it may continue to get worse.
There were a lot of April Fools articles floating around yesterday, and I thought this might be one of them. Upon reading again, I see it is not. I felt like a broken record criticizing long COVID research that treats it as a brand-new disorder. Now they *are* indeed reinventing the wheel.
The biggest problem with RECOVER, and long COVID research in general, is lumping all COVID-specific damages with post-viral syndrome. (Just the other day, NBC news reported “a treatment for a long COVID” and it turned out to be a treatment for loss of smell.) I don’t think they’ll make real progress till they separate post-viral MECFS, which is the biggest problem that long-COVID patients face, from organ damages caused by the corona virus.
Agreed! This is turning out to be a crucial need.
Stupidity has no limits. particularly in the public sector.
Who are the researchers?
A shame so much money goes into this.
I am appalled but not surprised.
This is a fantastic article from David Putrino PhD.
https://www.healthaffairs.org/content/forefront/long-covid-incidence-impacts-and-implications
“Although we still have much to learn, a simple way to conceptualize the vast diversity of Long COVID diagnoses is to start by differentiating between those who have symptoms related to observable organ system damage using mainstream clinical evaluations and those who do not.”
This is a very relevant article by Prof Todd Davenport and the Workwell team, from March 2021, ‘We Already Know Enough to Avoid Making the Same Mistakes Again With Long Covid.’
https://www.jospt.org/do/10.2519/jospt.blog.20210310/full/
Nurse: “Doctor doctor the patients had a huge loss of blood” Doctor “double the leeches, no, triple the dose” … Oh sigh, here we go again PACE repeated.
This study brings back very bad memories of so many doctors telling me that I needed to exercise more — even when I told them I was teaching yoga and exercise classes for a living and had to keep dropping the number of classes I was teaching because it was exhausting me. Because they had read a study saying exercise was good. Sigh.
The end result will be that long covid is psychosomatic (the group without organ damage). The doctors and insurance companies think that’s the best outcome. It’s about money, power and prestige of professors with a big ego. We saw the same with CBT/GET in ME/CFS.
Just like the so-called mRNA vaccines that would be so effective, safe and that would prevent you from getting covid, according to Joe Biden. It would also prevent the spread of corona. This also turns out to be wrong. Yet many people still believe in science and remain naive. Pharmacists want to make money.
True science – whatever that may be – does not exist. The researchers at the universities just want to raise money. The whole system is perverted.
There is one type of exercise study I would like to see. “High intensity interval training” sounds like a nightmare. However some people have improved with this approach: They use a heart rate monitor to stay under their anaerobic threshold (AT) heartrate estimate and establish a safe baseline of activity that avoids PEM’s – a way to do pacing. Then they add strength training, very slowly with no weights at first, still staying under their AT heartrate. However, they avoid aerobic exercise which can put them over their AT threshold and into a PEM, for a year, while progressing the strength training very slowly throughout the year. After a year, they improved enough to do more in the aerobic realm. They also did some movement every hour, during the first year, again staying under their AT heartrate. I have been trying this for a couple months and I have been able to increase the strengthening from 3 minutes to 7 so far, and my muscle are getting stronger. It feels good. Strengthening increases mitochondrial proliferation in muscles and I wonder if the signaling for this may counteract the immune signaling of the dysfunctional itaconate shunt pathway. Strengthening also increases glycogen storage in muscle and I wonder if this signaling can shift glycogen metabolism in a positive direction in ME. This is the study I would like to see, strengthening protocols while avoiding stressing the aerobic system that we know is weak in ME/CFS through mitochondrial dysfunction. I should note that I take low dose naltrexone, low dose abilify and mestinon, which may be allowing me to try the strength training at all.
This technique is also not a treatment. It suggests that you can get better with exercise. That is an outdated illusion. It is the best way for those who can still do some exercise. But it’s time to come up with a real solution.
So true. The illusions cost huge losses for huge numbers of people. And we all know about losses! Except we don’t even know for sure if it’s best for those who can still exercise. But you’re 100% on target.
Here’s one more way to look at it:
For the very mild, monitored exercise that is described here by Chris and also me, the name deserves to be really more descriptive – clearly identifiable!
My NP and I call it VLIIT. This is way more accurate (very low intensity interval training). It _is_ somewhat – very loosely – based on the slim possibility that movement done in alternating intervals will help some of us. Note, we’ve only got anecdotal information about VLIIT as far as I know. (Feedback,
comments, anyone?) As a former body builder, former serious athlete, and former healthcare practitioner I’m very slowly and carefully sampling 30 seconds of mild, weak, slow, recumbent pedaling and alternating it with 60-90 seconds of either rest or mild small foot movements. This is only in a cluster of 4-6 cycles, and not every day. That said… call me unforgiving, passionate & opinionated – but there’s too much past and ongoing damage/disregard of activity intolerance. I just see too many assumptions out there to trust most exercise studies. I also don’t go for anyone else risking what I’m doing. Other than this VLIIT, I’ve had too many crashes, losses, and limited ADLs to risk even the smallest blurring of details that crop up with institutional exercise studies. How can we get someone we can trust to design, define and accountably carry out even a safe, worthwhile study of VLIIT?
Yeah, you can get toned even with MECFS. I’ve tried it for years and it did strengthen my muscles, but it did not improve my PEM thresholds. I kept crashing whenever I went over my limits. Maybe it works for some people, but certainly not for everybody.
De-conditioning? I was mt biking 50–100 miles/week & kayaking as well. And in the winter I would ski on the weekends. I had a life and enjoyed going out with friends. Then my flippin ME/CFS returned (after being in ‘remission’ for about 3 years) and I fell back into a hole. Was so devastated. But they can’t tell me that the return of my ME/CFS was from de-conditioning. BS. Now…I can sometimes muster up enough energy to only hike about a 1+/- mile about 1x/month. When I do try to push myself….it’s hell for about 5 days. I no longer have friends. Sounds like this trial is just a rehash.
Absolutely true. Not a treatment, and, based on flawed assumptions. Here, all over again disregarding the damage of activity intolerance.
Totally agree ElizabethKay and Natalie i was also a very active person in good conditon till ME/POTS came along. When are doctors stop to believe their
patiënts ? These days docors and scientists think they know everything, so arrogant… and stupid…. They don’t know nothing…. Knowing what I know now, I smile at them and wish them much wisdom. They think the truth consists of models and statistics. It’s a trap. Best wishes
Has anyone else been prescribed a Vibratory Vest to literally shake the stuck mucus out of the lungs post infection?
My CFS-related bronchiectasis became much worse post-Covid and my lung doctor, with my agreement, finally prescribed a Vibratory Vest. Less than a week of use at one-quarter what they told me to do (we’ve all learned the hard way, right?), I find I’m stricken with a misaligned spine and big GI problems.
Has anyone else tried this Vest?
I asked my CFS doctor what she thought about my trying it and she had no knowledge or experience and so, of course, just recommended “start slowly.”