How to get to the promised land – good treatments for long COVID (and ME/CFS)
It was a most interesting webinar – the first in a series of programs from Solve M.E. and Biotechnology Innovation Organization (BIO) – on how to best advance the long-COVID treatments. Solve M.E.’s long reach and its ability to bring in a diverse array of experts in different fields was amply demonstrated.
Politicians, bureaucrats, doctors, drug companies, researchers, and one economist participated. While few directly addressed the question at hand, all the presentations at least tangentially touched on the issue. The needs, costs, research opportunities, new drug options, the work underway, and, at the end – an idea who to really move things forward, which the speaker asserted “could happen”.
Senator Kaine – It’s always nice to have a U.S. Senator open an event. In this case, it was even better having Tim Kaine – who may have been the driving force behind the $1.15 billion the Senate provided to the NIH for its long-COVID research initiative – open the event.
Both Kaine and Dr. Levine, an Asst. of Secretary of Health, spoke of a number of federal activities aimed at long COVID including three high-level research reports, a National Research Action Plan, and more than 72 projects across federal agencies like the NIH, CDC, and Veterans Administration that have produced over 170 publications to date.
Kaine, who has long COVID (he said his nerves feel like they were dipped in Alka-Seltzer) recently organized a summit in Virginia on long COVID and visited Yale University to learn about their work. He stated it was important to acknowledge that infection-associated chronic illness is not new and referred to dysautonomia and ME/CFS.
Lisa McCorkle – 3 years in now with long COVID, she spoke on the tremendous work the Patient-Led Research Collaborative has done.
Bottom Line – there appears a lot of activity at the federal level regarding long COVID. As the last speaker, Chris Austin will point out, though, more is needed to really move things forward.
David Putrino, Ph.D. – Disease Spectrum
“We need many more therapeutic targets and many more treatment options.”
David Putrino – is one of the most prominent long-COVID doctors and advocates. The New York physician glommed onto long COVID early and he’s right on the ground caring for and studying long-COVID patients. His own learning curve is mimicking that of ME/CFS experts of yore. Echoing them, Putrino said a doctor doesn’t need a biomarker to diagnose long COVID: it’s completely recognizable.
That was an interesting statement given how variable he said the symptoms – except, apparently, for the core ones – are. More than 200 symptoms have been reported (how many different symptoms can there be?) and 10 organ systems can be affected.
Putrino stated that you can throw the results of any long-COVID diagnostic study that starts before three months after COVID in the trash (my words, not his). That’s because it can take six weeks to recover from COVID-19. An Israeli study that showed high recovery rates apparently included COVID-19 patients who would have recovered anyway.
Putrino recommends vaccines (another study found they did reduce the risk of long COVID) but acknowledges that vaccine injury is a real, and sometimes debilitating, condition. He believes that understanding vaccine injury will help us understand long COVID.
Putrino’s been knee-deep in long COVID for years now – and has access to all the ME/CFS and POTS treatments – and said he’s not finding long COVID melting away at all. Three months of rehabilitation helps – his long-COVID patients tend to be “a little more functional”, but that’s about it.
As one would suspect, long COVID is hitting people hard: 50% of long-COVID individuals at their clinic have had to change their employment status, and 70% attempting to get disability have been denied.
Bottom Line – we need many more therapeutic targets and many more treatment options.
Katie Bach MBA – The (Rather Amazing) Economic Burden From Long COVID
“The enormity of these costs implies that policy to address long COVID are urgently needed.” David Cutler
I found Katie Bach’s presentation on the economic effects of long COVID the most interesting and potentially impactful of the talk. While the research is promising, long COVID clearly isn’t going to be solved overnight and will require a large commitment of funds for some time to come.
It should be noted that NIH’s RECOVER program was Congressionally funded for five years and has about three to go. Because long COVID is a brand new disease entity, absent more congressional funds, the NIH would have to divert funds away from other diseases to fund it. Given the NIH’s tawdry record of funding diseases like long COVID, one would not want to rely on it for continued funding.
Reports like hers and a recent one from Eric Topol (see below), though, make a very good case that long COVID should continue to receive substantial resources They indicate that long COVID is doing more than impacting people’s health – it’s prevalent enough that it may also be impacting the U.S., and undoubtedly other, economies.
The CDC’s Household Pulse Survey is designed to give information on rapidly evolving health situations. It’s found that about 12 million people have long COVID. Of those, 10 million say long COVID is limiting their daily activities and 3-4 million people, or about 1% of the U.S. population, say their activities have been severely limited by long COVID.
Their income is going down at the same time their health costs are going up. Families are getting hit twice. If caregivers are affected, others have to step or families have to pay for something like child care. The bottom line – long COVID can be financially devastating
Could long COVID be behind some of the strange labor shortages that no one has been able to figure out yet? (The number of people participating in the labor force has dropped considerably since the pandemic started. The labor force in the U.S. is shy about 3.5 million expected workers.
No one really knows, but long COVID could certainly contribute to them. She believed that long COVID is probably causing $27-$54 billion losses in lost wages annually – a figure that is likely going to go up because there’s often a considerable lag time between getting ill and dropping out of work. (That figure, of course, doesn’t include the 850,000 – 2.5 million people affected by ME/CFS.)
According to a recent study by the New York State Insurance Fund, a year after becoming ill, a staggering 18% of people with long Covid hadn’t returned to work. Of these, more than 3 in 4 were under 60 years old. In fact, the CDC’s household pulse survey suggests that younger people are getting hit harder than old people with long COVID.
The New York State Insurance Fund reported that “Long Covid has harmed the workforce,” and wrote that these findings:
“highlight long Covid as an underappreciated yet important reason for the many unfilled jobs and declining labor participation rate in the economy, and they presage a possible reduction in productivity as employers feel the strains of an increasingly sick workforce.”
Torsten Slok, chief economist and partner at Apollo Global Management, even believes that long COVID has directly impacted inflation:
“The bottom line is that long Covid is why the labor force participation rate has not recovered to pre-pandemic levels, even in a situation with solid wage growth. These ‘missing’ workers are why companies continue to report labor shortages and why wage inflation remains so high… Ultimately long covid is a key reason why the Fed will have to keep the Fed funds rate elevated for an extended period,”
The costs just ripple out and include a possibly serious rise in social security expenditures, workers compensation, disability insurance, shortage of workers in industries, and workers going to work sick.
David Cutler, of Harvard, and Larry Summers have been keeping a close eye on the costs of long COVID. In 2020, they were among the first to bring up the issue. Last year, Cutler updated their projections using, interestingly, an ME/CFS figure of quality-adjusted years of life for long COVID-patients who had 3 or more symptoms. Cutler conservatively came up with a cost of $3.7 trillion dollars (two-thirds of which was due to reduced quality of life) or more than the costs of the great recession of 2008. He concluded:
“The enormity of these costs implies that policy to address long COVID are urgently needed. With costs this high, virtually any amount spent on long COVID detection, treatment, and control would result in benefits far above what it costs.”
We know the NIH doesn’t care about “need”; if it did, it would find a way to fund diseases like ME/CFS and fibromyalgia, but Congress – which oversees the NIH – does, and reports like these are gems.
Besides the economics of long COVID, Eric Topol recently reported on 4 studies that have reported a dramatic increase in the risks of stroke and heart disease post-COVID – thus providing another reason for researchers to dig into what the coronavirus is doing to the body. Topol suggested that inflammation and blood clotting were the cause. Topol wrote:
“It’s an inconvenient truth that Covid is associated with an excess of heart attacks and strokes beyond the first month of infection. That can no longer be ignored or refuted.”
Bottom Line – given long COVID’s very high economic costs, we should be pouring more money into it.
Akiko Iwasaki Ph.D. – Pathophysiology of Long COVID
Iwasaki is right in the thick of things. As in her IACFS/ME conference address, she was a clear and effective presenter. As her talk mainly went over the paper that she reported on earlier, you can find it here. A few notable things:
A comparison to the recent Henrich papers finds some remarkable similarities: EBV reactivation, an enhanced Th2 response, problems with the antibody response, and no evidence of autoimmunity.
- Elevations in non-classical monocytes aka Bruce Patterson – didn’t assess
- T-cells focused on Th2 response (more allergy than pathogen seeking) – yes
- EBV reactivation – that appeared to be linked to the Th2 dominant immune response – yes
- Elevated antibodies to spike protein (in contrast to the Henrich paper) but poorly neutralizing (= similar outcome as Henrich paper) – similar
- Most differentiating factor in long COVID – low cortisol! – didn’t assess
- No significant autoantibody findings in long COVID – yes
Bottom Line – some high-quality long-COVID studies are getting similar results.
Michael VanElzakker Ph.D. – Potential Biological Targets
“Evidence for persistent virus and viral antigen/RNA reservoirs [is] becoming more and more prevalent […]” Akiko Iwasaki
Michael VanElzakker Ph.D. – filled in for Amy Proal. It was hard to believe that the virus wasn’t persistent in the body after VanElzakker’s talk. It’s been found in too many places over time to expect it to just disappear over time…
VanElzakker noted that Germany has a law on the books that if a new pathogen has emerged, they can do autopsies without consent. (Give them a reward for thinking ahead…You don’t do autopsies without people dying after all and if you’re dying from a new pathogen, you’ve obviously got quite a problem going on).
While the German researchers did, in the end, get consent, they found viral antigens (proteins that spark an immune response) in the brain tissue. Likewise, in a superb study published in Nature, Daniel Chertow found viral protein and RNA across the body. Other researchers that have taken “convenience” samples in patients with hemorrhoids, liver, and gall bladder in people who did not necessarily have long COVID found the virus persisting in these tissues as well.
Intestinal biopsies have found the coronavirus in the gut, and long after its disappearance from the nose, it’s been found in the stool. It’s even been found in tissue associated with endothelial (blood vessels) dysfunction in erectile dysfunction.
David Walt’s 2022 paper, which found the spike protein from the coronavirus in about half the long COVID patients’ guts up to 12 months after infection in long COVID but not in recovered patients, was exhibit number one for the existence of a viral reservoir. Because the spike protein does not last long in the body, a viral reservoir that keeps pumping that protein out must exist. Akiko Iwasaki recently noted:
“Evidence for persistent virus and viral antigen/RNA reservoirs [is] becoming more and more prevalent […] The presence of the spike protein in circulation in long haulers is adding to this emerging evidence.”
The question seems to be less and less if the virus or its proteins are still present, and more what impact it must be having.
VanElzakker’s own small long-COVID study suggests that inflammatory factors are making their way into the brains of long-COVID patients. He’s seen increased activity in the anterior cingulate cortex, activated microglial cells (immune cells of the brain), and densely vascularized (blood vessel-rich) parts of the brain – probably due to clotting. He believes the vagus nerve may be sending inflammatory signals to the brain in long COVID.
Bottom Line – The question seems to be less and less if the virus or its proteins are still present in the body in long COVID, and more and more on what impact it must be having.
Walter Koroshetz MD – NIH’s RECOVER Initiative
Noting that the RECOVER Initiative was a massive project that was designed to not leave any stone unturned, he said the infrastructure had been set up for the long term. (Their funding mandate, though, runs out in a little less than 3 years…) They have standardized protocols that are set up to try one intervention after another and see what really sticks.
The largest in-person study of long COVID in the world, the RECOVER Initiative has access to 60 million health records. Thus far, they’ve found a 4% incidence of long COVID (PASC) in children. As expected (did they expect that?), that’s far lower than the 20-30% prevalence of long COVID they’ve found in adults after 3-4 months. In a good sign, they appear to have cut back their pediatric enrollment (they were going to enroll about as many children as adults) to 6,000 – a number that makes a lot more sense.
Enrollment has been rather slow but is growing. Thus far, RECOVER has enrolled 11,706 adults (of 15,000 expected) and 2,917 (of 6,000 expected) pediatric patients. In a good sign, RECOVER is planning to follow a large chunk of patients (5,000) from acute illness to long COVID.
While their symptoms are similar, Koroshetz reported that people infected earlier in the pandemic – who were exposed to the first variants and had not been vaccinated – are having more severe symptoms. He noted that vaccination does reduce the risk of long COVID to some extent.
Koroshetz is not in the ‘many different kinds of long COVID’ camp. While many different kinds may exist, he’s holding out hope that one central dysfunction underlies them all… Here’s to that.
The RECOVER Initiative still seems to be getting its feet underneath it. The few papers it’s published have been underwhelming, to say the least, and it’s produced just one treatment trial so far. Still, it’s a massive, apparently well-conceived project that has hardly begun to show what it can do. Hopefully, things will start to pop more in year three.
Bottom Line – With less than 3 years left in its funding, now would be a good time for the RECOVER Initiative to start showing its stuff.
Drug Companies
Ampligen and Bruce Patterson – we recently heard about Ampligen, and Bruce Patterson’s talk will be covered in another blog.
Axcella – A Safe and Effective Mitochondrial Booster?
“highly statistically meaningful and clinically significant improvements in fatigue” in about 70% of individuals”
Margaret Koziel, MD, SVP, and Chief Medical Officer, Axcella Therapeutics, gave a most interesting presentation. A small company based just outside of Boston, Axcella is not developing the next monoclonal antibody or anti-cancer drug but is in its own words – “pioneering a new approach to treat complex diseases using endogenous metabolic modulator (EMM) compositions”.
Those EMMs are amino acids and their derivatives that are put together, Axcella says, “in distinct ratios” that target multiple areas, causing a synergistic metabolic effect to be produced.
Axcella, which calls its product “very safe”, has been testing it in fatty liver disease, where its been used it as a mitochondrial regulator. Thus far, the company reported seeing improvements in mitochondrial bioenergetics, oxidative stress and inflammation, and endothelial dysfunction – all factors, of course, of high interest in long COVID and ME/CFS.
With their interest piqued by the presence of post-exertional malaise (PEM) in long COVID, 1 1/2 years ago Axcella paired with Oxford University to begin a clinical trial. The long-COVID patients had to have experienced “severe fatigue” for at least 12 weeks, and the study was designed to explore the effects of AXA1125 on mitochondrial dysfunction.
The company reported they found “highly statistically meaningful and clinically significant improvements in fatigue” in about 70% of individuals in just 4 weeks. They also found evidence of significant mitochondrial dysfunction that improved with the product. They even think they may have found a mitochondrial biomarker. Their studies show, they said, that something has gone seriously wrong with the long-COVID patients’ biology.
A Phase III study design has been improved and they are now looking for funding.
Bottom Line – a metabolic approach to disease that doesn’t require harsh drugs seems, at least in the early stages, to be working.
The Gist
- The theme of the Solve M.E. / BIO Webinar – how to accelerate treatments in long COVID.
- Senator Tim Kaine – who said his nerves feel like they were dipped in Alka-Seltzer – and Asst. Secretary of Health Levine – cited numerous ways the federal government is working on long COVID.
- David Putrino Ph.D. – a New York researcher and physician who’s been in the thick of things from the beginning, said studies citing high long-COVID recovery rates were misleading and poorly run. His clinic – which has seen 1000s of long-COVID patients – finds that 3 months of rehabilitation results in minor functional gains. The bottom line – we need many more therapeutic targets and treatments.
- Katie Bach presented another reason to find a way to treat long COVID – its awful economic costs. A New York Insurance group reported that only 18% of long-COVID patients had returned to work after a year. Some economists even believe that long COVID could be substantially contributing to the labor force issues and inflation problems we’ve been having. Bottom line – given long COVID’s very high economic costs we should be pouring more money into it.
- Akiko Iwasaki Ph.D. reported on her study (which Health Rising has already reported on). Her findings, and those from Henrich and company, match up well with both studies finding evidence of Epstein-Barr virus reactivation, problems with antibody production, a strangely enhanced allergy or Th2 response, and no evidence of autoimmunity. Bottom line – high-profile studies are getting similar results.
- Michael VanElzakker Ph.D. – reported on the many places in the body the coronavirus has been found. A recent long-COVID gut study made it clear that a coronavirus reservoir must be present. Bottom line – it looks like the coronavirus is persisting in long COVID. The question is what impact it’s having.
- Walter Koroshetz MD – RECOVER Initiative enrollments are up and should finish up this year. Bottom line – at almost the halfway point in its funding, now would be a good time for the RECOVER Initiative to start showing some results.
- Axcella’s amino acid-based metabolic regulator may be getting some good results. The company reported they found “highly statistically meaningful and clinically significant improvements in fatigue” in about 70% of individuals in just 4 weeks. Bottom line – the early results are good and this company is looking for funding.
- Tonix – is using fibromyalgia endpoints to test its fibromyalgia sleep and pain drug in people with long COVID – about 70% of whom meet the criteria for FM. Bottom line – it’s about time the fibro/long-COVID connection got some play.
- Christopher Austin – a long-time director of the NIH’s treatment translation branch and a drug company executive asserted that long COVID shows we need a new approach to drug development – one focused on finding the mechanistic pathways behind symptoms and treating them. He believes drug development costs and timeframes would be reduced dramatically and called for a Warp Speed approach to drug development in long COVID. Bottom line – Austin believes it could happen if the government stepped forward.
TONIX
Tonix has been testing its sleep and pain drug, TNX-102, in fibromyalgia (FM) for several years, but it, too, is moving into long COVID. Why the FM-Long COVID connection has gotten so little attention thus far is a mystery to me.
Seth Lederman, MD, Co-Founder, CEO & Chairman, Tonix Pharmaceuticals X, reported that back in Aug. 2020, FM researcher Daniel Clauw predicted that an epidemic of chronic pain would follow the COVID-19 pandemic. Clauw turned out to be correct: while it’s gone virtually unnoticed, the kind of pain found in FM – central sensitization or nociplastic pain – has been reported found in 70% of long-COVID patients.
Hence Tonix’s decision to not just take on long COVID but to do so using the endpoints they’re using in their fibromyalgia trial; i.e. they’re treating fibromyalgia-like long-COVID patients like FM patients. Maybe a successful clinical is what’s needed to wake the world up to the long-COVID/fibromyalgia connection.
Unlike Axcella and Ampligen, which are apparently still looking for funding, Tonix has the funds to carry out a long-COVID trial and is currently enrolling long-COVID patients.
Bottom Line – a fibromyalgia drug company takes on long COVID.
Christopher Austin
“traditional drug development paradigm just doesn’t work”
The webinar question, “Long COVID: What Will It Take to Accelerate Therapeutic Progress?”, really didn’t get answered directly until the last section of the program when Christopher Austin stepped in – but what an answer he had.
Christopher Austin, MD, CEO-Partner, Flagship Pioneering – I don’t know how Solve M.E. dug up Christopher Austin but he was quite a find. Austin has a resume that suggests he must be listened to. Besides his post-doctoral genetics work, he’s had high-level jobs at drug companies and the NIH.
Among others, Austin was the first director of the National Center for Advancing Translational Sciences (NCATS) – a branch of the NIH focused on translating research into treatments. Upon leaving NCATS after ten years, NIH director Francis Collins called Austin an “innovator, a collaborator, a problem solver, and a challenger of the status quo”. He’s currently the CEO/Partner of Flagship Pioneering and Vesalius Therapeutics – an artificial intelligence-driven pharmaceutical company. Austin, then, knows the intersection between the drug development process and federal agencies like the NIH like no one else.
He didn’t mince words, stating that the “traditional drug development paradigm just doesn’t work”. For one thing, it focuses on a disease diagnosis and a diagnosis is not the same thing as a disease. Talk about turning things on their head – clinical trials are all about diagnosed diseases, but Austin believes we should throw that approach out and focus instead on symptom presentation.
Vesalius – the company Austin is now running – is focused on “common diseases” – chronic diseases that affect millions of people but which are unattractive to the drug industry. Long COVID is just the latest of them to pop up.
The classic traditional drug development paradigm just doesn’t work for them. It always starts with a diagnosis – but a diagnosis is not the same thing as a disease. Austin asserted that we have to throw out conventional wisdom and focus on what the patients actually have – their symptoms. Matching the symptoms to the mechanisms in the body that cause them (instead of focusing on X disease) is the key. By doing this, he believes we could drastically cut down the drug development phase from the current 12-15 years to a couple of years.
How to do this in long COVID? He thinks that Operation Warp Speed to develop vaccines at the NIH is a model. COVID, of course, was an all-hands-on-deck experience for everyone involved and ample funding was available. That’s not so with long COVID, but important aspects of Operation Warp Speed simply required collaboration; collaboration between the FDA, between the different 27 Institutes of the NIH, and dozens of companies.
That kind of collaborative network hasn’t shown up yet in long COVID, but federal agencies can send an absolutely pivotal message to the private sector regarding which areas to invest in. If the pathway is not clear, private industry will not engage.
Because we know the onset of long COVID, he believes it provides a unique opportunity that will benefit many, many other diseases.
Bottom Line – an NIH and industry expert asserts that an approach to drug development that focuses on the symptoms and mechanisms behind them could cut drug development times dramatically. A Warp Speed-like approach to developing long COVID treatments from the federal government that fosters collaboration can and should be done.
Thank you. The more structured Gist is helpful
Good! 🙂
Thank you! I’m bedridden, receive no disability benefits and not old enough to collect SS which isn’t enough anyway. Luckily my investment income is enough to cover my living cost. As an investor I’ve been puzzled by why there’s been a labor shortage. If Long COVID is the true reason for it, that would be an important insight to economy and stocks and bonds markets.
I would think it would really make lawmakers think – we’ve got to get on top of this. I hope your investments are hanging in there – it’s a been a rough year…
I recently read that there are potentially up to 19 million people who have been infected with Covid who haven’t returned to work.
Dear Kevin J.,
My heart is going out to you for being bedridden now and I wish you all the best!
My brain can’t get it that you could not see, even as a patient yourself, the connection with labor shortage, especially as an investor. And you are certainly not alone in that.
I watch CNN a lot, in the Netherlands, and I heard it only mention once or twice. It’s always put on early retirement or child- or family care.
As 30+ ME/CFS myself I have a learning problem, text to brain needs 20 times of reading. My thinking is not affected as is my intelligence. Is it like that in Long COVID too?
If your thinking still works can you try and find an answer to the question why it is nationwide ignored in the US that Long COVID patients can’t work (as much)?
I do hope my question is not offensive. I’m really interested in reading your thoughts and insights on finding an answer to the collective and selective ignoring of all Long COVID patients as if they were all just elderly and not working people before they got the disease.
hi Cort,
i can now not read. but will certainly do.
of topic, whati wanted to ask…a time ago i searched on the searchbar the recovery from someon with creatine and i thought folic acid. but could not find it. Please can you help? thanks!!!
You may be referring to following article. I am actually a patient of Dr Ambrus (after reading this article – thanks Cort!) and am undergoing treatment… we will see if anything comes of it!
https://www.healthrising.org/blog/2022/03/16/mitochondrial-abnormalities-fibromyalgia-diet-long-chain-fatty-acid/
Good to hear! Please let us know how it goes 🙂
thanks so much and yes it is the article Ryan M !!! but the tests the women got, i live in Belgium, mostly bedbound (98%). i will never get. or they do not excist here or no interest from specialists or knowledge of ME. Just because it is here still only cfs, get and cbt not ME/cfs, My gp would certainly not be able to do the tests at my bed. But i print it in case of… I really wish you so much luck and that you might get cured!!! please, let us know…
May i ask, do you have FM or ME/cfs or both or long covid? the women described had FM. I do not know if i have that, in ’94 diagnosed here with cfs, got get and cbt, (you know the drill), and declined dramaticly. so no more follow up… I really really wish you luck!!! no matter what you have… i guess my option is only to follow the supplements the women took..
I have post viral ME/CFS (EBV). I was previously able to use D-ribose, creatine, carnitine, NAC and methyl folate to great effect, but after coming down with Coxsackie B I am now unable to tolerate them for some reason.
Dr Ambrus diagnosed me with Myoadenylate deaminase deficiency, which would explain why d-ribose was effective for me. That appears to only be one piece of the puzzle however.
You may find some additional clues here:
https://irispublishers.com/arar/pdf/ARAR.MS.ID.000505.pdf
For what it is worth…. Based on my genetic makeup, Dr Ambrus recommended the following:
CoQ10
Creatine
Carnitine
NAC
Folic acid (I use methyl folate)
Glutamine
I am struggling to tolerate them, but am still in the process of working through different types of each, quantity, time of day, etc, etc
I am so sorry you where better and then got Coxsackie B!!! I looked up Myoadenylate deaminase deficiency and here it seems to be a rare desease. I really hope for you, the supplements you get now, even struggling to take them and trying to find when and the quantity to take, etc is hard and you are struggling to tolerate them, you find a way to build op or something else that is missing to tolerate them and get well again!!! thanks for the links, the info and effort!!! I really hope you are in good hands with Dr Ambrus! does he say something, has a clue why you tolerate them so badly? I can now not read the link you put there but searched it my own.
https://www.mda.org/disease/metabolic-myopathies/types/myoadenylate-deaminase-deficiency
I really hope for you in the near future for: development of enzyme replacement therapies; and
development of gene therapies. So no supplements needed. how where you in fact diagnosed with Myoadenylate deaminase deficiency? it is like searching after a needle in a haystack they would say here…
I love Christopher Austin’s way of thinking about treating symptoms and not a disease!
Question – I thought science had moved beyond a binary TH1/TH2 concept? I thought it’s much more complex? Ie. Aspects of both can be downregulated and up regulated.
TH1/TH2 is soooooo 2005, lol
I don’t know. You probably know more about this than me and I’m sure it is very complex and I haven’t heard anything about a Th2 shift in ME/CFS for quite a while. The presenters did not present Th2 as a binary issue, though – they reported there was a shift towards Th2 activity in the immune system.
Judging from recent papers the shift is still getting studied.
https://pubmed.ncbi.nlm.nih.gov/35416072/
The key pillars of AIT-induced tolerance include a shift from Th2 to Th1 response, an increase of regulatory T and B cells, pro-inflammatory effector cell downregulation and IgE suppression, in addition to IgG4, IgA and IgD induction.
https://pregmune.com/blog/th1-th2-inflammation-pregnancy-research/
The ratio of Th1 to Th2 can help determine a patient’s inflammation levels.
https://www.nature.com/articles/s41598-022-20515-x
Moreover, to better discriminate the pre-existing pro-inflammatory immune response, already described in patients with atherosclerotic disease, from the secondary response to ischemic damage18,19, we decided to evaluate the Th1/Th2 balance by comparing patients with atherothrombotic stroke compared to patients with cardioembolic stroke.
https://pubmed.ncbi.nlm.nih.gov/34261335/
Furthermore, as demonstrated in cutaneous T cell lymphoma, advanced disease is characterized by Th1 to Th2 switch allowing cancer progression and immunosuppression.
That’s a good way of putting it. A bias towards T2. But it’s only a bias, rather than a ‘T2 switch on, T1 switch off’ phenomenon.
Two comments:
1
AXA1125 contains NAC plus a few amino acids. My hunch would be that NAC alone works just as well (and probably better in higher doses). A therapeutic effect of NAC (=pro-drug of glutathione) is plausible given Dikoma Shungu´s findings of reduced glutathione levels in the brain. NAC alone is currently being trialled with dosing up to 3600 mg/day (which i think is reasonable): https://clinicaltrials.gov/ct2/show/NCT04542161
2
we cannot wait for the traditional process of compound/drug development to find one or two drugs in 10 years or so. There is now a critical mass of well-connected expert patients with access to approved medications (and even to the compound pipeline). For any compound or market drug currently being discussed or registered for a LongCovid trial, you can bet that there is already some experience out there – possibly even solid enough to give a thumbs up or thumbs down vote. My prediction: if a game changer was to be found – it will be found by this growing self hack community.
Again: classic drug trials will play a role, but in the year 2023 we should have means to select candidates more effectively than organizing million $ phase II trials and then find out they either don´t work or have marginal benefit (imho, often enough the results would be quite predictably by skimming Twitter with an appropriate AI)
Great ideas, thanks for sharing!!
Keep them coming.
Thanks for mentioning NAC and the trial. Seems a bit unusual for the NAC study which is a “simple” 4 week study to take 5 years. Do you know if any results have been made public?
Thanks for the reminder about NAC – it’s also being used in combination with Guanfacine and the Shungu trial with its higher doses is fascinating. It’s the only NIH funded ME/CFS clinical trial, I believe.
https://www.healthrising.org/blog/2021/09/09/mitochondrial-enhancers-chronic-fatigue-fibromyalgia-nac-n-acetyl-cysteine/
AXA1125 is as you say just some Amino Acids and NAC. You can actually find a formulation on amazon called Mutant (impressive red tub) that contains all the same ingredients +1 additional amino acid. Its obviously not the same magic ratio that AXA is using the same components.
It also didn’t do anything for me. When AXA tested this earlier on fatty liver the results were pretty underwhelming so I don’t anticipate much from this.
I don’t have the study results but this is Axsella reported:
The company reported they found “highly statistically meaningful and clinically significant improvements in fatigue” in about 70% of individuals in just 4 weeks. They also found evidence of significant mitochondrial dysfunction that improved with the product. They even think they may have found a mitochondrial biomarker. Their studies show, they said, that something has gone seriously wrong with the long-COVID patients’ biology.
I tried signing up for the RECOVER study, but it was like a circus of miscommunication and dropped communication. I ended up telling them forget it; if the significant lack of coordination is happening like this in the early phases, what’s going to happen when I summon the energy (and my partner takes time off from work) to travel an hour into NYC only to have them tell me they got the date wrong or something like that? It was seeming to stressful and you all know that’s the last thing we need. Also, there was no stipend for travel.
RECOVER really does seem to be repeating all the errors of the past. The way its requiring repeated visits over often long distances for pointless appointments with terrible organisation ensures only those with mild condition will be able to participate. They really seem to have learnt very little about how to deal with PEM sufferers in decades.
In no other disease would you use a system that selected those with the least disease.
Who will pay (for research)? How much money can be made (with a treatment)? How can we separate those with the disease (ICD Code) from those who do not do not fit the criteria (cheaters)? Why are the healthy ones (taxes and entitlements) having to support those who are sick and cannot pay? (resentment) Who will be chosen (financed) for research? (the power brokers) How can a new treatment be protected so the developers make most of the profits? (secrecy and Copyright) How can all those down the pipeline (insurance companies) receive their ‘cut of the pie’? And off we go…
Capitalism, greed, politics…
This isn’t a rant about a particular political system, but I think so much of the difficulties of getting to the bottom of ME/CFS or Long Covid are bound up in the System. We do need an overhaul.
Hello. I found you through a convoluted path. I do not know whether I have long covid, CFS/ME, or just Vit B12 deficiency. I was a vibrant and athletic person (long distance runner and still trying here and there) before catching some virus in Dec of 2021. I never tested positive for covid back then, and haven’t since then. I’ve been sick more times than I can count since then, with mild viruses. I stopped testing for covid because I think the tests are bogus. Anyway, I have lately been really, really hoping that my case was “just” vit B12 deficiency. (I am a vegan who stopped taking B12 about one year ago bc I developed reflux and other gastro issues after the first round of the virus…and my B12 supplement was acidic…thinking this would only be temporary (stopping B12)…and I’ve only gotten worse despite following every recognized lifestyle and treatment protocol.)
Anyway, my question is about NAC. I first found your name by way of Reddit, which led me to the old Phoenix rising forum, where there is a protocol that says NAC reduces B12 or something along those lines. I’ve been trying to find a simple B12 replenishment protocol. I have also been taking NAC (recently added Zinc + Copper bc I guess NAC can reduce those).
Now above someone is saying that NAC might be helpful? As those were old posts, could you please tell me what is the latest thinking on NAC — good or bad for those who are known to be Vit B12 deficient? Also, do you have any link to any updated online protocol for the best way to replenish B12? In my particular case, PEM symptoms pretty clearly correlate with worsening / less and less B12 (also I had surgery and dental work before catching this virus…which I guess can reduce B12 levels…and I was probably already low as I never could take as much B12 as I wanted).
I wonder whether vitamin deficiencies and especially B12 play a role in long covid? I had what I thought was an otherwise very healthy diet (whole food, plant based). But I didn’t have enough Vit B12, and I’ve only gotten worse and worse, I’m wondering now if from not taking it. (Last point: I knew that I needed B12; I just hoped / believed that not taking the supp would be temporary, and figured my liver had stores for a couple of years at least. Very stupid decision obviously.) Also– now that I’ve started B12, I have vascillated from dancing in my car because symptoms were GONE to devastatingly worse, on a daily basis. Of course I just started this past Sunday. LOL. But I had been consistently just on a slow decline. Now I’m up and down like all over the place. Searching for answers…!
Sorry anyway…what are your thoughts on the impact of NAC on Vit B12 deficiency? And do you have any online resource for updated info on Vit B12 supplementation and cofactor protocols (similar to what was on Phoenix Rising)? Or do you think the protocol listed there is still pretty good?
Thanks very much!! I subscribed and am looking forward to updates.
Sometimes it seems people have just heard about Long Covid’s economic impact (it’s so OBVIOUS and so HUGE), or about the fact that if we didn’t know what caused it, they’d all be diagnosed (assuming they were lucky enough to get diagnosed) with ME/CFS and/or FM – again, obvious and huge.
What do these ‘scientists’ do all the time? Ignore things? It’s pathetic.
In the magnetic fusion department, we always celebrated other people’s wins, looked to what might be usable for us from inertial confinement and even cold fusion. We examined the claims, allowed for the state of research, supported the other labs…
I don’t understand the attitude. As I don’t understand a ‘doctor’ seeing a patient with symptoms and telling them it’s all in their head, because somehow this patient has absorbed a world-wide conspiracy, is mimicking other sick patients exactly, and must be getting something out of it. From Argentina to Zaire.
Real scientists in the future will look back at this period as we look back at the NOT very distant period when the AIDS epidemic was killing people.
Alicia, this is EXACTLY what I was thinking. Your words are much more eloquent than mine, though.
Thanks! I’ve turned all those years of rage into a novel trilogy with a Main Character who has ME/CFS, on Amazon in ebook and print (search under my full name if you read mainstream fiction and are interested); the first two volumes took me 15 and 7 years, respectively, and have won awards; I’m working on the last, hoping it will be a little faster!
Being a novelist now gives me a bit of facility with words.
(…)Real scientists in the future will look back at this period as we look back at the NOT very distant period when the AIDS epidemic was killing people(…).
What do you mean with real scientists? Who are those people? The XMRV, CBT or GET saga? The mRNA vaccin promoters? Which you believed in because everyone who did not get a jab and have long covid now do not deserve any sympathy according to you earlier post.
It is the same as real scientists tell you that you don’t whan’t to get better because you refuse CBT or GET. The scientists you hate so much. Why do you deserve any sympathy from those real scientists the?
Sounds ironic to me.
Apologies for upsetting you. ‘Real scientists’ in the future will be those who FIND the solution to ME/CFS, FM, Lyme disease – and produce a cure or treatment. they won’t be promoting their own pet hypotheses, and trying to fit that to our illness. We will get better – or live better with these diseases, as people with AIDS can now lead an almost-normal life with the meds which suppress HIV so well that it can’t be detected – and for whom AIDS will no longer be a death sentence.
They won’t be like the physicians and scientists who insisted stomach ulcers were caused by acid reflux or some such theory, and more like Dr. Barry Marshall, who proved most cases are caused by H. pylori, and can be CURED by the appropriate antibiotic.
They won’t be promoting exercise for things which have vaccines which work.
We will be past the mystery stage which has bedeviled 33 years of my life, and longer in others’ lives – and at a stage where we can be healthy again.
If you mean the mRNA vaccines which have saved countless lives from covid, those are functioning very well, though a preventive vaccine would be better and more permanent.
You’re an erudite lady. I agree what you’re saying.
ME/CFS/POTS/FM/Lyme will be a major medical scandal in our history.
Insurance companies are fine with that. They don’t want to pay benefits.
The fact that our disease has been seen as a psychosomatic illness we owe that to the Wessely school.
I agree that the classic vaccines has brought many good things. But mRNA vaccines against COVID also have many serious side effects. Such as myocarditis in young men. While these young men almost never become seriously ill from COVID. The same applies to young children. I think it’s a medical scandal too.
Especially because they know exactly who the risk groups are ie elderly and obese people. Give those groups and everybody who wants it the vaccine but not en masse. The effectiveness is low and it does not stop the transferability.
The pharmaceutical companies make good money from it. Vaccines are business. I wouldn’t be too naive about that.
If all data on mRNA vaccines were transparent and judged by independent experts, I’m afraid people would be shocked.
But we don’t have to agree completely.
The most important thing is that we get better and will know what the cause of ME/CFS/POTS is in our lifetime.
Although I don’t think the medical community will ever make apologies to our community.
Best Wishes
About covid and autoimmunity, pubmed searches does reveal more papers linking covid and autoimmune thyroiditis
https://pubmed.ncbi.nlm.nih.gov/?term=Covid+autoimmune
https://pubmed.ncbi.nlm.nih.gov/?term=Covid+autoimmune+thyroiditis
=>
A review published May-June 22
Systematic review of COVID-19 and autoimmune thyroiditis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8930178/
“Current data suggest that COVID-19 may cause autoimmune thyroid disease or exacerbate the underlying thyroid disease in remission.”
I got covid-19 (PCR and antigen test positive, as did my husband too, despite he had got 3 mRNA covid vaccinations) i February 22, and I had to contact my GP due to worsening in my ME/CFS (developed post Lyme borreliosis+more coinfections), I especially suffer from neuropathic pains in feet (especially right leg, where borrelia radikulitis hit me back in 1996, also worsening fatigue
– and in June 22, I was diagnosed with hypothyreosis and positive anti-TPO antibodies, i.e. Hashimoto thyroiditis, which also runs in my close family (sister and daughter).
Autoimmune thyroiditis is associated with some HLA-DR subtypes, as is other autoimmune diseases, and CIRS (Chronic Inflammatory Response Syndrome), where the GENIE (Genomic Expression Inflammation Explained) test panel apparently show hypometabolism
https://www.progenedx.com/genie-surviving-mold
I wish I could get that test done!
Speaking of RECOVER, it appears a ME/CFS comparative group has been approved to be incorporated in this initiative, per the recent Newswise feature (3/1/2023) with Dr. Leonard Jason, if I’m reading this correctly:
“He is a vocal advocate and serves on the diagnostics committee of the NIH’s RECOVER initiative, which is studying more than 17,000 people to learn about the long-term effects of COVID-19. Recently, Jason won NIH’s support to include an ME/CFS group as part of the work.”
https://www.newswise.com/coronavirus/researcher-leonard-a-jason-pushes-discovery-on-long-covid-mecfs/?article_id=787890
I saw that OMF shared this development as well: https://twitter.com/OpenMedF/status/1631308894545870849
Do you know any details about this, Cort?
I thought the video that’s included above was fascinating. I was looking for the other speakers and I found that the talk has been divided into three parts. Here’s Part Two, if it works…
https://youtu.be/PER-oJ5PhlU
And Part Three…
https://youtu.be/10NNIS12g4E
Incredible summary, as always, Cory. I REALLY appreciate all you do!
Thanks!