Long-time ME/CFS expert Dr. Klimas is a co-author on the paper.
Every now and then my mouth gapes open with I read a paper. While the limitations of this paper must be noted – a small sample set involving three case reports – its conclusion – a very rapid return to health of people with severe long-term COVID – makes one sit up in one’s seat. Time, of course, will tell how this will all turn out
Oddly enough, the paper is heavy with authors who specialize in emergency medicine and rescue. They hail from the Florida and Texas Depts of Health Dept of Health, the Pebble Beach Fire Rescue, the Department of Emergency Medicine at an Oregon University, and an emergency management software company. But then there’s also Nancy Klimas (!) from the Institute of Neuroimmune Studies and the Veterans Administration to give us some comfort that all was done above board. (All, except for one author, were MD’s and PhD’s.)
God knows how they all got together but they were clearly determined to get the word out and so they did in a Journal they were apparently familiar with – the American Journal of Emergency Medicine (:)). Long COVID treatment papers are probably not common fare in that journal but it’s fitting in a way. With millions looking for answers, long COVID and its related diseases really ought to be on emergency status.
Three Severely Ill Long Patients – Three (VERY) Rapid Recoveries
The paper “Remission of severe forms of long COVID following monoclonal antibody (MCA) infusions: A report of signal index cases and call for targeted research” doesn’t say who these people but one suspects that the three “previously healthy, middle-aged, highly-functioning persons” were all involved with the emergency rescue departments.
Unexpected Recoveries
Everyone – the doctors, the patients, and their families were shocked by their response.
Noting the lack of satisfactory treatments for long COVID, they offered up what they called their “compelling” observations of three patients in this paper.
Interestingly, no one expected the patients to get well – the treatment – a monoclonal antibody called casirivimab/imdevimab antibody cocktail (Regeneron™) – was simply done in an attempt to keep them from getting worse. The treatment was called “incidental” and “serendipitous” ; i.e. it appears to have been a shot in the dark.
The authors went to great lengths to make it clear that the placebo response could not have been involved. They stated that all three of the patients “had already come to terms that their respective diseases were likely untreatable and permanent conditions”. Nobody, not the “medical personnel, the patients, nor their families had anticipated improvements, let alone complete remissions.”
They are apparently not the only ones to respond either. The authors stated that the first three cases in which this drug was tried were published in order “to remain concise” but that they were only the first “among many others”; i.e. this drug has worked in others.
These were not mild cases of long COVID. All occurred prior to any of them being vaccinated.
Patient #1
Even mild exertion (climbing stairs or walking) caused severe fatigue in one formerly healthy 60-year-old woman. Along with that, she experienced “chest discomfort”, joint pain, shortness of breath, numbness and tingling, sleep issues, brain fog (difficulties reading, and performing simple math calculations), “nerve pain feeling like bee stings”, and frequent nightmares. All these symptoms were new to her. A Pfizer vaccination did not help.
Approximately a year after becoming ill she received the casirivimab/imdevimab antibody cocktail (Regeneron™). Within 4-5 days all her long COVID symptoms dissipated completely. Two years later she remains in good health.
Patient #2
A 43-year-old woman came down with COVID-19 in early 2021. After getting over that she developed severe fatigue, extremely poor exercise intolerance, severe muscle and joint aches, dyspnea, palpitations, dizziness while sitting and standing, and “profound difficulty” concentrating and remembering. She also experienced headaches, sensory symptoms, vivid dreams, and some alterations in taste and smell. A later Pfizer vaccination produced only some mild relief.
In September 2021, testing positive for COVID-19 she received the casirivimab/imdevimab As with the first patient all her COVID symptoms disappeared entirely within five days.
Despite getting infected with COVID again in the summer of 2022, she remains in normal health 2 years later.
Patient #3
The 3rd person was not in such good health. He was overweight and had type II diabetes but was a highly functional individual in good health with good exercise tolerance – until he met up with the coronavirus. After getting over the initial infection his health plummeted and he experienced severe fatigue, extremely poor exercise tolerance, severe muscle aches, dizziness upon standing, brain fog, etc..
Five months after his long COVID onset, he met up with the coronavirus again. This time doctors gave him the casirivimab/imdevimab MCA cocktail. Once again all his long COVID symptoms disappeared within a week and he remains completely healthy two years later.
Warning – The authors warned that because the antibody mixture was developed prior to the development of some of the coronavirus variants it’s not clear that it will work as well with those who have those variants. (Indeed, the casirivimab plus imdevimab infusions proved to be ineffective against the omicron variant and are no longer used today.) Since then other MCA products have, however, been produced, and the authors reported that “they have become aware of other MCA products having similar positive effects in long COVID patients who likely were infected with the more recent SARS-CoV-2 variants”.
Most importantly for many of us, though, they stated “ these cases also provide mechanistic implications for treating/managing other post-viral chronic conditions.”; i.e. they provide a possible template for treating other postviral diseases.
Treatment Assessment
Using Arseneau’s assessment categories (credibility of the source/quality of the evidence/benefit-cost-risk) for determining whether or not to try a treatment we can say that with Dr. Klimas involved – the source has very high quality. The quality of the evidence – three case reports – is not high; i.e. it’s all anecdotal case reports which do not substitute for a placebo-controlled, randomized study, and, if you can get these drugs – and you probably can’t – the potential benefit is VERY high, the risk is probably more or less moderate, and I don’t know what the cost is but it’s probably quite high.
With only one of the criteria being met (excellent source) – monoclonal antibodies are a wait-and-see type treatment.
THE GIST
- This paper came from an obscure journal but boy was it exciting. While its limitations must be noted – a small sample set involving three case reports – its conclusion – a very rapid return to health of people with severe long-term COVID – makes one sit up in one’s seat.
- Nancy Klimas and others reported how shocked they were when a drug that they hoped might at best arrest a further drop in health in three long-term severely ill long COVID patients quickly returned them to health. Two had been ill with severe exercise intolerance and the rest for over two years. Within a week they were back exercising and have remained healthy since then.
- The drug used was casirivimab/imdevimab duo monoclonal antibody infusion. This drug was designed to neutralize the coronavirus by attaching itself to the spike protein the virus uses to enter the cell. The drug is actually no longer in use as it was not effective against later coronavirus variants but the authors reported that they know of more advance monoclonal antibody drugs which have had the same effect.
- The author proposed that the drug was either neutralizing whatever virus was left in the body, displacing detrimental autoantibodies, and/or enhancing the immune response.
- The authors didn’t speculate how a similar drug therapy might play out in diseases like ME/CFS, but ME/CFS was referred to throughout the paper. More to the point, they stated that “these cases also provide mechanistic implications for treating/managing other post-viral chronic conditions.” They also suggested that the drug could be helping to wipe out reservoirs of the Epstein-Barr virus (EBV) in the body.
- Finally, they noted the growing evidence that a “chronic, insidious infection” is present not just in long COVID but in people exposed to other ACE2-binding viruses. (ACE2 is the receptor through which the coronavirus enters cells and ACE2 dysregulation has been found in ME/CFS as well.)
- While the authors don’t mention it, the fact that a different coronavirus – one that causes the common cold but which can send people to the hospital – also enters cells through the ACE2 virus suggests it could conceivably be causing the ACE2 dysregulation in ME/CFS – and helping to trigger the disease.
- While the authors don’t mention it, the virus most commonly associated with ME/CFS
– the Epstein-Barr virus – also has a link to ACE2 dysregulation. Attempts to create a monoclonal antibody that attacks EBV are underway. - Noting the “compelling” results and the severe impact long COVID has on patients and families the authors proposed that at a minimum a prospective observational study employing a “very large series of volunteer patients with severe long COVID” get underway. (One small study at UCSF is underway.)
- The ability of this treatment to quickly return 3 severely ill long COVID to health (and the authors hinted they knew of more) was stunning. Time will tell, though, whether MAB therapy is kind of a one-hit wonder or if provides something more fundamental.
The Drug
The casirivimab/imdevimab duo monoclonal antibody (600 mg/600 mg) MCA infusion used was developed specifically to treat COVID-19. The antibody is designed to neutralize the coronavirus by attaching itself to the spike protein the virus uses to enter the cell. Laboratory studies indicated that each antibody was extremely effective (≥ 95%) at blocking the spike protein RBD from binding to the ACE2 receptor the virus uses to enter the cell.
It received emergency authorization to help prevent COVID-19 in at-risk patients in the US in Nov. 2020 and later in Canada, the EU, Japan, and the UK. It’s usually given in a single dose but can be given in subsequent doses to people who require further prevention.
Several different versions of the MCA infusion exist including a later one focused on more recent variants
Possible Pathways to Recovery
The authors hypothesized four ways the antibody infusion could be helping:
- Neutralization – The antibody infusion neutralized; e.g. stopped whatever coronavirus remained from replicating. Once the remaining coronavirus was fully eradicated the patient’s immune systems were able to return to homeostasis and they were well again.
- Displacement – The antibody infusion displaced auto-antibodies attached to Fc receptors that help drive B-cell response. Once those auto-antibodies were no longer able to turn on the immune response, the patients returned to health. Note that if #1 or #2 are occurring, IVIG becomes a possibility and the authors specifically mentioned ME/CFS in this regard.
- Enhancement – The monoclonal antibodies enhanced the immune response by attaching to sites (CD16) that activate the cytotoxic immune response – and thus were able to eliminate leftover viral particles or virus-infected cells, including, interestingly, viruses such as EBV.
- Combination – Any combination of any of these elements.
Ramifications for other Postviral Syndromes
Nancy Klimas’ influence (she was involved with the “conceptualization, methodology, resources, writing – review & editing” of the paper).is clear in the lengths the authors went to to associate long COVID with chronic fatigue syndrome (ME/CFS). Links to inflammation, autoimmunity, herpesvirus reactivation, brain fog, POTS, and endothelial (blood vessel) issues in both diseases are given.
Likewise, the first appendix proposes that the fatigue-dominated form of long COVID found in these case is analogous to ME/CFS cases featuring reactivated herpesviruses (cytomegalovirus (CMV), EBV, herpes type 6, herpes zoster). They propose that a low-grade endothelial (blood vessel) dysfunction in concert with a maladaptive immune response (involving INF-γ, CCL4, MIP-1 beta, or IL-6 or IL-10) may be causing widespread and severe mitochondrial dysfunction.
Other than stating that “these cases also provide mechanistic implications for treating/managing other post-viral chronic conditions.” and suggesting that the monoclonal antibodies could be helping to wipe out Epstein-Barr virus (EBV) reservoirs, the authors don’t speculate, however, about how this therapy could help diseases like ME/CFS, POTS, post-treatment Lyme disease and others.
The idea, though, that viral/bacterial remnants in hard-to-access reservoirs may be causing diseases like ME/CFS goes way back, however, and the authors specifically referred to EBV in conjunction with this idea. They proposed that these monoclonal antibody infusions may be able to reach places (gut, brain, prostate, eye) that the immune system (and antivirals) have trouble getting at.
If they are right then what may be needed in other post-viral disorders is to find a way to finally clear the initial infection. The good news is that a concerted effort is underway to assess the role viral reservoirs in the body may be contributing to long COVID.
Could a Common Coronavirus Cold Virus be Causing ME/CFS?
Finally, they noted the growing evidence that a “chronic, insidious infection” is present not just in long COVID but in people exposed to other ACE2-binding viruses.
The ACE2 receptor is so interesting because small ME/CFS and POTS studies have implicated it in those diseases as well. It was initially linked to the RAAS paradox and low blood volume in ME/CFS and POTS but it could be linked to increased sympathetic nervous system activation, blood vessel narrowing (vasoconstriction), inflammation, and oxidative stress.
Having ACE2 dysregulation show up in these three diseases has been bizarre, to say the least. Understanding its connection to long COVID is easy – the coronavirus enters cells through this receptor. How to explain its appearance in ME/CFS and POTS – two diseases that showed up long before the SARS-CoV-2 coronavirus appeared on the scene?
Could the other human coronavirus that enters cells through the ACE2 receptor be triggering some cases of ME/CFS and POTS?
There is a way. It turns out that another coronavirus – the human coronavirus NL63 (HCoV-NL63) also enters cells through the ACE2 receptor. This virus was first identified in 2004 but is believed to have been circulating in humans for centuries. It’s a common respiratory virus; i.e. a cold virus that has been found worldwide – meaning that many of us may be been exposed to it.
Symptoms are usually mild but can put people into intensive care and it “provokes an eerily similar immune response to the SAR-CoV-2 coronavirus that causes long COVID. One wonders whether this common cold virus could be triggering ME/CFS and POTS (and dysregulating ACE2) in some people as well?
Monoclonal Antibodies Against EBV?
Or could EBV be the link between long COVID and ME/CFS? EBV does not enter cells through the ACE2 receptor but in a rather remarkable coincidence, it does impact that receptor. When EBV replicates it turns on the ACE2 enzyme which then facilitates entry of the coronavirus into the cell. Plus an ACE2 promoter also turns on EBV and helps it wake up from latency. EBV, then, enhances coronavirus infections and the coronavirus enhances EBV replication. It’s no wonder that the two have become closely linked.
Antibodies mucking up a virus.
If monoclonal antibodies directed against the coronavirus can help with long COVID what about monoclonal antibodies for EBV? Efforts to develop monoclonal antibodies against EBV are underway. Using X-ray crystallography and electron microscopy researchers recently uncovered “multiple sites of vulnerability” at the site where the virus attaches to cells that antibodies could attack. Mice studies suggested that a monoclonal antibody may be able to achieve “near complete” neutralization of the virus. This year another study used monoclonal antibodies to target a different part of EBV (glycoprotein 350 (gp350) on the EBV envelope).
Things are heating up in the EBV world. Recently a new high-throughput method that promises to better assess EBV antibodies and monoclonal antibodies was published and two new vaccine candidates, from the National Institutes of Health and Moderna, have entered or are about to enter clinical trials.
The authors suggested that the COVID-19 vaccines are at least somewhat preventative against long COVID either because they’re shifting the immune balance and displacing dysfunctional antibodies or they’re enhancing the ability of the immune system to clear the infection. If the coronavirus vaccines are able to shift the immune landscape and help prevent or ameliorate long COVID, could EBV vaccines help with ME/CFS as well?
Moving Forward
The rapid recoveries were compelling indeed. Given the antibody mixtures “relative therapeutic safety” the authors proposed that at a minimum a prospective observational study employing a “very large series of volunteer patients with severe long COVID” get underway and that a registry of persons receiving therapy be established. (Prospective studies do not involve randomization or placebo but simply follow patients over time.).
One small trial is already underway. Michael Peluso’s “OutSmart” trial at UCSF (n=30) will use the AER002 monoclonal antibody in long COVID patients infected by a specific coronavirus variant.
We need to be careful. We already have comments indicating that this approach did not in others. Everyone should be aware that small studies produced wonderful results with antivirals and Rituximab in ME/CFS which were later overturned by larger, more rigorous studies. There’s obviously some potential here but it needs to be assessed by better studies before we have any solid ground.
Urgent Need
In an appendix, the authors noted that “both patients and family members uniformly expressed that the disabilities had produced overwhelming, unremitting physical and psychological distress that affected work and family.” (No argument there!).
- Check out Health Rising’s Lives Interrupted program to get the many costs of these diseases.
The authors ended with this:
“With millions still debilitated by long COVID, this initiative should receive immediate attention, not only for the patients themselves, but also for the many millions of loved ones, employers, and healthcare professionals also impacted by long COVID.”
Health Rising’s End of the Year Drive Update!
Thanks for getting our year end drive off to a great start!
Thanks to the 50+ people who got Health Rising’s BIG (little) donation drive off to a great start!
This blog is a good example of what Health Rising does best. The paper comes from an obscure journal and its findings – which have great ramifications for long COVID and possibly other postviral diseases – have gotten very little attention. But not here. Health Rising quickly jumped on it (thanks Yvette!) and expanded on them. If that kind of focus appeals to you please support us.
;
Since access to this drug combo will be out of reach for most of us, I’m curious if you think that nicotine (which I believe also binds to ACE2) could be a viable alternative? I’ve been following #renegaderesearch and nicotine patches do seem to be helping people – nothing as stunning as what is reported in this study, but still quite a lot of clear improvement. I’m thinking of trying it and this study makes me more like to move forward.
I didn’t know that about nicotine and ACE2…Very interesting! I haven’t looked into it but a blog on the nicotine patch is coming up. 🙂
I’ve had good effect (more energy, brain working better, improved balance and walking distance increased. Greatly reduced PEM) from low dose nicotine patches.
In addition to the commonly proposed method of health improvement, it appears to me it may also be effected by activating AMPK, which tells the body to make energy.
Nicotine is a great AMPK activator.
Metformin is also an AMPK activator, as well as many other things. From my brief review of studies, it appears monoclonal antibodies also activate AMPK, but I’m no scientist.
Our common theme for years has been a lack of energy. Could be our AMPK was deactivated. Inflammation such as from infections and toxins can deactivate AMPK.
Laura – can you please describe in more detail how you use the patches? Dose? How long do you wear the patch, and how often?
Will try to paste a link to the info, which I would be doing you a disservice if I tried to put it in my own words.
If this fails, you can access it through Facebook at Renegade Research the Nicotine Test
https://linktr.ee/thenicotinetest?utm_source=linktree_profile_share<sid=44884da7-fe75-4193-9d2f-f2141d902249
Thank you! All that info is dauntingly complex – I’m really looking forward to Cort’s promised blog on nicotine!
Please disregard my question above! I wish there was away to delete comment after posting
Does it cause nicotine addiction?
Diana, I believe the Renegade links discuss that pretty extensively. In the short term, patches do not seem to cause nicotine addiction.
Laura, what dose nicotine patch do you take?
The Renegade folks talk a bit about how nicotine binds to ACE2, I know I read a paper on it. And vaping nicotine has helped me personally a great deal this past year; I only stopped because a) my asthmatic lungs were getting a bit irritated and then b) I learned about exploitative mineral mining in Congo using children, to make vape batteries. So no more buying any disposable vapes! And with ME, dealing with the rechargeable one I already had is too much trouble.
Nicotine patches are very expensive in Germany, so now I just tactically smoke a cigarette when I need strength. Whatever, I’ll be 57 soon, I’m already past our average lifespan. But my husband is going to the US soon and I’ll have him bring patches back!
Cort I’m sorry these comments seem to be taking over.
I thought by posting the link to the info, that would be enough.
I can’t possibly keep up with all the comments, haven’t done this before:
I believe this is why the experts were saying smojers were less likely to contract Covid.
Nicotine patch is cheap ($20 for 30 patches from Amazon) and safe; you don’t have to wait for anything to try it. I don’t buy the receptor theory but I tried it anyway. And, boy, I was flush with energy for 2 days. My body quickly adapted as I expected though. So now I’m only using it tactically like I do with Sudafed . 3.5mg after 40 mi bike ride a few days ago seemed to have prevented PEM. It’s now another arsenal in my toolbox.
TK, so what are your thoughts on why Sudafed helps?
And 3.5 mg of nic patch? How much Sudafed do you take when you take and what are your strategies in using? In both cases, you wouldn’t take when you begin exercising?
Yep, I cut 7mg in half. My guess is that Sudafed works similarly. It’s a stimulant that forces the brain to produce dopamine. I started taking it in 2010 to relieve the head pressure and found it also helped fatigue and ache. Nicotine works better though. I use the patch one day then take Sudafed the next and then back to the patch after an exercise when I’m expecting PEM.
TK, can you email me? I’m at traceyellisfa@gmail.com.
Just to clarify, I slap on the patch the morning after the exercise, or the day I expect the PEM. PEM doesn’t set in till the afternoon, so that gives time for nicotine to kick in.
You found 3.5 mg patches? The lowest have found is 7 on Amazon. Maybe you cut in half?
Yes nicotine patches can work well. They work on multiple biological levels. Including, importantly for ME/CFS and long covid, preventing monocytes passing the BBB.
I have mentioned several times before about nicotine (curcumin is another thing I have had help from, and have mentioned).
it’s all coming down to neuroimmune factors
I posted this piece on nicotine and MS a couple of years ago, wasn’t much interest shown by anyone. It’s helped me a fair bit and it’s one reason why I am a huge believer in the neuroimmune theory on ME/CFS
https://mscanada.ca/ms-research/latest-research/ms-society-funded-study-shows-that-nicotine-reduces-the-invasion-of
thanks for sharing this
Thanks Matthias !
BTW do you have an email? Are you Dutch? My sister has MS, I’d like to ask you a few questions. Thanks again!
An MCA that targets remains of EBV – could it be that simple? EBV is implicated in a lot of our cases – no one ever offered me an antiviral for it.
I looked it up – there doesn’t appear to be one. I guess no one cared enough, and they all assumed humans could ALL handle EBV.
If this MCA works for long covid, maybe the right one would work for ME/CFS.
Just the kind of answer we’d love.
No kidding! It brings me back to Dr. Lerner’s antiviral treatment – they were very long and he felt they needed to be very long to get at EBV buried deeply in the body because the antivirals weren’t that good. We have some recovery stories from them.
I was put on an antivirals as soon as I was diagnosed and it definitely stabilized my decline. It helped but is not a cure.
Roger – specifically what antivirals were you on, and for how long?
Famciclovir 500mg. Started in April 2021 as soon as I was diagnosed and still on it. They say the sooner you take it the better, i was one year into ME when I started.
Thanks, Roger. What specifically was your diagnosis, and what virus(es) were involved? EBV? CMV? Covid?
My ME started in Nov 2019, so not COVID related. Besides usual CFS symptoms I had high tiers for ebv, cmv, HPV 6, low platelets, low pneumococcal and few others I can’t remember. Recently metformin has helped noticeably.
Roger, how does metformin help?
More energy, clarity, sleep and recovery. For instance, as long as I stay within my envelope I’ll get tired at the end of the day, but not fatigued. So next day I wake up recharged. My base line has improved 10 to 15%. My days are manageable instead of being a struggle. Not I’m not diabetic.
Thanks Roger? Does it help with PEM?
Yes. When I do get PEM it’s more like a headache rather than a migraine
I was put on a course of retroviral meds ( I think it was Paxlovid) after testing positive for COVID as I regularly take immunosuppresants for rheumatoid arthritis.
I felt fantastic while taking the retroviral. My brain fog went, I had energy. The changed was remarked upon by my family before I really recognized the change myself.
Now, a few months later and I’m back to the usual feeling knackered all the time.
Any thoughts?
My ME dr said that you have to keep pacing even after antivirals or else it will come back. I don’t know the science behind that but others on paxlovid have had the same reaction- completely better but then a relapse.
Another question is would MCA help people with FM or Gulf War Syndrome? I started taking TUDCA a couple of months ago for FM. It has been helpful, and I know it also has some anti-viral properties as well, likely on a much lower level than MCA. I had chicken pox and Hep A as a child, but not EBV to the best of my knowledge. The first couple of days I took TUDCA I developed a couple of cold sores on my lips. The reaction was surprising.
This is very interesting. I have been taking TUDCA for a few months now, and it has completely stopped my reactions and hives, but I was not aware of its antiviral properties. Unfortunately when i tried stopping it the symptoms returned, so i am not sure if it’s the antiviral efect or something else. The nicotine patches, on the other hand, only gave me insomnia and had almost no impact on the fatigue. Recently, I also started taking Floradix which is a combination of iron and B vitamins and have notices a definite increase in energy.
Fascinating possibilities. It appears Regeneron is still in development of an updated treatment and possible vaccine. I hope they stay in the game. EBV is certainly my issue, with Mild ME/CFS that went to Moderate ME/CFS after a run-in with COVID that triggered a serious EBV reactivation.
https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-agreement-barda-supporting-development-next
I volunteer!
🙂
I just sent an email asking if they’re still accepting study participants. It looks like they might be, from the study page. I sure would love to be involved if they are!!
Cort, I cried when I read this. I didn’t think I’d live long enough to hear about anything like this drug that appears to put very sick people into complete remission. After nearly 40 years dealing with ME/CFS/FM and then Covid when it first was reported on, at age 84 I would love to be able to vacuum my living room in one felt swoop instead of 3 or 4 stages with rest breaks. Thank you so much for sharing all this with us.
We shall see! My enthusiasm is tempered a bit by Brandon pointing out that people with long COVID tried it and it did not work out for them. So it may be that a certain subset reacts really well to this drug. Crossing my fingers for some bit, complete studies that can tease out those subsets.
Cort, As you know there will always be sceptics. But look at how well ampligen worked for a group of people. But it was just too expensive for average people to be included in any kind of study. But it helped. We need help. We can live without a total cure if we can get better – maybe not cured but better. We need the government to get on board and take this seriously so enough studies are done to tease out subsets. Sadly, that will take a miracle.
I’m one of the lucky ones diagnosed with moderate CFS decades ago by Dr. Lapp. But I never got better. However, Dr. Lapp had been trying a variety of treatments and they helped so that I could continue working until I retired at 55. I had to hire people to clean my house, etc. I would collapse after any effort to have people over for Christmas, etc. But at my current age who knows what causes the profound fatigue.
Cort, I am confused by your comment and perhaps I am misunderstanding. Your blog here is about 3 LC patients it helped?
Cort, please disregard. I see you were talking about Regeneron or something similar!
Is there a way to retract a comment after you submit it?
The skeptic in residence here. I don’t know why they wrote a paper with 3 cases. They could’ve waited at least till they had a dozen or so. Not that that make makes much stronger case. But that would make it a bit more difficult to dismiss it as annecdotal.
That said, I wouldn’t hold my breath. It’s not as if antibodies or antivirals haven’t been tried before. Retuximab failed rather spectacularly and Montoya’s antiviral study quietly disappeared, after making splashes in both cases. It’s hard to imagine something incidentally curing an intractable disease like MECFS. I’d wait till the first trial with a dozen subjects before getting any hopes up.
As I remember they wrote about the first three cases; i.e. they were not cherry-picked. Yes – one monoclonal antibody has been tried – hundreds have been approved and the antiviral trial was quite small. Neither have been given a good shot. Maybe not time to give up on them yet?
When I was diagnosed with ME the first thing I was put on was an anti viral. It stopped my downward spiral and stabilized me. It did not cure me, but allowed me to get a little better in conjunction with other treatments. So I’m a big believer in using anything available to feel functional versus wanting not to go on. Of course your lucky to not be that desperate considering you can bike 40 miles.
I’m not only lucky, I’m “fully recovered” after 15 years. Trust me, I know how it feels to struggle just to sit upright day in day out. I’m labeling myself “fully recovered” despite occasional PEM under certain circumstances because it would otherwise do a great disservice to other patients since people can point to me and think MECFS is not serious.
How did you fully recover after 15 years? My son has been sick 11 and he just keeps getting worse.
I would like to know as well how you fully recovered. Never met one personally yet.
Suzanne/Roger,
Every patient is different, so I can’t vouch that what I did is applicable to others. (If it was universal, someone would’ve found it out long time ago). I’m not even sure if what I did is responsible for my own recovery, to tell you the truth. It could well have been just a coincidence that I recovered. But my stories are in these two:
https://www.healthrising.org/blog/2018/06/02/tks-big-adventure-an-me-cfs-cross-country-trip/
http://tkcfs.blogspot.com/2023/04/turning-nomadic-one-mans-search-for.html
Basically, I noticed almost from the get-go that I was able to get away with doing more for a few weeks when I moved to a new place. So, I kept moving from place to place throughout my MECFS career till I finally achieved a full recovery at home this year.
I am similar.
I wouldn’t call myself ‘fully recovered’ otherwise I wouldn’t be here!
But I would say I am 90% of my non ME/CFS former self.
I can walk quite a bit but struggle very much with PEM after more strenuous exercise.
I have enough energy to work full time but I need to pace myself a lot.
So I would describe myself as having a mild form of MECFS.
I think like most illnesses there is a spectrum of disability in this illness.
I am unlucky to have the illness but count myself lucky to have a mild form of it.
Well, I hope you would stick around and contribute when you do recover 🙂 100% agree on the spectrum. I went through the whole spectrum myself and saw how the MECFS behavior changed over time, with only the PEM remaining consistent throughout. Yet people focus too much just on the severely ill, which resembles a chronic viral infection. I don’t think we’ll make a progress till we look at the whole spectrum rather than just the severely ill.
Hi TK,
I read the two blog links you posted. How wonderful to be able to expand the soul by being to travel that much!
At the end of the second link it appears that you had reverted to your usual plateau. Could please kindly share how you went from there fully recovered?
I just kept on traveling. In 2022, I crossed the country once again and climbed several fourteeners in CO. This year, I spent months backpacking CA mountains. Again I was struggling 2 weeks after I came back. Then, when I stabilized, I was able to jog 4 blocks consistently. That’s all I need to get my heart rate up and get my juice flow.
Roger N, May I ask specifically what antiviral? Thx
Famciclovir 500mg once a day. I also recently started on metformin 500 mg once a day, increased my baseline 10/15%. I’m not diabetic.
Roger, found it in a post- famciclovir, thx
Totally agree TK.
I will file this under ‘Quite interesting but far from convincing’
There were a lot of long haulers trying this in 2021 when the mabs were still available. A couple people tried it and it helped, and of course it spread through the groups like a wildfire. There was even a specific FB group for it. Overall the responses were very underwhelming, helped a few, but also hurt a few. It mattered to get the right MAB for the strain you got sick with. But like everything else it seemingly flamed out.
Darn! That is so at odds with these doctor’s reports. I see that the Facebook group, though, has mostly petered out…
It has petered out. There was a group for everything back then because we were all trying anything we could. And they’ve all pretty much petered out because nothing really worked. I wonder if the combination of them getting reinfected and then getting the MABs was a factor. I’ve seen some people massively up their baseline from reinfection alone. While I was sick with my 2nd infection my ME symptoms massively improved. But of course fell back to baseline after I was over it. Maybe the immune system turns back on upon reinfection and something with the combo with MABs sort of knocks things back in place and cleans up the debris.
That’s possible. Wouldn’t that be something – it works during the reinfection phase. The immune system is soooo complex.
That makes sense to me intuitively, based on all the stories of people who’ve had ME remissions during Covid infections and similar situations. And my own experience of several months’ remission after Shingrix. I lean slightly towards something Tess Falor said about “resetting the Cell Danger Response.”
Pacing does work! : ) I hope there was a group also for that!
Very interesting! My question (and concern) is for the group of people that have ME/CFS not due to a virus, but trauma. I got ME/CFS in Jan 2014 from severe medical trauma where I bled out, coded, and ended up intubated in the ICU. I never recovered. I had been an athlete most of my life and training for a triathlon when I ended up in the hospital after a routine surgery, and it took years for me to be able to simply walk up a flight of stairs. Even now, I’m mostly housebound and bedbound about 25-40% of the time. I’m constantly fighting PEM. How would a treatment like this help the subset of people like me? Serology indicates active EBV and CMV, but I suspect thats a symptom of my immune system. Not the cause of my issues.
Yeah, this has been my complaint too. My main issue with virus theories, asides that some of us comes into MECFS without a viral cause, is that they don’t explain PEM. A typical response is that “maybe it is a subgroup” or “maybe you were infected but don’t know about it”. Lots of maybes. This notion of subgroup has allowed people to propose all kinds of theories that does not explain PEM which is just about the only thing consistent throughout the spectrum of severity and causes. And thanks to long COVID, the virus theories are making a huge comeback. I don’t think we’ll start making meaningful progress till we stop focusing on fatigue and focus on PEM instead.
“The authors of the present study noted that reactivated herpes viruses in ME/CFS appear to result in mitochondrial dysfunction (remodeling) that pushes cells toward a hypometabolic (Dauer) state, and suggested that exercise in ME/CFS may be resulting in herpes virus reactivation.”
https://www.healthrising.org/blog/2023/06/17/exercise-immune-system-letdown-chronic-fatigue-syndrome/
Thanks for the link, Cort. I quickly read through (mostly your “gist” and the abstract), and it seems like quite a speculation from the transcriptomic changes they observed with lots of “possible”, “may” and “potentially” through a complicated chain of events. Even if true, I’d wonder how the viral reactivation can last as short as 6 hours with 24-48 hr delay after the stressor. (A possible micro-hibernation, maybe?) I think I’d wait for a simpler, and more objective, explanation.
Thanks – I go back to the post-infectious onset. If an infection triggers ME/CFS, long COVID, etc and PEM, even though we may be able to understand how a pathogen could create PEM, I would just leave that possibility open 🙂
The theory of the abortive herpes virus reactivation in ME/CFS (HHV6 is the main suspect) can explain all severity levels and many more features of the illness. Especially also PEM of a short duration or flu-like inflammation symptoms that go away after 1-2 days.
It states that HHV6 and possibly also EBV are able to reawake and show a smoldering activation where the immune system is able to block the retrovirus from replicating but not from showing a smoldering activation where the first biochemical steps of the replication cycle are executed.
The reason for that seems to be some changes in the immunesystem after an infection or other comparable events.
Bhupesh Prusty has shown that some of the first enzymes that are created in HHV6 replication hinder the mitochondria from normal functioning and even can damage them completely.
https://www.youtube.com/watch?v=0dI7uaTni5g&t=9s
I believe in this theory because in my case the brain inflammation can be stopped with Aciclovir which has proved very good activtiy also against HHV6 in clinic.
Maria Ariza wrote an overview paper of the development of the theory of abortive viral reactivation. It was only discovered about 15 years ago in a virus that was studied intensively because it could trigger cancer. From there she explains how they think this phenomenon is the key to understanding ME/CFS.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912523/
I have said already but I want to repeat: I bet a beer that Ariza, Prusty and the others involved in the research around abortive herpes reactivation in ME/CFS will have the Nobel prize in 2035.
It is particularly important to understand about Bhupesh Prusty’s research and PEM or more specifically mitochondrially caused exhaustion that he started in a virology lab specialized in the herpes field.
When they realised that many viruses (not only herpes and retros but many more) create enzymes that hinder the mitochondria from normal functionig (the reason for this feature might possibly be a facilitation of the replication process) they decided to study this feature specifically in herpes.
Prusty explains that back in 2016 he went in to ME/CFS because this was just about the time when it got clear that something not on the level of the mitochondria but “upstream” was hindering the mitochondria from normal funtioning in ME/CFS. Therefore they thought that ME/CFS would be the perfect model illness for their herpes & mitochondria basic research.
Here is an article that summarized these findings about ME/CFS and mitochondria in 2019. Already back then they understood that in ME/CFS people had something in the blood that provoked mitochondria damage. This was not first shown by Prusty but by some other ME/CFS researchers.
https://www.tandfonline.com/doi/abs/10.1080/21641846.2019.1580855
Then in 2020 Phupesh Prusty and colleagues could show in Nature that one of the early enzymes in HHV6 replication was just the factor that they were looking for.
Thanks TK for asking the right questions.
I think that smoldering herpes reactivation theory in ME/CFS can explain everything. Mitochondrially caused exhaustion directly after exercise (I realise that this is what I call PEM. But its wrong because PEM is definded differently as an exacerbation of many or all of the symptoms). What can come 24-48 hours later after exercise is how I observe it not just mitochonrial exhaustion but it is the starting of a new inflammatory episode.
The 1-2 days are required to drive up the inflammation process to a level where you feel very sick again. Probably similar to catching a cold. It takes a while until an inflammation process runs smoothly. The body has only 37 degrees celsius. It’s not a pizza oven!
For the theory of the smoldering herpes virus reactication in ME/CFS by Maria Ariza and colleagues see the links below.
I’ve said this before on here, but we have had so much information for so long, and no one has taken it to the next stage. As a teenager in the early 80s I had lunch with my father one day and he said he had just read a New York Times article about “chronic herpes” or herpes reactivation causing ongoing illness. “Maybe that’s why you’re always sick”, he said. Maybe indeed. Maybe that’s why Valtrex helps me a bit!
Thanks Suzanne, for your information about herpes research in the 1980. I just had a look at the NYT archive. I couldn’t find an article about chronic herpes activity. Still it was very interesting because herpes was a big topic in the 1980 because of HIV/Aids and an epidemic of other venereal diseases.
More importantly I found an excellent ME/CFS research overview article from December 4, 1990. That’s exactly 33 yeary ago. It was very interesting to see that they main strands of research already back then were just the same as now.
The theory of the overactive immune response and the stealth virus brain infections. Already back then they thought that HHV6 was the main suspect. It had just been detected.
What was very interesting and new to me: In Japan ME/CFS is or was called the lack-of-natural-killer-cells-disease. Thus pointing to the fact that people with ME/CFS have problems with fighting challenges to the immune system.
It was very helpful to read this 30 years old article because I understand a lot better what it means to be sick for a long time and not having the research really advancing.
The developments around ME/CFS remind me of a book by the historian of science, Londa Schiebinger, from Stanford university. She wrote a book on Agnotology: The Making and Unmaking of Ignorance. She and other researchers have presented many examples where the process of gaining a proper understanding of a problem was forcefully hindered over decades by cultural values and through political processes.
oh WOW- the “lack-of-natural-killer-cells-disease.” Wow. They knew so much, even decades ago!
I could certainly be wrong about it being the Times he read it in; he was a daily Times reader but also read voraciously so it could have been somewhere else. And also in those days writers said “cold sores” as often as they actually said “herpes”, unless they were talking about HSV2.
How cool that you found that 1990 paper, and how sad that the science has moved so damn slowly.
I recently read a study on reactivation of retrovirus due to head trauma 🤔 It was not a ME/CFS-study. Maybe a bit off topic, but I put it here anyway. I’m not up to read the whole article, so I read a describtion in a online research website – in swedish.
https://doi.org/10.1016/j.celrep.2023.113395
I wouldn’t discard reactivated EBV as a possible cause. EBV is associated with Infectious mononucleosis, lupus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and several cancers. It can do a lot!
I haven’t discounted the active EBV, the problem is finding a doctor who takes it seriously. I’ve met so many specialists, including infectious disease, hematology, immunology, GI, cardiology, etc. who all look at my positive IGM and EA for EBV and shrug. An ID doctor actually said to me, nobody really knows how to read those tests anyways. My DNA PCR EBV is always negative so no one seems to know what to do. I did a few years of monolaurin and lysine, cat’s claw, oil of oregano, Valtrex, Famivir, nothing seemed to help. I did SOT for EBV, which helped for a few months, but then came roaring back. To be fair, I am dealing with a bacterial illness that I suspect is responsible for keeping the EBV and CMV igm positive. I read with interest about Metrodora and Nancy Klimas, I might have to check them out, even though I’m in PA. Keep up the good work with the blog! It’s been so informative and helpful.
I totally discounted viruses more than 15 years ago and stick by that. Other than having a role in triggering the illness ( but not perpetuating it)
MS is also associated with other viruses, found this study when I searched for the one abt brain trauma and virus reactivation above.
https://doi.org/10.1093/brain/awad374
Colleen, have you been checked for Pituitary issues, specifically low pituitary? There is something called Sheehan’s Syndrome that happens when a person giving birth loses a lot of blood. Of course that wasn’t your cause, but you did have massive blood loss as you mentioned. It can cause a lot of low hormones like cortisol, ACTH, growth hormone, and more. Low in any of those can cause what could be seen as ME/CFS. It is worth a shot to have a doctor test all of your hormones.
Thank you for thinking of me! I have had my various adrenals checked. Cortisol tends to run lower but not crazy low. I did a short stint of hydrocortisone which went horribly. I’ll have to go through my labs to see if the others have been run. I’ve had more bloodwork than I can count, especially since 2019. I have a 3 ring binder full of them!
You sound like me…loads of mostly endocrine labs over the years. Mine have been wonky, with cortisol starting a little elevated and then years later dropping into low-normal. It is all irritating, the way I’m “normal”, but not really(lab-wise).
Colleen (and Karen17 too) – when your cortisol tests low, do they look to see if your ACTH is also low, or is it high? I have had Addison’s disease (primary adrenal failure) for most of my history of CFS, and I sometimes have wondered whether my ability to adjust my hydrocortisone has in fact helped me also to moderate the CFS – what started as severe CFS (for about 9 years) has settled into the moderate range. I seem to need more hydrocortisone than “normal” Addisonians. But of course if you don’t have Addison’s, taking hydrocortisone can really mess with your adrenal (and pituitary) functioning.
Wouldn’t that be reversible with time and nutrition?
Sorry you went through that Colleen, and with such an aftermath… Ending up in the ICU like that will be a blow to the immune system and I assume you were given blood. I looked it up and blood for transfusion is not tested for the possibility of mononucleosis.
Why not? You say you have an active EBV reading ?? Why can’t a traumatic impact on the body reactivate a dormant EBV virus? Makes sense to me. ?? I only ever have test results showing a former EBV but throughout my life I’ve had recurrent experiences with ME/CFS just like my terrible EBV infection in my 20s. I’m not challenging you. Just thinking out loud here.
I’m not sure who you are responding to? Or what your challenge is about?
I am sure she is a lovely lady and means well, but I find your enthusiasm for Klimas a bit curious, Cort. Perhaps I am being harsh, but her track record has been pretty poor on research. Wasn’t she talking up some supposedly promising research for our illness 4 or 5 years ago? What happened to that? Seems to have disappeared without a trace
Nancy Klimas allways promising, never happening trial on ME/cfs. yes, years and years and years of promising…. falls hope..
IMHO 🙂 she is doing great research. There’s the ME/CFS clinical trial with two drugs that has been promised for years but just never seems to happen. It seems like it’s the trial that’s always about to begin. We should note that the pandemic did get in the way of things. Hopefully its underway!
Very hard to say “went to great lengths to make it clear that the placebo response could not have been involved”. We know Long-Covid patients report improvement from all kinds of things, sometimes even reinfection (which could potentially be happening here). The authors of the paper didn’t treat these patients, everything is retrospective by selecting recovery stories, we don’t even know how many patients were treated, but we do know that it didn’t work for everyone since they state that in the paper. Of course it may be and isn’t even unlikely that only a subgroup (possibly a viral persistence subgroup) would respond to such a mAb, but at the same time it isn’t less likely that they improved via a different way.
If anything should be learned from the Rituximab trials is that placebo-effects, regression to the mean and other natural recoveries are indeed not too uncommon and at least common enough to know that anything provided outside of double blinded placebo-controlled trials should be taken with a grain of salt.
Well said.
There’s a whole bunch of assumptions in here. It’s the doctors who write up the case reports. I don’t know if you can write up a case report unless you were the treating doctor. I would bet you can’t actually.
As I remember these were the first three patients treated this way by these doctors.
I agree – placebo-controilled trials are critical.
As you will know Cort this was not a pilot study. Instead they were “the first three index cases reported to the investigators” (quote from Appendix B) and “Among other cases being followed by the investigators, MCA infusions did not improve long COVID patients with isolated (but persistent) anosmia/dysgeusia.”.
Regeneron also has a study site in Miami, which is of course where Klimas and some of the other authors of this paper are based. It could be possible that one of the authors indeed was prescribing Regen-COV2, so perhaps that was a bit too much speculation by me.
The cost for Regen-COV2 is actually not that high (relatively speaking) at $1000-$2000 per dosage, depening on the source. I agree that if there’s viral persistence possible benefits (both of mAbs and antiviral cocktails as well as their combinations) clearly outweigh possible risks such as https://www.biorxiv.org/content/10.1101/2023.11.21.567575v1. But it would naturally also be good to report on the numbers of those who didn’t benefit from this treatment. We’d definitely be asking for those numbers if it was a non-pharmaceutical intervention.
I still believe such a case report is very valuable and deems further investigations, I just don’t think we should allow ourselves to make the same mistakes that we criticise the utterly horrible CBT/GET fanatics for.
PS: Perhaps I initally missed it, but I just read your “Moving Forward” section and I think you provided some very important nuance within it which reflects everything I’ve said in a more elegant manner. Let’s hope Peluso, who recently announced that the recruitment for AER-002 is close to completion and is hoping for a read-out by the end of 2024, can provide us with more results soon.
Dr. Klimas is the only reason I have gotten medical help. Cort – keep up your support for her efforts. Her videos concerning recommendations to patients and her 2011 video lecturing to Doctors in New Zealand were the saving grace of my situation where I was getting no answers as to what happened to me and how to work on it. I self diagnosed POTS based on her instructions and took the information to a cardiologist where I got the official diagnosis.
I have tried to find out about her trial of a two step process to substantially decrease inflammation and then stop/start the HPA axis. I know that the pandemic interfered and there were problems getting participants…a lot of patient trialed research just stopped during the pandemic. I once thought I saw it may have failed but am not sure about that. If it is in process, I would not expect her to publish anything about it until completed.
Please share how to stop inflammation and restart hpa access. Klimas did not respond to my emails.
Great blog!
– For those interested, I found a good explanation on Wikipedia about: What is a monoclonal antibody? https://en.m.wikipedia.org/wiki/Monoclonal_antibody – Cort, would you agree with the following explanation in my own words: It is a lab-produced antibody designed to bind to a specific binding site on an antigen (e.g. a virus). The name monoclonal comes from the fact that these antibodies are produced from a unique lineage of identical cloned white blood cells.
– Chosen journal very good for raising awareness of these conditions for when severe patients turn up in Accidents&Emergencies!
The Geneuro company has just completed recruitment of its phase 2 clinical trial against long Covid, with 203 patients in Switzerland, Italy and Spain.
The study evaluates TEMELIMAB on fatigue and cognitive disorders. Telemilab neutralizes the pro-inflammatory and pathogenic W-ENV protein, found in more than a third of long-term Covid cases. Study results in June 2024
https://youtu.be/LdCa0xXkkOg
Thank you for this article, Cort!! I was so down after reading the previous posts. It was disheartening that some unelected Bureaucrats in NIH can make such sweeping medical decisions for millions of people! Thank God for Nancy Klimas, she’s such a blessing. This article offers a glimmer of hope. Please let us know if she needs volunteers for EBV testing or treatment.
Please stop saying EBV as if it’s only EBV. It is EBV AND CMV. I do not have EBV and COVID reactivated CMV and caused long COVID/CFS syndrome 2.5 years now.
Could the patch just be working as a stimulant ?
That too. But in some people it does much more than that. Theory is it can clear some receptors of Covid viral protein due to nicotine’s own higher affinity for these receptors, and in the best case do some kind of reset in the central brain/nervous system possibly involving microglia, plus other mechanisms of action. In the original publication by Dr. Marco Leitzke, the getting-better effect sometimes occured with a delay of a couple of after the end of nicotine patch application, so in that case not a stimulant effect.
couple of days
what do people think of this article???? She wants us to wait years for all the double blind studies to come in!!!!I for one am not going to wait!!!!
https://www.cebm.ox.ac.uk/news/views/nicotine-therapy-for-coronavirus-the-evidence-is-weak-and-contradictory
I just wish there was more academic research on Nicotine patch and CFS. All the studies I have seen are on long co vid and nicotine. If only Dr Jay Goldstein was still around!!!!!!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1079499/
The external use of the plant was widely used by native peoples in the distant past for medicine
Longevity expert Dr Peter Attia is fan of both Nicotine and Rapamycin. His book Outlive is excellent.
One sucess story with nicotine patchs for CFS
https://docs.google.com/document/d/1-wZoQ0W8UmNcFlz705EBAGI43WwhfqIep_-S8rzaC9o/edit?fbclid=IwAR3wTIjM7DJX8243Nsl8MQG1BLDX5o99o0tg1GkuksgUJUuHSPHDk5LDHUw
https://www.frontiersin.org/articles/10.3389/fphar.2020.594591/full
shamanism and tobacco
Given the massive numbers who Developed TINNITUS and related issued following CV19/VAX, I have to wonder if help could be gained from this treatment.
I don’t understand the vax connection (????)