“A lot of what’s happening in CFS is probably not happening in the blood.” Amy Proal
Amy Proal – who has ME/CFS – is the co-founder of PolyBio and the leader of The Long COVID Research Initiative.
If we’re going to get to the promised land, it’s probably going to come through better technology – which is a good thing – as technological advances are exploding seemingly everywhere. Amy Proal – the dynamic co-founder of PolyBio and the mastermind behind the Long COVID Research Consortium – recently interviewed a UCSF researcher, Tim Henrich, who is pushing the boundaries of science in long COVID and other diseases further. (Thanks, Gail, for the link to the interview :))
The Long COVID Research Consortium is going to throw at least $15 million into one of the great questions facing the long-COVID and chronic fatigue syndrome (ME/CFS) fields: could a persisting but hard-to-find virus be causing at least some long COVID and ME/CFS? Proal, who has chronic fatigue syndrome (ME/CFS), has said that viral persistence is “the trend we see the most evidence for.”
Proal has a personal reason to think so. She – but not her fraternal twin – suffered from a series of severe infections between the ages of three and five. Twenty or so years later, her ME/CFS reared its head when she was a premed student in 2004, but then it really bloomed after she came down with infectious mononucleosis. The more viruses you’re exposed to, or as the coronavirus has shown us, the more times you’re exposed to the same virus – the more impacted your immune system may be.
She said, in an interview, “Reactivated Viruses Causing Chronic Fatigue and Long COVID“, with the Mitchell Medical Group, that she remembers being in a pre-med class when the writing on the chalkboard started looking like gibberish.
(Her fraternal twin sister is apparently fine. One of the few differences between my identical twin, who is fine – and myself – is the Giardia infection I contracted a couple of years before becoming ill.)
She noted that researchers are not good at finding viruses buried deep in a patient’s tissues that have adapted themselves to hide out from the immune system. Because the genetic material from the viruses tends to show up less and less in the blood over time, Proal stated that we have to get into the tissues to see if they are present.
These viruses don’t need to replicate to be causing problems. They can change the gene expression of the cell. By stealing resources from them, they can inhibit mitochondrial function. They can express proteins that interfere with the ability of an immune cell to fight off other viruses. (Over the past decade, an Ohio State University team has been demonstrating that a protein produced by EBV called EBV dUTPase may be doing just that in ME/CFS.)
Michael VanElzakker, Proal’s partner at PolyBio, hypothesized that in chronic fatigue syndrome (ME/CFS) small viral infections around the vagus nerve could be impacting its ability to transmit immune signals to the brain but, short of an autopsy, finding evidence of those viruses has been difficult in the extreme. Biopsies are limited to certain tissues and even then can be misleading as only small areas can be assessed. How effective can a couple of biopsies of a 20-foot gut really be?
EXPLORING For Deeply Buried Pathogens
Deeply buried pathogens may not show up in the blood – they can’t hide, though, from the new EXPLORE machine.
That’s all changing. Proal recently interviewed Tim Henrich MD at the University of California at San Francisco – one of the top medical research universities in the country. Heinrich’s going to use the EXPLORE PET scanner, developed by researchers at UC Davis, to look for viruses buried deep in the tissues.
The EXPLORE is a beast. Henrich explained that EXPLORE is essentially many PET scanners plus a CT scanner incorporated into one. This monster PET scanner can produce 3-D images of deep tissues in the body. How big of a technology jump is the EXPLORE? It’s 40x’s more sensitive than commercial scanners.
Henrich puts a radioactive tag on a monoclonal antibody that he knows will bind to a virus and then uses the scanner to find where the virus is hanging out.
HIV researchers have had the same question about HIV that EBV researchers do about EBV and other viruses. Where is the virus? Is it still active? Is it producing proteins? Even when the virus has been fully suppressed, it’s still present in deep tissues in the body and, in fact, comes roaring back within weeks of the HIV drugs – even after they’ve been used for decades – being stopped.
The efficacy of this EXPLORE technique was first demonstrated in HIV patients last year. The approach was sensitive enough to illuminate places where HIV protein was being produced, even in people who were on antiretroviral drugs.
Now Henrich and his colleagues have turned their focus to the SARS-CoV-2 virus and are about to begin using the EXPLORE PET scanner to see if the virus is persisting in long-COVID patients. He’ll soon inject monoclonal antibodies that latch onto SARS-CoV-2 proteins into people with and without long-COVID symptoms, and then use a scanner to see where they light up.
If the long-COVID patients light up like a Christmas tree compared to the people without symptoms, that will suggest that increased viral persistence is contributing to their symptoms. Since he’ll be looking throughout the body, he also may be able to uncover areas of the body where pathogen persistence is possibly most problematic. Because the scanner will also be able to uncover areas of damage, he’ll be able to determine if the virus is associated with tissue damage.
Henrich can use the EXPLORE scanner to find anything that can be radio-tagged. For instance, In a study whose results he’s now analyzing, Henrich has tagged a molecule that attaches to activated T-cells – to see where the activated T-cells that play such an important role in the immune response are. Finding higher levels of activated T-cells in the gut, or the brain, or elsewhere will tell him where immune activity and/or inflammation is increased in long COVID.
Whether the T-cell is engaged in fighting off the virus or is activated due to autoimmune processes, Henrich will be able to pick it up – not just in the gut or elsewhere – but across the entire body. Since Henrich will be using the same group of patients for both studies, he’ll be able to tell if T-cell activity tracks with viral persistence. If they don’t, then another possibility opens up – overzealous T-cells are shooting blanks and missing the target. (A preprint of that study was just published – a blog on it is coming up.)
The Gist
- Co-founder of the PolyBio project and leader of the Long COVID Research Initiative, Amy Proal is no stranger to ME/CFS – having come down with it while a pre-med student. Proal’s history is potentially illuminating – she came down with three severe childhood illnesses and suffered through a bout of infectious mononucleosis – all of which her fraternal twin, who remains healthy today, missed.
- Proal has called persistent viruses “the trend we see the most evidence for”, and she and the Long COVID Research Initiative are devoting $15 million to search for them. Deeply buried viruses, though, are hard to assess. Aside from autopsies and the limited biopsies that can be done, they’ve been difficult to find.
- Recently, she interviewed Tim Henrich at the University of California at San Francisco, who has found a way to uncover the beasties that may be lurking deep in our tissues. Even if they’re not replicating, these deeply buried pathogens could be altering the gene expression of the cells they live in, tweaking the immune system with foreign proteins, and swiping resources from the mitochondria.
- Working with UC Davis researchers who developed a super-PET scanner called EXPLORE, Henrich was able to find, for the first time, deep reservoirs of HIV virus in the body. EXPLORE – which combines together multiple PET scanners and a CAT scan – is 40 x’s more powerful than commercial scanners.
- In the first effort outside of HIV, Henrich and colleagues are turning EXPLORE’s powerful beams on long COVID. Henrich and his colleagues, Stephen Deeks and Michael Peluso, glommed onto the potential long-COVID pandemic early and have been following long-COVID patients for three years now.
- Throwing the academic research playbook out the window, they formed the LIINC group (Long-term Impact of Infection with Novel Coronavirus), freely shared their findings, data, and samples, have produced over 20 long-COVID papers, and are part of the NIH’s RECOVER Initiative.
- The LIINC group has also just finished up a study that screened hundreds of thousands of protein sequences to look for evidence that molecular mimicry is causing autoimmunity in long COVID, are taking a deeper look at inflammation and exhausted immune cells, and are exploring novel approaches using non-traditional anti-inflammatories in treatment trials.
- Both Proal and Henrich agree that many flavors of long COVID probably exist and that combination therapies will probably be the key to stopping it. If Proal was in charge of things, she’d develop a moonshot initiative to develop the best antivirals possible.
- Many new technologies are being brought to bear on long COVID – each of which has the potential – since investigators like Henrich appear to be essentially studying ME/CFS – to illuminate ME/CFS as well.
- The PolyBio Foundation recently announced that Akiko Iwasaki – the keynote speaker at the recent IACFS/ME conference – received a grant to assess pathogen proteins in ME/CFS. The twist is that Iwasaki is using a custom pathogen panel that will include 100 enterovirus proteins – making it the first deep dive into enteroviruses – the first virus ME/CFS was putatively associated with decades ago.
- Coming up – Henrich et. al’s paper using the EXPLORE machinery to assess T-cells in long COVID was just published.
Not many EXPLORE machines apparently exist, but this technology could be used in the same way to determine where the Epstein-Barr virus, or where enteroviruses, or the Lyme bacteria are hanging out as well. Henrich and his colleagues were one of the first to show, in fact, that Epstein-Barr virus reactivation is happening in long COVID. Of the three viruses they assessed (EBV, cytomegalovirus, HIV), EBV was most associated with fatigue in long COVID. The herpesviruses, he said, were of “huge interest”.
EBV and its herpesvirus cousins were the next “low-hanging fruit” that he wants to look at. Antibodies specific to EBV do need to be developed – not an easy process, apparently, but if and when they are, Heinrich and his team would clearly jump at the chance to use them in long COVID, ME/CFS, and other diseases.
A Long-COVID Collaboration Engine – the UCSF’s LIINC Project
Henrich, Dr. Stephen Deeks, and Dr. Michael Peluso at the UCSF team have been tracking COVID patients in the LIINC project (Long-term Impact of Infection with Novel Coronavirus). They started gathering samples early in the pandemic. By May, they knew of COVID patients who were no longer shedding viruses but were still sick – making it clear that long COVID was a thing. Scrambling, they applied for grant after grant, only scoring a hit when they were able to tag a supplemental grant to one of Heinrich’s ongoing NIH grants.
From the beginning, they were committed to sharing their data, samples, expertise, and resources with everyone and collaborating as widely as they could. Calling this “not normal”, Heinrich said the scale of the pandemic required a frameshift. Instead of protecting their findings, they spread them as widely as they could.
Over time, LIINC has shared thousands of samples with other researchers. Since the pandemic began, LIINC’s collaborated on over 20 long-COVID papers. (Compare their rapid response to the NIH’s RECOVER project, which failed to start gathering samples for a year – thus missing out on what the virulent Delta variant was doing to unvaccinated people.) They’re also about to begin their own clinical trials and are part of the NIH’s RECOVER project.
The LIINC group has also just finished up a study that screened hundreds of thousands of protein sequences to look for evidence that molecular mimicry is causing autoimmunity in long COVID. They’ve also moved downstream a bit to take a deeper look at inflammation, exhausted immune cells, and novel approaches to interrupting that inflammation to improve symptoms.
Proal said there’s unlikely to be one type of long COVID, and Henrich agreed many flavors (viral persistence, autoimmune, clotting, etc.) probably exist. She noted that combinations of therapeutics were used to tame the HIV virus – she asked if Henrich thought that was the future of long COVID. Heinrich thought 100% yes. Combination therapies work best in many chronic illnesses. If you can disrupt inflammation at the same time you stop an aberrant clotting cascade, for instance, you’re probably going to have a better impact.
That said, testing combination therapies is hard to do with the FDA’s current structure, and it can be difficult to get different companies to work together. It did, however, happen with HIV.
About those antivirals. In the Mitchell interview, Proal said she thought the best thing that we could do we could do right now – for many chronic conditions – was to develop better antivirals. Drugs like Valtrex and Valcyte are not targeted on the Epstein-Barr virus. If it were up to her – and she ran the National Institutes of Health – the first thing she would do is create a program that fast-tracks research on new antivirals. She said, “There’s a huge potential for the development of new and better antivirals, and if we were to do that, I think we could really make a dent in these cases.”
Technological Advances Bring Hope
The greatest hope for people with complex diseases like ME/CFS and long COVID lies in the technological advances that seem to be happening all around us. Not only is the EXPLORE scanner 40x more powerful than commercial PET scans but note that long COVID was the first disease after HIV that Henrich and colleagues brought it to bear on – and every long-COVID advance has the potential to move the ME/CFS field forward. In fact, given the types of patients that Heinrich is studying, we could say he’s probably studying ME/CFS right now.
Ditto with Dr. David Walt, who’s using a new technology in long COVID which allows him to “literally count the number of molecules present” and is 1,000 to 10,000 x’s more precise than standard ELISA techniques.
We have our own creators in the ME/CFS field. Jarred Younger is pioneering two new technologies: a cheaper, easier, and potentially more accurate brain scan using heat mapping, and a new immune cell tracking technology that allows him to track immune cells to see if they’re getting into the brain.
The First Major Enterovirus Study in ME/CFS in Decades Begins
Then there’s the latest Polybio project. Funded by Tempi Stiftung via the Johadamis ME/CFS Research Grant, Akiko Iwasaki – the keynote speaker at the last IACFS/ME conference – and Michael VanElzakker will use “advanced technologies” to uncover pathogen proteins in the blood and cerebrospinal fluid of ME/CFS patients.
The clincher here is a focus on enteroviruses like we’ve never seen before. Besides other pathogenic proteins, the study has been custom designed to assess over 100 different enterovirus proteins that no one ever looks for. Finally, after literally decades of questions regarding the enteroviruses – which were the first viruses putatively associated with ME/CFS – we’re going to get a deep dive into the enteroviruses in this disease. John Chia, MD. – who has proposed for over a decade that bits of enteroviruses are causing ME/CFS – is undoubtedly happy at that.
- Coming up – the Heinrich T-cell study finds evidence of systemic inflammation in long COVID.
Maybe it’s just me, but I can’t find the link to the Proal-Heinrich interview! Thanks so much for reporting. for indicating where it is.
It was me – I forgot to put it in :). The interview is in the blog now.
I hope this is a useful tech that filters down soon to general practice. I had active mononucleosis for 20 months when I was 19-21 years old. I probably had mild ME afterwards with moderate level following my first hip replacement at 33 and a severe level following my second hip replacement with other reconstruction procedures. I’ve never had an MD suggest looking for EBV reactivation when I’ve had ME flare-ups.
New anti-virals? How about monolaurin? It’s a long chain fatty acid found in coconut and human breast milk. I read about it here some time ago and I just started taking it. It’s already helping me, even with the tiny dose I started with. The first dose gave me a stomach ache, but “underneath” that (if you know what I mean) I could feel something happening. After two weeks my bloating is significantly reduced. I have been able to ramp up to 1 gram three times a day and I feel better. Fewer pains, more stamina. Lauricidin.com has a deal on 6 jars.
@Ann1, do you have any brain fog or cognitive impairment? If yes, does the monolaurin help with that at all or does it make the brain fog temporarily worse?
Yes, monolaurin helped my fatigue and brain fog. I’m still not up to the recommended dose of 3 grams with each meal, but I will get there. I’m going slow. It’s expensie, but I found a source here in Canada that will ship free if I order a certain amount. Others have said they had the “die-off” symptoms for a week or so, but that it went away. I will probably avoid that if I ramp up slowly.
Does monolaurin helps your fatigue?
Monolaurin did nothing for me.
I’m not a medical professional and have no solid basis for believing it, but I have long felt intuitively that my chronic fatigue and soreness were due to a chronic, stealth viral infection, probably in the herpes family. This EXPLORE technology and Dr. Heinrich’s research is the most hope-inducing thing I have read to date about this. I really hope it leads to some breakthroughs.
My story is similar to Proal’s. Several rounds of infections as a young kid. EBV at 21 in boot camp did me in. I’ve never been the same. I tried to convince my docs I still had issues with EBV for years. I have reactivated EBV several times and now have a chronic EBV dx in addition to ME/CFS.
Well there is an idea that really ties the immunology to the physiology. Viral micro-infections near the vagus nerve could explain why David Systrom’s CFS patient’s have reduced return of blood to the right atrium. He’s a Cardio Doc, who was astonished by just how much blood was sitting in the large veins of his ME/CFS patients. A viral comprised vagus nerve could cause the entire parasympathetic nervous system to underperform in it’s vasoconstriction role at the veins.
I wonder about a viral infection that’s damaging the shunts that should be driving blood to the muscles.
Cort, Dr. Systrom mentioned “shunting” in terms of the blood flow problem. I’m trying to tie in all of the other problems that come with ME/CFS (IBS, disrupted sleep, temperature regulation problems, etc) to the parasympathetic nervous system. Dumping all of that extra acetylcholine into the ganglion synapse via Pyridostigmine, should slowly help with all of these symptoms. If, we are looking at a dysfunctional vagus and its fellow parasympathetic nerves.
Can you see if you have a lot of blood in your veins? My phlebotomists always comment on how big my veins are where they draw blood in the mid arm area.
Yawn, more studies on viral persistence?
I will eat my hat if persistent viruses are found to be the cause of ME/CFS.
In my opinion it’s a big distraction.
🙂 With things like this I do tend to defer to the experts. If Amy Proal thinks its a possibility (and has been able to raise $15 million to explore that possibility) I say time will tell! 🙂
People love the idea of a virus because it’s simple. And it also appeals because if a viral cause is found, there is, at least conceptually, a clear path to treatment (ie. antiviral)
The hunt for a persistent virus as the cause of ME/CFS over 30 years has been futile. That’s not to say new technologies may not reveal something, of course.
Of course I can’t dismiss the idea out of hand. I just think it is unlikely.
Far more likely, in my opinion, that viruses trigger the illness but do not perpetuate it. That it is perpetuated by neuroimmune derangement.
But hey, happy to be proven wrong and eat my hat…
Have to completely agree / echo what Matthias is saying. Viruses and pathogens as triggers. Less likely to be causing the (active) illness known as ME/CFS.
That’s been the consensus really for many years in ME/CFS – and it makes sense – and I would guess that that will be true for a major subset. Long COVID, though, is having researchers take a new look at what viruses can do. It’s going to be interesting!
Cort — I’ve also been trying to understand how to reconcile some of the “spontaneous” (though temporary) remissions some people with MECFS has experienced (including myself also temporarily) from low doses of Abilify / aripiprazole?
How does the sudden “switch back” to homeostasis / non-pathology via Abilify have anything to do with recurring / active / pro-latent viruses?
I agree. Amy’s ideas have been attacked on the internet in the past (not here). For years, she has been pealing back the onion with very sound questions and ideas. She stood there, and defended her ideas with superior knowledge. I am glad that she is in this fight. I am mainly referring to way she was attacked over her Vitamin D hypothesis. Which to me, needs to be researched. As it makes sense!
!
Once you have had a virus in the herpes family (EBV, CMV, HHV 1 & 2, HHV6 A & B, HHV7), these viruses become immortalized in your body where they live forever. If something perturbs the immune system, then one or more of the viruses can reactivate and cause havoc. So the idea of viral persistence is not a matter of debate.
What scientists haven’t found is the triggering agent for immune suppression that allows the virus(es) to activate.
Sounds a lot like pseudoscience to me. What’s the evidence for this?
Sorry to be so skeptical, but after having CFS for nearly 30 years I have seen so many of these sorts of viral theories and they never amount to anything.
Human herpes viruses have a unique capacity to establish a life-long latent infection in the host, whereby the virus can persist within specific host cells, and protects itself from immune recognition by limiting viral gene expression. The establishment of EBV latency is the final phase of the four different EBV infection stages: the growth phase in which the virus activates resting B cells to became proliferating lymphoblasts, the default phases in which EBV provides survival signals to infected lymphoblasts to induce their differentiation into memory B cells and the maintenance of persistently infected memory cells and finally the latency phase that allows persistence of the virus in resting recirculating memory cells in a way that is non-pathogenic and not detectable by the immune system.
The human immune response is generally very successful at controlling infections and minimizing symptoms during primary and persistent infections; however, herpes viruses are responsible for several diseases including conditions associated with primary infections. These clinical problems are more common and severe in immune-compromised individuals such as transplant patients on immunosuppressive medication and human immunodeficiency virus (HIV)-infected individuals, because of an impaired adaptive immune system. In particular, the most benign transient infection that affects adolescent or adult is the infectious mononucleosis, in which 50% of T cells and 25% of the memory B cells are specific for the virus during peaks of infection. From this infection EBV will latently persist in the individual’s B cells life-long and can wake up in the moments of immune weakness.
I came down with ME/CFS five years before I contracted EBV.
Great explanation, thanks!
They’ve said the same thing about chronic Lyme for the last several decades but new technology has found the spirochetes hiding in the brain. So just because Immune testing is negative and massive doses of antibiotics are used does not mean there is no Lyme disease and it’s “just” the body over reacting to something that happened in the past. There are many pics of Lyme spirochetes in people’s brains on autopsy.
My husband’s MD suspects persistent tick borne diseases to be the underlying factor causing his ME/CFS symptoms. He’s working on targeting these bacteria (crossing blood brain barrier) to see if it will reduce or eliminate his ME/CFS symptoms.
Look up Thomas Grier chronic lyme on FaceBook if you can. He’s been researching this for a long time. He has pics of spirochetes in brain and I remember him saying that killing them in the body with anti-paradite meds will release them in the brain so anti-biotics are needed. There are many autopsies that show live spirochetes in the brain after years of antibiotics. I got ME/CFS after clearing up (at least for the last 2 years) the tick illnesses with herbs and I stopped the CFS by stopping B12 and taking big does of B! & B2 vits as well as Solgar amino acids. Won’t work for everyone but worth a try. Many prayers!
T Allen I am fascinated for more information please on B12 involvement, because I’ve been on weekly B12 injections for severe pernicious anaemia for a long time. Initially the injections would give me a bit more energy (have had CFS for 15 years following a head trauma) but now they seem to do nothing. I too have experimented with various amino acids and supplements again with very limited success. I apologise for asking but any leads or links would be awesome. Thank you so much.
Hi Ruth, I’m still searching for info myself. It could be genetic, there is a MAT gene that causes B12 issues. I’m going to try taking larger doses of B1 & B2 (up from 2-300mg) and see if that will allow me to take more B12 I don’t think it will because I suspect this is an MTHFR issue. I don’t have many of the genes causing this but all it takes is a few not functioning right. I started with post viral, got a concussin and have been going through the list of issues ever since. From chronic tickborne illness to ME/CFS to MCAS to ICH and cerebral spinal leak over 6 years. They all have similar symptoms. Has it always been post viral causing ICH and CSF leak from the concussion? Only time will tell. I did read a study that showed that big doese of B1 seemed to lower cranial pressure so that’s my next step. Much of my info comes from this website (thanks Cort!) and I use that to look up other info online. I’m praying we all find answers soon! Blessings.
Thanks so much for your response, all the very best, it’s a long journey back to health isn’t it.
There are more classifications of pathogens as you know. Researchers tend to have bias towards viral infections but seldom talk about other organisms such as bacterial, protozoal etc.
I think this area may be relevant to me. Like Amy Proal PhD, I had repeated infections as a child and then had EBV when I was seventeen. Throughout my twenties and early thirties, I felt that my EBV infection ‘reactivated’. If I became very tired and run down, I may have developed a sore, scratchy throat, my glands around where my jaw met my neck would swell up and I’d be exhausted. I also have always had a curious sensation that felt like ribbons of nausea running down my stomach, gut area. I wonder now whether I was feeling my vagus nerve? I seemed to manage to quieten down these ‘reactivations’ so that by my forties they’d gone.
I don’t think I’ve had Covid yet but what Tim Heinrich and Amy Proal were talking about in the video, trying to work out what to target and working on different areas simultaneously, is what I’ve tried to do in my own DIY, Tracey’s own, ‘treatment plan’ of my chronic issues after various infections. With some success 🙂
I think that the viral persistence hypothesis is a dead end, for two reasons:
Reason 1: If SARS-CoV-2 peristence was causing Long Covid – how would one explain that the exactly same clinical phenotype can be triggered by mRNA vaccination?
Reason 2: If influenza virus and SARS-CoV-2 and Ebola virus and name-the-virus can all cause the same persistent clinical picture it would be more logical to look for a common denominator rather than separate causes for each entity. Think Occam´s razor.
So yes, we will find a lot of viral persistence in Long Covid and it may possibly explain some subtypes – but not the ME/CFS subtype. Here, we will have to wait until more researchers focus on viral reactivation. The time will come.
Exactly. Cfs is caused by different viruses.
Mine started after dengue virus infection
This viral persistence theory is shit.
I think on cell energy cycle or gut dysbiosis.
Why not viral persistence of the dengue virus or another virus? It doesn’t have to be the whole virus – it could be pieces of it – that are triggering an autoimmune or inflammatory response. Chia proposed that pieces of enteroviruses are causing ME/CFS.
Proal noted that viruses can impact the mitochondria. And viruses can certainly impact the gut as well. If it’s the cell energy cycle – what’s causing that to go awry? (We actually have a non-viral blog on that coming up :))
No viral persistence. I can bet
And if there’s viral persistence then forget a treatment for CFS IN NEAR 100 years
There are many viruses against which we don’t have antiviral (no antivirals for zika virus or dengue virus and many more)
The gut bacteria is trigggering problem in Cell
Don’t forget that viruses in the gut could be what’s throwing the gut bacteria off – as to the future – it’s the future – we don’t know what will happen.
The coronavirus has reinvigorated viral research. The multiple sclerosis EBV finding has cast a new light on EBV. We know the current antivirals do not target EBV. I would leave open the possibility that much more effective antivirals will and are being developed.
Read Dr. Dan Dantini’s book. He has been successfully treating himself and many CFS patients with antivirals for years
Is the book _ fibromyalgia remedy : treat pain with antivirals or can you put the link of book here
Amish,
He only has one book, as he is a clinician. It is an easy read. Dantini contracted ME/CFS when he was in his residency at the Uni of Miami. He’s an ear, nose, and throat Doc, who also treats ME/CFS. I personally know several folks who routinely travel down to Florida to see him. His results can be that good. Unfortunately, he’s getting old.
Yep, viral persistence is a dead end, which has been reached many times over the past 30 years by researchers.
A waste of energy, resource and $$$.
Take a look at this blog, though, Matthias – the past is not necessarily prologue: these kinds of technologies have never been brought to bear on the issues of viral persistence in ME/CFS. John Chia has proposed for years that pieces of enteroviruses are triggering ME/CFS but except for him, no one has tried to determine whether this is true. Let’s see what these more powerful studies show.
Ok, I look forward to the possibility of being surprised, even shocked!
Hey if this is causative, and more critically if there is a prospect of treatment, I would be delighted!
Then this (persistence of non-replicable antigen) should be a common mechanism for *all* microbes known to trigger ME/CFS, shouldn´t it? Yet I have never heard of persisting influenzavirus or parts of it, for example. Also there are cases of ME/CFS following non-infectious “immune events”…
So what we know is: ME/CFS is related to significant immune events. And: ME/CFS is marked by viral reactivation. Bringing those 2 together…: significant immune events could cause viral reactivation could cause ME/CFS. But I agree: we don´t know (yet)!
I hear what you’re saying @ Herbert Renz-Polster, and as someone who has moved from years of a daignosis of ME + fibro (pre Covid, post EBV), to someone being classified with possible neuro-Sjogren’s, I’m always inclined to think the immune system itself is to blame i.e. an aberrant immune response that goes a bit crazy even when a virus has ‘passed’ the acute phase.
But I’d love to know if people who have developed the same phenotype post-Covid but triggered by the mRNA vaccines, could it be that whatever immune-cascade the mRNA vaccine triggers, allows an already present virus to become re-active again (e.g. smouldering VZV or HSV in the autonomic and/or sensory ganglia – which is very difficult to biopsy/find in living humans, and if it’s known these viruses can wreak havoc even without replicating it would explain why current antivirals have been mostly useless to help). The fact there are reports of outright shingles reactivation after the mRNA vaccine makes me think there might be some credence to the post-vax cases also being linked to viruses, just not the covid virus, rather most likely an already present herpes family virus, my money is on VZV and/or EBV.
I suspect many of us with post-viral issues might have immune ‘defects’, perhaps genetically, which means we don’t deal with herpes and corona viruses very well, and that this may also be the case in things like autoimmunity e.g. MS lupus, Sjogren’s disease. Of course it’s all just hypothetical unless the research can somehow be done and at a large enough scale.
Thanks again Cort, you keep us so well informed ! I can relate to many posts ; a history very similar to Amy Proal’s (she is great ) as many infections as a child then acute unidentified viral pneumonia age 16 . From then until late 30’s fine then health deteriorated. Always high IgG antibodies to viruses , sometimes high IgM in particular to CMV .IVIG helped ( years ago ) , some weak antivirals .
Anyway time moved on , just about hung in semi recovering from infections , flus until Covid last June , that did it , just one infection too far.
Also reacted to mRNA vaccines with very high ANA’s , and symptoms .
I personally feel it is due to viral reactivation causing mayhem ! I have mitochondrial dysfunction , some kind of autoimmune dysfunction , autonomic dysfunction , cardiac issues , fatigue etc ,and the dreaded brain fog which is much worse as I seem to have just had another episode of viral reactivation , even though I do not socialise and mask wear everywhere .
I cannot really believe that ME/CFS research has hardly advanced since I was told by a San Francisco immunologist in 1992 , I had post viral syndrome , and no one believed me so I shut up ! Just hoping that now with long Covid on the scene there will be more solutions , as I also believe that we are not all the same , and need different approaches re treatments . Not sure I will be around though, but I really feel for all the young long haulers and ME?CFS sufferers , so let’s hope for the best !!
Sorry to go on …..
and yes, this may indeed be the mechanism in post vacc cases: immune stimulation which, in some, goes astray and causes viral reactivation … (with autoimmunity upstream or downstream or in between?…)
Dear Professor,
Reading your comment (and the last one on the ‘orchestra’ hypothesis), it would be fantastic to hear your thoughts on tje following doubt (sorry for the ignorance):
-if me/cfs can be triggered after different viruses, I understand from your comment that your take is that they are all reactivating the same pathogen, then? (Herpes as per Prusty’s files?).
Otherwise, why not considering that some cases of me/cfs might be caused by different pathogens but all affecting the same body location (cns), hence the ‘same’ clinical phenotype? Is there any way to consider as the common denominator the organ/tissue affected, instead of the pathogen causing it?
For reason 1… it does look def to reactivation….
Many thanks to you and this blog for another inspiring entry!!!
Didier
Didier, i am not a professor, just a MD 😉
All this is possible and plausible: different viruses could reactivate the same virus, or the same set of viruses – also, they could do so to different respective extents – which may explain the different clinical severity? Also it is possible – as you suggest – that reactivation of different pathogens (even in different body locations) could feed into a common pathyway which may affect certain structures or functional units in the CNS – this may then cause the clinical picture (or parts of it). For example, one hypothesis holds that reactivation of herpesviruses could go along with the release of certains proteins (like the EBV dUTPase) – which in turn may initiate and/or sustain neuroinflammation (https://pubmed.ncbi.nlm.nih.gov/31040055/). Many greetings! Herbert
It can be because SARS-CoV-2 may activate latent Epstein-Barr / HHV-6 virus and this causes “Long Covid”. Many got CFS after Mycoplasma Pneumoniae infection during last decade and reason for this could be the same.
Cort – thanks as always for bringing us such fascinating research, and in doing so fanning the flames of hope for us all. I really hope they consider looking for both covid and herpes viruses in the ganglia – and activated t cells going after virues in the ganglia. Ganglionitis can explain so many symptoms that people with ME, fibro, post-viral issues, POTs, etc. experience, and can be found throughout the body, including the vagus nerve…just a thought
Herpesviruses hang out in the dorsal ganglia – it’s such a great connection. 🙂
I’m so glad to see researchers of this calibre working on ME.
I recommend watching interviews by Amy Proal – she is impressive! There’s a fascinating one she did with Dr. John Chia (pioneer in enterovirus connection to ME) that a doctor recommended to me.
She is very impressive 🙂
With myself, I have noticed that over the years, every time I had a significant flu, my fatigue symptoms got significantly worse–and it took longer and longer to rebound–until finally I had full blown ME/CFS. I even had Giardia too. I have often wondered if the repeated infections were the events that finally wore down my immune system–until it became broken.
I so wanted to make this point to a certain doctor at Stanford, but no, in his mindset, only one event was what dealt the blow in ME/CFS. Ms. Proul (and others) may be on to something here, but I think it will be much more complicated than any will imagine. Anyway, you go girl!
EBV remains a candidate for a subset of ME patients. I think Professor Scheibenbogen is fully engaged in this.If I understand correctly, there is a piece of protein missing that should keep EBV under control in ME patients. Easy said. Correct me if I’m wrong.
https://www.frontiersin.org/articles/10.3389/fmed.2022.921101/full
Biomolecules /Free Full Text/ Exogenous Players in Mitochondria- Related CNS Disorders : Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis
https://www.mdpi.com/2218-273X/13/1/169
Just look at alll the effects on the body systems of these various pathogens; the effect on the terrain of the gut, brain, mitochondria, T cells & B cells of the immune system etc, maybe epigenetics, transcription and the ribosomes…..
All the repeated infections many of us have been exposed to; Herpes viruses, CMV, enteroviruses, viral particles in polio & other vaccines, influenzas,HPV, gut dysbiosis, antibiotics, allergies, perrenial rhinitits, sinusitis, vagus nerve sensitization, via gut, inflammation, basal ganglia, fight flight freeze/ dauer, tinnitis caused by vagus over stimulation……migraines, abdominal migraine, various inflammed lymph nodes, trying to carry on a normal fit life/ working life, with all these symptoms; boom & bust; PEM, /OTS Carrying on because you are not believed, being diagnosed as depressed, given SSRIs, anti migraine pills which compound the PEM and down grade the mitochondrial energy production; poison the mitochondria [as well as antibiotics]……. The metabolic Trap!
hi Cort or anyone, can you help me out please? (brain issues) Is the EXPLORE scanner also going to be used in real ME/cfs patients? I mean “now” not after first long covid? by Heinrich? thanks a lot! again a glimmer of hope…
I would assert that it IS being used on people with ME/CFS because many of the patients in the study will likely meet the definition of ME/CFS whether the SARS-CoV-2 virus caused it or not.
Other than that it’s not being used on ME/CFS patients per se. This is new technology and I was very gratified to see these researchers choosing to use it on long COVID after they’d validated it in HIV. That’s a good sign!
What they need, though, are monoclonal antibodies for the different pathogens to assess it in ME/CFS. Those are expensive to make and are not available, for instance, for EBV.
They can, however, do other studies such as the T-cell study which was just published in a preprint.
thank you so much for your explanation!!!
would for excample precisionlife be interested in there work and could say a good word for ME/cfs research to. they are working on ME/cfs and the heterogenosity of it. it is ofcource on a total different way, but maybe they can learn from eachother, have same interests? My brain is so bad i can not think this through. but otherwise i would try to mail them (precisionlife) with your blog if i may ofcource???
This is really exciting work being carried out and absolutely fascinating. To find something that can look at the tiny particles within the body has got to change the way these illnesses are looked at. Searching for viruses with ME/CFS patients more of a challenge unless there is a known viral onset. I got sick after a flu shot. Whether that somehow triggered some sort of viral reactionI don’t know, I wish there were some answers to that. Definitely a hopeful area of research though. Feel we are getting nearer.
Not that it directly pertains to the article at hand, but I recently read a book titled ‘The Why, The Historic ME/CFS Call to Arms’ by Hillary Johnson.
Cort, I can’t imagine that you haven’t come across this, but it is an investigative reporter who delved into the reasons why ME/CFS was not fully funded and in fact, attempts were made to bury it.
I know this is probably ‘old news’ but reading it made me so angry. Fortunately, ME/CFS is at least riding on the coattails of long-Covid, so some of this is now being rectified.
Now for a little levity. In the movie City Slickers, Jack Palance, who played Curly shared the secret of life… One thing. Just one thing. You stick to that and the rest don’t mean ****. Mitch : But, what is the “one thing?”. That’s what you have got to figure out. So it is with ME/CFS, I truly believed one thing is the cause of this, but different people have different symptoms according to their genetic makeup, environment, etc.
Many integrative oriented patients and doctors think that the one thing is actually a missed perspective: That the germ theory is incorrect or too partial (leaving the whole person, nature, and the environmental interactions out of the loop, thereby creating infinitely complex, chronic, difficult cases). Too many unknowns always being rediscovered and up for endless review!
The terrain theory of natural immunity and whole person healing is ignored by those with the most to gain financially. These are the forces at the top who profit from people suffering long term bandaid approaches and keep the upper echelon policymaker allocation of research funds for less profitable cures nil. Too much useful info is suppressed; some good doctors sneak their families into integrative and energy medicine practices anonymously for fear of reprisals.
It is said that on his deathbed Pasteur agonized that he had gotten it all wrong, and that the terrain theory was the correct one. A medical approach that gives fair use of both perspectives could yield some more promising outcomes.
How would this technology be used in MECFS patients when the offending viral trigger is unknown? As discussed in the interview, HIV reservoirs can be found because they can label known HIV antibodies. They can use antibodies for SARS CoV 2 because there are numerous commercially available antibodies. Even if enterovirus is a trigger in subset of MECFS patients, I am not aware of any commercially available antibodies for subspecies of enterovirus. This obstacle would be formidable.
In regards to viral reactivation in tissue such as herpes virus or Epstein Barr, I am unclear as to how a specialized PET scan would explain the potential complex interactions between latent or reactivated virus, host immune system, and host mitochondrial network.
If they had a monoclonal antibody they could tell if EBV was more present in more places in people with ME/CFS and they could pinpoint EBV hotspots.. I don’t know about activation or reactivation. They could also tell if damage was associated with those hotspots. Other than that I don’t know. We’ll probably know more when the paper is published.
Yes, the way Henrich was talking it is a formidable challenge to produce monoclonal antibodies for that target some of these pathogens.
It would be interesting to see if there was quantitative difference in EBV burden between MECFS/LC patients vs healthy controls. It may be more significant where EBV is localized such as CNS, brain stem, muscle or spinal cord. Do they have a monoclonal antibody for EBV?
This is what I mean by long-COVID being more of a distraction to MECFS than a help. they find viral persistence in COVID, so they extrapolate that MECFS and resurrect/recycle old viral theory of MECFS that has been around for decades and failed multiple times.
Some of the symptoms in long-COVID could be caused by the viral persistence, I’m sure. By extrapolating long-COVID to MECFS, however, they simply overlook the fact that there are non-trivial number of MECFS cases that does not involve viral infection. Had they started with MECFS instead, they would’ve had easier time separating COVID-specific anomalies from MECFS portion of long-COVID.
After we’ve seen cases of long COVID pop up in people who didn’t know they’d been infected with the coronavirus – can we say that we know a non-trivial number of ME/CFS cases do not involve a viral or other infection?
It is probably true that most “non-viral” MECFS cases didn’t look for antibodies before/after the start of MECFS, so we wouldn’t know for sure if they involved viral infection or not. But then same thing goes for some “viral cases”: many sudden cases were simply assumed to be viral without actual testing. Bruce Campbell and Dean Anderson, for example, initially assumed theirs were viral infection without any test, and then reclassified as MECFS when they failed to recover. Both had signs of OTS prior to it.
In my personal experience, I ruled out viral cause because all my episodes of OTS between full recoveries were precisely synchronized with my exercise schedule. (What are the chances that viral infection happening only on Fridays, 6 times in a row?) If OTS is not viral, and I’m yet to hear about any hypothesis that OTS is viral, then OTS that turned into MECFS probably is not viral either.
What is OTS? Overtraining syndrome – I got it.
I agree that we just don’t know! While they are quite convincing at times, the viral onsets are anecdotal…
How about this crazy angle? A past infection – like years earlier ends up in ME/CFS? That’s what’s happening in multiple sclerosis with EBV – it usually takes years for MS to manifest itself. I wonder about the Giardia infection I had a couple of years before coming down with MECFS without any apparent trigger…
THis is really difficult – were those earlier cases of OTS the result of a prior mild viral infection? I know that seems a reach but something started this…Hopefully, it will be figured out at some point.
Yeah, that’s possible I guess: previous infection could have predisposed some people to OTS/MECFS. Leaving all these possibilities open can bog you down though. I learned that in my previous life as a system debugger 🙂 Resorting to Ocam’s Razor and sticking to what’s known has been the winning strategy for me when solving complicated problems with so many unknowns.
After a five day course of paxlovid last summer my 11 years of CFS was “cured” for two glorious days. Since paxlovid targets RNA viruses my immunologist figures my CFS is probably due to RNA coxsackie virus which I had as a child. I also had EBV and HHV6 but they are DNA viruses.