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Episode 8 – Dr. Nancy Klimas – Long Covid/Long Haulers and ME/CFS Policies

Podcast The Rezilir Way

Researcher and physician, and the director of the Institute at Nova, Dr. Nancy Klimas joins us on our podcast to discuss ME/CFS and the groundbreaking work being done to find the core issues behind the illness. Listen to Dr. Klimas discuss in detail how to navigate these illnesses in a world of prolonged COVID policies with Dr. Craig Tanio as they try to figure out what new biomarkers must be found and how exciting jumps in funding are opening the door for chronic illness relief. Dr. Klimas leads us through the difficulty in making people accept its reality. Dr. Klimas also discusses some of the similarities in symptoms between ME/CFS and long Covid, and the boost in funding and research.

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Show Notes

Researcher and physician, and the director of the Institute at Nova, Dr. Nancy Klimas joins us on our podcast to discuss ME/CFS and the groundbreaking work being done to find the core issues behind the illness. Listen to Dr. Klimas discuss in detail how to navigate these illnesses in a world of prolonged COVID policies with Dr. Craig Tanio as they try to figure out what new biomarkers must be found and how exciting jumps in funding are opening the door for chronic illness relief. Dr. Klimas leads us through the difficulty in making people accept its reality.

  • (1:16) – How Dr.Klimas got involved in the area of ME and CFS and opening the door into new discoveries, definition of ME/CFS
  • (7:00) Is there a common, triggering event? Percentages of people in the US today with ME/CFS and the difficulty of identifying the illness
  • (11:50) Finding the core issue, rebooting our networks to get back to health, and eliminating the excess noise in our systems, biomarkers and their roles
  • (18:20) What subgroups are clinically relevant? The scope of the neuro-autoimmune center
  • (26:25) ME/CFS and getting people to accept its reality, COVID’s role in all this
  • (35:00) Funding and getting clinical trials up and running, changing the experience of the average patient
  • (40:25) In a COVID world, what percentage of patients still have persistent problems? How do we improve primary care?
  • (50:50) New agents that could be good candidates with testing in COVID, the onion approach and going through the layers of sickness

Transcript

Nancy Klimas:

Having done this for four decades, I can tell you that underneath it all there is grain inflammation, there is grain oxidative stress. There is body oxidative stress, and body inflammation. And all of those things put together affect every system.

Jacob Gordon:

Hey guys, and welcome to the Rezilir Way with Jacob Gordon. I’m your host Jacob, and I’m so excited to have you here today. In today’s episode, we have Dr. Nancy Klimas. She’s a researcher and physician who is the director of the Institute for Neuro-Immune Medicine at Nova and has focused a large portion of her studies in the world of ME and CFS.

Jacob Gordon:

In today’s episode, we’ll be talking about the definition of ME and CFS, along with its relation to multiple pathologies that could be the onset of it. We’ll be talking about long COVID, illness and as possible new grant for over a billion dollars into the research of post-viral illnesses. This has been one of the most interesting interviews we’ve done and I hope you stick around till the end of the episode.

Jacob Gordon:

So, without further ado, let’s get started.

Jacob Gordon:

Thank you Nancy, for coming on the show today.

Nancy Klimas:

Well, it’s a pleasure to be here. Thank you for inviting me.

Jacob Gordon:

It’s a pleasure having you. How did you get involved in the area of ME and CFS?

Nancy Klimas:

It goes back a long time because I’ve been at this for a very long time. But early in my career in the mid 80s maybe, I was seeing patients that found me. I’m a clinical immunologist by training and I was working at the time at the University of Miami, running their immunology diagnostic clinic. And I had a patient come to see me that had basically ME/CFS. But at the time the attitude towards this was so bad and she had been going doctor to doctor to doctor and being told there was nothing wrong and to go away and see a psychiatrist. The psychiatrist she did see, and he said, “Well, there’s nothing wrong there, you need to go see somebody else.” She was so frustrated.

Nancy Klimas:

And she came in and she basically begged me to look at her immune system. So I did. That’s what I do, I look at immune systems and so I … I threw the book at it. I just did everything I knew how to do and came back to her a couple weeks later and said, “Look, I’m sorry to tell you, but your cells antiviral don’t work, there’s things and you’ve got all kinds of inflammation that’s coming out of the …, there’s cytokine things going on, and your cell pattern is all distorted. There’s a lot going on here.” And she burst into tears. And I thought, “Oh man, I handled that wrong.”

Nancy Klimas:

But she was happy because I was the first person to tell her that there was really something wrong with her. Next thing I knew, she apparently had been networking with a whole other bunch of people that had similar symptoms, so suddenly I had worked up about 24, 25 patients. So I wrote a paper. It was in 1989 ish. And it was in a good journal, but not one that every doctor reads. It was in The Journal of Clinical Microbiology I think is where I put it.

Nancy Klimas:

Anyway, somewhere in that article, I said there was a form of an immunodeficiency going on in this illness, and because it was clear that it wasn’t congenital, it was some form of an acquired immun deficiency. Well put that in the time frame of 1989, 90 ish, that one little sentence got yanked out by the Associated Press and it went all over the world. In a kind of angry way, I got all kinds of attitude back from AIDS activist, because I’d called this illness AIDS, which I did not, I called it a form of an acquired immunodeficiency disease, not AIDS.

Nancy Klimas:

But anyway, many hundreds of thousands of patients must have seen that article and got validated by it because I just go slammed with referrals and research requests and so on. So that was sort of my door. I opened that door with my colleague Mary Ann Fletcher who’s an amazing immunologist. And we walked through it and we’ve spent the rest of … she just retired last year. I’m still at it. It’s been a long time, but we’ve been working on this ever since.

Craig Tanio:

What a great story. And for our audience, can you give us what is the current definition now of Myalgic encephalomyelitis and chronic fatigue syndrome? What is the clinical definition?

Nancy Klimas:

There’s been a number of definitions, and Myalgic encephalomyelitis, you can do this Craig, I know, just say it real fast, it’s like Peter Piper picked a peck of pickled peppers. And then you have to pick up the tempo.

Jacob Gordon:

ME

Nancy Klimas:

Anyway, ME/CFS has gone through iterations of definition and it’s been a little messy because we mostly had definitions that researchers put together so that we could be comparing apples and apples instead of apples and oranges. But it’s definitely very restrictive case definitions. So about five years ago now I think, the Institute of Medicine, which is now the National Academy of Science, put together a panel, I was on that panel and we created a clinical case definition, much different than all the others, where a person had to have fatigue as a primary symptom. And it was a substantial reduction in activity, or ability because of fatigue that had persisted more than. And that was not improved by rest. And was made worse by effort and also in the context that had an unrefreshing or non restorative sleep. So people wake up exhausted, can’t rest their selves out of the exhaustion, it’s just a constant state of exhaustion. And when they try to exert themselves, it makes them feel worse more often than not, was a requirement of the case definition.

Nancy Klimas:

They also had to have at least one of two things, which is cognitive complaints, cognitive impairment. That’s typically what people call brain fog, where they’re able to concentrate for a little bit and they just can’t, it’s done. Their brain is shut down. And then Orthostatic Intolerance. That’s when you stand up and you get dizzy, a sense imbalance and then it lasts for a period of time. So you have to have the fatigue part and you have to have one of the two others, the cognitive or orthostatic intolerance part to meet the base definition.

Craig Tanio:

And then if you have those things and let’s say you have something that could be a contributor to fatigue, like you have mycotoxin exposure, or you have celiac, or you’ve had prior Lyme, is that, do patients still qualify to have a diagnosis of MS/CFS?

Nancy Klimas:

So basically you’re asking, is there some common triggering event? And the answer is, there’s a lot of different types of triggers. So you could have had a Lyme trigger or you could have had a post-viral illness, like we’re seeing now with COVID, very frequently follows mononucleosis, it’s not uncommon. About 11% of people with mono have a long drawn-out illness that folks, they don’t necessarily ever recover after mononucleosis. And they fit this criteria.

Nancy Klimas:

But we also, we see a lot of toxic exposures. And one of the group illnesses I do a lot of work in, is something called [inaudible 00:07:35] illness, you can’t clinically tell them apart. They look exactly like ME/CFS. But their trigger was actually a neurotoxin exposure at the time of the first Gulf War. So a brain inflammation that resulted in a long-term, persistent neuroinflammatory that is ME/CFS like.

Craig Tanio:

So there can be multiple root causes and multiple triggers into this syndrome, but having any one of those triggers doesn’t rule out getting that diagnosis. What do you think are the people that are affected in the US today, let’s call it pre-COVID?

Nancy Klimas:

Yeah, pre-COVID numbers we were estimating one to one and half million-ish rates and prevalence, work that was done by the CDC and by a group up in Chicago. I think that’s about right. That’s a huge number, but the number of people that have this illness that are diagnosed, are much smaller because the clinicians and doctors and other clinicians actually do a pretty poor job of identifying this illness. And most people with this illness don’t know they have it.

Craig Tanio:

So, a pretty common condition, one and a half million, and then you’re saying the vast majority of people don’t actually carry that diagnosis. What do their clinicians think they have instead?

Nancy Klimas:

I think most clinicians when they see these walk through the door, recognize what they can. Like if they have a fibromyalgia overlay, they’ll diagnose the fibromyalgia part. Or if they have the orthostatic intolerance part, postural orthostatic tachycardia syndrome. And now they’re right, that’s it. POTS. But the problem is they’re not seeing the bigger illness that created what was needed to create all those symptoms and spin-offs diagnoses. There’s a lot of co-morbid conditions under the umbrella of ME/CFS.

Craig Tanio:

What is … just give us a sense of how this sort of unfolds for a particular patient, say they get a viral illness and have fatigue and kind of hit that first six months where they meet a lot of these specific criteria, what percentage of people are getting better and over what time?

Nancy Klimas:

Well sadly actually there’s no … First we don’t know still, this is a whole area, there haven’t been any really longitudinal studies to see what percent of people get better over time. I would say the early group, and that group in the six months to three years, that that’s where you’re likely to see the recovery group. And it’s going to be relatively small unless someone really gets in there and starts really helping them. So maybe 15, 20% will get better just because they will. But the rest of heading down that path of a long-term chronic disease.

Nancy Klimas:

The later group, the people who were sick 10, 20, 30 years, at this point, they not only have the illness ME/CFS, they also have a lot of things that can evolve in an immune system that’s been this messed up for this long. For instance you’re much more prone to autoimmunity if your immune system’s activated. And these people have a lot of chronic immune activations, so they might start picking up new diagnoses, like say rheumatoid arthritis or … we see all kinds of things.

Nancy Klimas:

That is not that uncommon. And then they’re are also extremely deconditioned from all this fatigue. And so that itself adds a layer of illness. If you magic wand away the underlying illness they wouldn’t just jump upstart and start doing, they have a long road to get better after the underpinnings of the illness have improved.

Craig Tanio:

So that’s a pretty significant disability burden if you’re having one and a half million people, maybe 20% get better after let’s say everybody got the diagnosis, after three years, and then what you didn’t say but what I’m assuming is that after three years at this point, the prognosis is worse, that there’s only a small percentage of people who get better after three years?

Nancy Klimas:

Well, that’s true. Yeah, if they’ve been sick for decades, it’s likely you’re on a path, it’s chronic.

Craig Tanio:

And what do you see as the real central problem in the body in ME/CFS after doing decades of research? What do you think is the core issue?

Nancy Klimas:

Thank you for asking the question. Our group is really taking a unique way of looking at something this complicated. You know that old story about the elephant and the whatever … all the people, you know the trunk and leg and depending on what pair of blinders you were looking at you were seeing different things, well, we’re really taking the whole elephant perspective here. We take long view. And we have a lot of different specialists in our research clinical group looking at this through all these different lenses.

Nancy Klimas:

And then we put it all together using a computational biology using Watson-like computers to help us understand all of the complexities and put it back together. And then, what we end up seeing is a chronic sick state that is stuck because that’s the way homeostasis, the thing that balances everything has it programmed at that point. So we can now create this understanding that there’s an endocrine problem, that there’s an immune problem, that there’s an autonomic nervous system problem, that there’s basically a brain problem. And we put all of those things together in this formula and we can actually see the network of things that are maintaining the illness. And then really cool for research, we try in a computer system, to reboot all of those networks back to normal and see if we can put people back to health.

Nancy Klimas:

Now having done this for over four decades, I can tell you that underneath it all, there is brain inflammation, there is brain oxidative stress, their is body oxidative stress and body inflammation. And all of those things put together affect every single sys that talks by chemicals. So hormones are chemicals, the immune system talks to chemicals. But your brain, this neuropeptide system is all chemicals and it just puts a … I often tell people, think of it as … and you can get my age off of this one, CB radios. Back in the day when your little hand radio people would try to get the signal, right?

Nancy Klimas:

They would go too far and it’d be really noisy and too little and you couldn’t quite hear it. Well, there’s a lot of noise in this system. And it really makes it difficult for these fine-tune systems to get all the signals just right and keep everything in the perfect little balance. So we’re trying to get the game down, the noise down by blocking inflammation in our models, and then rebooting the neuroendocrine system so it can do its job properly and keep everything fine-tuned and balanced the way it should be.

Nancy Klimas:

So that’s the bottom line. Oxidative stress in the brain, oxidative stress in the body. Inflammation everywhere, and then all the systems that require a quiet system to operate are working in a tremendous amount of noise. To make it a little more complicated, all of that broke the immune system a bit, so viruses will reactivate over old latent garbage that you carry around all this is trying to resurface every single day. All of us have latent viruses trying to come out. But the cells that survey for that, that prevent that, are in essence in a state of immune exhaustion. They’ve been working so hard at it for so long that they don’t have the stuff they need to do a good job.

Nancy Klimas:

And so little viruses escape and then they activate the immune system, the activated immune system causes a lot more inflammation, this vicious cycle goes on and on.

Craig Tanio:

So, a chronic sick state that really needs rebooting caused by inflammation and oxidative stress where the neuroendocrine system, the immune system is just not working. And the whole systems are getting exhausted. It sounds like, if we’re understanding that, what’s your thought about the ability to get a good diagnostic test for this soon? Like through a biomarker? I know that’s been one of the challenges here is to get a biomarker that has some good sensitivity and specificity. Do you think that’s coming up soon?

Nancy Klimas:

First I need to say, we have lots of biomarkers. It’s not that we don’t have them, we have … we know what’s wrong and we can look for it. The problem is that if I look for a biomarker that’s say inactivation, I’ll find that. It’s easy for me to find that. But I’ll find it in rheumatoid arthritis, or I’ll find it in MS or some other disease, specifically for MC/CFS. But it’s not a healthy system. I could give you a biomarker that says there’s oxidative stress, now I won’t be alone in that oxidative stress because we know there’s lots of things that cause oxidative stress.

Nancy Klimas:

So therein lies the problem. We can give you panels of biomarkers that describe, not just well what’s going on in this illness, and definitely tell you this is an ill person where these things are going on, but we’re still going to have to use our clinical judgment to say, and these .. ME/CFS, we’re still going to have to rule out Addison’s disease for the adrenals or you’re going to have to rule out some lupus or something for inflammation.

Nancy Klimas:

So you still have to use your clinical judgment. Any specific biomarker for a disease, it has to have a single, ideological cause, we get them when there’s virus. You know, HIV, good biomarker. COVID antibody, good biomarker. It would just circle the right group for those diseases. But how are we going to get that with an illness that had multiple doors of entry to get a common pathophysiology that is driving a long-term, persistent illness. I think we have to give it up. I think we have to say, there is a panel of things that help a clinician identify and treat this illness.

Nancy Klimas:

But I’m going to stop arguing with people about the perfect biomarker. There’s going to be a bunch of stuff. Now there might be biomarkers that come along that help me subgroup really well. For instance there’s an autoantibody biomarkers that can circle the group that have immuniated fibromyalgia. And then you find that group, that’s a small fiber neuropathy group, you could say, wow, not only do I know these people have fibro by way of this autoantibody that’s attacking their nerve endings, II also now know it’s an autoimmune disease and I have a whole host of things I might be able to do for that. I learned that from all these other auto-immune diseases.

Nancy Klimas:

So, I think biomarkers serve a lot of roles, and it’s not that we don’t have them, we should be using them.

Craig Tanio:

And just run with the subgroups a little bit more. I mean if there are relevant subgroups within this syndrome, so it sounds like autoimmunity is really one of them, are there a couple of other subgroups that are clinically relevant??

Nancy Klimas:

There’s a number of things. Again, I’m a very practical … I’m a clinician who happens to be an investigator, so I kind of like to look through the lens of, does it help me to know this about this person? Can I do something?

Nancy Klimas:

So what do I need to know? I need to know if they have a current toxic exposure that is helping drive the severity of their illness and any of us know or think in our practice, except for you Craig, you know all about them. But many people are living in a micro toxin stew, their health might be moldy or they have something in their diet that has a micro toxin in it. Or what not. And then you’re taking this broken system and just feeding it additional toxins that aren’t going to let it recover because you’re poisoning it.

Nancy Klimas:

So that’s an important subgroup, the micro toxin subgroup. And it deserves a good look. This autoimmune thing as I was saying, the easy one is the fibromyalgia group because that’s the group we pick out to do the biopsy for the small fibro neuropathy and identify small fiber neuropathy. So that’s an easy subgroup.

Nancy Klimas:

The hard subgroups are the infectious disease things. I find them very difficult as a clinician to sort through. I think that’s the hardest one. First Lyme hardly ever comes by itself. It comes with a whole cast of characters that came in with the initial infections. So you’re focused on Lyme and you’re looking at what are the other bugs that came along at the time. Or you’re looking at a post Lyme, Lyme is coming on, you know what I call the hit and run, Lyme came in, did some damage, left and now you’re dealing with the sequelae of Lyme, that was call MBCFS and we’re trying to … patients will go after antibiotic course after antibiotic course, chasing this Lyme that’s not even there, helping them to feel better because sometimes Lyme is chronic persistent and antibiotics do help.

Nancy Klimas:

But they don’t help everyone with horrible symptoms after Lyme by any stretch. So you see people then screw up their whole microbiome in their gut and now they have a microbiome-driven illness that … that were chasing Lyme so hard, they created a whole nother area of chronic inflammation by disrupting their gut microbiome. So it’s a lot. It’s a little complicated, but you have to take each patient and the way a good doctor does this is to just really block enough time in their schedule when one of these complicated cases come in to hear the whole story, from beginning to end. How did it start, what were the things that happened along the way, what’s going on right now. Where do you live, what do you eat? All these really important factors that contribute to really understanding who you’re looking at and what you can do for them.

Craig Tanio:

Absolutely. Time is critical. And you mentioned the neuro autoimmune center. You’ve really put together a terrific research and clinical group at Nova. Do you want to just tell us a little bit about the scope of the group at this point?

Nancy Klimas:

Oh wow, that’s an open invitation. I could talk for the next two hours. We were all at different Universities about 10 years ago writing a grant together that sort of pulled us together around chronic illness. And we had an opportunity to create a center grant and we got funded. And with the funding we were able actually to create a brand new research institute at Nova at Southeastern University where we had animal modelers, laboratory in vitro, modelers as well as people discovering bio essays and so on. And then the clinical research team, that’s my group. And we brought our fancy immunology laboratory were the best that we had in that can do all these kinds of essays and assist the clinicians clinically as well as providing a lot of research background to our group.

Nancy Klimas:

So we pulled that all together and we added some new people. We have [inaudible 00:22:36] running the genomics group. And we have Travis Craddock who is running the computational biology group. And we call it computational medicine, which is pretty cool using these amazing tools and knowledge of human physiology and applying it to complex diseases. That’s exciting. And we partner with the VA hospital in Miami and have a team at the VA there that is also doing a lot of the clinical trials work as well as some of the laboratory work.

Craig Tanio:

Terrific. It really sounds like a multi-disciplinary approach and the systems, the metabolic approach is going to be the way we’re going to advance the research further.

Nancy Klimas:

What’s interesting about the team, it’s kind of been fun for me, because I was in a traditional medical school, the University of Miami for a long time. And then I moved to Nova and I joined the Osteopathic medical school which is a new thing for me. And I realized it was the right home base for our group because one is … if you look at what we’re doing and in interdisciplinary]way we’re looking at a really complicated illness through all these different specialty lenses and trying to think of the whole body and the whole person physiology, how it all knits together. Well that turns out to be a very osteopathic principle, that you don’t off cardiology and pulmonary and so on, but rather you integrate your knowledge of the patient and you bring it all together.

Nancy Klimas:

So we knit our clinical practice around that same practice as well and took my more traditional clinical neurology practice I was practicing, instead we created an integrative functional medicine kind of clinical base there and we had six clinicians at the Nova clinic with different types of experience. We have functional, integrative, environmental medicine experts. Every single one of them certified after they had already been certified in internal medicine or something else. So it’s pretty cool.

Craig Tanio:

That’s great. And if I just kind of get back to what you were saying before about the whole systems issue, let me just test the analogy, and maybe this works or not. If the biomarkers are like letters in the alphabet, are we at the stage where we’re really trying to understand what are the sentences, what are the language that we’re really trying to get out of these patterns and we’re going to get a better insight into what these patterns look like over time?

Nancy Klimas:

I guess my point is in talking about biomarkers, is that it’s the same point I’m talking about looking through the lenses. That this is an illness that can’t be approached just by saying there’s oxidative stress. It’s not just that. It is an illness that has a lot of complexity and you actually have to look all over the place and try to put it all together to have a good understanding of what’s going on.

Craig Tanio:

Perfect. And I guess with that notion of lenses, maybe we can flip the lens now from a bit of just the definition to the history and societal context on ME/CFS and I guess, if you look at medical history, fatiguing illnesses has always been a part of medical history and I guess in the 19th century, there was the name, neurasthenia and there’s been other names for fatiguing illnesses, but I guess I’d love to just kind of get your sense of … since you’ve been working in ME/CFS, there’s been a fair amount of controversy just with its acceptance as a condition. And I just would love to hear how that has evolved from your perspective. Why was there such a problem in people accepting this as a real thing?

Nancy Klimas:

Man, I’ve been in this since the beginning, just about, if you were to imagine that and the name ME/CFS came up after I was in it, but as you say neurasthenia and other things, like celiac disease have been going back hundreds of years. There’s been this illness for a while. There were a couple of incidences where there were clusters. And one of them was in a village, Dan Peterson and Paul Chaney reported to the CDC, a cluster, a small town. And they came out investigated after a severe flu epidemic in the area and then they found all these post-viral syndrome people there.

Nancy Klimas:

It might have been one of the early rollouts, in the mid-80s that was one of the early reasons why it came under the focus of researchers. But this business of acceptance has been very hard because we didn’t have a blood test and a clear understanding of this illness, back then, it often felt under psychiatric somatoform disorder. There were just too many symptoms. When you’re in medical school they say, if everything about the entire medical history is positive…symptoms then you probably have a psyche patient looking at you right then.

Nancy Klimas:

So this was assumed to be that. These patients were almost always referred to psychiatry. That was a problem. When someone has a really severe chronic illness it’s painful. About half the time there will be major depression. I mean if you looked at anything, pick anything that’s chronic and serious and painful, and you look at the instance of depression, it’s going to be significant. So you look, you find it. So they looked and they found depression in about half the patients.

Nancy Klimas:

Turns out to be lower than people with chronic renal disease and lower than people with late-stage HIV, but it’s still a high number and so the psychiatry dove in with two feet into this illness early on and really this illness was, in terms of funding for research, was really pretty much funded to look at psychosomatic or somatoform types of illnesses for a long, long time.

Nancy Klimas:

It was so frustrating. Because I’m looking at patients who’ve absolutely … there’s a lot of people, society that have anxiety or depression or whatever, that’s just kind of okay, but there are a lot of people with this illness that didn’t have any history of any of that, or have any of that, and yet they were being assumed to have it just because their symptoms were crossing many systems. So that was really frustrating. I found that probably the most frustrating thing in my career has been my sense that having done this for, like I say, almost 40 years-ish, that they still haven’t pushed this to the point where it’s accepted broadly.

Nancy Klimas:

And I’ve told people that ask me, when will that happen, I’ve always said, “The day that we have a drug that’s gone through phase three trials and has a label for this, and then the pharmaceutical company will send out their army of pharmaceutical reps and they educate every primary care doctor in America, the way they did for fibromyalgia for Lyrica, right? I mean fibromyalgia was all in your head and then all of a sudden they had a drug that treated the central nervous system, and then all of a sudden it wasn’t in your head. Oh my God, it’s a nerve problem, here take this drug. And we all learned that it was real.” Another amount of  people with mental health issues that is not coming from me, that I’m putting some parenthesis around these things.

Nancy Klimas:

I said that and now I’m going to take it back. Because of post-COVID. Okay? So we’ve been struggling for 30 plus years to try to get enough word out there that ME/CFS is serious, that it’s biologic, yes sometimes people have secondary depressions or anxiety. Actually an illness that turns on your whole nervous system is likely to give you anxiety symptoms, but we’ve had the kind of success you get when you reach people whose family members are affected. And actually to the study that shows that roughly 15% of providers know all about this. And that 15% that have a family member with this.

Nancy Klimas:

So that’s the doctor you want to find, is the doctor that actually has a family member with this illness and you’ll get the respect you deserve. But enter COVID and now we’re seeing this post-COVID so-called long-hauler’s disease, which looks and tastes and smells like ME/CFS right? And acute onset virus is serious, prolonged recovery period in a subset of people, where most people recover or die. But that the people that survive, there’s this percent, we don’t know how big it’s going to be, but it’s going to be more than 10% of people that are going to have a prolonged illness, appears to meet the case definition for ME/CFS every way you look.

Nancy Klimas:

So we’re recently funded by the CDC to take that deep look and we will be doing that deep look. What I’m loving at the moment is that the long haulers, the advocates, these people who have been sick, have gotten in front of social media and in front of journalists and got their story out in a way that the ME/CFS patients have never been able to do. They were carrying this horrible baggage of this attitude that was early put on to them by the way the medical establishment reacted to this illness. And they just were constantly trying to shake it and move on. And here comes a group of people that didn’t have the baggage. They just … and they’re stage right. And they are sick, they’re post-COVID, who’s going to argue? It’s a post-viral syndrome, like just get on with it and find out what’s wrong with people and get them better.

Nancy Klimas:

And I love that. It’s going to sweep the ME/CFS grouping right where they belong. Into this post-viral illness post-injury illness model and we’re going to get them better too.

Craig Tanio:

Absolutely. I think what’s been striking to me in terms of just some of the initial findings on long COVID, you know, probably more from the journalists than the researchers, but is that people were initially reporting on papers on science about autoimmunity in COVID or neuroinflammation and kind of the tone is, we’ve never seen this happen before in an illness and all the ME/CFS people are saying, “We’ve been seeing this for 30 years, you just haven’t been listening. And when we said it was in your head, what we meant is that there was neuroinflammation in your head and other things going on, not necessarily the way that people think about psychiatric and psychosomatic theme.”

Nancy Klimas:

Yes, it’s nice. It is true. And not only are we able to say, it is ME/CFS, we’re also going to be able to say, Hey, and there’s a literature. You’re not starting from scratch here, right? So one of the issues is for us in ME/CFS is that we never had a funding opportunity at any point did it move briskly towards clinical trials. We had funding that was completely focused and very small, but completely focused on mechanisms. What’s the underpinnings? What was the first 15 years? And then the next 15 years is, okay, so what’s going on there?

Nancy Klimas:

But if you look there’s a lot of literature over that period of time that said these things that I just said about inflammation oxidative stresses on, but what we haven’t had the opportunity to do is to take that knowledge and put it into interventions and then roll out phase one, two and three.

Nancy Klimas:

So if you can come back to my other world, just for a moment and say, “Well, why did those guys get all these clinical trials?” Their advocates went to congress and they got their money put into a pot of money called the CDRMP, Congressionally Directed Medical Research, where the congress gives a line item budget every year to the DOD, the army, to give out money. And every year they get an advisory group that includes a tremendous number of advocates. That’s the wrinkle on the policy-making group that’s going to be said how that money’s going to be spent. When they write the call for proposals that said, Well, we’ve learned all this, we don’t want to do that over again. Let’s learn from that and go to the next step.”

Nancy Klimas:

So every single year they write a brand new call for proposal so it moves us forward. So an example that grant I told you about where I was able to start a whole institute, was a consortia grant, for illness consortia grant, funded by the DOD nine years ago. And when it was over, the next grant was a clinical trials consortia. They said, “Great, you did four or five years of work understanding mechanisms, well now let’s move that on. Phase one, phase two studies.”

Nancy Klimas:

And now we’re sitting on a great big clinical trials consortia grant where we’re rolling out the new knowledge rapidly based on those modeling systems and things I talked about. We’re in phase one and we’re funded to do phase two. ME/CFS, I knew this stuff eight years ago. I was ready for my clinical trial eight years ago. But I didn’t have the mechanism where I could get the funding needed to move our computational modeling forward into human trial, because the NIH ‘s strategy in that the call for proposals in our field doesn’t mention clinical trials.

Craig Tanio:

What I hear you saying is that the advocacy community really does need a shout out because a lot of these conditions have not been getting sufficient attention by the powers that be, that determine budget allocations and it’s only when the advocates have pushed for it in the past, that there has been budgets that have been set aside.

Nancy Klimas:

Advocates.

Craig Tanio:

Yeah. You’ve got a ….

Nancy Klimas:

Do you want to hear the big shout out?

Craig Tanio:

Sure, please.

Nancy Klimas:

Big shout out. The budget for post-COVID illness, it’s just released, $1.15 billion with a b dollars-

Jacob Gordon:

Oh my God.

Nancy Klimas:

… to do research. Directed to the NIH to do post-COVID research with a carve-out for biomarker discovery and the language clearly directing them to get into intervention as early as possible. Very exciting. All advocates, thank you advocates, to give you a frame of reference, our average amount of money for ME/CFS research for about 20 years was $3 million a year. Three.

Craig Tanio:

Three million.

Nancy Klimas:

For the whole thing. And that’s a study, one, good study. For $3 million right?

Craig Tanio:

That’s three cents … that’s less than two cents for every person that had [cross-

Nancy Klimas:

… when they cranked the budget up, they cranked it up to 12 million, a mind-blowing 12 million, which is nothing. Now gets more money a year than $12 million. But that’s what I’ve been dealing with for all these years.

Craig Tanio:

So if you were the research tzar, So let’s put yourself in the research tzar of that billion-dollar funding.

Nancy Klimas:

Ha ha. Well, we’re going to be in it. We already have like I say this CDC group which formulated our grant to start on our post-COVID ME comparisons and doing some prevalence work for post-COVID illness. And we’re very excited about it, it’s a great study.

Craig Tanio:

Yeah, and congratulations on that. I understand you guys were the first people to get long COVID research funding from the CDC, so that’s…

Nancy Klimas:

Entirely my team. We had 12 days to write the grant.

Craig Tanio:

That’s terrific. You’ve got to move when the opportunity

Nancy Klimas:

Kick ass team. Shout out Beth, you did it! Derrick, Beth, Gilbert. Whoohoo!

Craig Tanio:

And I guess that a billion dollars, there’s a time frame on it that’s pretty tight. I think it’s like … is it three years or something like that?

Nancy Klimas:

Yeah, yeah. It’s quite a bit of money. They’re going to have to roll it out. But I think that’s probably incumbent, so they’ll probably pull out $300 million a year-ish kind of budget. But that’s a huge amount of money. I remember with hepatitis … was it hepatitis C, we had like the big huge influx is $40 million and it really jump-started that field, with this $40 million call for proposal. So this is going to bring everybody into the field. You’re going to see a lot of brilliant investigators that are going to finally turn their attention down this path.

Craig Tanio:

I think I guess two things, before we get into the research priorities, I guess my personal hope is with this attention being shined on, that what it will do is change the experience of the average patient who goes into a physician who doesn’t necessarily get their condition acknowledged, and that kind of needs to be order number one for medicine to adjust that. We’ll see, but usually when…

Nancy Klimas:

We will see. I don’t see that coming right away. Because usually, science drives knowledge and knowledge drives change and attitude. But I will say that the other thing that I said, doctors who have a relative with ME/CFS created knowledge about ME/CFS, there are going to be a lot of people with relatives that have post-COVID illness. So you can just double down at least on the number of physicians. And I know a lot of physicians with this illness. We were in the frontline of COVID and the docs got sick fast and there’s a whole lot of people haven’t come back yet.

Craig Tanio:

So what’s your sense right now of the prevalence, let’s say, if you took all comers with COVID, so six months into it, what percentage of them do you think still have persistent symptoms if you had to have a guess?

Nancy Klimas:

So there’s only been a few papers out so far. This one from China that looked at everyone who had been hospitalized and 60% percent of people at six months were still significantly ill.

Craig Tanio:

Yeah, I saw that. That was the one in Wuhan, right? They were doing that at the Wuhan hospitals-

Nancy Klimas:

Yeah, exactly, that was the Wuhan, but these were hospitalized, so that’s the sicker end of the illness. And that should be the worst group in terms of having this. But we’re seeing plenty of people who weren’t sick enough to go to the hospital that are having post-COVID illness. Take from the chronic fatigue syndrome experience, the post Epstein-Barr and other infectious disease six month and one-year data sits around 11 percent nine percent. So I’m anticipating that the six-month group is going to be at least 11 percent.

Nancy Klimas:

Now it’s a little more complicated, because COVID infects and affects lungs, heart. There’s going to be a group of people that have pulmonary fibrosis, or a group of people that have a damaged heart. And that’s going to sequela. It won’t be ME/CFS per se, but it will be something we have to deal with as conditions and do our best job.

Craig Tanio:

So if we take that number just for the US, and if I take a round number that I think I had seen with the CDC where just because we report on cases, doesn’t mean that we understand the true prevalence of COVID. And there are a lot of people who don’t get tested, and so it may be 20 to 25 percent let’s say. You know we’re at least nine million people.

Nancy Klimas:

It’s going to be huge. It’s going to be … it’s the next part of this pandemic that people aren’t really anticipating is that when it’s over, it is not over. Actually early on this pandemic, I was thinking, Man Nancy, you’ve better rest up. Because a year from now you’re going to be so damn busy. Thinking nationally and working with a coalition of ME/CFS providers that have developed their own coalitions and trying to get the word out, come up with some treatment protocols, diagnostic protocols and try to approach this thing in a way that it’s not just the experts that are doing the work, the primary care doctors are getting the knowledge they need to be able to manage when they see a patient.

Craig Tanio:

Yeah, and having trained in primary care myself, and run some large primary care groups, and now I’m in this whole area, I think the critical barrier is going to be, how do you teach primary care to recognize that there’s objective changes if you just look for it. And what you need to do is just be very clued into looking for it. And know how to look for it. And I think the real challenge is going to be, it doesn’t fit in a 20-minute quick visit, as you said in the beginning. You have to spend time with people and really understand what’s going on.

Nancy Klimas:

We can work also the policy level, and Medicare has this extra payment for extra time for a certain list of complex illnesses, if we could get this on the list of complex illnesses, that sort of doubles

Craig Tanio:

Yeah, well, if I had to raise my hand and say what could go on the research as well as the basic science, would be maybe for people to acknowledge that there’s been a bit of … I think there needs to be a little bit of research on how the general physician community works with patients here. I found it very troubling myself on why when I started to see patients with these illnesses and they came in with stories of how many physicians did not accept that they had, was real, and they were just kind of told again and again, it’s all in their head. And we kind of came up with the answer, it probably is in your head, but it’s neuro inflammation, it’s not the psychosomatic story that they’ve been told.

Craig Tanio:

Do you feel like that’s still a barrier that’s going to have to be addressed with long COVID? That physicians are going to just kind of look at patients and say it’s psychosomatic? How do we really break that, so that doesn’t happen?

Nancy Klimas:

Yeah, it’s already happening. I mean that’s definitely already happening if you look at the social media chat rooms, they’re already about that. There has just been a lot of good, solid, well researched, lay press articles out there and I think that’s going to help us a lot. We didn’t have that before. So I think that’s useful. I’ve read four in the last week and … I think New York Times did two in the last week, that’s impressive.

Nancy Klimas:

And there’s another one coming out I think next week. So that’s very helpful when the light press gets in there. Other thing is that things are coming to publication around COVID much quicker than the standard usual way. We had to because we were dealing with acute COVID and you were seeing … we were even reading people’s articles before they were peer-reviewed. It was a way of seeing data before it was even officially out there.

Nancy Klimas:

So I think that a lot of the journals have expedited the way knowledge is going to be disseminated. So I think there’s a lot of work to do. There’s no doubt, this isn’t going to be easy and every primary care doctor will want to do this, but they’re going to have to. They’re going to have patients, every primary care doctor in the country is going to be seeing post-COVID ill patients. They’re already seeing ME/CFS patients whether they know it or not.

Craig Tanio:

And do you see a difference in Europe, how Europeans view ME/CFS versus the US? Are the practices fundamentally different right now in how patients are getting taken care of?

Nancy Klimas:

This I think has been kind of worse in Europe because in the United States, just because of our healthcare system, you can doctor shop. If you don’t like your doctor, you can get rid of your doctor and you move on. But in the UK in particular, you’re assigned someone and that’s your doc. And they have these guidelines that direct them what to do and they’re very much evidence-based. In ME/CFS there’s a lot of literature to suggest that cognitive-behavioral therapy is helpful. And it is, don’t get me wrong, cognitive behavioral therapy is great for any chronic illness. It helps you reframe your illness, it helps you be paced, so you’re not constantly … So it can teach you a lot of good skillsets to coexist with a chronic illness. But it’s not curative.

Nancy Klimas:

The other thing in the nice guidelines is exercise, graded exercise. And that is very controversial because it relied on a study that was not retracted but highly criticized even by the editors of the journal it was published in. And yet it’s the basis of guideline in UK that you should try to exercise your way out of this illness. And some patients, they might be able to do that, but most patients, it will be very hard on them and potentially very dangerous too to take on that approach.

Craig Tanio:

Maybe just elaborate on that a little bit in the spirit of doing no harm, my understanding is certainly in patients how are having post exhaustion myalgia and malaise, that if their mitochondria are crashing, just cranking up the exercise is exactly the wrong thing to do and could really set them back further.

Nancy Klimas:

Exactly, it’s not that exercise is a bad thing, obviously you’re going to have to recondition, but before one can recondition you have to fix the underlying problem that makes exercise cause you to crash. And so this, in particular, is that bio energetic space of oxidative stress. If you push a cell that can’t clean up the mess that energy makes to do more, you will crash that cell and it will make even more inflammatory mess that it leaves behind and the cycle goes on and on and on.

Nancy Klimas:

In recent studies, we put people on an exercise bike and we measure blood before, during the exercise, five minutes later, 15, 20 … whatever. Eight times in four hours and then time it the next day. And we measure every gene that’s turned on, every cytokine that’s expressed, every hormone that’s circulating, cells, what they’re doing, their function. Everything. We put it in that big computational model and try to get a handle on things.

Nancy Klimas:

But one of the big handles is that anyone who exercises and the first thing that happens is that they generate … first they start their energy system, their bio energetic system, but then they generate inflammation. Inflammation happens in anyone that exercises. But almost immediately in a healthy person you shut it down. There’s a pathway that starts shutting the inflammation allowing you to continue. Where that doesn’t and in ME/CFS their anti-inflammatory mechanism shuts off during exercise. So they just keep cranking.

Nancy Klimas:

So exercise is a very touchy subject for me because it’s very personal what a person can do. And we put people on these metabolic parts and figure out where their…. we keep them below the level on when they go from aerobic to anaerobic. And one person that could be two minutes, another person it might be eight. It’s not much more than that ever. And yet, I hear doctors saying, “Well, go do 15 minutes and then do 30 and then do an hour.” And I’m like, “What are you doing? These people are going to be flat out. Go do two minutes, go lie down. If you feel okay, go back and do another two minutes in a couple of hours and see how you are and then work it up real, real slow. Don’t go pushing yourself through.”

Nancy Klimas:

I take care of veterans a lot, and they all have this drill sergeant in their head. I mean I spend half my time fighting with the drill sergeant because the drill sergeant says, “Work through your pain, work through your pain.” And I’m like

Craig Tanio:

Yeah, that no pain, no gain.

Nancy Klimas:

Listen to your body.

Craig Tanio:

Yeah.

Nancy Klimas:

If your body says stop, stop.

Craig Tanio:

Protect the mitochondria. Yes. On the research side, are there a set of off-the-shelf agents that have been … you’ve been thinking could be tested in ME/CFS that would be good candidates for long COVID? In terms of…

Nancy Klimas:

Oh sure. The first thing I recommend to people who don’t have research to go to, is to go find an integrated or a functional doctor, because they’re at least thinking through this pathways, right? They don’t ask for energy without fixing the energy pathway, and then there’s a lot you can do to work on oxidative stress. And there’s a lot of different approaches. You can also measure everything and know what’s deficient and fix it. There’s even more precision medicine ways of looking than just blanketing people with anti-oxidants. You also have to be aware of what gets into the brain, the barrier since it’s the oxidative stress in the brain that’s driving most of this illness.

Nancy Klimas:

And so you have to get things to penetrate the brain, and again, it takes a knowledgeable clinician that knows about that to give you really good advice about that. So I usually preach to people, go functional or integrative, that you can always find functional and integrated medicine people, there’re just lots and lots and lots of them and there aren’t too many ME/CFS experts. Two dozen. So you start there.

Nancy Klimas:

Neuro inflammation is a special place and it’s a part of this and there are things that can be done for neuro inflammation if again, if you find the source, if it’s a virus or something you should shut it down. But if you can’t, you can at least gently work on that with nutraceuticals that are anti-inflammatory. We use a compounded drug, low dose naltrexone a lot in our practice because it’s an anti-inflammatory that crosses the blood-brain barrier, it quiets neuro inflammation. It’s very helpful.

Nancy Klimas:

But there are other things they cross as well. So, I think that’s part of what you can do for the brain part of this. You have to work wider than that though because the patient’s living in their family and in their environment and you really have to understand the dynamics around … I have a lot of patients that have been in less than supportive families. I remember one patient who had this great husband, he was fantastic, he came to every visit, he was so supportive. He went to the gym and he was working out next to a doctor, and the doctor told him that it was all in his wife’s head, that she’d been messing with him all these years. And he went home angry, and they’re divorced and now she’s got no one.

Nancy Klimas:

And I’m like, “Wow, what happened to Mr. Compassion?” He listened to the dude next to him and believed the MD credentials meant something and pulled the rug out from underneath his sick wife. Geez, what was that about? So you got to know the whole story because sometimes there’s a lot going on in that patient’s emotional and social environment as well as physically. And then living with ME/CFS, what’s the situation with the people around them, and so on.

Craig Tanio:

I noticed, at this point it’s going to be hard to go super deep into the treatments and maybe that’s something we can do at a later podcast, but when you’ve seen patients who have been able to significantly recover, are there any commonalities in their experiences that you’ve seen? Is it …

Nancy Klimas:

This is one of those books I want to read. I want to do individual patient stories about what they think made them recover. They have so many different stories. It’s really interesting. My perspective, I always think what I did help them because you know, I got plenty of ego and I can believe that my clinical acumen was so impressive that I helped them. And I presume sometimes that is true.

Nancy Klimas:

But sometimes they found it their own way. They did their own thing. Like I had a patient before I was understanding the mold thing at all, that moved from her home in San Francisco to Hawaii. When she got to Hawaii, living on the side of the Hawaiian island, she had an almost miraculous recovery. I wouldn’t say to 100% but to 85 or so. And she was bed-bound, house bound, sick as hell. And she was … turned out the house in San Francisco, major mold environment, they didn’t know, and it took her about two years to get really her feet under her in Hawaii, but she did. So it wasn’t anything I did. She changed her environment out of the toxic space she was living and she transformed herself and that’s exciting.

Nancy Klimas:

But then in my world, I call it the onion approach. We just layer things and we try to be logical. I mean bioenergetics, fix that early because how can you make anything better if cells don’t function well? And then once you got the oxidative stress piece and the nutrition piece and all the different elements that might make a cell healthier, now, what else can you do? For instance, if there’re viruses in the system, and this immune system’s exhausted, in HIV I learned this, if we shut off the HIV pump, the immune system recovered. We meet people who’s T cells went to zero. They went all the back up to normal once you shut off the HIV pump.

Nancy Klimas:

Well, if viruses are constantly in the system, if you can suppress them somehow, you should because it allows the immune exhausted state to recover. The cool thing about the body is it’s programmed for recovery. I keep telling my patients that. You do know that you’re programmed for recovery? We just have to find a way to get you there. Your body doesn’t want to stay sick. It wants to get better.

Craig Tanio:

And it does feel like … What I’ve seen clinically is that recovery is not always linear. People do have these tipping points where something seems to work and they’re getting better, sometimes they will get … and some people will have bigger tipping points than others. But the challenge is that everybody’s tipping points are personal and unique to them in their social and environmental context. But have you seen that phenomenon where people do get better over a short period of time even though they’ve put in a lot of work and weren’t getting better? And then they kind of had that little curve

Nancy Klimas:

Well, I think the big one we see is, as people seem to be improving … this is in human nature, but it just drives me crazy, if you have a system that its bioenergetics has been off for a long, long time, it’s going to take you a pretty long time to build up the energy reserve, the mitochondria in each cell that you need, right? So you start feeling better and you say, “Well you know, I need to do that list of things that I haven’t been able to do for the last decade.” And like, thanks a lot, because if you take a good day and attack it, you won’t have but one day.

Craig Tanio:

Right, right.

Nancy Klimas:

So you could make that a week or two weeks or a month or a year, who knows if you just don’t overtax your system. If you just try to grow with the mitochondrial …when it’s coming back up, you come back up slowly right behind it. But not to exceed it. It’s very difficult though because we don’t … Well, first you have to have an awful lot of insight to yourself about yourself to recognize that you’re even doing this.

Craig Tanio:

Yeah, I’m finding that the Oura ring in some of those biometric devices are really helpful to the ones that have the recovery index at night. You know, to kind of show where you’re resting heart rate is, because in almost all cases, when people are crashing, and even if they just pushed it a little bit, the body doesn’t lie at night. The resting heart rate is not going down and it can be a really early reminder to people that they’ve got to take it easy.

Nancy Klimas:

Yeah, that’s a good piece of advice. I often tell people to take their pulse in the morning and say, if you wake up with a pulse that’s already racing, you don’t have anything extra today. You’re done. But that’s sort of the same thing. My friend Cindy Bateman uses Oura ring in her practice a lot. She really relies on it.

Craig Tanio:

I think some of the big takeaways for me is that this has been a very neglected area and with post-COVID, this whole area’s going to change and it’s going to be a major public health issue, really across the globe. And it’s really the responsibility of the medical community and the research community to serve patients appropriately. So let’s hope that people are up for the challenge here. How can our audience get in contact with you or the neuro autoimmune center for questions??

Nancy Klimas:

So we have a webpage. It’s on Nova Southeastern University. If you just Google that with Institute for Neuro-Immune Medicine, you’d find our web page. And there’s contact information, we have videos, we have lots and lots of patient information on there. We’ve done lots of conferences over the years. They’re all up there. It’s a very rich place if you want to teach yourself more about these illnesses.

Craig Tanio:

Well terrific, thanks so much for being on the show today.

Nancy Klimas:

Hey, it’s a pleasure. Thanks for inviting me.

Jacob Gordon:

This episode really hit home with me. I’d been suffering with CFS for quite some time back in 2010. And that lasted for about five years. For me the onset was Epstein-Barr virus a.k.a. mononucleosis. I wrote about my entire experience with this on mybiohack.com. So I recommend you go check that out. And if you want to learn more information about CFS and ME and Nancy Klimas, I recommend heading over the rezilirhealth.com

Jacob Gordon:

Dr. Craig Tanio is doing some amazing work with his patients over there. And I may be biased because I am one of his patients. So thanks guys for listening and I’ll catch you in the next episode.

 

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