Exercise Intolerance in ME/CFS and Long COVID
What Your Body Is Actually Trying to Tell You
A conversation with Dr. David Systrom, Physician at Brigham and Women’s Hospital, Assistant Professor of Medicine at Harvard Medical School, and Director of the Massachusetts General Hospital Cardiopulmonary Laboratory
For years, patients with ME/CFS walked into doctors’ offices with life-altering symptoms and walked out with nothing. No diagnosis. No treatment plan. Often, they were told it was all in their head, or that they were simply out of shape and needed to go to the gym. Dr. David Systrom has spent the last decade proving otherwise.
In this episode of the Fast Metabolism Method podcast, Haylie Pomroy sat down with Dr. Systrom to talk about exercise intolerance, the invasive cardiopulmonary exercise test (CPET), mitochondrial dysfunction, dysautonomia, and two active clinical trials that could change how these diseases are treated.
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The Test That Changed Everything
Dr. Systrom’s work centers on the invasive cardiopulmonary exercise test, or CPET. Patients cycle on an ergometer for about six or seven minutes while a metabolic cart measures oxygen uptake, carbon dioxide output, and breathing. Two catheters, one placed in the wrist artery and one in the internal jugular vein, allow the team to measure blood flow and oxygen extraction by the muscle during exercise.
“Those two catheters really take that testing to another level. They really allow us to measure blood flow and oxygen extraction by the muscle, for instance, during exercise.”
The test was originally developed to detect early heart disease and early pulmonary vascular disease. But over the past decade, Dr. Systrom and his team began noticing patients with exercise intolerance who had no identifiable heart or lung disease at all. Something else was going on.
Importantly, the test is brief enough that it typically does not trigger post-exertional malaise (PEM), the hallmark crash that follows exertion in ME/CFS and long COVID patients.
The Diagnostic Maze Patients Face
Before reaching Dr. Systrom’s lab, most patients have already been through an exhausting cycle of referrals. They see a cardiologist, get an echo and a cardiac stress test, and nothing is found. They see a rheumatologist, blood work suggests some inflammation and possible nonspecific autoimmunity, but no diagnosis is given. They see a pulmonologist for breathlessness, pulmonary function tests and chest imaging come back clear. And then, in Dr. Systrom’s words, “around and around they go.”
“We were very used to this kind of pattern of well-meaning health care providers coming up empty-handed. They’re frustrated. The patient’s frustrated. There’s no answer. There’s no treatment.”
The referral patterns for long COVID patients, which began arriving at Brigham and Women’s in late 2020, looked nearly identical to the ME/CFS patients they had been seeing for years.
ME/CFS and Long COVID: Virtually Identical in the Exercise Lab
When Dr. Systrom’s team began evaluating long COVID patients using the invasive CPET, the results were immediately familiar.
“As soon as we started to see these patients and take their history and do their workup, including the invasive CPET, it became immediately abundantly clear we’re seeing familiar things and very familiar things, meaning we had seen it all with ME/CFS. So in the exercise world, these two diseases are virtually identical.”
His team had been seeing ME/CFS patients with these patterns for five or six years before the pandemic began.
Mitochondrial Dysfunction: Beyond the Buzzword
Mitochondria are the power plants of the cell. They convert food substrate and oxygen into energy, primarily ATP, and are present in virtually every cell in the body. They are especially critical in high-energy tissue beds: the brain, the peripheral nervous system, the heart, and skeletal muscle.
While classical mitochondrial diseases are largely genetic and tend to run in families, Dr. Systrom explained that there is a growing body of evidence for an acquired form of mitochondrial dysfunction in ME/CFS and long COVID. This form does not have a well-defined genetic origin.
“Rob Wüst, in particular, has had a couple of nice high-profile papers describing this in both ME and long COVID,” Dr. Systrom noted, referring to his collaborators in Amsterdam.
The causes are still being mapped, but the common thread appears to be post-infection, autoimmunity, and associated inflammation. Inflammation is particularly damaging to the mitochondrion. Additionally, abnormal blood flow means oxygenated red cells do not reach the mitochondria, which over time affects mitochondrial biogenesis and function. Chronic low oxygen levels or low blood flow, Dr. Systrom explained, “can affect mitochondria adversely.”
Known triggers in ME/CFS include EBV (mononucleosis), Lyme disease and other tick-borne illnesses, and various bacterial infections. Long COVID is, by definition, post-viral.
Dysautonomia: The Autonomic Connection
Disrupted blood flow in these patients is likely due to both inflammation and autonomic nervous system dysfunction. Dr. Systrom’s most recent data, presented at a focused research meeting in Cambridge, suggests that two-thirds of patients with ME and long COVID have evidence of small fiber autonomic neuropathy. That number may be even higher in long COVID.
Dysautonomia can present with the full range of symptoms used to clinically diagnose ME/CFS and long COVID. The most recognized presentation is orthostatic intolerance, particularly POTS (postural orthostatic tachycardia syndrome), where standing or upright exercise triggers a significant increase in heart rate. But dysautonomia also shows up as:
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Fibromyalgia and amplified pain sensation
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Cardiovascular dysregulation, including abnormally high or low heart rate and blood pressure
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GI symptoms including constipation, diarrhea, and gastric motility issues
On the GI front, Dr. Systrom noted that while the primary driver appears to be autonomic dysfunction rather than classic gut inflammation, emerging data from Cambridge suggests microscopic inflammatory changes in ME and long COVID that affect the gut blood barrier. There is growing evidence that bacterial or viral leakage from the gut, combined with an abnormal microbiome, may have whole-body effects.
Three Pathways, Three Treatment Targets
Dr. Systrom described three major biological pathways that drive symptoms in these patients, each pointing toward a different treatment approach:
Inflammation is likely addressed by low-dose naltrexone.
Dysautonomia is addressed by pyridostigmine, also known as Mestinon.
Mitochondrial dysfunction currently points toward antioxidant support. The Mitochondrial Medicine Society recommends a combination of three antioxidant vitamins known as the Mito cocktail, which appears to help roughly half of patients with known mitochondrial dysfunction, though the evidence in ME/CFS and long COVID is still developing.
“So it’s an iterative process where we’re really, in a sense, using clinical trials with drugs, largely FDA-approved off-label drugs, to learn more about the disease, be smarter about prescribing specific drugs and really creating some precision medicine for these patients.”
Two Active Clinical Trials
The LIFT Trial is recruiting 160 patients in a 1:1:1:1 randomized design. Participants receive either placebo, low-dose naltrexone, pyridostigmine (Mestinon), or the combination of both drugs for three months. Outcome variables include wearable device data, questionnaires, and omics panels drawn from blood, including metabolomics, plasma proteomics, and transcriptomics. Noninvasive exercise tests, including a three-minute step test, are also part of the protocol. The LIFT trial is funded by Linda Tannenbaum and the Open Medicine Foundation.
The Muscle Biopsy Study involves a needle biopsy of the vastus lateralis (thigh) on day one and day eight. On day seven, patients undergo an exhaustive exercise protocol designed to provoke a small amount of PEM. The goal is to better understand the role of the muscle mitochondrion in fatigue, post-exertional malaise, and other symptoms.
To inquire about participation in either trial, contact senior clinical trial coordinator Johanna Squires through Brigham and Women’s Hospital.
A Shift in Physician Awareness
One of the most meaningful shifts Dr. Systrom has observed is among physicians themselves. Long COVID has forced the medical community to reckon with post-viral illness in a way that ME/CFS alone did not.
“What we hear repeatedly now is I have a family member with long COVID and, oh, by the way, maybe I was wrong about ME/CFS back in the day. Didn’t know about it. Didn’t pay attention to it, but now I sure am.”
Dr. Nancy Klimas, a longtime voice in this space, had said early in the pandemic that this would happen. As Haylie noted, Dr. Klimas was clear: “We’ve seen this, we’ve seen it before, and we’re going to see it again.”
You Are Not Alone
If you or someone you love has been dismissed, misdiagnosed, or told that debilitating exercise intolerance is simply deconditioning, know that the research is catching up to what patients have been reporting for decades. Physicians like Dr. Systrom are building the evidence base to change how these diseases are diagnosed and treated.
To watch the full conversation with Dr. David Systrom, visit the Fast Metabolism Method podcast. To join Haylie’s private membership community for support, personalized guidance, and access to podcast guests, visit HayliePomroy.com/member.
Transcript
Seeing patients who had been severely compromised in terms of exercise tolerance, could have been a year, two years, 20 years, many of them in the prime of life, many of them becoming disabled, no longer able to work. The patients being told that it's all in their head, or it's simple deconditioning, you're out of shape, you're going to be able to work this out in the gym, go to the gym and fix it. Right.
All these patients coming in with very similar stories.
[Haylie Pomroy]
Hi, it's Haylie Pomroy, your host. I've written six New York Times bestselling books on metabolic pathways. And my latest book, Toxic Overload, tells you exactly what to do when your body's overburdened.
If you go to hayliepomroy.com/book, for a limited time, you can download a digital copy of this book completely free. That's hayliepomroy.com forward slash book, grab your free copy while supplies last. Now back to our show.
I'm your host, Haylie Pomroy, number one New York Times bestselling author of The Fast Metabolism Diet, a leading health and wellness expert. And that's right, you guys, I am back in school getting my PhD in neuroimmunology. As always, I will be a fierce advocate for those in a little bit of need.
Today, we're going to tackle the subject of exercise intolerance, both in ME/CFS and in long COVID. Today, I'm joined by a dear friend of the Institute of Neuroimmune Medicine, Dr. David Systrom. Dr. Systrom has done research seminars for our institute. He is one of our keynote speakers at our annual INM conference. And Dr. Systrom, I got the pleasure of finally meeting you in person, but I had to go all the way to London where we were hanging out together in Cambridge.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
All true.
[Haylie Pomroy]
So tell everybody, tell our community, like what were we doing there?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
So there was one of these focused small meetings on ME and long COVID, and I'll probably refer to ME/CFS as ME repeatedly here. And this year's particular focus, I think this was the 12th or 13th year they've done it. This was my third.
The focus was on immunologic aspects of both ME and long COVID. And like a lot of these very small focused meetings, really there's a world-class assembly of speakers, and they really are fabulous. A quick little story.
In the course of the month of May, I went to Stavanger, Norway, then Berlin, and then to a big lung meeting, the American Thoracic Society in San Francisco, and then back to Cambridge. And the three smaller meetings in the European countries I just mentioned were highest yield. And they were really nice examples of where we could focus on ME and long COVID, not be distracted by the breadth of cardiopulmonary disease, which would have been the larger meeting I mentioned, and really assembled.
There are some wonderful physician investigators and basic scientists who are all attempting to do the same thing, and that's end up with a solid diagnosis and a cure of these diseases.
[Haylie Pomroy]
Well, it was a phenomenal meeting, and it was incredible to get to spend time with you and so many colleagues. Dr. Systrom, you are a physician at MassGen Brigham. You're also assistant professor at Harvard Medical School.
And currently, you are an active investigator and director of the Brigham and Women's Hospital Advanced Cardiopulmonary Exercise Laboratory. Tell me a little bit about what that means.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Sure. Well, we have a tool that we have found incredibly useful in the investigation of exercise intolerance in ME and long COVID. But the brief backdrop is that this tool is the invasive cardiopulmonary exercise test.
It's a cycle ergometer. Patients cycle away for about six or seven minutes. It usually does not produce PEM, post-exertional malaise, which I'm sure we'll come back to because it's very brief.
There are two catheters and a metabolic cart involved. So the metabolic cart measures oxygen uptake or consumption and carbon dioxide output and breathing. The two catheters allow us a much deeper dive into the physiology and pathophysiology of what goes on during acute exercise in ME and long COVID.
One goes in the wrist artery and the other goes in a big vein in the neck, the internal jugular vein, and it's called a pulmonary artery catheter. And those two catheters really take that testing to another level. They really allow us to measure blood flow and oxygen extraction by the muscle, for instance, during exercise.
And we've got a bunch of findings. We got going with that type of testing many years ago. It was initially created to detect early heart disease and early pulmonary vascular disease.
And then along the way, really over the past decade, we began noticing there were certain patients referred to us with exercise intolerance who didn't have any heart or lung disease that we could identify, but who had something very different. And that's what we'll be talking about today.
[Haylie Pomroy]
So, which I love the way you described that. When we look at those types of testing, first we were looking for manifestation of the lung, manifestation in the cardiovascular system. But then there were these kind of, we talked about outlier patients when we were together, these patients that were presenting.
Was it mostly just the post-exertional malaise, the exhaustion post-exercise? Or were there other things that made kind of the team perk up and say, something's going on here?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Yeah, I think early on, it was a combination of symptoms. It included fatigue just in its own right. And I think 10 years ago, many clinicians didn't know to ask about post-exertional malaise.
You specifically have to frame those questions, especially to get that answer. But broadly speaking, we were aware that there were patients previously normal who might have had some sort of sentinel event, maybe a viral infection pre-COVID, and then afterwards were not normal in terms of exercise tolerance. So, we knew about fatigue and occasionally when we would ask about post-exertional malaise.
But additionally, orthostatic intolerance, lightheadedness, and some of that can occur with exercise, especially upright exercise. And then shortness of breath would be the other symptom that we would be referred patients for.
[Haylie Pomroy]
So, I love that you described those symptoms because so many people in our community, it's more than just, I'm tired after exercise. They're having sometimes cognitive issues, balance issues, shortness of breath, and then they are referred for maybe a pulmonary investigation or cardiovascular investigation. You mentioned post-viral episode.
When, at what point did you start seeing our ME-CFS patients and their profile, did you start seeing the similarity with individuals with long COVID? Were you referred people with long COVID right away? Was it because of the respiratory stress during that infection?
Or how did that start to come out of the fog?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Well, as a card-carrying pulmonary and critical care doc, we certainly saw our fair share of patients during especially the acute initial pandemic early in 2020. But we saw them acutely ill. We saw them on the floors and in the intensive care unit and intubated and on a ventilator and all that.
And then probably toward the end of 2020, this notion of long COVID began to rear its head nationally and globally. And yes, we were then sent patients. The referral patterns at the Brigham and MGB, Mass General Brigham, for the type of testing we do with the invasive CPET really were very similar to what we had experienced with ME before the pandemic.
And it's basically a very well-trained, well-meaning clinician. It could be really from any of the ranks of medicine. It can be a referral from neurology, from rheumatology, from cardiology, from other pulmonologists.
On and on it goes. But generally speaking, patients in primary care have presented to their provider with these exertional symptoms that we just mentioned. And there's been some testing done.
And the type of testing generally depends on which silo the patient finds themselves in. So they see the cardiologist and they have an echo and maybe a cardiac stress test and nothing is found. Or they see the rheumatologist and there's a bunch of blood work and there looks like there's some inflammation and maybe some nonspecific autoimmunity, but no specific diagnosis is given.
They see a pulmonologist for dyspnea, for breathlessness. And pulmonary function tests are done and chest imaging, including a CAT scan. And for the subset of patients, the overwhelming majority of patients, nothing is found.
And then around and around they go and maybe they see their provider again a year later and the testing is repeated and it's still negative. And so the types of patients we saw pre-pandemic and after the establishment of the pandemic and long COVID in 2020 really had undergone similar testing. The referral patterns were the same.
We were very used to this kind of pattern of well-meaning health care providers coming up empty-handed. They're frustrated. The patient's frustrated.
There's no answer. There's no treatment. And that's the type of patient we have seen.
[Haylie Pomroy]
Well, kudos to on both levels. One, to you being out there and being a massive advocate and speaking every opportunity that you get coming on to this podcast. Because it is for patient advocacy, for them to feel empowered and be able to make decisions.
But it's also to educate our upcoming and our current physicians, well-meaning physicians, like you mentioned, that actually provide the referral. In our community, we get so many comments about people having these kinds of, you know, what would appear to be a cardiovascular episode or a pulmonary episode and pretty massive symptoms. And because the testing comes back negative, they're told to, you know, not be stressed, maybe change the relationship, change their job and everything would go away.
And so it's, you know, Dr. Klimas, when we put together this podcast, it was so important that we brought people on that were doing this kind of work. So that people out there know that there are places to go and that there's hope to understand what's going on in your body. Specifically, in a lot of your talks, you speak about mitochondrial dysfunction.
And it's a bit of become a huge buzzword right now. But can you, in some layman terms, for myself, for our community, help us understand what that means, both that's happening in the body and the potential health implications with it?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Sure. So I think many in the audience will know the mitochondrion is the power plant of the cell. And it basically converts food substrate and oxygen into energy.
And that energy is mostly ATP. The mitochondrion is in virtually every cell in the body. There are a couple like the red blood cell where there is none.
But it's particularly important for high energy tissue beds. So that would include anything neural, that's both the central nervous system, the brain, and the peripheral nervous system. And I'm sure we'll come back to that one.
And the heart and the skeletal muscle. These are tissue beds that require enormous increases above resting values of their metabolism, their oxidative metabolism, meaning using oxygen. And so, of course, we've known about the mitochondrion forever.
I think historically, the mitochondrial diseases have been largely assessed by a very special subset of our neurology colleagues and geneticists. And that's because the readily identifiable ones are in fact genetic. Either the nuclear genome has been affected or the mitochondrial genome itself has been affected.
And they tend to run in families. So there can be family history. That's the time-honored way of approaching it.
And then more recently, of course, we've had high-tech ways of getting at the DNA and its function. So those are the classic forms. And they were largely thought to be the more severe forms, appeared in kids, and they ran in families.
But I think what's gained some traction, as you suggest, Haylie, over the past year and a half or so, maybe two, is that there is also an acquired form of mitochondrial dysfunction. Generally speaking, it doesn't have a well-defined genetic origin. It's dysfunction.
And we've added to some of that our collaborators in Amsterdam. Rob Wüst, in particular, has had a couple of nice high-profile papers describing this in both ME and long COVID.
[Haylie Pomroy]
So when we say that it's acquired, do we usually find it? Is it infectious in nature? Is it viral in nature?
Can it be environmental toxin in nature? Is it some hormetic event that the body can't reestablish homeostasis with? Explain to me a little bit about how we get here.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Yeah, we wish we had all the answers. I think, as you suggest, there are many inciting causes. And mitochondrial dysfunction may be sort of a final common pathway that begets symptoms, in particular fatigue and post-exertional malaise, cognitive issues.
So this is an active area of research, trying to map out these pathways, determine which are kind of the frequent flyers or maybe not so frequent flyers, identify subsets of patients. But broadly speaking, I think you hit on what's thought to be the pathogenesis of mitochondrial dysfunction in ME and long COVID. Obviously, long COVID is post-viral because these, by definition, are patients who are normal before the virus.
They're not normal after the virus, and it sticks around. But a very similar thing has been described in ME as well. Most of the attention has been given to EBV, mononucleosis, and a phenomenally high history of mononucleosis in patients with ME.
But there are other infections as well. So Lyme disease and other tick-borne illnesses are kind of frequent flyers. But I've seen in the clinic all sorts of post-infectious ME patients.
They can be bacterial infections and others. But what seems to be the common theme is not exclusively, but post-infection, autoimmunity, and associated inflammation. We know that inflammation is particularly bad for a number of tissue beds and organelles, including the mitochondrion.
So inflammation begets mitochondrial dysfunction. So that may be one of the major pathways. The other one I'll just mention up front, and I'm sure we'll talk a little about, is that the mitochondrion, both in the muscle and in the peripheral nerves and the central nervous system, is highly dependent on normal blood flow.
So if blood flow is abnormal, oxygenated red cells don't get to the mitochondrion, it can't do its thing. And it probably does substantively affect mitochondrial biogenesis and mitochondrial function over the long haul, meaning chronic hypoxia or ischemia, low oxygen levels or low blood flow, respectively. Can affect mitochondria adversely.
[Haylie Pomroy]
And is the disruption in blood flow due to an inflammatory response or an autonomic nervous system response?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
So another good question, and the answer is probably both, maybe with disproportionate effects from one of the pathways that you just mentioned in subsets of patients. So we have found a phenomenally high evidence of dysautonomia or autonomic nervous system dysfunction in both ME and long COVID. And our most recent data that I presented briefly at Cambridge suggests that two-thirds of patients with ME and long COVID, maybe even a little bit higher in long COVID, have evidence of this small fiber autonomic neuropathy.
So that's neural, that's dysautonomia.
[Haylie Pomroy]
Just for our community, give me maybe the top three to five symptoms that a person would express if they were dealing with dysautonomia. We're individuals that are already expressing it or maybe starting to become familiar with that term, but what are you seeing clinically? How is it presenting?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Right. Well, honestly, dysautonomia can present with all of the cardinal symptoms that we make the clinical diagnosis of ME or long COVID, every one of them. But what's classic is largely orthostatic intolerance.
So POTS or postural orthostatic tachycardia syndrome would be kind of the granddaddy of them all, and they're very strict criteria of heart rate change during an upright tilt table test in pediatrics and adults. So that's a subset of dysautonomia. So what many are aware of and seems intuitive is this quick assumption of the upright position or prolonged standing and or exercise in the upright position can beget more symptoms in these folks, and that's dysautonomia.
But there are other clues sometimes that the autonomic nervous system is at play. One would be things like fibromyalgia. So that's kind of nociception, or the pain sensation is exaggerated in small fiber neuropathy in many patients.
There are other issues, including cardiovascular, other non-POTS cardiovascular things, high heart rates, low heart rates, high blood pressure, low blood pressure, and then the GI symptoms, constipation, diarrhea, both ends of the spectrum, gastric motility issues, all of those things can be related to the autonomic nervous system dysfunction.
[Haylie Pomroy]
No, no, I love that you mentioned the GI aspect of it because we had a referral the other day that was referred to us by a GI doctor, and they had read everything on this patient, and you know there was motility issue, and they had gone through a diagnosis, you know, a workup around Crohn's, a workup around IBS, a workup, and all of it, you know, came back from a negative perspective. Sometimes there's overlapping or cross-diagnosis that can occur, but I'm really glad that you mentioned that. And is that the peristalsis, like the nervous system telling the bowel to move, or is it an inflammatory response, or is it both there also?
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[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Yeah, I think what's been best documented has been non-inflammatory irritable bowel syndrome. So it's really the, and you can actually document to a degree, small fiber neuropathy by doing small intestine biopsies. It's not a GI doc, but I hear all these things in the clinic for sure.
And so I think more dysautonomia than an inflamed gut. Though, having said that, there are emerging data, some of which we heard in Cambridge, that suggest that at a microscopic level, in ME and long COVID, there are inflammatory changes, not classic like inflammatory bowel disease, but small microscopic changes that beget abnormalities of the gut blood barrier. And there is a growing body of evidence to suggest that leakage of certain bacteria or even viruses out of the gut, the microbiome is abnormal and that either the organisms themselves or their byproducts are deleterious and may affect the whole body.
So there is a super exciting and active area of folks studying the microbiome and the relationship between the microbiome and inflammation and the gut, as you suggested.
[Haylie Pomroy]
Well, that's a lot of my work with my PhD right now. So I have you teeing that up for me.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
You can have this talk.
[Haylie Pomroy]
No, no. But it's been incredibly fascinating and a massive rabbit hole. For 30 years now, I've been in the clinical aspect of working with individuals.
I'm a cytomegalovirus girl, and autoimmune ITP. So that's how things manifested in my body. And now that's been my personal...
I'd gotten into vet school. I was going to be a vet and changed my path, or someone changed my path. It wasn't by choice.
It was by no choice, right? So it's become kind of obviously my life's work and my passion. And I live a very vibrant, healthy life because of getting to work with brilliant individuals like yourself and just learning.
As a pulmonologist, I've read tons of your bio. It's extremely eclectic and it's fascinating to me. But what's been the passion to work in this space?
Dr. Klimas always says, these are the patients that are so complex and so hard to figure out and need hope more than anything else and need all of the people like yourself, like myself, that are working just diligently on a really tough, complex problem. Why? Why this?
Why you?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Maybe, Haylie, before I answer that question, I'll just echo what you said. It takes a village and it takes folks coming at this from all angles. And we have a lot of mutual respect about doing exactly that.
No, for me in particular, my fascination with the disease and then really a career change beginning about a decade ago came out of that exercise testing. So I had an innate interest, as it were, in exercise physiology. I'm a marathoner, done a few other things related.
And I was fascinated by the physiology and the fact that there was this entity initially, ME-CFS, that really defied our usual diagnostic algorithm. This was not heart or lung disease. And it was something else.
And as, again, a pulmonary and critical care physician, the overlap with another entity, which we're very familiar with in a very different setting, which is the ICU, sepsis was not lost on me. So there are vascular abnormalities in sepsis. There are high flow states and dilated blood vessels.
There is mitochondrial dysfunction in sepsis. So there's a huge amount of overlap. And so it was sort of up my alley to study ME-CFS and to try to gain some insight into the pathophysiology of exercise intolerance.
Once I got into it, though, in the clinic, there was maybe a more humanistic side that has helped drive what I've done and many, I would add, if not all in the field. And that was seeing patients who had been severely compromised in terms of exercise tolerance, could have been a year, two years, 20 years, many of them in the prime of life, many of them becoming disabled, no longer able to work. And having been seen, and I mentioned the well-meaning physicians, and I would reiterate that.
But in the end, with frustration by the physician and not being able to find a specific cause that really was in their area. And on the other hand, having a frustrated patient in the clinic, the patient's being told that it's all in their head, or it's simple deconditioning, you're out of shape, you're going to be able to work this out in the gym, go to the gym and fix it. All these patients coming in with very similar stories, to me, there was this human side.
And that has helped drive things for me.
[Haylie Pomroy]
Right. And again, being together and talking about and hearing the stories and just having such a global perspective on the needs that these patients have. And you mentioned, we have sick and frustrated patients.
And absolutely, because a lot of our patients that come in, we have people that were running marathons, were having success in their life. And suddenly, and we're seeing this with long COVID, and suddenly their whole trajectory is completely changed. There's a couple of things that I want to jump in.
If someone wanted to get a referral or come in and participate in some of the studies and trials and testing with you specifically, how would they contact you?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Right. So our senior clinical trial coordinator is Johanna Squires.
[Haylie Pomroy]
Okay.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
S-Q-U-I-R-E-S. Okay. She's a master's level, really exercise physiologist background.
And she's been working with us for four plus years now. And she's absolutely wonderful. And she has organized and is actively overseeing two of our major clinical trials now.
One is called the LIFT trial and a special call out to Linda Tannenbaum and Open Medicine Foundation who have funded this couple million dollar study. We are recruiting 160 patients. They're randomized to receive, this is one to one to one to one ratio, either placebo, which makes it special, or low-dose naltrexone.
[Haylie Pomroy]
Right.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Or pyridostigmine, also known as Mestinon, or the combination of the two drugs for three months. And then we have a couple of, we have actually multiple outcome variables. We're measuring everything from a wearable device to questionnaires to many of the omics.
Metabolomics, plasma, proteomics, transcriptomics, all drawn from blood. And then two non-invasive exercise tests. There are three minute step tests called the shape test.
So she organizes it. Her email is the key way to get screened for that.
[Haylie Pomroy]
I'll make sure our community gets that. And I want to comment that in meeting with all of you and looking at the, I mean, it is a massive workup that you're doing with these patients. It was, you know, I think oftentimes we look at a variable, but and I know that it's your extensive history in the complexity of these syndromes or these issues in the patients, but it's massive.
I mean, just, you know, I was kind of going, when we get in and have all that run, it would just be so fascinating to understand that about the body. We're always trying to strive to lean in and understand what's happening in the body because when we understand it, that's where we can find how to help it or correct or do that. That's the lift.
What's the other one that's running right now?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
So we've got a two-day muscle biopsy. So there's a needle muscle biopsy done of the thigh. It's the lateral, the vastus lateralis done on day one and day eight.
And on day seven, patients undergo an exhaustive exercise protocol. It's noninvasive. It will last about 14 or 15 minutes.
It's designed to provoke a little PEM. And the idea is to better understand the role of the muscle mitochondrion in both the fatigue and post-exertional malaise and potentially other symptoms as well.
[Haylie Pomroy]
In helping with that, does that help the patient look or define a path for support? I mean, if they're positive for that, there's different therapies versus if that's negative?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
No, that's a great point, Haylie. So yes, exactly. So we've mentioned various potential pathways that patients end up with symptoms from.
So for instance, inflammation is likely addressed by low-dose naltrexone. Dysautonomia is addressed by Mestinon. And then there is this third bucket or category, mitochondrial dysfunction, whose current treatment is totally different.
I will say, I'll add this, the Mitochondrial Medicine Society, the U.S. National Society, recommends three antioxidant, basically vitamins. We call it the Mito cocktail. That treatment probably helps, to a degree, half of patients with known mitochondrial dysfunction.
I think the jury's out in ME and long COVID. But you just hit a really important point, which is we are hoping to learn about subsets of patients with these diseases. And those three pathways are kind of major, but they're not the only ones.
And we're hoping to learn by treating them, you know, were we right in treating them with X drug? And if we're wrong, is it possible, meaning the patient doesn't have a great outcome from drug X, can we learn something about the disease and be smarter the next time around? So it's an iterative process where we're really, in a sense, using clinical trials with drugs, largely FDA-approved off-label drugs, to learn more about the disease, be smarter about prescribing specific drugs and really creating some precision medicine for these patients.
[Haylie Pomroy]
And I love that you just said my favorite word, precision medicine. I think that through these types of trials, and it's what we do at the Institute, is we really try to understand metabolically, not even, I don't want to use the word just, but not just metabolically, but what's actually happening in that human body that's experiencing all of those symptoms. Because that's a person right there that's having all of that experience and something's happening, whether, you know, we're looking at cause and the pathophysiology, whether we're looking at function at this point or dysfunction to try to create a new balance or a new homeostasis.
And so, again, one of the things that we all walked away from after you were speaking in Cambridge and we were putting our heads together was the vast amount of looking under the hood that happens during this trial. I know that that's where we're going to find answers, but I know that it's an inexpensive process and a difficult one to do, but it really punctuates the understanding of the complexity in this body. I know everybody's going to have a million questions for you, so I'm going to be asking you to come back if that's okay.
I want to hit on two quick things before I let you go. One is, were you, and I'll share with some of the, you know, we have our Friday, put our heads together clinical meeting every Friday and I love it. It's like my favorite thing.
I actually was in Ireland and I could not help myself, but zoom into the meeting. I know, but we just get so many clinical gems there. Were you shocked or surprised that we were going to see long COVID have this reflection or this mirroring of, or is, is it, you know, and that's the big question, ME/CFS.
Were you shocked or did you see it coming?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
I don't know if I'd be so strong to say I saw it coming, but as soon as we started to see these patients and take their history and do their work up, including the invasive CPET, it became immediately abundantly clear we're seeing familiar things and very familiar things, meaning we had seen it all with ME/CFS. So in the exercise world, these two diseases are virtually identical. There may be nuances.
[Haylie Pomroy]
In every case.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Yeah, exactly. But, no, we, we had been seeing such patients for five or six years before the pandemic.
[Haylie Pomroy] Right. And I will, I'll never forget our clinical meeting and Dr. Klimas said to us, you know, cause they were talking about a 14 day clearance of the virus and we're all going to get it and it was, or maybe not or whatever, but it was going to be gone and it was going to clear the body and the body, we would, those of us that didn't have comorbidity and had the resilience or the ability or the luck or whatever it is to survive the initial infection.
And I mean, Dr. Klimas was pretty adamant, like early on. And, and, you know, it was, I just, I will just never forget that moment. She said, we've seen this, we've seen it before and we're going to see it again.
That brought up for us. And I want to end with this about teaching physicians. And I know your position in, in the Harvard Medical School.
We kind of have a theory in the clinic where we say, you know, for so many years we were kicking doors down. And Dr. Harris said the other day, you know, patients don't get to him until they've seen 20 other docs. Right.
And sometimes misdiagnosed or underdiagnosed or frustrated and confused, but physicians for so long, weren't aware of this, of ME-CFS to the degree that, that we all felt like they needed to be. Do you feel like it's been fast-tracked or, or put on the forefront in, in the medical school environment, because doctors it's undeniable, like doctors are such a massive amount of patients in such a condensed amount of time that physicians are having to skill up fast?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Absolutely. I think those factors you just mentioned that it, it's been concentrated in time, but the sheer numbers as well. And so what we hear repeatedly now is I have a family member with long COVID and, oh, by the way, maybe I was wrong about ME-CFS back in the day.
Didn't know about it. Didn't pay attention to it, but now I sure am.
[Haylie Pomroy]
And one of the things my son and I walk our block a lot, he, he works in one of my companies and he said to me, and I, again, I've been doing this for 30 years. And he said to me, mom, is it, is it just more common or are people more aware of it? And I said, when I moved into this neighborhood, it was maybe one every cul-de-sac, an individual had some sort of post-viral syndrome.
I mean, I always so concerned about getting the nomenclature right. And I said, now, you know, we had this big barbecue dinner. And I said, to your point, everybody has themselves a friend, a family member.
It's touched so many people's lives and individuals like yourself that have just been the pioneer in research and are continuing to do such extensive and elaborate investigation into what's going on to these human bodies that are experiencing this is where we're going to find the health.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Oh, amen. We sure hope so. And we hope it's soon.
[Haylie Pomroy]
Hey, this is Haylie Pomroy. And right now we're going to transition into our Q&A portion of the podcast. And you'll notice that we have live viewers asking us questions.
They're my fast metabolism members, and they get all kinds of amazing benefits, like member discounts on my world-class supplements and shakes, every product, every day, personalized guidance and support from myself and my team, and even the ability to ask questions of our podcast guests. If you have questions and want to get them answered, you should absolutely join my membership. And if you go to HayliePomroy.com forward slash member, you can join for free for 30 days. Again, that's HayliePomroy.com forward slash member and join for free for 30 days. I can't wait to see you there. Well, Dr. Systrom, I'm going to make sure that everybody knows how to get a hold of Johanna. What a beautiful human being. I got to spend time with her in Cambridge, too. Our community, I know, is going to have many questions.
I beg you to please come back and let us know how things are going and what a valuable resource you are to all of our millions of viewers that just don't get the opportunity to see you like we do. And so we appreciate you. And, you know, from all of our viewers, thank you so much for doing all the work that you're doing.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
All right. Well, Haylie, back at you and for what you're doing and helping really spread the gospel here. Super important.
And I'm happy to come on back. Thanks for being here.
[Haylie Pomroy] And everybody, I want you to know you're not alone in this journey. Dr. Systrom, myself, Dr. Klimas, all of us at the Institute are here for you. Let us know what you need, and we will continue to pull brilliant minds together to help make sure that you every day feel a sense of hope and know that we are working so hard to get you the help you need and deserve.
Thank you, Dr. Systrom. Always a pleasure to spend time with you. All right, Haylie.
Thank you.
What Your Body Is Actually Trying to Tell You
A conversation with Dr. David Systrom, Physician at Brigham and Women’s Hospital, Assistant Professor of Medicine at Harvard Medical School, and Director of the Massachusetts General Hospital Cardiopulmonary Laboratory
For years, patients with ME/CFS walked into doctors’ offices with life-altering symptoms and walked out with nothing. No diagnosis. No treatment plan. Often, they were told it was all in their head, or that they were simply out of shape and needed to go to the gym. Dr. David Systrom has spent the last decade proving otherwise.
In this episode of the Fast Metabolism Method podcast, Haylie Pomroy sat down with Dr. Systrom to talk about exercise intolerance, the invasive cardiopulmonary exercise test (CPET), mitochondrial dysfunction, dysautonomia, and two active clinical trials that could change how these diseases are treated.
Are toxins making you gain weight? Download the Toxic Overload book: hayliepomroy.com/book
The Test That Changed Everything
Dr. Systrom’s work centers on the invasive cardiopulmonary exercise test, or CPET. Patients cycle on an ergometer for about six or seven minutes while a metabolic cart measures oxygen uptake, carbon dioxide output, and breathing. Two catheters, one placed in the wrist artery and one in the internal jugular vein, allow the team to measure blood flow and oxygen extraction by the muscle during exercise.
“Those two catheters really take that testing to another level. They really allow us to measure blood flow and oxygen extraction by the muscle, for instance, during exercise.”
The test was originally developed to detect early heart disease and early pulmonary vascular disease. But over the past decade, Dr. Systrom and his team began noticing patients with exercise intolerance who had no identifiable heart or lung disease at all. Something else was going on.
Importantly, the test is brief enough that it typically does not trigger post-exertional malaise (PEM), the hallmark crash that follows exertion in ME/CFS and long COVID patients.
The Diagnostic Maze Patients Face
Before reaching Dr. Systrom’s lab, most patients have already been through an exhausting cycle of referrals. They see a cardiologist, get an echo and a cardiac stress test, and nothing is found. They see a rheumatologist, blood work suggests some inflammation and possible nonspecific autoimmunity, but no diagnosis is given. They see a pulmonologist for breathlessness, pulmonary function tests and chest imaging come back clear. And then, in Dr. Systrom’s words, “around and around they go.”
“We were very used to this kind of pattern of well-meaning health care providers coming up empty-handed. They’re frustrated. The patient’s frustrated. There’s no answer. There’s no treatment.”
The referral patterns for long COVID patients, which began arriving at Brigham and Women’s in late 2020, looked nearly identical to the ME/CFS patients they had been seeing for years.
ME/CFS and Long COVID: Virtually Identical in the Exercise Lab
When Dr. Systrom’s team began evaluating long COVID patients using the invasive CPET, the results were immediately familiar.
“As soon as we started to see these patients and take their history and do their workup, including the invasive CPET, it became immediately abundantly clear we’re seeing familiar things and very familiar things, meaning we had seen it all with ME/CFS. So in the exercise world, these two diseases are virtually identical.”
His team had been seeing ME/CFS patients with these patterns for five or six years before the pandemic began.
Mitochondrial Dysfunction: Beyond the Buzzword
Mitochondria are the power plants of the cell. They convert food substrate and oxygen into energy, primarily ATP, and are present in virtually every cell in the body. They are especially critical in high-energy tissue beds: the brain, the peripheral nervous system, the heart, and skeletal muscle.
While classical mitochondrial diseases are largely genetic and tend to run in families, Dr. Systrom explained that there is a growing body of evidence for an acquired form of mitochondrial dysfunction in ME/CFS and long COVID. This form does not have a well-defined genetic origin.
“Rob Wüst, in particular, has had a couple of nice high-profile papers describing this in both ME and long COVID,” Dr. Systrom noted, referring to his collaborators in Amsterdam.
The causes are still being mapped, but the common thread appears to be post-infection, autoimmunity, and associated inflammation. Inflammation is particularly damaging to the mitochondrion. Additionally, abnormal blood flow means oxygenated red cells do not reach the mitochondria, which over time affects mitochondrial biogenesis and function. Chronic low oxygen levels or low blood flow, Dr. Systrom explained, “can affect mitochondria adversely.”
Known triggers in ME/CFS include EBV (mononucleosis), Lyme disease and other tick-borne illnesses, and various bacterial infections. Long COVID is, by definition, post-viral.
Dysautonomia: The Autonomic Connection
Disrupted blood flow in these patients is likely due to both inflammation and autonomic nervous system dysfunction. Dr. Systrom’s most recent data, presented at a focused research meeting in Cambridge, suggests that two-thirds of patients with ME and long COVID have evidence of small fiber autonomic neuropathy. That number may be even higher in long COVID.
Dysautonomia can present with the full range of symptoms used to clinically diagnose ME/CFS and long COVID. The most recognized presentation is orthostatic intolerance, particularly POTS (postural orthostatic tachycardia syndrome), where standing or upright exercise triggers a significant increase in heart rate. But dysautonomia also shows up as:
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Fibromyalgia and amplified pain sensation
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Cardiovascular dysregulation, including abnormally high or low heart rate and blood pressure
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GI symptoms including constipation, diarrhea, and gastric motility issues
On the GI front, Dr. Systrom noted that while the primary driver appears to be autonomic dysfunction rather than classic gut inflammation, emerging data from Cambridge suggests microscopic inflammatory changes in ME and long COVID that affect the gut blood barrier. There is growing evidence that bacterial or viral leakage from the gut, combined with an abnormal microbiome, may have whole-body effects.
Three Pathways, Three Treatment Targets
Dr. Systrom described three major biological pathways that drive symptoms in these patients, each pointing toward a different treatment approach:
Inflammation is likely addressed by low-dose naltrexone.
Dysautonomia is addressed by pyridostigmine, also known as Mestinon.
Mitochondrial dysfunction currently points toward antioxidant support. The Mitochondrial Medicine Society recommends a combination of three antioxidant vitamins known as the Mito cocktail, which appears to help roughly half of patients with known mitochondrial dysfunction, though the evidence in ME/CFS and long COVID is still developing.
“So it’s an iterative process where we’re really, in a sense, using clinical trials with drugs, largely FDA-approved off-label drugs, to learn more about the disease, be smarter about prescribing specific drugs and really creating some precision medicine for these patients.”
Two Active Clinical Trials
The LIFT Trial is recruiting 160 patients in a 1:1:1:1 randomized design. Participants receive either placebo, low-dose naltrexone, pyridostigmine (Mestinon), or the combination of both drugs for three months. Outcome variables include wearable device data, questionnaires, and omics panels drawn from blood, including metabolomics, plasma proteomics, and transcriptomics. Noninvasive exercise tests, including a three-minute step test, are also part of the protocol. The LIFT trial is funded by Linda Tannenbaum and the Open Medicine Foundation.
The Muscle Biopsy Study involves a needle biopsy of the vastus lateralis (thigh) on day one and day eight. On day seven, patients undergo an exhaustive exercise protocol designed to provoke a small amount of PEM. The goal is to better understand the role of the muscle mitochondrion in fatigue, post-exertional malaise, and other symptoms.
To inquire about participation in either trial, contact senior clinical trial coordinator Johanna Squires through Brigham and Women’s Hospital.
A Shift in Physician Awareness
One of the most meaningful shifts Dr. Systrom has observed is among physicians themselves. Long COVID has forced the medical community to reckon with post-viral illness in a way that ME/CFS alone did not.
“What we hear repeatedly now is I have a family member with long COVID and, oh, by the way, maybe I was wrong about ME/CFS back in the day. Didn’t know about it. Didn’t pay attention to it, but now I sure am.”
Dr. Nancy Klimas, a longtime voice in this space, had said early in the pandemic that this would happen. As Haylie noted, Dr. Klimas was clear: “We’ve seen this, we’ve seen it before, and we’re going to see it again.”
You Are Not Alone
If you or someone you love has been dismissed, misdiagnosed, or told that debilitating exercise intolerance is simply deconditioning, know that the research is catching up to what patients have been reporting for decades. Physicians like Dr. Systrom are building the evidence base to change how these diseases are diagnosed and treated.
To watch the full conversation with Dr. David Systrom, visit the Fast Metabolism Method podcast. To join Haylie’s private membership community for support, personalized guidance, and access to podcast guests, visit HayliePomroy.com/member.
Transcript
Seeing patients who had been severely compromised in terms of exercise tolerance, could have been a year, two years, 20 years, many of them in the prime of life, many of them becoming disabled, no longer able to work. The patients being told that it's all in their head, or it's simple deconditioning, you're out of shape, you're going to be able to work this out in the gym, go to the gym and fix it. Right.
All these patients coming in with very similar stories.
[Haylie Pomroy]
Hi, it's Haylie Pomroy, your host. I've written six New York Times bestselling books on metabolic pathways. And my latest book, Toxic Overload, tells you exactly what to do when your body's overburdened.
If you go to hayliepomroy.com/book, for a limited time, you can download a digital copy of this book completely free. That's hayliepomroy.com forward slash book, grab your free copy while supplies last. Now back to our show.
I'm your host, Haylie Pomroy, number one New York Times bestselling author of The Fast Metabolism Diet, a leading health and wellness expert. And that's right, you guys, I am back in school getting my PhD in neuroimmunology. As always, I will be a fierce advocate for those in a little bit of need.
Today, we're going to tackle the subject of exercise intolerance, both in ME/CFS and in long COVID. Today, I'm joined by a dear friend of the Institute of Neuroimmune Medicine, Dr. David Systrom. Dr. Systrom has done research seminars for our institute. He is one of our keynote speakers at our annual INM conference. And Dr. Systrom, I got the pleasure of finally meeting you in person, but I had to go all the way to London where we were hanging out together in Cambridge.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
All true.
[Haylie Pomroy]
So tell everybody, tell our community, like what were we doing there?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
So there was one of these focused small meetings on ME and long COVID, and I'll probably refer to ME/CFS as ME repeatedly here. And this year's particular focus, I think this was the 12th or 13th year they've done it. This was my third.
The focus was on immunologic aspects of both ME and long COVID. And like a lot of these very small focused meetings, really there's a world-class assembly of speakers, and they really are fabulous. A quick little story.
In the course of the month of May, I went to Stavanger, Norway, then Berlin, and then to a big lung meeting, the American Thoracic Society in San Francisco, and then back to Cambridge. And the three smaller meetings in the European countries I just mentioned were highest yield. And they were really nice examples of where we could focus on ME and long COVID, not be distracted by the breadth of cardiopulmonary disease, which would have been the larger meeting I mentioned, and really assembled.
There are some wonderful physician investigators and basic scientists who are all attempting to do the same thing, and that's end up with a solid diagnosis and a cure of these diseases.
[Haylie Pomroy]
Well, it was a phenomenal meeting, and it was incredible to get to spend time with you and so many colleagues. Dr. Systrom, you are a physician at MassGen Brigham. You're also assistant professor at Harvard Medical School.
And currently, you are an active investigator and director of the Brigham and Women's Hospital Advanced Cardiopulmonary Exercise Laboratory. Tell me a little bit about what that means.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Sure. Well, we have a tool that we have found incredibly useful in the investigation of exercise intolerance in ME and long COVID. But the brief backdrop is that this tool is the invasive cardiopulmonary exercise test.
It's a cycle ergometer. Patients cycle away for about six or seven minutes. It usually does not produce PEM, post-exertional malaise, which I'm sure we'll come back to because it's very brief.
There are two catheters and a metabolic cart involved. So the metabolic cart measures oxygen uptake or consumption and carbon dioxide output and breathing. The two catheters allow us a much deeper dive into the physiology and pathophysiology of what goes on during acute exercise in ME and long COVID.
One goes in the wrist artery and the other goes in a big vein in the neck, the internal jugular vein, and it's called a pulmonary artery catheter. And those two catheters really take that testing to another level. They really allow us to measure blood flow and oxygen extraction by the muscle, for instance, during exercise.
And we've got a bunch of findings. We got going with that type of testing many years ago. It was initially created to detect early heart disease and early pulmonary vascular disease.
And then along the way, really over the past decade, we began noticing there were certain patients referred to us with exercise intolerance who didn't have any heart or lung disease that we could identify, but who had something very different. And that's what we'll be talking about today.
[Haylie Pomroy]
So, which I love the way you described that. When we look at those types of testing, first we were looking for manifestation of the lung, manifestation in the cardiovascular system. But then there were these kind of, we talked about outlier patients when we were together, these patients that were presenting.
Was it mostly just the post-exertional malaise, the exhaustion post-exercise? Or were there other things that made kind of the team perk up and say, something's going on here?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Yeah, I think early on, it was a combination of symptoms. It included fatigue just in its own right. And I think 10 years ago, many clinicians didn't know to ask about post-exertional malaise.
You specifically have to frame those questions, especially to get that answer. But broadly speaking, we were aware that there were patients previously normal who might have had some sort of sentinel event, maybe a viral infection pre-COVID, and then afterwards were not normal in terms of exercise tolerance. So, we knew about fatigue and occasionally when we would ask about post-exertional malaise.
But additionally, orthostatic intolerance, lightheadedness, and some of that can occur with exercise, especially upright exercise. And then shortness of breath would be the other symptom that we would be referred patients for.
[Haylie Pomroy]
So, I love that you described those symptoms because so many people in our community, it's more than just, I'm tired after exercise. They're having sometimes cognitive issues, balance issues, shortness of breath, and then they are referred for maybe a pulmonary investigation or cardiovascular investigation. You mentioned post-viral episode.
When, at what point did you start seeing our ME-CFS patients and their profile, did you start seeing the similarity with individuals with long COVID? Were you referred people with long COVID right away? Was it because of the respiratory stress during that infection?
Or how did that start to come out of the fog?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Well, as a card-carrying pulmonary and critical care doc, we certainly saw our fair share of patients during especially the acute initial pandemic early in 2020. But we saw them acutely ill. We saw them on the floors and in the intensive care unit and intubated and on a ventilator and all that.
And then probably toward the end of 2020, this notion of long COVID began to rear its head nationally and globally. And yes, we were then sent patients. The referral patterns at the Brigham and MGB, Mass General Brigham, for the type of testing we do with the invasive CPET really were very similar to what we had experienced with ME before the pandemic.
And it's basically a very well-trained, well-meaning clinician. It could be really from any of the ranks of medicine. It can be a referral from neurology, from rheumatology, from cardiology, from other pulmonologists.
On and on it goes. But generally speaking, patients in primary care have presented to their provider with these exertional symptoms that we just mentioned. And there's been some testing done.
And the type of testing generally depends on which silo the patient finds themselves in. So they see the cardiologist and they have an echo and maybe a cardiac stress test and nothing is found. Or they see the rheumatologist and there's a bunch of blood work and there looks like there's some inflammation and maybe some nonspecific autoimmunity, but no specific diagnosis is given.
They see a pulmonologist for dyspnea, for breathlessness. And pulmonary function tests are done and chest imaging, including a CAT scan. And for the subset of patients, the overwhelming majority of patients, nothing is found.
And then around and around they go and maybe they see their provider again a year later and the testing is repeated and it's still negative. And so the types of patients we saw pre-pandemic and after the establishment of the pandemic and long COVID in 2020 really had undergone similar testing. The referral patterns were the same.
We were very used to this kind of pattern of well-meaning health care providers coming up empty-handed. They're frustrated. The patient's frustrated.
There's no answer. There's no treatment. And that's the type of patient we have seen.
[Haylie Pomroy]
Well, kudos to on both levels. One, to you being out there and being a massive advocate and speaking every opportunity that you get coming on to this podcast. Because it is for patient advocacy, for them to feel empowered and be able to make decisions.
But it's also to educate our upcoming and our current physicians, well-meaning physicians, like you mentioned, that actually provide the referral. In our community, we get so many comments about people having these kinds of, you know, what would appear to be a cardiovascular episode or a pulmonary episode and pretty massive symptoms. And because the testing comes back negative, they're told to, you know, not be stressed, maybe change the relationship, change their job and everything would go away.
And so it's, you know, Dr. Klimas, when we put together this podcast, it was so important that we brought people on that were doing this kind of work. So that people out there know that there are places to go and that there's hope to understand what's going on in your body. Specifically, in a lot of your talks, you speak about mitochondrial dysfunction.
And it's a bit of become a huge buzzword right now. But can you, in some layman terms, for myself, for our community, help us understand what that means, both that's happening in the body and the potential health implications with it?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Sure. So I think many in the audience will know the mitochondrion is the power plant of the cell. And it basically converts food substrate and oxygen into energy.
And that energy is mostly ATP. The mitochondrion is in virtually every cell in the body. There are a couple like the red blood cell where there is none.
But it's particularly important for high energy tissue beds. So that would include anything neural, that's both the central nervous system, the brain, and the peripheral nervous system. And I'm sure we'll come back to that one.
And the heart and the skeletal muscle. These are tissue beds that require enormous increases above resting values of their metabolism, their oxidative metabolism, meaning using oxygen. And so, of course, we've known about the mitochondrion forever.
I think historically, the mitochondrial diseases have been largely assessed by a very special subset of our neurology colleagues and geneticists. And that's because the readily identifiable ones are in fact genetic. Either the nuclear genome has been affected or the mitochondrial genome itself has been affected.
And they tend to run in families. So there can be family history. That's the time-honored way of approaching it.
And then more recently, of course, we've had high-tech ways of getting at the DNA and its function. So those are the classic forms. And they were largely thought to be the more severe forms, appeared in kids, and they ran in families.
But I think what's gained some traction, as you suggest, Haylie, over the past year and a half or so, maybe two, is that there is also an acquired form of mitochondrial dysfunction. Generally speaking, it doesn't have a well-defined genetic origin. It's dysfunction.
And we've added to some of that our collaborators in Amsterdam. Rob Wüst, in particular, has had a couple of nice high-profile papers describing this in both ME and long COVID.
[Haylie Pomroy]
So when we say that it's acquired, do we usually find it? Is it infectious in nature? Is it viral in nature?
Can it be environmental toxin in nature? Is it some hormetic event that the body can't reestablish homeostasis with? Explain to me a little bit about how we get here.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Yeah, we wish we had all the answers. I think, as you suggest, there are many inciting causes. And mitochondrial dysfunction may be sort of a final common pathway that begets symptoms, in particular fatigue and post-exertional malaise, cognitive issues.
So this is an active area of research, trying to map out these pathways, determine which are kind of the frequent flyers or maybe not so frequent flyers, identify subsets of patients. But broadly speaking, I think you hit on what's thought to be the pathogenesis of mitochondrial dysfunction in ME and long COVID. Obviously, long COVID is post-viral because these, by definition, are patients who are normal before the virus.
They're not normal after the virus, and it sticks around. But a very similar thing has been described in ME as well. Most of the attention has been given to EBV, mononucleosis, and a phenomenally high history of mononucleosis in patients with ME.
But there are other infections as well. So Lyme disease and other tick-borne illnesses are kind of frequent flyers. But I've seen in the clinic all sorts of post-infectious ME patients.
They can be bacterial infections and others. But what seems to be the common theme is not exclusively, but post-infection, autoimmunity, and associated inflammation. We know that inflammation is particularly bad for a number of tissue beds and organelles, including the mitochondrion.
So inflammation begets mitochondrial dysfunction. So that may be one of the major pathways. The other one I'll just mention up front, and I'm sure we'll talk a little about, is that the mitochondrion, both in the muscle and in the peripheral nerves and the central nervous system, is highly dependent on normal blood flow.
So if blood flow is abnormal, oxygenated red cells don't get to the mitochondrion, it can't do its thing. And it probably does substantively affect mitochondrial biogenesis and mitochondrial function over the long haul, meaning chronic hypoxia or ischemia, low oxygen levels or low blood flow, respectively. Can affect mitochondria adversely.
[Haylie Pomroy]
And is the disruption in blood flow due to an inflammatory response or an autonomic nervous system response?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
So another good question, and the answer is probably both, maybe with disproportionate effects from one of the pathways that you just mentioned in subsets of patients. So we have found a phenomenally high evidence of dysautonomia or autonomic nervous system dysfunction in both ME and long COVID. And our most recent data that I presented briefly at Cambridge suggests that two-thirds of patients with ME and long COVID, maybe even a little bit higher in long COVID, have evidence of this small fiber autonomic neuropathy.
So that's neural, that's dysautonomia.
[Haylie Pomroy]
Just for our community, give me maybe the top three to five symptoms that a person would express if they were dealing with dysautonomia. We're individuals that are already expressing it or maybe starting to become familiar with that term, but what are you seeing clinically? How is it presenting?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Right. Well, honestly, dysautonomia can present with all of the cardinal symptoms that we make the clinical diagnosis of ME or long COVID, every one of them. But what's classic is largely orthostatic intolerance.
So POTS or postural orthostatic tachycardia syndrome would be kind of the granddaddy of them all, and they're very strict criteria of heart rate change during an upright tilt table test in pediatrics and adults. So that's a subset of dysautonomia. So what many are aware of and seems intuitive is this quick assumption of the upright position or prolonged standing and or exercise in the upright position can beget more symptoms in these folks, and that's dysautonomia.
But there are other clues sometimes that the autonomic nervous system is at play. One would be things like fibromyalgia. So that's kind of nociception, or the pain sensation is exaggerated in small fiber neuropathy in many patients.
There are other issues, including cardiovascular, other non-POTS cardiovascular things, high heart rates, low heart rates, high blood pressure, low blood pressure, and then the GI symptoms, constipation, diarrhea, both ends of the spectrum, gastric motility issues, all of those things can be related to the autonomic nervous system dysfunction.
[Haylie Pomroy]
No, no, I love that you mentioned the GI aspect of it because we had a referral the other day that was referred to us by a GI doctor, and they had read everything on this patient, and you know there was motility issue, and they had gone through a diagnosis, you know, a workup around Crohn's, a workup around IBS, a workup, and all of it, you know, came back from a negative perspective. Sometimes there's overlapping or cross-diagnosis that can occur, but I'm really glad that you mentioned that. And is that the peristalsis, like the nervous system telling the bowel to move, or is it an inflammatory response, or is it both there also?
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[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Yeah, I think what's been best documented has been non-inflammatory irritable bowel syndrome. So it's really the, and you can actually document to a degree, small fiber neuropathy by doing small intestine biopsies. It's not a GI doc, but I hear all these things in the clinic for sure.
And so I think more dysautonomia than an inflamed gut. Though, having said that, there are emerging data, some of which we heard in Cambridge, that suggest that at a microscopic level, in ME and long COVID, there are inflammatory changes, not classic like inflammatory bowel disease, but small microscopic changes that beget abnormalities of the gut blood barrier. And there is a growing body of evidence to suggest that leakage of certain bacteria or even viruses out of the gut, the microbiome is abnormal and that either the organisms themselves or their byproducts are deleterious and may affect the whole body.
So there is a super exciting and active area of folks studying the microbiome and the relationship between the microbiome and inflammation and the gut, as you suggested.
[Haylie Pomroy]
Well, that's a lot of my work with my PhD right now. So I have you teeing that up for me.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
You can have this talk.
[Haylie Pomroy]
No, no. But it's been incredibly fascinating and a massive rabbit hole. For 30 years now, I've been in the clinical aspect of working with individuals.
I'm a cytomegalovirus girl, and autoimmune ITP. So that's how things manifested in my body. And now that's been my personal...
I'd gotten into vet school. I was going to be a vet and changed my path, or someone changed my path. It wasn't by choice.
It was by no choice, right? So it's become kind of obviously my life's work and my passion. And I live a very vibrant, healthy life because of getting to work with brilliant individuals like yourself and just learning.
As a pulmonologist, I've read tons of your bio. It's extremely eclectic and it's fascinating to me. But what's been the passion to work in this space?
Dr. Klimas always says, these are the patients that are so complex and so hard to figure out and need hope more than anything else and need all of the people like yourself, like myself, that are working just diligently on a really tough, complex problem. Why? Why this?
Why you?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Maybe, Haylie, before I answer that question, I'll just echo what you said. It takes a village and it takes folks coming at this from all angles. And we have a lot of mutual respect about doing exactly that.
No, for me in particular, my fascination with the disease and then really a career change beginning about a decade ago came out of that exercise testing. So I had an innate interest, as it were, in exercise physiology. I'm a marathoner, done a few other things related.
And I was fascinated by the physiology and the fact that there was this entity initially, ME-CFS, that really defied our usual diagnostic algorithm. This was not heart or lung disease. And it was something else.
And as, again, a pulmonary and critical care physician, the overlap with another entity, which we're very familiar with in a very different setting, which is the ICU, sepsis was not lost on me. So there are vascular abnormalities in sepsis. There are high flow states and dilated blood vessels.
There is mitochondrial dysfunction in sepsis. So there's a huge amount of overlap. And so it was sort of up my alley to study ME-CFS and to try to gain some insight into the pathophysiology of exercise intolerance.
Once I got into it, though, in the clinic, there was maybe a more humanistic side that has helped drive what I've done and many, I would add, if not all in the field. And that was seeing patients who had been severely compromised in terms of exercise tolerance, could have been a year, two years, 20 years, many of them in the prime of life, many of them becoming disabled, no longer able to work. And having been seen, and I mentioned the well-meaning physicians, and I would reiterate that.
But in the end, with frustration by the physician and not being able to find a specific cause that really was in their area. And on the other hand, having a frustrated patient in the clinic, the patient's being told that it's all in their head, or it's simple deconditioning, you're out of shape, you're going to be able to work this out in the gym, go to the gym and fix it. All these patients coming in with very similar stories, to me, there was this human side.
And that has helped drive things for me.
[Haylie Pomroy]
Right. And again, being together and talking about and hearing the stories and just having such a global perspective on the needs that these patients have. And you mentioned, we have sick and frustrated patients.
And absolutely, because a lot of our patients that come in, we have people that were running marathons, were having success in their life. And suddenly, and we're seeing this with long COVID, and suddenly their whole trajectory is completely changed. There's a couple of things that I want to jump in.
If someone wanted to get a referral or come in and participate in some of the studies and trials and testing with you specifically, how would they contact you?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Right. So our senior clinical trial coordinator is Johanna Squires.
[Haylie Pomroy]
Okay.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
S-Q-U-I-R-E-S. Okay. She's a master's level, really exercise physiologist background.
And she's been working with us for four plus years now. And she's absolutely wonderful. And she has organized and is actively overseeing two of our major clinical trials now.
One is called the LIFT trial and a special call out to Linda Tannenbaum and Open Medicine Foundation who have funded this couple million dollar study. We are recruiting 160 patients. They're randomized to receive, this is one to one to one to one ratio, either placebo, which makes it special, or low-dose naltrexone.
[Haylie Pomroy]
Right.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Or pyridostigmine, also known as Mestinon, or the combination of the two drugs for three months. And then we have a couple of, we have actually multiple outcome variables. We're measuring everything from a wearable device to questionnaires to many of the omics.
Metabolomics, plasma, proteomics, transcriptomics, all drawn from blood. And then two non-invasive exercise tests. There are three minute step tests called the shape test.
So she organizes it. Her email is the key way to get screened for that.
[Haylie Pomroy]
I'll make sure our community gets that. And I want to comment that in meeting with all of you and looking at the, I mean, it is a massive workup that you're doing with these patients. It was, you know, I think oftentimes we look at a variable, but and I know that it's your extensive history in the complexity of these syndromes or these issues in the patients, but it's massive.
I mean, just, you know, I was kind of going, when we get in and have all that run, it would just be so fascinating to understand that about the body. We're always trying to strive to lean in and understand what's happening in the body because when we understand it, that's where we can find how to help it or correct or do that. That's the lift.
What's the other one that's running right now?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
So we've got a two-day muscle biopsy. So there's a needle muscle biopsy done of the thigh. It's the lateral, the vastus lateralis done on day one and day eight.
And on day seven, patients undergo an exhaustive exercise protocol. It's noninvasive. It will last about 14 or 15 minutes.
It's designed to provoke a little PEM. And the idea is to better understand the role of the muscle mitochondrion in both the fatigue and post-exertional malaise and potentially other symptoms as well.
[Haylie Pomroy]
In helping with that, does that help the patient look or define a path for support? I mean, if they're positive for that, there's different therapies versus if that's negative?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
No, that's a great point, Haylie. So yes, exactly. So we've mentioned various potential pathways that patients end up with symptoms from.
So for instance, inflammation is likely addressed by low-dose naltrexone. Dysautonomia is addressed by Mestinon. And then there is this third bucket or category, mitochondrial dysfunction, whose current treatment is totally different.
I will say, I'll add this, the Mitochondrial Medicine Society, the U.S. National Society, recommends three antioxidant, basically vitamins. We call it the Mito cocktail. That treatment probably helps, to a degree, half of patients with known mitochondrial dysfunction.
I think the jury's out in ME and long COVID. But you just hit a really important point, which is we are hoping to learn about subsets of patients with these diseases. And those three pathways are kind of major, but they're not the only ones.
And we're hoping to learn by treating them, you know, were we right in treating them with X drug? And if we're wrong, is it possible, meaning the patient doesn't have a great outcome from drug X, can we learn something about the disease and be smarter the next time around? So it's an iterative process where we're really, in a sense, using clinical trials with drugs, largely FDA-approved off-label drugs, to learn more about the disease, be smarter about prescribing specific drugs and really creating some precision medicine for these patients.
[Haylie Pomroy]
And I love that you just said my favorite word, precision medicine. I think that through these types of trials, and it's what we do at the Institute, is we really try to understand metabolically, not even, I don't want to use the word just, but not just metabolically, but what's actually happening in that human body that's experiencing all of those symptoms. Because that's a person right there that's having all of that experience and something's happening, whether, you know, we're looking at cause and the pathophysiology, whether we're looking at function at this point or dysfunction to try to create a new balance or a new homeostasis.
And so, again, one of the things that we all walked away from after you were speaking in Cambridge and we were putting our heads together was the vast amount of looking under the hood that happens during this trial. I know that that's where we're going to find answers, but I know that it's an inexpensive process and a difficult one to do, but it really punctuates the understanding of the complexity in this body. I know everybody's going to have a million questions for you, so I'm going to be asking you to come back if that's okay.
I want to hit on two quick things before I let you go. One is, were you, and I'll share with some of the, you know, we have our Friday, put our heads together clinical meeting every Friday and I love it. It's like my favorite thing.
I actually was in Ireland and I could not help myself, but zoom into the meeting. I know, but we just get so many clinical gems there. Were you shocked or surprised that we were going to see long COVID have this reflection or this mirroring of, or is, is it, you know, and that's the big question, ME/CFS.
Were you shocked or did you see it coming?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
I don't know if I'd be so strong to say I saw it coming, but as soon as we started to see these patients and take their history and do their work up, including the invasive CPET, it became immediately abundantly clear we're seeing familiar things and very familiar things, meaning we had seen it all with ME/CFS. So in the exercise world, these two diseases are virtually identical. There may be nuances.
[Haylie Pomroy]
In every case.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Yeah, exactly. But, no, we, we had been seeing such patients for five or six years before the pandemic.
[Haylie Pomroy] Right. And I will, I'll never forget our clinical meeting and Dr. Klimas said to us, you know, cause they were talking about a 14 day clearance of the virus and we're all going to get it and it was, or maybe not or whatever, but it was going to be gone and it was going to clear the body and the body, we would, those of us that didn't have comorbidity and had the resilience or the ability or the luck or whatever it is to survive the initial infection.
And I mean, Dr. Klimas was pretty adamant, like early on. And, and, you know, it was, I just, I will just never forget that moment. She said, we've seen this, we've seen it before and we're going to see it again.
That brought up for us. And I want to end with this about teaching physicians. And I know your position in, in the Harvard Medical School.
We kind of have a theory in the clinic where we say, you know, for so many years we were kicking doors down. And Dr. Harris said the other day, you know, patients don't get to him until they've seen 20 other docs. Right.
And sometimes misdiagnosed or underdiagnosed or frustrated and confused, but physicians for so long, weren't aware of this, of ME-CFS to the degree that, that we all felt like they needed to be. Do you feel like it's been fast-tracked or, or put on the forefront in, in the medical school environment, because doctors it's undeniable, like doctors are such a massive amount of patients in such a condensed amount of time that physicians are having to skill up fast?
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Absolutely. I think those factors you just mentioned that it, it's been concentrated in time, but the sheer numbers as well. And so what we hear repeatedly now is I have a family member with long COVID and, oh, by the way, maybe I was wrong about ME-CFS back in the day.
Didn't know about it. Didn't pay attention to it, but now I sure am.
[Haylie Pomroy]
And one of the things my son and I walk our block a lot, he, he works in one of my companies and he said to me, and I, again, I've been doing this for 30 years. And he said to me, mom, is it, is it just more common or are people more aware of it? And I said, when I moved into this neighborhood, it was maybe one every cul-de-sac, an individual had some sort of post-viral syndrome.
I mean, I always so concerned about getting the nomenclature right. And I said, now, you know, we had this big barbecue dinner. And I said, to your point, everybody has themselves a friend, a family member.
It's touched so many people's lives and individuals like yourself that have just been the pioneer in research and are continuing to do such extensive and elaborate investigation into what's going on to these human bodies that are experiencing this is where we're going to find the health.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
Oh, amen. We sure hope so. And we hope it's soon.
[Haylie Pomroy]
Hey, this is Haylie Pomroy. And right now we're going to transition into our Q&A portion of the podcast. And you'll notice that we have live viewers asking us questions.
They're my fast metabolism members, and they get all kinds of amazing benefits, like member discounts on my world-class supplements and shakes, every product, every day, personalized guidance and support from myself and my team, and even the ability to ask questions of our podcast guests. If you have questions and want to get them answered, you should absolutely join my membership. And if you go to HayliePomroy.com forward slash member, you can join for free for 30 days. Again, that's HayliePomroy.com forward slash member and join for free for 30 days. I can't wait to see you there. Well, Dr. Systrom, I'm going to make sure that everybody knows how to get a hold of Johanna. What a beautiful human being. I got to spend time with her in Cambridge, too. Our community, I know, is going to have many questions.
I beg you to please come back and let us know how things are going and what a valuable resource you are to all of our millions of viewers that just don't get the opportunity to see you like we do. And so we appreciate you. And, you know, from all of our viewers, thank you so much for doing all the work that you're doing.
[David Systrom, MD | Physician, Brigham and Women’s Hospital | Assistant Professor of Medicine, Harvard Medical School | Director, Massachusetts General Hospital Cardiopulmonary Laboratory]
All right. Well, Haylie, back at you and for what you're doing and helping really spread the gospel here. Super important.
And I'm happy to come on back. Thanks for being here.
[Haylie Pomroy] And everybody, I want you to know you're not alone in this journey. Dr. Systrom, myself, Dr. Klimas, all of us at the Institute are here for you. Let us know what you need, and we will continue to pull brilliant minds together to help make sure that you every day feel a sense of hope and know that we are working so hard to get you the help you need and deserve.
Thank you, Dr. Systrom. Always a pleasure to spend time with you. All right, Haylie.
Thank you.
