The 3 TOP Symptoms Of Long Covid & What You Need To Know To Protect Yourself | Dr. Leo Galland

In the year after having COVID, there's a virtual doubling of the rate of heart attacks. How did COVID-19 change your body?

Maybe you had COVID and you're suffering. How can someone know if they have long COVID? What are the most common symptoms, Leo?

Well, I think there are two things to really be aware of. There's what is being defined as the long COVID syndrome. and that has many different faces to it. But there's something else that happens with COVID-19 and my approach has been not so much to ask the question, do you have long COVID? But rather, how did COVID-19 change your body, impact your physiology, and how is that relevant to your present state of health and the health problems that you have? The people who, there are people who are really disabled as a result of COVID often they get sick with COVID and in the early days at least they would get sick and they would not recover. That is they would partially recover but they go on to stay impaired in their functioning in some way and symptomatic. More recently, there's been this phenomenon where people seem to get over COVID. They might even have a mild case. And then over the next several weeks or several months, something else happens. They get another infection and all of a sudden they crash. And the crash may take two forms. Maybe that you're back to having symptoms that you had with COVID or that you have a whole new set of symptoms that didn't even seem to be part of COVID And of course, the symptoms that get attention, as they should, are fatigue, brain fog, and shortness of breath, impaired exercise capacity. And I think the shortness of breath is a phenomenon that I've seen a lot of patients with. And, you know, it usually goes like this. Person cannot, is limited in their ability to do things just because their breathing is impaired. They see cardiologists, cardiologists say there's nothing wrong with your heart, see pulmonologists, there's nothing wrong with your lungs. The problem there, most of the time, is that there's an impairment in the circulation to the lungs, which is very hard to measure.

It's like a vascular thing that happens.

COVID-19 is essentially a vascular problem. I mean, it enters the virus, enters the body, it enters the body through the respiratory tract, but it goes to the blood vessels. It homes there and it creates inflammation of the lining of the blood vessels. That then creates a kind of cascade of effects in which blood clotting occurs because the blood vessels, when you have inflammation in the lining of the blood vessels, you start to get activation of the blood clotting cascade. And then there's impairment in flow to different organs. And that happens in the brain and in the lungs. And in the lungs that effect will produce the shortness of breath. What you really need is to restore blood flow. It's not a problem of the lung tissue itself. It's not a problem of the heart pumping. It's the microcirculation. The same thing happens in the brain. In the brain, the brain is very sensitive to inflammation. Around the blood vessels, you start to get what's called perivascular inflammation. And that really impacts the brain in many ways and is the cause of what I would say are the two major kind of neurologic problems that occur after COVID-19. One is brain fog and the other are disturbances in the regulation of the autonomic nervous system, this phenomenon called POTS, which stands for Positional Orthostatic Tachycardia Syndrome. And that has really become one of the factors that creates disability after COVID-19.

Yeah.

Wow.

So basically what you're saying is after COVID you can get all sorts of complications like shortness of breath because of how it affects your lungs, brain fog and headaches because of and cognitive dysfunction because of how this affects your brain. You get mitochondrial dysfunction, which is your little energy powerhouses where you can't have exercise capacity and you feel tired and fatigued. And it seems to have these long lasting effects of fatigue, brain fog, exercise intolerance, shortness of breath that persist and that are really difficult to treat and conventional approaches seem not to work that well. And then of course you've got, as you mentioned, this nervous system effect, the autonomic nervous system, where you actually have trouble, you know, with standing up and getting dizzy and your heart rate races and you get, you know, just trouble functioning. How many people you think have post-COVID? What is the literature telling us about it? Because I was, earlier reports were kind of all over the place, but it seems like it's a persistent problem.

Oh, it's definitely a persistent problem. Estimate is that there are about 20 million Americans right now.

People about maybe 10%.

Yeah. And.

It may be higher. See, there's another complication of COVID-19 that is sort of distinguished from long COVID. but it is really a post-COVID complication. In the year after having COVID, there's a virtual doubling of the rate of heart attacks, onset of diabetes, high blood pressure, strokes, and the development of some new neurologic or psychiatric disorder. Also GI disorders, the latest study that I saw. So there are all of these problems that don't seem to be COVID, but their incidence is increased after COVID. And I think that's a real phenomenon. I think it's related to what COVID does in your body. I've been tracking blood clotting, for example, microscopic blood clots and disturbances in T-lymphocyte function, memory lymphocytes, the ones that are involved in controlling viruses, for example, old viruses. And I found that there are people who have fully recovered from COVID And I'm seeing this mostly, I'd say, in adult men, middle-aged men. They think they're totally back to normal. But when I look at these parameters, they have evidence of microscopic blood clotting for months after COVID.

How would that show up for somebody? What would be the symptoms of that?

Well, actually there's a panel of tests that Quest Laboratories does. Quest is a national lab, and you can get them through almost any lab. Quest calls it the thrombotic marker panel. Now you can't use that name with other labs, 'cause they'll change it, but it's a measure of four indicators of blood clots. It's very sensitive.

And.

It'S something that I've used for years in trying to evaluate people with certain kinds of chronic inflammatory disorders and chronic fatigue syndrome. But I have never seen as many positive results since the onset of the pandemic.

What is it actually testing for? What is on that rhomboid panel?

It's looking for evidence that a blood clot occurred. And it doesn't have to be a major blood clot.

So, what are the analytes on that test? What are the analytes?

Okay, they look at, okay, the three markers that people aren't familiar with, there's something called fibrin monomers. These are strands of the fibrin that creates the clot. There are thrombin antithrombin complexes. which thrombin is part of what's involved in generating the plot. And there are prothrombin fragments and prothrombin, there's a whole cascade of events involving different proteins. And so we look for activation of those proteins.

Yeah, so basically when your blood's clotting, it has a whole system of clotting and those factors are part of the clotting system that you can measure when they're increased. And that's what we're looking at. Yeah, this is kind of it.

It's kind of like the smoking gun.

Yeah, that's fascinating. So they may not be symptomatic, but they might have these abnormal markers, is what you're saying?

Yeah, and I found them persisting for months and months. And that is what's been all of the research that's looked longitudinally at people who were recovering from COVID find that it takes between two and eight and people who recover. and don't seem to have any symptoms. It takes about two to eight months for different immune parameters and parameters of blood flow to return to normal, even in healthy young people.

That's quite amazing.

This is not like most other infections.

Yeah, it's interesting because we think of COVID as a respiratory problem. but it actually is more of a blood vessel disease than it seems like, and it affects everything. And the things you were talking about, hypertension, diabetes, the gut issues, these are all inflammatory problems. So how does this COVID-19 sequelae happen? Is it because there's some part of the virus that persists, like the spike protein? Is it still activation of the virus at some low level? What is the thinking around how this continues to go on in the body after you recover from COVID the acute infection.

Well, yeah, there are a number of different theories about that and the concept of viral persistence is a prominent one. And the question there is, is it live virus that's persisting or is it just viral fragments? Now, this is not a new question. I mean, you and I have dealt with this issue in patients with chronic fatigue syndromes and various inflammatory disorders for a long time because it's clear that there are a lot of people who get infections and once they've had the infection, they go on to develop a chronic inflammatory state. I think it's way more common after COVID-19 than most other infections. And that might have to do with a kind of cascade of effects. And on my in what I have on my website in the document Long COVID Prevention and Treatment is a graphic that I call the Web of Long COVID. I've been working with this graphic for a little over a year now since the beginning of 2022. And it really and so far it really seems to be the best representation of all of the factors that contribute and that interact to create this kind of spider's web that we get caught in. But I think one thing that happens is the inflammation of blood vessels triggers the clotting phenomena, which involve these tiny fragments in blood called platelets. Platelets are involved in clotting, they clump together. When the platelets clump together on the lining of the blood vessel, they actually transmit signals that get from the inside of the blood vessel to outside the blood vessel where they activate various cells in the immune system. And that phenomenon keeps the cycle moving forward. And it's aggravated by many things. And then it impacts on the immune system. And so the big question, research question is, to what extent is there just something that triggers the chronic inflammation that doesn't go away? And to what extent is there an ongoing presence of the virus in the body. And actually, I think both occur and sometimes the virus is live and the main place where it's living is in the GI tract. And sometimes the virus is no longer live and replicating, they're just fragments. They may be in the lining of the GI tract, for example. This is really interesting study which tells us a lot about this phenomenon. People who were getting routine colonoscopies after COVID-19, when you get a colonoscopy, they do biopsies of the tissue. These were people who had inflammatory bowel disease, so they were doing, but they weren't symptomatic. They were quiescent inflammatory bowel disease. And what these researchers found was that In people who had long COVID symptoms or post-COVID symptoms, they could identify fragments of the virus in the biopsies, whereas people who had fully recovered and had no issues, they couldn't. So at least for some groups of people, the persistence of either live virus or viral fragments in cells of the body, especially in the GI tract, is an important driver of inflammation.

So, yeah, so this is really this whole chronic inflammatory process that happens, right, that's triggered by this persistence of the virus or particles of the virus or some cascade that starts it kind of as a feed forward cycle that you can't get out of.

Right, and then there's this research from Italy that I would love to see confirmed by other researchers, but it changes the whole concept of where that virus may be hiding in your body. The Italian researchers found that the SARS-CoV-2 virus, which causes COVID-19, could actually be isolated from gut bacteria in people who have COVID-19. I mean, we know that when you get COVID, the virus is in your blood, is in your stool. It's in the GI tract and people will shed it in their stool for weeks and weeks, even after the respiratory part is cleared and they have negative nasal swabs and they may be free of symptoms. And the question is, is this because it's part, it's in your body, it's in the lining of this, of the gut or is there something else going on? So these Italian researchers found that if they took the bacteria from people who have COVID-19 and they grew it in culture to the point where there were no viable human cells, that they could actually find the live virus there that was replicating. And that's a very, that's an unusual phenomenon, but it's not unheard of in which A virus that attacks humans or other mammals can also enter into bacteria and become what's called a bacteriophage. What's especially interesting about those findings is that the bacteria that are most infected by the virus are the important beneficial bacteria that are also depleted by having COVID-19. And I think when we talked about this before, Mark, I had mentioned this bacterial species, Figula bacterium prasinitzi, which is a keystone species that's anti-inflammatory. It's a major producer of beneficial short chain fatty acids in the gut. that are not only anti-inflammatory in the gut, but throughout the body. And they even help the brain repair and restore itself.

And.

This particular bacterial species is decimated in the course of COVID People who recover from COVID they have a normalization, a return to normal of the levels of F. Prosznyci. People who develop long COVID are depleted of F. Prosznyci. And if you look at people at the time when they're just recovering from the acute infection, the levels of F. Prosznyci and a couple of other species and the production of beneficial butyrate, that is reduced in people who get long COVID and it's normal in people who don't. So that's it. And that reflects something that COVID-19 is doing in the gut.

So you think that people don't have this particular bacteria and that's why they're susceptible to long COVID or is it the COVID that actually interferes with the bacteria that reduces its benefits?

Oh, I. Well, that's the question. You know, originally I thought, well, the, because F. Probiotics is, is really an important beneficial bacteria that maybe the people that go on to get long are those who lack it to begin with. But the more recent data indicates.

That.

The level of F-prostanoid C drops, at least during hospitalization, while you're in the hospital. It's not impaired to begin with. It drops while you're in the hospital with long COVID. And in outpatients, the people who recover have normal levels. the people who go on to long COVID don't. There's also, and so this gets into another aspect of COVID I talked about the blood vessel aspects. There's this is yet understudied but important effect in the GI tract where there is a marked dysbiosis associated with long COVID. What's interesting is It's similar to the dysbiosis that occurs in chronic fatigue and ME/CFS/ME. There's a leaky gut, there's a loss of these butyrate producing bacteria that are beneficial. There's also an overgrowth of some toxic bacteria.

And.

One that in the study that looked, the one prospective study, It said, okay, we're going to look at the gut microbiome of people who have just recovered from acute COVID. And we're going to see what happens down the road, six months later, who has long COVID and who doesn't. And the one marker was the loss of F-prostanoid and the loss of butyrate production. But the other was an overgrowth of a species called Ruminococcus nasus. and there were a few others. But this ruminococcus species, actually, when I saw that at the same time, I found some data indicating that ruminococcus produces toxins and neurotoxins. And the effect of these neurotoxins in experimental animals is to accelerate the rate of age related decline in brain function. Now, all of the researchers, yeah, so all of the researchers looking at the effect of COVID-19 on cognitive function are basically saying it looks like an acceleration.

Of.

Age-Related decline in cognitive function. I don't believe in age-related decline in cognitive function, by the way.

Being 80 years old, you're smarter than ever. So, I think you're doing it.

I don't think it happens in humans. They're healthy.

But.

It'S not that many of us left, though. There's not that many healthy humans.

Right. So.

This substance called isomylamine, which is produced, can do that. So, what we have basically are the effects of what we'll call post-biotics. Postbiotics are substances made by gut bacteria. They may be beneficial, they may be toxic. And so you get into an imbalance in the production of postbiotics that occurs with COVID and is probably part of the long COVID syndrome. So that's another area that really needs to be addressed is how do we restore a normal healthy gut microbiome? after COVID.

That's a really important point because I think most people don't understand how important your microbiome is to your overall health in terms of your immune system, inflammation, cognitive function, mood, so many aspects. And we, we're, you're talking about are something called postbiotics, which are essentially metabolites of bacteria. They're compounds that bacteria produce in the gut that then are absorbed and affect our entire biology. And so we could actually start to measure, you know, the the relative amounts of different postbiotics, we can measure the amounts of different kinds of bacteria, and we can see, like you're saying with post-COVID, people have a depletion of the good guys and an increase in the bad guys that are producing toxic stuff. And the good guys are producing beneficial stuff, like you said, butyrate, which is a very important compound that regulates immune function, inflammation, is fuel for the gut, has many, many benefits throughout the body, and you need the good bacteria to produce this. So that's depleted. And then at the same time, these toxic bacteria kind of emerge and start to take over, which is driving more inflammation. So it just seems like a vicious cycle. You talk about this web of long COVID. I think it's really important and it sort of explains why we're seeing all these inflammatory problems. You talk about how people are twice as likely to get diabetes, heart disease, high blood pressure, GI problems, neurologic issues, stroke, neuropathy, psychiatric issues like depression, when they have had COVID. And that is all can be explained in my mind through this underlying biology of inflammation. Is that how all these conditions are related to COVID-19?

Oh, yeah, yeah, I think so. And I think the two areas that really need to be focused on the.

Most.

Are the circulatory issues that I mentioned and then the gut dysbiosis. And there's an interesting study. I don't think the final version has been published yet, but it was called the COVID Out study. It was a large study that looked at people at acute COVID-19 and who were given three different alternative treatments. That is not standard treatments. One was ivermectin. The second was a drug called fluvoxamine, which is a kind of antidepressant that was getting a lot of attention as a possible treatment for acute COVID. And the third was metformin, a drug that's ordinarily used to treat diabetes. Well, there were no effects of these on the immediate outcome. and they got them for short periods of time, that is fluvoxamine and metformin were only for 14 days, ivermectin for three days. There was no immediate effect on the outcome, but 10 months later, people who had gotten metformin were 42% less likely to have post-COVID fatigue compared to placebo.

And.

What is very surprising in this is that fluvoxamine actually had a negative effect long term. People who had gotten fluvoxamine, ivermectin had no effect on its own and it didn't interact with the other drugs, but people who had gotten fluvoxamine were more likely to have post-COVID fatigue and people who got both Metformin and fluvoxamine, the Metformin did not work as well. So there clearly seems to have been some negative impact of fluvoxamine in this particular study. I tried to figure out what's the difference, why when we look at Metformin has a lot of different effects on the body, anti-inflammatory effects, but fluvoxamine does also. The one thing that fluvoxamine Metformin does that these other substances don't do is Metformin is known to impact the gut microbiome. And many of the beneficial effects of Metformin are in reversing diabetes and improving insulin sensitivity because Metformin is basically an anti-diabetic drug, although it also has longevity enhancing effects. A lot of the effects of Metformin are realized through the gut microbiome. They're changes in the microbiome that accompany the use of metformin. And, that's the one distinguishing characteristic. That's fascinating. That highlights the importance of the microbiome. Yeah, that's fascinating.

And, I mean, I think, you know, there's so many aspects of our health that are impacted by this virus. It's quite amazing. It's almost like chronic fatigue syndrome, which just affects everything. I had that 25 years ago. You helped me with that. And, I think mine was triggered by mercury, but anything that tips the system into an inflammatory state, whether it's a toxin and virus or infection, can create these long-term system-wide effects that people treat symptomatically instead of dealing with the causes of it. And, I think we're seeing this a lot in medicine now that people are trying to treat it, but they're using drugs that treat the symptoms and not the cause. So I'd love to sort of dive in a little bit and we've talked about, you know, some of the consequences on cognitive function, on these chronic diseases, autoimmunity, developing allergies, chronic digestive issues. This web of long COVID, I think, helps explain why this is all happening. It's a little technical, but I'd love to kind of break it down for people because I think There's this phenomena that happens where we have sort of a tipping point with the virus that actually causes something called ACE2 deficiency, where the virus enters your cell, ACE2 is basically an enzyme that is involved in so many aspects of our health and that causes mitochondrial effects, which are the energy producing cells. I mean, the energy producing little organelles inside your cells. And that has sort of eight different things that happen after that which cause organ damage. So can you talk about how these eight things are connected, what they are, and when we start to sort of thinking about treatment, how we start to treat this? Because it's not necessarily treating all of them separately, it's understanding what the common themes are and then kind of resetting the system. Would you mind sort of walking us through this? Because it's in your, it's in your, it's in your long COVID and prevention treatment document on your website. And also you have a, a guide for, for providers called understanding long COVID, a comprehensive presentation for health professionals on your website. Highly recommended. It's a little technical, but you present all the data, you present all the research. This isn't just kind of pulling, you know, straws out of the air. It's really deep understanding of what, what scientists are now finding that are at the causes of some of the suffering that people are having with long COVID and COVID itself.

I love to go through that, Mark, because I spend most of my time thinking about it.

Yeah, yeah, let's get into it. I might stop you to clarify here and there, but I think if I don't understand it, multiple people, I'm going to help people get this.

Okay, so the central event in COVID-19 is the entry of virus into cells. And in order to do that, In order to enter your cells, it needs a gateway. And the gateway for most cells, not for all cells, is this enzyme called ACE2, which was only discovered around 25 years ago. And ACE2 is a vitally important enzyme. ACE2 is like the fire department. ACE2 is like the police. It's there to correct and reign things in. It's there to balance your body in so many different ways. And when the virus enters your cells through ACE2, it damages ACE2 and decreases its function. And almost all of the severe complications of acute COVID-19 can be linked to that damage to ACE2, the cytokine storm and the overexuberant immune responses and the scarring and the fibrosis and the blood clotting, the damage to blood vessels. The loss of ACE2 just amplifies all of that. With the loss of ACE2 in cells, there is also damage to mitochondria. The mitochondria are these little tiny powerhouses that are responsible for generating most of the energy in your body. That's a pretty complex phenomenon, and it's not only ACE2 deficiency that causes mitochondrial damage, but it's clear that ACE2 deficit and mitochondrial dysfunction persist for months after they are part of this disturbance and function that occurs for months after a person recovers from COVID-19. So the foundation for the program that I use with my patients that I described is trying to restore H2 activity and mitochondrial function. Mitochondria are especially, in the immune system, mitochondria are especially important in restoring immune function back to baseline, to homeostatic conditions. Strangely enough, It's the anti-inflammatory response that is most dependent on mitochondria, not the post, not the pro-inflammatory response. The pro-inflammatory response actually damages mitochondria and it does it for a purpose. So when there's a lot of inflammation going on, metabolically, the immune cells are acting like cancer cells.

And.

You need to restore mitochondrial function for the restoration of homeostasis. That's at the center of the web. Now, disturbances in mitochondrial function in ACE2 create all the strands that go out from there in one way or another, sometimes directly, sometimes indirectly.

And.

The first strand is the one that I mentioned. It's inflammation of the lining of blood vessels, which then contributes to the clotting phenomena, which is the second strand, these microclots. Microclots have gotten a lot of attention. I think they're important. But you can't really understand the microclot phenomenon unless you understand that it's the blood vessels that are promoting the microclots.

Yes, the inflammation is driving the clotting, basically, right? The inflammation of the blood vessels.

Yes, the inflammation and specifically the inflammation, yeah, and specifically the inflammation at the lining of blood vessels. And then that begins to attract different kind and impact different kinds of cells. And so we have an exaggerated response and a dysfunction in the immune system. And there are four different types of cells in the immune system that make up the next four strands in the web. One that is very important that we haven't spoken about, but in people who are really sick and are not responding well, I think it's critical. Those are mast cells. And there's a condition called the mast cell activation syndrome. It's been getting increasing attention, certainly in functional medicine over the past several years. Mast cells are these large kind of primitive cells that don't circulate in the blood. They're in the tissues.

And.

They release a couple of hundred different chemicals, including histamine. Now, the role of histamine in long COVID has gotten some attention because the use of histamine blockers, drugs like Pepcid, have been used to treat it. And low histamine diets have sometimes been used if you look online and you go into chat rooms, people will talk about the benefits of low histamine diets. There's this phenomenon of mast cell activation that occurs, and it's very much tied in with POTS and with some of the neurologic dysfunction that occurs.

So, mast cells we think of as typically in allergies, right? When you have allergies, your mast cells increase histamine. which then creates this sort of hives and allergic symptoms. That's what you're saying happens as part of post-COVID for people?

Yes, except that this can happen without hives. Mast cells in the skin, for example, are very different from mast cells around blood vessels. The mast cells around blood vessels or in the GI tract They react to blood platelets and to blood clotting, whereas the skin mass cells don't. This whole blood vessel inflammation, blood clot phenomena, that can impact your gut or it can impact your organs, internal organs, with no effect on your skin. you might have redness, but you're not necessarily going to get hives or the more obvious symptoms of mast cell activation. In my experience, I would say that the people who do not respond in a smooth way to the program that I use or who are the most disabled almost always have mast cell activation. as what has taken over. And so you have to address that directly.

You mean with antihistamines?

Well, okay. So there's a whole series of things that are done. And what conventional specialists in mast cell activation will do is they'll start you with an antihistamine. You know, any of the ones that are used. Clarinex, Zyrtec, Allegra. And sometimes those are helpful. Sometimes they're not. One of the rules of mast cell activation is that there are no rules. Anything that may help you can make you worse.

Yeah, interesting.

And because the mast cells kind of become like loose cannons. in this situation and you never know exactly how they're going to respond and what they're going to do. You have to go very slowly, very methodically.

How does someone know if the mast cells are going on and activated in their post-COVID phenomena?

There are some blood tests that can be helpful and some urine tests, but they're not very sensitive. You can have It certainly will look at plasma histamine, we'll look at an enzyme called triptase that's produced by mast cells. But as I said, there are 200 different chemicals that are produced, and unless the timing is right, you may miss the peak of those chemicals. So ultimately it is a clinical diagnosis. based upon the nature of the symptoms, the pattern, the response to treatment.

So, you mentioned like four, so that's one of them. What are the other?

Well, then there are a group of white blood cells called monocytes.

Which.

Have.

A tissue component that is the monocyte circle. In the tissues, they're called macrophages, which means a large eater. And these are cells that gobble up bacteria and viruses and damaged cells. And they have important regulatory functions that are definitely imbalanced. I call it the phenomenon monocyte polarization, but they're imbalanced in long COVID. And I think we can trace a lot of that imbalance directly to the ACE2 deficiency and to some extent to the mitochondrial dysfunction. So it's not as if the mast cells need to be treated on their own. The monocyte macrophage polarization, that will usually respond if you deal with the other factors. Then there's the production of autoantibodies. So that involves a type of cell called a B lymphocyte. B lymphocytes produce antibodies. Antibodies are proteins that your body makes to protect itself basically from foreign invaders. I would say I view antibodies like the artillery. The cells themselves are not involved in the combat. The cells produce these antibodies that fly like cannonballs to be involved in the combat. One of the phenomena that occurs in COVID-19 is the production of autoantibodies, antibodies that recognize your own cells and components of your own cells. There are many reasons why this happens. Part of it is that there are proteins in your body that are similar to the proteins that are in the virus. There's this confusion in the immune system. As many as 20% of people with COVID-19 may be making these autoantibodies. There's a lot of debate as to how significant they are. There are some people, because often the autoantibodies kind of need inflammation to be activated. They're just, most of the time, if the inflammation comes down, they're just there, they're not doing anything. But, There are some people for whom they really become part of the problem. That is, aside from calming inflammation, that's very hard to treat on your own. You need a, you know, you'll need a medical professional to treat that. And probably the most effective treatment that I've seen so far has been intravenous gamma globulin, IVIG, which ties up these antibodies.

So the antibodies, you're giving antibodies with IVIGs. So how does that work? Because you're giving immunoglobulins and you're trying to fight the autoantibodies.

What they do is they tie up the autoantibodies basically.

They kind of bind them up.

Yeah, they bind them up. See, there's a complex phenomenon called immune networks in which antibodies recognize proteins called antigens. and they bind to them. But in doing that, they can damage your tissues. There can be fallout from that. Also, the antibodies can lead, can themselves act as antigens and stimulate other antibodies against them. And you get this kind of feed forward cycle of antibodies to antibodies, and then antibodies to the antibodies to antibodies. And Sometimes that actually helps to control inflammation and dampen it down. But sometimes it aggravates the inflammation. It all depends on the specifics of the individual case. So that's a very complex area which no one can navigate on their own. We don't have the tools for self-care there.

However, and you can measure these different antibodies though, right?

Yes.

What are the common antibodies that we see?

Well, the one that I've seen in terms of what you can measure through a standard lab, the ones that are most common are the antiphospholipid antibodies. And those are significant because they may be contributing, there's this phenomenon called antiphospholipid syndrome in which you get blood clots. So they may be aggravating the blood clots. but there are other antibodies that are only identified in research labs, or in highly specialized clinical labs. There's like one lab in the US and one lab in Germany that will measure these. And some of these are antibodies directed.

Against, not specific to COVID-19, but they autoantibodies.

Some of them are. The ones that may be specific to COVID-19 are antibodies directed against ACE2. This was research done at the University of Arkansas.

And.

These were functional, that is they were interfering with ACE2 function and they developed in people who had been hospitalized in almost 80% of people. But in people who had relatively mild infection and were not hospitalized, about 5% of people. So they may play a role. However, most of these antibodies are only active if there's cell damage and inflammation. So if you can calm down the cell damage and inflammation, the autoantibodies don't make a difference.

Interesting.

And that's one of the goals. And then the fourth type of cell are the T cells, T lymphocytes. So T lymphocytes are kind of the generals of the immune system. They are the most evolved cells. They have the most complex sets of functions. And there are many different types of T lymphocytes and one type can morph into another. And it is very clear that there's dysfunction of T lymphocytes in COVID-19.

But.

It isn't clear exactly what it may not be the same in everybody. And maybe the most intriguing study that I saw was a study from Northwestern University where they took people with what they call neurologic, neuroPASK. PASC stands for post-acute sequelae of COVID It's another word for long COVID. And they took people with neurologic symptoms, which included chronic fatigue. I mean, chronic fatigue is often a neurologic symptom. They took people with fatigue, with POTS, with other complications, and they found that there was a major impairment of a group of T-lymphocytes that are called TEMS, T effector memory cells. These are cells that are really important for antiviral immunity. They remember what you've been infected with and they go after the cells that harbor them. And they are T effector memory cells are the cells that keep viruses in check. Epstein-Barr virus, for example.

Yeah.

Okay. Everybody in the world gets infected with Epstein-Barr virus during the course of their life. It never leaves your body. It stays in a dormant state, actually living in B lymphocytes. And what keeps it normal is the activity of these T effector memory cells. When those cells take a hit, Epstein-Barr virus gets more active. That's why antibody levels go up. and I think there's a widespread misinterpretation of the significance of increasing antibodies to EBV in people who have had COVID. I've seen it even in people who are asymptomatic. It's a sign that the effector memory cells, the T effector memory cells, took a hit. Yeah, and so the B cell memory kicks in to keep the virus under control. It's a sign that you need to activate, that you need to support T effector memory cells. They happen, by the way, they happen to love fat. They love on fat. They run on fat, fatty acid oxidation. They don't like sugar, those cells. So you need to support them with an adequate amount of fat in your diet. Inflammation like sugar, and cancer cells like sugar and that metabolic pathway that is activated when the immune cells are multiplying fast and, yeah, that runs on sugar. It's a complex kind of phenomenon, but when you want to calm it down, you really, you need the fat.

Amazing. So, I think I want to soon get into the treatment because we've been talking about the cause. I know there's two other strands of the web that you want to talk about, the viral persistence and the microbial dysbiosis, which we kind of hit on. Do you want to say anything more about those two? Because I want to dive into what people can do about this because it is a daunting problem and it caused a lot of suffering and unnecessary suffering in my mind because there are good treatments.

Oh, yeah. I think there are definitely things that people can do. And of course, it starts with diet, which is really important. There's not one diet that works for everybody. But what we know is that the best way to correct the dysbiosis that occurs is with food.

And.

The most important components of diet for recovery from long COVID or from COVID probably are a group of nutrients called polyphenols, bioflavonoids, and related chemicals that naturally occur in plants, in vegetables, fruits, especially berries, herbs and spices, teas. These play an important role in immune regulation, in curating the gut microbiome.

And.

In regulating the nature of the immune response. A high polyphenol diet is important. I think it's important before COVID It impacts how sick you get with COVID but it's definitely important in recovery from COVID Now, there are some, if you happen to have a mast cell problem, a mast cell activation problem, you should, there are other types of diets. that you may need. One of the characteristics of the people with mast cell activation problems is they're outliers. That is, everything that seems to be helping other people backfires for them. That's the main characteristic that they have.

So.

They have to be, if you find that that's happening, that everything that helps your friends actually backfires on you. There are unpredictable effects. You're very sensitive to a lot of environmental factors or foods, and you can't make any sense of it. Look to mast cell activation as being the thing that got triggered that has to be controlled. Patterns of exercise matter.

Yeah. I mean, basically what you're saying is, you know, a lot of conventional treatments to kind of, before you dive into what you're recommending, a lot of conventional treatment is pharmacologic based medications, and they have limited or marginal benefits. What you're talking about is a whole comprehensive approach is based on a functional medicine framework of how do we actually get to the root causes of long COVID, right?

And, and the food is oh, it's totally functional medicine. Functional medicine is the only successful way to approach long COVID. Because the problem with the conventional paradigm is it works, it says, okay, well what disease do you have? It tries to split everything up into disease categories. And that just doesn't work for lots of chronic ailments. And it really falls flat with long COVID.

Yeah.

So take us through, you talked about the restoring the microbiome with polyphenols, which I think is something people may not have heard before. I mean, we know about probiotics and prebiotics, but all these plant compounds are really important for fostering a healthy, healthy gut microbiome. Those bugs like, they like to eat fruits and vegetables, basically.

Right.

So that's important.

Yeah.

Well, the term that I use is it curates it. They, it shapes the microbiome. And the other thing, fermented foods. fermented foods support the activity of these T effector memory lymphocytes. You know, things like sauerkraut, yogurt. Now, of course, if, and if you have a mast cell problem, you may not be able to eat fermented foods. So that becomes a tip off. Okay, I've got to go in that direction. You know, I'm in the 5% that has to approach this differently. And of course, I'm very tuned into people like that because most of the patients that I wind up seeing are the ones that are the outliers and they fall into those categories. Probiotics can be helpful. In fact, there was a study, I think it was an Italian study, that used a multi-strain probiotic in people who were hospitalized with COVID-19. It was kind of a randomized trial. Some people who were hospitalized got probiotic when they had acute COVID-19 and others didn't. The people who got the probiotics eight to ten months later had a markedly reduced level of fatigue. I think there was like a 40 to 50% reduction in fatigue and over an 80% reduction in severe fatigue. So probiotics definitely make a difference in recovery from COVID-19. The one that I've used that I like the most for short periods of time is a soil-based organism. that it's a strain of Bacillus subtillus, that it's B7092. It produces alpha-interferon and the virus is very sensitive to alpha-interferon. So I will give people that it's available in the US under the name Tundrix. It was originally developed in Ukraine, actually, during the Soviet era.

And.

It was never intended to be a long-term probiotic. It's a short-term, two to four weeks. But I found it really helpful in two settings with regard to COVID-19. One in acute COVID-19, and the other is for people who have GI symptoms. after COVID-19, which a significant number of people do. It really helps control the GI symptoms.

Where can people get that?

It's available online, T-U-N-D-R-E-X. I don't think it's in stores. I've been using it for years, mostly to help people who had been sick with some kind of GI infection. The GI infection got treated, but they didn't get better. The Tundrix, the Bacillus subtillus 7092, was very helpful in restoring balance in the GI tract. So that their post-infectious irritable bowel syndrome, as it's been called, improved. Other probiotics that may be helpful are Lactobacillus plantarum, which basically is what ferments our crap. Lactobacillus plantarum is the ingredient in fermented foods that helps stimulate these T-effector memory cells. Now, for people who have mast cell activation, there may be specific probiotics that would be helpful that actually reduce histamine rather than create it. So again, we get into, if you're somebody in whom all of the treatments that help other people don't work for you, you need to open that door. that becomes, that dominates the web, the mast cell situation. Then there are two strains of probiotics that have been shown to enhance the growth of fecal of bacterium praznintzi. You can't, there's no probiotic of F praznintzi. You need it, right? You can use prebiotics. These are foods that support the growth that are high in fiber or high in certain kinds of resistant starch that support its growth. There are supplements that you can take of certain oligosaccharides, complex starch molecules that support its growth. And So, those two strains are the strain of Bifidobacterium and I listed all of these on the website. So, people are listening and they want.

To know about what to take and they're listening to this and wondering, okay, how am I going to find these probiotics and where can I learn more? Please go to Dr. Galland's website, drgalland.com, and you'll see most of this on there.

Right, on the landing page right at the top, there's this document called Long COVID prevention and treatment.

And.

I try to make it accessible to people who are not health professionals. There's a lot in there, but it tries to, what I try to do is to walk readers through the different steps and also deal with some of the specific problems. they can't be dealt with just by dealing with the fundamentals of the web.

Yeah.

So you talk about the establishment of a healthy gut microbiome as a key part of getting better. So it's really what we've been doing in functional medicine for a long time is how do we restore healthy gut microbiome. But there's specific tips you provide in there about specific probiotics and specific prebiotics that can really help to do this in addition to the things we typically normally do. So that's really important. You talk about some of the other ways of addressing this in terms of viral eradication and addressing the antibodies and sort of helping some of the problems that we have to treat specifically that are occurring from long COVID. Can you talk a little bit about that as well?

Yeah, sure. So the issue of viral eradication. Not everybody has persistent virus in their body, but it's kind of hard right now we don't have good tests for determining that. There are some herbal protocols that I've used to try and ensure that the virus has been eliminated from your body. It's kind of the foundation for moving on with restoring normal function.

And.

There, and so the Tundrix probiotic is part of that. There's an Indian herbal formula called Vedicinals Nine. I've had some very good results with. There are nine different herbs in a liquid form. The main problem with it is the taste, but if you can get past.

That.

It'S really made a difference for a lot of my patients. And it deals with, aside from having antiviral effects, it deals with some of the strands of the web as well. There's a product that was developed in Israel called Tolavid. It's derived from a Chinese herb called Red Gromwell root. It's been used for thousands of years in China that works very similarly to the drug Paxil. And so, you know, I've recommended that for a lot of people. It's not as if there's one formula that actually works for everybody, but that's true for all chronic conditions.

So you're finding that herbs are very helpful with the antiviral effects, right?

Yes. I will often start with, let's make sure that the virus is gone. Let's use the probiotics, and these herbs for viral elimination. And then see where you are. While you're doing that, let's try to build up healthy gut bacteria with diet and with probiotics and prebiotics. You can compensate for the deficit of butyrate by taking butyrate, which is readily available as a supplement, and not necessarily very expensive, if you use sodium butyrate, for example. And let's try to restore ACE2 with not only a high polyphenol diet, but vitamin D, Curcumin and resveratrol. Curcumin and resveratrol are polyphenols that are widely used in functional medicine. Among their protective effects is that they help to restore ACE2 activity in cells.

Yeah, they're also good for longevity, too.

Yeah, they're good for a lot of things. I find they make the biggest difference early on. They're really part of the way that I treat people when they first have COVID.

And.

Then I try to use a person's symptoms as a guide. If fatigue is a significant problem, coenzyme Q10 can be very helpful. other supplements that help mitochondrial recovery. CoQ10, various forms of vitamin B3 niacin make a difference, especially with energy in the recovery stage.

So, you can use all the mitochondrial supports like N-Acetyl Cysteine, L-Carnitine, CoQ10, Carnitine, things like that.

Yeah.

Alpha-lipoic acid and NAC and acetyl cysteine also support ACE2 because ACE2 really gets damaged with the inflammation that occurs. So I use them frequently at the onset of infection because they've been shown to help prevent the damage to ACE2 that occurs with the inflammation. NAC is good for the lungs and alpha lipoic acid is good for the nervous system and is one of the standard natural treatments for neuropathies for damage to nerves.

Yeah, interesting.

So, you get there are multi-functional benefits of these supplements.

And, so you basically personalize the treatment based on what you're finding in this in each patient based on their symptoms and the way the mechanism of actions are working with what we described as part of this sort of web of long COVID. So we talked a little bit about diet and high polyphenols, good fats, we talked about sort of limiting sugar, talked about restoring the gut microbiome, viral eradication. What else do you do for these patients?

There are certain specific problems that people have afterwards that represent around the outside of the web is the organ damage. So certain specific problems people have that are really due to organ damage and dysfunction, which may need to be directly addressed. So for example, the shortness of breath. due to the loss of blood flow to the lungs. There are certain specific supplements that may help that. And you want to prevent, I mean, you want to reverse the blood clotting. But Vinpocetine. Vinpocetine is an extract of periwinkle. It's been around for a long time, mostly used for enhancing brain function. and brain blood flow. Turns out that vinpocetine also enhances blood flow to the lungs. So that is part of the protocol that I use for dealing with shortness of breath in post-COVID shortness of breath.

And.

I have a description of a way you can test some of the mechanisms that might be involved. in your shortness of breath in there. POTS is a very big problem in the people that told me.

And.

With POTS, the first thing, and first of all, you can make that diagnosis yourself. I can't tell you how many patients have consulted me who clearly had POTS. and there is a home test that you can do. I mean, you can do it just by checking your pulse. It's helpful though to be able to check your blood pressure at the same time. Just looking at the changes in heart rate and blood pressure if possible that happen when you go from lying down to standing up. And you stand leaning against a wall to kind of relax your body. for 10 minutes if you can do it. You can't do it for 10 minutes, it's really a big problem. But an increase in your heart rate without a drop in blood pressure of 30 beats a minute or greater is pretty strong evidence of POTS. So we want to address that first of all with you need a lot of salt. if you have pots. You need to expand your blood volume, so you have to avoid dehydration. Diet has complicated effects on pots. On the one hand, carbohydrates tend to help fluid retention. Certainly very low carb diets pull fluid out of your body that may not be desirable, but Carbohydrate, but eating a high carbohydrate meal causes a lot of fluid to go into your gut. And if you eat a high carb meal and you feel like you're going to pass out and your pots gets worse, you probably need to cut back on the amount that you're eating. And there are a number of other resources, there are a number of resources available online. for dealing with pots. One of the things that is really critical for overcoming that is exercise. The problem is you can't exercise because.

You get too... You get too tired.

Too bad when you're exercising. So I will often have people start with supine exercise that is lying in bed using resistance bands as a way to get started exercising and recondition. because deconditioning aggravates POTS. The bottom line here, Mark, is that there are really a lot of things that people can do to recover from this condition. It's taken a long time for.

The.

Medical profession in general and even these special centers for that have been set up to deal with long COVID to really become comprehensive.

Yeah.

So a lot of the traditional conventional medical centers aren't addressing all these issues. They're just treating them symptomatically with medication, but not actually curing them or getting these people better. Do you think these people can get better? People who are suffering from long COVID can fully recover, or is this kind of a lifelong thing?

Oh, yeah, yeah. People can. And I'll just give you one example of a woman who first consulted me, I don't know, maybe over about a year ago, maybe a little longer. No, I'm sorry. Yeah, it was less than a year ago, but she had gotten married a year and a half ago and she was so debilitated with COVID at that time that she needed a wheelchair just to get through the airport.

Wow.

That there was long COVID. About three months ago, she ran a 5K race and had no adverse effects. But you have to be very careful in building up. There's this other phenomenon which occurs in chronic fatigue fibromyalgia called post-exercise malaise. That name actually doesn't really represent how severe this is. Although exercise and conditioning is critical for recovery, there's some people who just can't do it because even normal amounts of exercise will set them back not just for a day or two, but for weeks or months. That, I think that phenomenon is the result of nerve damage and there's been some very interesting research done on that. And so I'm looking into ways of overcoming the nerve damage that creates this phenomenon of post-exercise malaise. IVIG may be helpful there, but I'm looking into peptide therapy.

Yeah, so I want to ask you about, just before we close, I want to sort of talk about a few of the things that are out there in the kind of ether which are around peptides, exosomes, plasma phoresis, ozone, things that people are doing that are a little outside the box that seem to be working for people.

Right.

I think ozone has to be done really carefully because ozone can be, puts a lot of oxidative stress on the lining of blood vessels. We already have inflamed blood vessels. Hyperbaric oxygen may be helpful and has been shown to enhance mitochondrial function. And I have to say, I've seen mixed responses to both hyperbaric oxygen and ozone. I don't have much experience with exosomes. but I have heard reports of benefit. One of my patients benefited from exosomes. It really seemed to impact the neurological response to exercise. So as far as peptides go, I think peptides are very exciting approach to treatment. Of course, this isn't something you can do yourself. You know, you need a doctor to do it. May not be covered by insurance. The peptides generally have to come from compounding pharmacies. But right now, I'm looking at a peptide protocol for treating the neuropathic, the neuropathy of COVID-19 and other neuropathies.

What are you finding works for that?

I just don't have enough data.

What are the peptides you're finding hopeful?

Okay, so yeah, there are three peptides that I'm looking at, and two of them actually are also useful in dealing with mast cell activation. So, two of them are thymus derived peptides, thymulin and thymus and beta four. Thymus and beta four, I really like. It really seems, I think it has beneficial effects in the nervous system. I found great responses to it in people who have had head injuries. And these just, there are some oral forms. Thymus and beta-4 is available in pill form, but they're more effective if they're given by injection. So I use I'll use thymulin and thymus and beta 4 by injection. And then there's another peptide called ARA 290, which actually is FDA approved for the treatment of neuropathy. It's just not really available and relatively expensive. But there have been controlled randomized clinical trials with it for autoimmune neuropathy, which have shown improvement. And it's based on a natural peptide that's found in the body, as most of these are. That's one of the things about peptide therapy is they're all based on natural substances that are important for healing responses.

Yeah, interesting. Yeah.

So, the thymus-derived peptides may also help stabilize mast cells. And then there's another peptide called BPC-157, which is a mast cell stabilizer. That's available in oral and injectable form. So I think that is, that's certainly a frontier of treatment and I think very promising.

It's great. Well, it sounds like there's a lot of things that are available. This is sort of a, when this first came on the scene, you know, COVID was driving so much suffering through post-COVID and nobody really knew what to do or how to deal with it. And, you've spent the last three years deeply researching this, looking at all the scientific papers and coming up with a set of recommendations and a framework for thinking about it through the web of long COVID and a way of actually addressing each of the aspects of this from the root cause and helping people recover. And, I've seen many people with post-COVID as well and I've seen them recover by using this approach. and also by using sometimes things that are a little out of the box. I know, for example, I had not exactly post-COVID, but I mentioned earlier that I had arthritis develop after I got COVID and my hand blew up and I was really feeling terrible. And it has something called plasma phoresis, which is a way of cleaning the blood of inflammatory compounds. So there's a lot of ways to do this. I think people shouldn't get discouraged. They should feel hopeful, actually, if they're suffering, because by using a functional medicine framework, and by looking at these various aspects and finding someone to work with who can help you with some of these other treatments, whether it's peptides or exosomes or, or plasma for resus or even ozone, it can be very, very helpful. Hyperbaric oxygen as well is great for recovery of a lot of the brain issues. So people suffer, but they don't need to. And I think your work has really paved the way for a new way of thinking about how to deal with coven and post-covid syndrome, which is creating so much suffering. But there is a way out, and I think all this is really in your in your website, drgallon.com, both a professional guide which you've created for providers as well as a guide for your average person who can kind of try to figure out how to navigate this because they're not going to necessarily get this from their doctor. So are there any final thoughts you want to share about what we're learning, what's next, how we can kind of take what you're doing and apply it?

Well, I think there are a lot of lessons from the pandemic that we need to absorb. I do think that long COVID is maybe going to be the major public health complication of COVID-19 as it now becomes endemic because the data suggests that that's not going away. And I mean, most people are going to get COVID-19 once a year. and having had COVID before doesn't reduce your risk of getting long COVID. So I think this is really, I mean, this is a wake up call to how we create a sustainable healthcare system.

Yeah.

If you love that last video, you're going to love the next one. Check it out here.

Histamine.

What the heck is histamine? Why should we care? And tell us why it's so important and why it contributes to so many people's unnecessary suffering.

So histamine is found naturally in the body. The body makes histamine. We also consume.