153 - Dr Amir Hadanny - Hyperbaric Solutions to Long Covid Challenges

What if you could harness the power of oxygen to heal the brain? Uncover the potential of hyperbaric oxygen therapy (HBOT) with guest, Dr. Amir Haddany, a leading neurosurgeon and hyperbaric medicine expert. Dr. Haddany takes us through his pioneering research since 2008, sharing how HBOT is transforming treatment for neurological conditions like traumatic brain injuries and long COVID. Through the lens of advanced imaging techniques such as MRI, we explore the profound effects of COVID-19 on critical brain areas and how HBOT might offer a beacon of hope for recovery.

Dr. Haddany's insights reveal the intricate pathways through which long COVID disrupts cognitive functions, backed by compelling imaging evidence. Our conversation delves into the innovative treatment protocols adapted from conditions like ME and fibromyalgia, focusing on the role of oxygen fluctuations in stimulating mitochondria and facilitating healing. The protocols, akin to cellular interval training, illustrate the regenerative potential of HBOT when applied consistently over extended periods, offering a glimpse into the complex process of brain healing.

We unpack a study suggesting long-term benefits for long COVID patients, emphasizing the significance of a rigorous, randomized controlled trial. Dr. Haddany's generous sharing of his knowledge and willingness to engage with our listeners provides not only an insightful discussion but also a platform for future inquiry and exploration into the world of hyperbaric medicine.

Links

• https://aviv-clinics.com/disease/long-covid-syndrome/ (Aviv clinic page)
• https://www.nature.com/articles/s41598-022-15565-0 (published July 22)
• https://www.nature.com/articles/s41598-024-53091-3 (fo

For more information about Long Covid Breathing courses & workshops, please check out LongCovidBreathing.com

(music credit - Brock Hewitt, Rule of Life)

Chapters

• 0:00 Hyperbaric Oxygen Therapy in Medicine
• 20:34 Neurological Impact of Long Covid
• 28:40 Long COVID Treatment Protocol and Research
• 37:17 Long-Term Benefits of Hyperbaric Oxygen
• 49:46 Expertise Sharing in Science

Transcript

Speaker 1: 0:56

Hello and welcome to this episode of the Long Covid Podcast. I'm delighted to be joined today by Dr Amir Haddani and we are going to be diving into the magical world of hyperbaric oxygen and on Covid and all sorts of stuff around this. So a very warm welcome to the podcast today. It's lovely to have you here.

Speaker 2: 1:19

Thank you so much. Pleasure to be here.

Speaker 1: 1:23

Yeah, maybe before we dive too deep into this really interesting topic, can you just say a little bit about yourself, and kind of yeah, what is it that you do?

Speaker 2: 1:33

Sure, so I'm a physician, I trained in neurosurgery, I did fellowships in functional neurosurgery and I also specialize in hyperbaric medicine. I've done this since 2008. And we did over this period of time a lot of research and high-quality research, which started off preclinical studies and then moved on to translational studies and randomized control trials that you'll probably talk about today, really to investigate what is the effect of hyperbaric oxygen therapy and hyperbaric medicine on different neurological indications. So we've been doing this since 2008. And I guess another title I have I have a PhD in bioinformatics, which is all those hype words we hear all the time AI, artificial intelligence, machine learning which is basically taking a lot of data and trying to construct models to predict the future or new patients outcomes and how to optimize our therapies. That's me in a nutshell.

Speaker 1: 2:52

Amazing. So I mean, it's very interesting to me that you started this work. You know you said 2008,. I 2008. I think you know that's a long time before long covid came along, but it's not a long time before things like ME were around, because they've been around for much, much longer. Um, so, yeah, you know you've been kind of laying this groundwork, um, which is very, very cool. Um, what is hyperbaric oxygen or hyperbarics? Are they the same thing, and can we talk a little bit more about what that actually means?

Speaker 2: 3:27

Sure, sure. Before I touch that, I will just address what you mentioned Exactly. Like you just said, I think we started 2008,. I was a neurosurgery resident and I was really intrigued in traumatic brain injuries and I was really looking for ways to help our patients even better. You know, I was doing a lot of trauma surgeries and those patients we saved their lives. But when we talk about function, there was still a lot of disabilities and we were looking for ways to even improve that.

Speaker 2: 4:03

So we went in and investigated hyperbaric medicine, because there was a lot of case reports about it. So we wanted to take this next step and see how can this be done in a methodical way? And that's kind of one thing led to another. Long COVID came. That's kind of one thing led to another. Long COVID came. You know, we never predicted it back then and it just came and we wanted to see if we can help that as well.

Speaker 2: 4:30

So what is hyperbaric oxygen therapy? So we're talking about a method, a medical intervention, to elevate oxygen in our bodies in a very, very specific way. What we do is we take patients, people, and put them in a huge metal room. Think about a huge, huge, huge metal room that is completely closed, and then we elevate the pressure. We do it by compressing more and more air inside that metal room or chamber, if you will. What it does. So think about like an air conditioner that pushes more and more air inside and because it's built of metal, it increases the pressure inside of it. And it's similar to going lower from where you live, like if you're driving down or when you're landing on a plane. The atmospheric pressure is actually increasing when you're going down and then, when you hit the specific point of pressure that you want your patients to be in, you deliver oxygen through oxygen masks, and it has to be 100% oxygen to breathe it.

Speaker 2: 5:56

And the reason we do it under pressure is we're utilizing an interesting physics law called Henry's Law that said that you can dissolve much more gas molecules, in this case oxygen, in the blood or in a liquid. The best way to grasp that is a Coca-Cola can. Right, when you think about it, they're putting a lot of carbon dioxide in this case not oxygen in the liquid of that sweet Coca-Cola liquid, and they do it with pressure. The moment you open the can, you hear that because all the pressure is gone and now you have less and less co2 dissolved in it. If you put that coca-cola can out in the open, you'll have a very flat liquid eventually, because all the pressure is gone. That's what we're doing with hyperbaric medicine we're turning people into soda cans, but in this case we're putting oxygen and we're dissolving a lot more oxygen molecules in the blood, while it's not possible to do it without this pressure.

Speaker 2: 7:12

Wow, I feel like I just need to take a moment and actually take that in Sure um, yeah, so, so when it works better at that, heightened pressure correct, and and the reason why, uh, is we need to go even a little bit deeper again. We got a little bit of physiology 101. Physiology 101 in our body, in the human body. There are two ways that we carry oxygen. One is red blood cells. Red blood cells have four areas that can grasp oxygen molecules and that's um the usual way.

Speaker 2: 7:54

You know, if we ever um went into a you, know, emergency room or anywhere, they had this pulse oximetry that put on your finger and then you'll see on the screen 96, 97, 94, 100. What it means? That 96% of those red blood cells are occupied. They're already fully occupied and those 3%, 4% left are nothing. You don't need them. So that's why, even if you breathe oxygen through a mask, you just increase that with 3% of those oxygen molecules grasped by the other red blood cells and you get to 100. But that's not a significant increase in oxygen content in our bodies. So we go to the other.

Speaker 2: 8:45

The second way that we can carry oxygen in our bodies is just molecules, just oxygen molecules dissolved in the liquid, not carried by red blood cells, but free oxygen molecules, that in room, air and in normal pressure.

Speaker 2: 9:05

That's an insignificant number.

Speaker 2: 9:08

But if you're utilizing that Henry Law that we mentioned earlier and you pressure down, compress inside a lot of oxygen molecules all of a sudden, inside a lot of oxygen molecules all of a sudden, the second method is having a lot more to do and you're increasing that insignificant to a very significant level of oxygen that is added to the normal level of oxygen you already have.

Speaker 2: 9:34

So now we're able to actually boost up the oxygen levels in our body in a very specific way. It's so significant that back, I think already 80 years ago, they did an experiment and they had pigs drained of their blood and instead of blood they ran sort of saline or salted water inside their vessels in a hyperbaric chamber and those pigs survived on hyperbaric oxygen without blood. Why? Because they switched between the second method and the first method. So now no first method with red blood cells and just those three oxygen molecules. That goes to show you that the second method could be so significant and this is the one we're utilizing with hyperbaric medicine, dissolving more oxygen molecules in the plasma of our blood.

Speaker 1: 10:42

Right. So in addition to those, say, 97% that you have in your red blood cells, which is what you measure on the little thing you put on your finger you've got these extra oxygen molecules bouncing around your system effectively, which is a good thing. Now, why? Why is that a good thing? Why is this extra oxygen going to help?

Speaker 2: 11:10

great question. So we're talking about why is it going to help? It's going to help what needs to be healed if we have wounds, and there are different types of wounds. Um, you know, and that's how hyperbaric medicine actually started by wounds in our legs. You know, there are a lot of patients, let's say, with diabetes or other problems, that they have those wounds in their legs that do not heal by themselves. And what we discovered long years ago, many decades ago actually, that if you apply hyperbaric medicine in a very specific protocol, you're able to heal those wounds, because those wounds do not heal on themselves. But if you bring and you supply specific components needed to heal wound we can talk about that you're able to heal a wound. So there are very basic concepts.

Speaker 2: 12:13

To heal a wound, you need four things. Basically, you need energy. That's supplied by oxygen, so you need extra oxygen in order to heal a wound. That's the first one. The second one you need a trigger. You need something that will tell those, all those cells, all those components, to get to that specific wound. That's called a trigger. The third one probably heard of stem cells. Stem cells are building the tissue back to their normal shape and size. So we need stem cells. And the fourth is what we called angiogenesis, or the creation of new blood vessels. So any tissue that was destroyed needs to be rewired to our blood vessels in order to get those oxygen and nutrients in order to survive. So all those four components are needed to heal a wound, and that's what we utilize with hyperbaric medicine. Hyperbaric medicine, if you do it in a very specific protocol, you're able to provide all four components extra oxygen, the trigger stem cells and creating new blood vessels.

Speaker 1: 14:18

So you're able to heal a wound new blood vessels so you're able to heal a wound. Wow, okay, that's cool. So if we're talking about you know a physical wound, say you cut your finger, you know that's that's a sort of very a sort of obvious and, for most people, relatively trivial example. Um, so, putting this into the context of something like long covid, where you know there's, there's a whole host of processes going on in the body. You know you've got a dysfunctional nervous system, you've got potential mitochondrial dysfunction, you've got, you know, some people may have clotting, there might be histamine issues. Um, you know, and all of these things are obviously very connected. But also, you know, it's a kind of jigsaw puzzle piece of you know, all sorts of things going on. So does this same principle that you could apply to a cut on your finger is that that is applicable to this sort of plethora of things going on in long COVID?

Speaker 2: 15:24

So a couple of things. So a common finger usually, as you know, would heal on its own right. That's what our body does. It knows how to heal most injuries, unless it's a very, very severe injury or there is a factor that limits the body to heal itself, because our body has its own mechanism to heal. So A cut in the finger usually heals on itself, but a diabetic foot with a wound, there's so many complex components that really restrict. It's the lack of blood vessels, it's a neurological injury, it's the lack of immune system there that causes that wound to stay. That's when we need to add an external force, like hyperbaric medicine, in order to heal that wound. So that's when we need to add an external force, like hyperbaric medicine, in order to heal that wound. So that's why I wanted to touch back on that cut in the finger, because for the cut of the finger we don't need hyperbaric medicine, but for a complex wound we do discovered in 2008 that wounds in the brain are very similar to wounds in the periphery, like a diabetic food. But you need to know how to optimize your protocol in order to work in the brain, in order to supply those four components to heal a wound in the brain.

Speaker 2: 16:55

So what is a wound in the brain? A stroke, a brain injury from trauma or long COVID? We discovered that and that's our initial work when we started scanning patients with both MRI and SPECT scan. We were able to see, to visualize those brain wounds. Those were areas in the brain that they were dysfunctional, they were not creating metabolism as they should, and the reason is very complex. We think it's inflammation, mitochondrial dysfunction, histamine, thrombotic events.

Speaker 2: 17:35

There are many, many theories that can cause that and some of them are true. Some of them are intertwined. We're not really sure. As you mentioned earlier, there are several theories that we cannot really land on one. What's causing? But the end result is always the same. When we scan the metabolic function of long COVID patients, we see dysfunction, we see specific areas in the brain that are not working. They're alive, they survive. They're not. You know they're alive, they survive. They're not, you know, completely destroyed. No, they're there. They have the minimal energy to support themselves alive, but they don't have enough energy to create action. We call it action potential, but basically they're not creating metabolism to do what they're supposed to do in the brain.

Speaker 1: 18:34

So it's like they're on low power mode.

Speaker 2: 18:39

They've gone into that kind of yeah shutdown, yeah, like in our phone sleep time, or yeah, low battery.

Speaker 1: 18:43

Yeah.

Speaker 2: 18:44

Exactly.

Speaker 1: 18:46

Right, and it's really interesting that you're seeing this. You know, no matter how each patient is presenting, whether it's predominantly, I don't know, nervous system dysfunction or clots or you know whatever, you know all of your different, you know pick and mix bag of many different things. That kind of brain activity is the same or similar in every single patient.

Speaker 2: 19:13

Correct, correct. We always see that in very specific regions. We already know those areas, published about these and that's how we also select patients for our treatment, by the way. So any patient that we want to see all right, they're long, covid we always scan them, they go through assessments cognitive, physical but most importantly is the imaging to tell us if we see those areas in the brain, if we do see them, we know we can help them. If we do see them, we know we can help them. If we don't see them, we might turn them down and say you know, I don't think this protocol will help Right.

Speaker 1: 20:01

So this is starting to come into the research that you've done and, like I'd love to dive like way deep into this. We'll see how far we go. But so you've been scanning people, was it mri? You said, I think, um, where you can see these different regions in the brain and that is how you sort of know. Okay, this, this is someone that would benefit from this protocol because you've been working in it for longer and you recognize that, I guess um Does this presentation you mentioned brain injury from trauma. You mentioned a couple of other things that I can't remember. Does this presentation that you see in Long Covid? Does that look similar to these other presentations or is it different?

Speaker 2: 20:48

So, first of all, we're using two type of modalities of imaging modalities. One is the MRI. On top of it we do functional MRI, and the third one, or it's the actual other imaging modality, is a SPECT scan. A SPECT scan is a whole different machine that measures metabolism. We're injecting a tracer that's connected to our brain cells. We're injecting a tracer that connected to our brain cells and we wait about 45 minutes before we take the image to make sure we reach a steady state and then we image it in order to get a metabolism image of our brain. So it's both MRI and a SPECT scan and we need all that data together in order to find those wounds. And I would say for your question no, each injury, each neurological indication has a different type and a different wound location. For instance, stroke is so diverse. People have strokes in very, very different locations in their brain. It can be cortical, it can be subcortical, which is deeper in our brain tissue, it can be in the brainstem, it can be in the cerebellum. Very, very, very different.

Speaker 2: 22:05

For long, covid, because of the pathways that the virus, the coronavirus, go through through our nose. There is a really, really tiny plate above our nose called the cribriform plate. That's where our olfactory nerve, our smell nerve, is going through. So the smell nerve goes through that plate and goes down into the nose. That's how we smell. So the smell nerve goes through that plate and goes down into the nose. That's how we smell. So the virus goes in through that plate.

Speaker 2: 22:38

And above that plate we have the frontal lobes, right here behind our forehead lying down. They're lying down on the clibufon plate and that's the typical area that we see dysfunction, dysfunction on the lower part of the frontal lobes. We call it orbitofrontal. A lot of times it goes even a bit posteriorly or backwards Sorry, if I use medical terms and for the temporal poles and the hippocampi which are very, very close to the crib front leg. So it's a very typical way to see that. Some, you know, in our case, some of our physicians call it the COVID horns, because it looks like horns on several images. But yeah, those are very, very specific for long. Covid, because that's the pathogenesis of the virus right.

Speaker 1: 23:46

So each individual virus will will have a sort of a signature, I suppose, and that is the one that is showing up from the COVID virus.

Speaker 1: 23:57

Now, you mentioned the plate that sits above the nose. You know that is to do with our olfactory, so that's our sense of smell, isn't it? And I'm going, ok, well, you know, covid virus is probably not the only virus, but it's certainly one that we kind of hear about, this distorted sense of taste and smell. That is quite specific, I think, to this individual virus and I'm thinking, oh, okay, well, that makes a little more sense now, because you just described how that is. But also, you were talking about the bit of the brain that sits kind of above that and that is where you're seeing sort of more specifically with this particular virus, that that's what's showing up in your scans. So that bit of the brain that sits above the plate, sort of in the forehead, what, what is it that that bit of the brain does? Because I feel like this is going to be quite relevant to the kind of presentation of long covid, isn't it?

Speaker 2: 24:54

right, exactly, um. So it had to do a lot. So, like you said, obviously the smell and the taste. So the taste is um disrupted because of the smell. I don't know if people know that, but you know we have to have smell in order to taste it. If we become anosmic, that the medical term of um losing the sense of smell, the taste is um is uh, disrupted as well. The taste, um. We have three other nerves that gives us the tongue uh, uh, senses taste. Those are not disrupted at all with long COVID or COVID acute COVID. It's only the number one cranial nerve that we call olfactory nerve and that is being disrupted again from here in the cribriform plate and that's what disrupts both smell and taste because of that.

Speaker 2: 25:56

Now, as for the frontal lobe, those areas of orbitofrontal regions, those are the areas that eventually lead to that sense of brain fog and cognitive injury or cognitive decline, because those areas are very, very associated with cognitive function, especially attention and executive function.

Speaker 2: 26:27

The more posterior areas that I talk about temporal poles and the hippocampus are more related to memory.

Speaker 2: 26:35

Now, the main thing that people need to understand about the brain, you know, we used to think about, I would say, 30, 40 years ago we used to think that a specific area in the brain does one thing or is associated with one thing. Since we have the functional MRI and some more sophisticated imaging abilities, we know that our brain works in networks, so meaning that one area is connected to about unlimited number of areas in our brain and it's not just those one thing. So every time a specific area is injured it has the proposed function, but because it's part of other networks, it can really disrupt other functions. But the classic to answer your question shortly it would be mainly brain fog and cognitive dysfunction, but, like I said, because of and also a lot of dizziness and headaches, but because of the disruption of networks, it can lead to other symptoms, as well, yeah, I mean, that makes total sense because you know, we, we know that everything in the body is so connected, don't we?

Speaker 1: 28:07

so it would make complete sense that everything you know within the brain is also totally connected. You know, you can't poke one part of your body without it having an impact on on another part. Um, you know, even though the sort of initial feeling or injury would would be felt in that one place. Um, yeah, this, this is fascinating. Um, now we've got really, really sciencey here, which I'm absolutely loving. Um, and if anyone listening needs to like rewind and go back and re-listen to some of that, like that's, that's totally cool.

Speaker 1: 28:40

Um, so I'd love to talk a little bit about you know, your, your protocol and your research, and you know you'd been through since you know, 2008, what, that's like nearly 20 years ago now, which is kind of terrifying. You know you've been laying this groundwork. You've been sort of, you know, doing this, doing this stuff before in a sort of totally unscientific language. And then you know COVID and long COVID came along. And then you know COVID and long COVID came along, and you know you must have known from the work that you'd already done that, oh, I think we could do something here. This, this could help. So maybe you could talk a little bit about you know what, what brought you into the long COVID world, and how that, that sort of thing right.

Speaker 2: 29:33

So, um, again, going back, uh, to how we started, like I said, with traumatic brain injury and stroke patients. Traumatic brain injury patients got us into the world of fibromyalgia and me, um, so we did randomized control trials with them and then, uh, we started working with PTSD patients. We still we just finished our latest randomized control trials. It's going to be published, hopefully next month. But all of a sudden, covid hit right, the pandemics, and, you know, nobody expected anything. But then, when we started seeing those patients, and long, covid was starting to become a thing, we were seeing a lot of similarities to ME patients, fibro patients, and we said, all right, you know, the moment we saw more and more and more and more patients, we said, all right, let's scan them, let's see what they have in their brains. And the moment we saw those metabolic dysfunction that I talked about, I said, okay, perhaps we can help them. And back then again, there was literally no literature, no therapies talking about, you know, the late 2020. So we said, all right, let's set up a randomized controlled trial and see what we got. You know, we went into this. Now, the one thing that we did know is to do our protocol. We have perfected our protocol for ME and for other neurological indications in a very specific way that we do it. So in order to provide those four components we talked about.

Speaker 2: 31:31

So I'm going to touch again a little bit sciencey here. So we talked about we need the atmospheric pressure, we need the oxygen, but we also need to do oxygen fluctuations. So the patients are inside the chamber for about two hours it's not about it's exactly two hours and then we do what we called breaks, so they're breathing for a certain period of time with the oxygen and then take a break without it. On off. On off.

Speaker 2: 32:04

What it does, it creates a very high level of oxygen in our brain and then back to normal, very high, back to normal, very high, back to normal, very high, back to normal, very high back to normal. That's what we call oxygen fluctuation. What it does, it tricks, I would say, our mitochondria. As you know, our mitochondria, in each cell all over our body, but also in our brain, is the oxygen sensor. It's utilizing oxygen and it knows what's the level of oxygen near it. All of a sudden it sees very high back, normal, very high back, normal. So the mitochondria thinks hey, I have a low level of oxygen Because it doesn't sense absolute numbers. It senses relative changes and all of a sudden you see that decrease. It thinks that there is a lower level of oxygen.

Speaker 2: 33:32

So it starts a whole mechanism, a whole cascade of processes to heal the cell, that the mitochondria is inside of it. That's the trigger component that we talked about one of them. So you have to do those oxidant fluctuations in order to get a trigger and to draw stem cells to this area to build new tissue, to build new blood vessels, only by that protocol. So, again going back to when COVID hit, we knew we had to utilize our protocol with oxygen fluctuations in order to heal those wounds, again based on our previous studies studies.

Speaker 1: 34:27

Right, okay, so it's. It's kind of giving the mitochondria a sort of a boot up the backside, almost, um, you know, by using these fluctuations the best way I I usually describe it.

Speaker 2: 34:35

You know those. A lot of people are doing heat um uh exercises or intervals. When you're running, that's what we're doing. You know, intervals running go really fast for one minute walk slower for two minutes. Very fast for one minute to slower two minutes. That's what we're doing.

Speaker 1: 34:53

We're doing a heat exercise to the mitochondria right, so interval training for mitochondria um, cool, um, so. So there's the two-hour protocol. You have these oxygen fluctuations throughout that, and how many sessions do you do? Because this is over a period of weeks or months, I guess.

Speaker 2: 35:21

Right. So again, hopefully we'll get to talk about the randomized control trial. But I would say that in the randomized control trial we did 40 sessions, which is eight weeks. So day in, day out, five days a week, two hours each day for eight weeks. That's the original randomized control trial. Since then we learned it's actually not enough for patients with a long, long COVID, if you will. So patients who have long COVID, more than six months those 40 sessions usually will not suffice and usually we need to go to 60 sessions. So that's 12 weeks, five days a week, two hours every day. So talking about three months of therapy. Why is it so long? Right, the reason is exactly those four components.

Speaker 2: 36:14

If we're trying to heal a wound in the brain, that's what it takes Because, remember, we need to build new tissue, new blood vessels. You cannot accomplish this in a shorter period of time. I'm literally publishing a study or an article, with an associate from USF in Florida talking about the time needed to build blood vessels. And you know, we even know this time from when we were fetuses, right, when we look at fetuses, the babies growing in the womb, we know how much time it takes to grow blood vessels. That's what it takes. We can visualize it, we can see it in animals, we can see it in ourselves, in humans. So we know two months is probably the minimal, but it's anywhere between two months and three months in order to create new blood vessels and new neurons. So that's the reason behind that. You know unbearable you would say eight to 12 weeks of therapy in order to get that wound healed right.

Speaker 1: 37:25

So it's that consistency over time that you maybe wouldn't notice anything after one session, or maybe even after a week, but after 8, 9, 10 weeks you would, over time, start to notice this and this, this. I mean I can tell you're dying to talk about the study, um, so let's dive into that. Um is, is this what you were seeing in that study?

Speaker 2: 37:51

exactly. So what we did in the study? Um, and you know the the goal of every study to provide data that will be very, very clear, clear and very, very cut and very, very you know that there won't be a debate behind it, so that's why we design it as a very strict, randomized, controlled trial and we take pride in it, right, so it won't be biased and people will not say, ah, but you didn't do this and you didn't do that. People will not say, ah, but you didn't do this and you didn't do that. So what we did here, we took about 90 patients and we split them to two groups where one would get the actual treatment and the other half will get a sham treatment. That's really, really. We need to stand on this for a little bit. What is a sham treatment? So these are patients that will come in for the exact same period of time in this case eight weeks, five days a week go inside the chamber and the chamber won't be working and the masks will provide regular air. But the trick here is they cannot know this, right, because if they know this, they know they're not getting treated. You're missing out the whole sham or placebo effect. We can have an entire podcast on what is the placebo effect.

Speaker 2: 39:17

But that was the main goal here is to create a sham group that they wouldn't know, and this took a lot of effort. We prepared for it on previous studies on how do we trick people to go inside and not know it's not working. So we developed a really, really sophisticated protocol that elevates the pressure just a bit. So they need to equalize pressure in their ears, like the other group, and they hear a lot of noise, just like the other group, and the mask is flowing. It's just air, it's not oxygen. So basically they're unable to detect it. And not only we did this, we wanted to be even more kosher than this. So we asked the patients after their sessions what do you think you got? Do you think you got the real one? Do you think you got the placebo? Because you have to tell them. When any participant comes in to join the study, they have to sign and inform consent and they know that there's a 50-50 chance they will get either the treatment or not. So we asked them what do you think you got? And I would say it was a 50-50 guess because they didn't know. So the guessing was exactly the same in the treated people, as well as the shampoo, which means that this is a really, really good randomization and blinding from what they're getting.

Speaker 2: 40:49

And then we wanted to evaluate their symptoms. So, like I said, we treated them for eight weeks and we evaluated their symptoms. They filled out symptoms questionnaires, quality of life questionnaires, which is, I would say, that's the subjective part right, because you can argue why did they fill this, why did they fill that, but that's what it is and I would say that most long COVID trials only use that. So on that, we saw improvement in symptoms, significant improvement in quality of life, improvement in energy and fatigue, improvement in sleep quality and in pain or how they're feeling pain on their own. So that's on the questionnaire part.

Speaker 2: 41:38

But then we wanted to have objective data. So, like I said, we do an MRI scan and a functional MRI scan. What we found there is we actually saw specific areas in the brain that improved their perfusion. What does it mean perfusion? They had more blood vessels there that were built and that improved the blood flow there, there that were built and that improved the blood flow there. They have improved their structures because they repaired the neurons that were hurt and built new neurons. So we saw that on microstructure, what we call an MRI, dti, and we did a functional MRI to look at brain networks and we saw the networks. The connectivity of the brain has significantly improved in the treated group compared to the sham group. Not only that, we also did a correlation between those. We wanted to see, all right, that everybody that improved in their brain also improved in their symptoms. And their answer is yes. And if you have that correlation, you understand that objective goes with subjective, you're on the right spot. If it doesn't go in the same area, then these are non-significant finding on your objective mris. So that was a really good validation we had.

Speaker 2: 43:04

So that was the first part and, like I said, we did those evaluation at baseline and after eight weeks of the therapy. But then I think the main criticism of myself to the study was okay, but that's short-term, right, what's going to happen long-term? So what we did? We traced them back almost a year and a half after that okay, after that time, and we did the evaluations to see are you guys good right, are you sustained? To see, are you guys good right, are you, are this sustained? And that's the second, the third publication out of this study that to show that basically everything that they gain and what we measure at the eight weeks point, sustained one year and a half later, and that's a really, really, really good validation. So it's not just short-term effect but it's actually a long-term effect and why, do we get that long-term effect?

Speaker 2: 44:07

Because we repaired the pathogenesis. We repaired those brain wounds that we discussed about them earlier. If you're only going to do symptomatic and that's a lot of the approaches that a lot of COVID clinic or long COVID clinics are working at treat this symptom, treat that symptom and treat that the moment you stop the therapy you'll get the symptom. What we're doing is we're treating the pathogenesis, the cause of those symptoms, and repair it, so you won't have anything generating symptoms. That's the main effect and that's the main conclusion of this. We get short-term effect and long-term effect by repairing the wounds.

Speaker 1: 44:54

Right. So those brain regions that you were talking about earlier that were showing up, as you know, less responsive or less less good, um, in the earlier scans, had improved by the end, and that matched up with the fact that the people said they felt better, which is what people care about. People don't care about their brain scans, they care about how they feel, don't they? Um? But at the same time, in terms of your study, I guess it's important to have that kind of data to back up what people are saying about how they feel. Um, I guess, um, and isn't that cool as well that also.

Speaker 1: 45:34

Then, 18 months later, you were able to track these people back down and that they were still. It wasn't like a short-term improvement hey, I feel good but next month it all kind of went down the plug hole and they weren't feeling good. Those improvements actually stuck like that's that's cool, um, yeah, so I guess the sort of you know what's next. Where do we go from here? Because you've got this study that says that this helps. That's amazing. How can we make this accessible to people? And, yeah, are you doing further research into this? Where are you going next?

Speaker 2: 46:25

Right. So, as you may think about or imagine, doing randomized controlled trials is hard work. It takes years. We're always doing one randomized controlled trial at least, but we have to pick each couple of years what to focus on. We have a couple that are going right now. We cannot really tell them about until they're published, but we're treating patients.

Speaker 2: 46:56

We are seeing a lot of patients myself in Aviv and other physicians. We see them in Israel, we see them here in Florida, we see them in Dubai and we're providing the exact same protocol that we did in the study, in the caveat that, again, if the long COVID was more than six months period, then we're doing 60 sessions instead of 40 sessions as in the trial. But we're doing exactly the same. We're doing the evaluations, we make sure that we have those injuries in the brain and, if so, we're taking the patients and providing the same protocol and seeing great results. And the next step is actually accumulating all that data. We have hundreds of patients outside that randomized control trial that came to our clinics and did this. We're going to publish their data and show hundreds of patients getting such improvements both in their brain scans and, obviously, their subjective symptoms. But also not only that, we added several other objective evaluations, such as their physical abilities, their cardiopulmonary aerobic function, their physical evaluation, their cognitive evaluation. So all that is going to be shown retrospectively on hundreds of patients.

Speaker 2: 48:26

Which reminds me I think I haven't mentioned it on the original randomized trial, we talked about questionnaire, we talked about imaging. We didn't talk about cognitive. For some reason, we measured all the patients in the randomized controlled trial pre and post on their cognitive function, on all the different domains, in an objective battery in front of the computer. We couldn't intervene in that, we couldn't help them or anything like that to create bias, and they had phenomenal improvements in all their cognitive function, clinically significant, obviously statistically significant. So really really nice improvements there, also on the cognitive. So again, that was already published what the next steps is going to be? Showing hundreds of patients that went through the protocol in the past uh, I would say three years or even a little bit more than that now, um, and yeah, showing that data out there? How, yeah?

Speaker 1: 49:36

yeah, that I mean, that's so cool and it's so interesting to kind of understand. You know what and and why, um and everything. Um, so, yeah, well, thank you so much for coming along and um giving up your time, sharing your expertise, diving into the big science rabbit hole. Um, I will make sure that all those studies that we've mentioned go into the show notes, um, so if anyone wants to check out anything that is published, we can definitely make sure that's available. And, yeah, I would love to catch up and hear more when you've published more and done more research into all of this. So, yeah, thank you so much.

Speaker 2: 50:20

My pleasure, I would love to. So, yeah, thank you so much. My pleasure, I would love to. And you know, if any of the listeners has specific questions, they're welcome to email me at my email published and you can publish it as well for further evaluations, questions. And if someone wants to discuss their own private case, happy to do that. And yeah, thank you so much for having me. I had fun and it's always great to talk science. Thank you.

Speaker 1: 50:48

Thank you, my pleasure.