 Hello everyone and welcome to another episode of Resiliency Radio with Dr. Jill. Today you're in for a real treat for multiple reasons. One is in this post-pandemic error. We have more complex chronic illness than ever before and more sequelae of this virus called COVID and today we're going to dive deep with one of the world's leading experts. If you listen to us on iTunes, Spotify, YouTube, please stop and leave a review and there's many more episodes that you can find there. But today without further ado, I wanted to introduce my guest, Dr. Bruce Patterson. Dr. Bruce Patterson, medical doctor, received his undergraduate degree in training in molecular biology from the University of Michigan in Ann Arbor. He then received his MD at Northwestern University, Feinberg School of Medicine followed by a residency in pathology. During the early stages of the AIDS epidemic, Dr. Patterson began investigating cellular reservoirs of HIV using molecular and in situ cell-based technology patented in his laboratory and used today around the world. He would determined that enough HIV virus was present in infected individuals to account for the massive destruction of the immune system. This paradigm altering the work, I'm sorry, this paradigm altering work was published in Science in 1993 and featured in the Scientific America, Rolling Stone and on the Discovery Channel. Dr. Patterson has authored over 150 manuscripts and book chapters focusing on single cell biology and diagnostics. He was formerly associate professor of pathology and infectious disease and director of virology at Stanford University. He currently serves as CEO and founder of Incell DX Incorporated, a growth stage company that has translated his research discoveries into state-of-the-art single cell diagnostics and cancer, immuno-oncology and infectious diseases, especially our topic of today, COVID. Welcome, Dr. Patterson, that is quite a history and I'm so glad to have you here today. Thank you, Dr. Jill. It's a pleasure to be here. Yeah, so I always like to start, and I mentioned this before we get on, is you have quite the journey and it's interesting because you at Northwestern, I was at Loyola, so we're both in Chicago for some time during residency and training, but this journey through all that you've been through, tell us, first of all, how did you get into medicine and then what was your path into all the scientific discoveries that you made through the years with HIV? I mean, really a family affair. My grandfather and my aunt are both PhD scientists and my aunt was a classical virologist from the 60s and 70s. So back in the days where we didn't have all this great molecular biology and he had to grow the viruses on chick embryos, that was her thing. And then I think I was about 17 or 18 and I went to her lab and she showed me an electron microscope with magnified virus 100,000 times and I was sold. I'm like, this is what I want to do for the rest of my life. And what's interesting is back then they called it the Norwalk agent and it's actually the Norovirus, which is our cruise ship virus, which lands a few cruise ships in port unexpectedly. So that was the start of it and then of course molecular biology was in its infancy and I just have been riding that molecular wave as it infiltrated medicine all that time. And the interesting thing was the AIDS epidemic really pushed the envelope on molecular medicine and molecular diagnostics and those techniques, much like COVID, as we'll talk about, has really pushed the envelope on new wave immunology techniques and discoveries. What I love that because it's really been such a lifelong and you can tell because it really takes, I always say that curiosity is a mark of genius, but you clearly had that way back at 14 or the first time you looked at the microscope and it really takes that, especially in a new era of medicine with these complex and crazy viruses like COVID. You have to be curious and you have to think outside the box to get the answers that you've been coming up with. So then obviously I read a little bit in your bio about your work, but you made some massive discoveries with HIV. Do you want to tell us a little bit about that because I think it's fascinating. Well, when I first started in HIV, there was this two different things. There was patients dying of these horrible immune deficiency syndromes, Kaposi sarcoma, lymphomas, etc. And then of course there was this virus, but putting together it's the virus causing AIDS was the big question when I first started. And there was even very prominent scientists saying, well, you know what, HIV virus doesn't cause AIDS. So my training in molecular biology and pathology really was instrumental in saying, well, maybe we're just not finding it. Maybe we're missing it. And I think that was the big thing that I was working on at the time was, hey, maybe we can't find it. I'm going to try and do molecular biology in these single cells of the bodies, body instead of fluids, etc. And try and find where the virus is hiding. And we were able to do that. And again, able to quantify that, which allowed a lot of early work in antiretrovirals, including I was just talking the other day about my involvement when they're developing the protease inhibitors and figuring out that it really took people at CD4 counts of single digits, seven or 10, and a few months of therapy, and they're back up in 100. So it's one of those moments that you never forget. You look back and say, wow, that really changed the course of everything as HIV infected individuals are living healthy, long lives now and still have it. But you've been really effective at treating it with drug therapy. Amazing that you have that background. And then again, now we're in this new era, well, we really need to think outside the box because what is your, what's the big overview? COVID is such a different thing than we've encountered before. So do you want to frame it for, I told you before we have a lot of physicians and people interested, but I know a lot of patients, clients give us a framework for this virus. And why is it so different from things that we've experienced in the past? You know, it was interesting, you know, it's different, but it's not in some ways. And, you know, I was in China in January of 2020, actually doing, we had developed a new immune profiling test, over 150 different biomarkers, both cell-based and plasma-based, for looking at CAR T therapy and cancer. And we're in China talking to a company over there, and I was in Shanghai. Someone said, well, there's this, I was supposed to go to Wuhan, you know, the next day to visit another lab, another customer of Insultia X's. And it was canceled because of this, there was this virus and everyone was talking about it. I saw one of the really, really early papers of this virus and some of the lab results. And, you know, the immune system was just, you know, on fire. As we later learned, you know, the cytokine storm, but, you know, it was in immunology, you know, we have all these different arms of the immune system, adaptive immune system, humoral cellular immunity and hypersensitivity, et cetera. But this was clearly an innate immune response, which is basically what our body has when it hasn't seen an infectious agent before, you know, and it was heavily macrophage burdened, meaning macrophages were playing a very significant role. And that was one of my major areas of research in HIV. So you had this massive immune activation of macrophages production at Interleukin 6 and TNF Alpha, which, you know, really were part of the initial pathogenesis and QCOVID and elements of that still exist in long COVID as well. And are, you know, part of what we target with some of our diagnostics as well as some of our therapeutics. But and then the other thing in our first study in acute COVID found that, you know, the CD8 T cells were just as low as the CD4 T cells were in HIV. So acute COVID patients with the Alpha variant were supremely immunosuppressed. And that is the nugget that people aren't considering as we're dealing with the post-acute speli of COVID is that people are are immunosuppressed to varying degrees with acute COVID. What does that do? Well, it reactivates chronic herpes family viruses, EBV, CMV, HHV6, herpes simplex, etc. It also, in patients who have either undiagnosed or poorly treated Lyme, the bugs start to replicate again. And so, you know, and so what happens is all this is going on. And then all of a sudden we find, oh, there's this post-infectious syndrome that has, you know, fatigue, brain fog, post exertional malaise, joint muscle pain, you know, the whole headaches, etc. And that's all well and good as when we first described it in long COVID. And but the fact of the matter is all of those chronic inflammatory diseases have the same primary symptoms. So symptom-based diagnosis of long COVID is highly, highly non-specific. It could be long COVID, it could be long Lyme, as we call it, it can be MEcfs, it could be fibromyalgia, it could be long VAX. So all of those have the same primary symptoms. So the necessity for a diagnostic was critical. And the fact is we have it and nobody is saying we have a diagnostic for long COVID. It's absolutely absurd. We published it two and a half years ago this signature for long COVID and we developed a long hauler index and it's still highly, highly sensitive, highly specific for long COVID. And now our latest paper, we can differentiate long COVID from Lyme, MEcfs, long VAX and fibromyalgia. And you know what? It is the most critical tool that we have. I need to be long-winded, but- No, this is so relevant. So I would get excited because you're right. I mean, I deal with this complex chronic disease, so CFS, ME, Lyme, long COVID. And for me, when I heard you really speak about in depth about the cytokine patterns, which we'll talk about, and your lab tests and how to differentiate. And I've been using your lab tests for a while, but the more data that you guys bring out and the more patterns that you're showing us, it is a game changer for those of us dealing in this chronic world because we can say, this is much more likely to be your Lyme Borrelia reactivated or it's more likely to be a true long COVID panel and it's treated differently. Absolutely. And another important aspect is negative predictive value. As physicians and scientists, everyone loves to talk about sensitivity and specificity. And as I used to teach residents both in Northwestern and Stanford, I always said that sensitivity and specificity work after the fact statistics. Like you do a study, you look back and say, well, what was the sensitivity and specificity? But as a physician, you get a lab report. You're looking at a number and a test result. What is going through your mind saying, what are the chances of that actually being positive? Or what are the chances of that actually being negative? What your mind is doing is actually positive predictive value and negative predictive value. And having a negative predictive value for long COVID of 98 percent really says we can say who doesn't have long COVID. And you know what? In the days of all this inflammation and the major symptom being fatigue, it's almost important to say who doesn't have long COVID as it is to say who does have long COVID. Because as you say, the treatment is subtly different. We had this other discovery which showed that all four of those chronic inflammatory conditions have vascular inflammation at their heart. But there's also subtle differences and subtle changes in this drug combination that we just submitted to the FDA for our clinical trial. Hey everybody, I just stopped by to let you know that my new book, Unexpected, Finding Resilience through Functional Medicine, Science and Faith is now available for order wherever you purchase books. In this book, I share my own journey of overcoming life-threatening illness and the tools and tips and tricks and hope and resilience I found along the way. This book includes practical advice for things like cancer and Crohn's disease and other autoimmune conditions, infections like Lyme or Epstein Bar and mold and biotox and related illness. What I really hope is that as you read this book, you find transformational wisdom for health and healing. If you want to get your own copy, stop by readunexpected.com. There you can also collect your free bonuses. So grab your copy today and begin your own transformational journey through Functional Medicine in Finding Resilience. Yeah, so gosh, there's so much I want to cover here. First of all, just for those listening, what you're talking about is innate immune system, which I've been dealing with for decades with mold and Lyme and complex chronic illness. And most of our patients have had some things like that or know someone who has many of our physicians who listen treat these conditions. So a lot of our listeners are going to be aware of that. But just to frame it, this is this arm of the immune system. Like you said, it's kind of the first activator or first responder that maybe doesn't have antibodies already made or those kinds of things. And it's typically cytokine driven, which is why we saw with just regular COVID, it so much of the disease and the mortality was related to this. It's literally like the activation of our own systems and our own systems are killing us because they're in the cycle of activation that cytokines, right? Right. I mean, it's an imperfect system and it's just trying to do something. Right. And my colleague Joe Balanti always talks about, you know, damaging immunity. And the reality is, yes, some of these inflammatory products that are indeed trying to help clear a virus or clear a bacterium or otherwise are damaging, our tissue damaging. IL-6, TNF-Alpha are two great examples. And in our February paper, we showed that TNF-Alpha is the major driver of fatigue. So, you know, if you if anyone remembers, I mean, acute COVID was just the fatigue and the respiratory symptoms were just the major findings. But, you know, when you looked at the pathology more closely, it was blood vessel inflammation. Because what was happening is these activated monocytes, macrophages, non-classical monocytes, where we later found the S1 protein months after infection, they bind to blood vessels through the fractal kind, fractal kind receptor. And, you know, obviously, one of the reasons we use statins is because they decrease fractal kind. So, you don't bind the pro-inflammatory white blood cells to your blood vessels and cause endothelitis. The other thing is Moravarok, the CCR5 antagonist, is elegant in the immune system because it does two things. Number one, it restricts the migration of inflammatory cells all over your body, including through your blood-brain barrier. But what it also does is it repolarizes monocytes, macrophages away from that pro-inflammatory phenotype where it's making interleukin-6 and TNF-Alpha. So, this drug combination we use is absolutely exquisite in terms of targeting the pathways that are underlying the symptoms in long COVID, long Lyme, ME-CFS. And that's driven by the fact that the blood vessels are inflamed and dilated, well, dilated blood vessels do, headaches, migraines, brain fog, tend to this. Post-exertional fatigue, right? All that, yeah. Cotton cold and sensitive. Yes. I can't tell you how many times I'm telling this, and I've seen a patient literally come on telemed with a blanket over their shoulders because they're so cold. And so temperature regulation is just completely thrown off, and that's my window into their blood vessels before I even look at their lab report. Oh, that makes so much sense. Because of your research, I've been talking to patients that really COVID is like a disease of endothelium, which is what you're saying, right? At the core, this macrophage activation. And let's talk just briefly, because one of the things you're testing in your panels as well is the retaining of the spike protein in these atypical macrophages, right? And that's part of the problem is they become activated, and then they go. Do you want to talk just a little bit about what happens in the macrophages with that spike protein? So, you know, flashback to, you know, 2020, we had this 158-byel marker panel, and, you know, we used it on acute COVID, and, you know, and we followed these patients 30 days, 60 days, 90 days, and 90 days, you know, a lot of them got better. They were home, but by no stretch of the imagination, was their immune system the same. It was abnormal, but it was abnormal in a very different way than in acute COVID. And that's where we used machine learning and AI to say, okay, how is it different? Why? And that's where we found this signature for long COVID. And the long hauler index is interleukin-2 plus interferon gamma divided by CCL4. Well, if you look at literature from the early 2000s, atherosclerosis, with unclassical monocytes bind to blood vessels and basically migrate into the blood vessels, what's liberated is type 1 cytokines, interleukin-2, interferon gamma, which just happens to be the numerator of our long hauler index, which was found by machine learning and AI 20-some years later. Wow. Unbelievable. And then you also mentioned, I've heard you speak multiple times about this triad of the vascular inflammation with the SCD40L, the CCL5 rantes, and then the VEGF that's at the 3. Can you tell me about those and what the pattern you've seen with that triad? Well, that was very helpful because obviously the first protein of the thrombotic pathway on blood vessels is SCD40L, CCL5, and VEGF. So that's the instigator. That's like, you know, the macrophages have activated endothelium if that is elevated. And is that, you see the timeline as well, see that up first, and then the rest of them follow over time? Well, usually by the time the patients come to us, they've had, you know, long COVID for three months or 18 months, or I just had a patient, she had it for three years. And it was an unbelievable telemed session a couple of days ago that after eight weeks of therapy, she was 95% back to normal after having suffered for three years. And so these stories are just almost daily during our telemed of patients getting better. And the reason is we're treating the underlying cause and we're not. So anyway, these macrophages bind to blood vessels. Well, let me just be clear for those listening, because a lot of people think the virus is still around. The virus is long gone, correct? This is not about the virus retaining its fragments and then this activation of immune system. Is that right? Yeah, okay. And it's an RNA virus. You don't expect it to be around for a long time. It doesn't have the latency machinery that the chronic herpes family viruses have. And so and we were the only ones who've done whole genome sequencing of the entire SARS-CoV-2 genome. We did that in the non classical monocytes when we published that two years ago. And then we looked into tissues of long COVID patients before all this reinfections going on. And we found fragments just like we found in, you know, in monocytes macrophages. And those fragments represented less than 5% of the genome. And my point is, you know what, you can't build a building with 5% of the bricks. So in all the techniques that they're using to say, oh, there's, you know, viral persistence tissue, which I believe. We published it, you know, there was a viral, there's persistence of fragments of RNA and persistence of protein S1 in the non classical monocytes. But at the end of the day, they're all using techniques like droplet digital PCR, very short fragments, insight to hybridization, short fragments. You know, they're not doing whole genome sequencing when they're, and it's a big stretch and I keep saying this over and over again. We can talk about persistence. I love talking about persistence, but it's persistence of fragments or as Jez many years said, viral debris, I love that. But the fact is, there's a huge difference between persistence and replication competence. Yes. And it makes sense to me, like even on a microbiome level, we know the fragments like LPS cause a massive immune response, right? So we can have fragments of viral particles that cause immune response, which is very different from the virus continue to replicate. And, and you know what, the Paxilvid trial failed at, you know, several universities for long COVID. And the reason is there just isn't any viral replication, except the caveat is, and we published this in 2021 that we found viral replication out to 87 days in one long COVID patient who had very low CD8 counts. So yeah, three months, you know, which is the cutoff for long COVID. So I'll always admit, you know, if you're at three months or four months of long COVID, yeah, there could be viral replication. But when you're talking six years or months, three years, you're not going to see it. I'm still waiting for that paper that says whole genome sequencing reveals alpha variant RNA in long COVID patient three years after infection. I haven't seen it. And it's not common. Well, that makes sense. Because where do you again, I've been doing 20 years of the chronic fatigue, fibromyalgia, the long Lyme, all those things before COVID. And we've been seeing these immune dysfunction activations. And the same question has been in the Lyme community. Yes, we know these spirochetes persist. But is it truly that infection, or is it the immune response that's creating inflammation? I agree. I think more and more we're determining it's actually this long immune response that is dysfunctional and weakened immune system that's more likely to be part of the culprit than just purely the infection. Absolutely. And I brought that question to the Lyme community. There's articles showing the peptidoglycan cell wall peptidoglycan and in arthritic joints from patient Lyme arthritis, I'm like, those are just setups for phagocytosis by monocyte macrophage lineage cells and persistent presentation to the immune system. And that would be another mechanism for post treatment Lyme disease, chronic Lyme disease, whatever you want to call it, where your refractory antibiotics, that's where we come into plagues. We found the blood vessel inflammation in chronic Lyme. And you kind of alluded to, but I want to be really clear for those listening. So first of all, you can actually determine through the long haul index, the height, like the likelihood and what's the percentages of like sensitivity and specificity of how accurate that test is. And this is the long haul panel, the cytokine 14 panel through your lab. Healthly about that and the specific cytokines and patterns. So, you know, so like I said, machine learning and AI brought our 158 panel down to 14. We're now using that on all of our machine learning for various different immune conditions. And now we're getting a little bit into some of the autoimmune diseases like chogrens and others. But what it basically shows, when I look at a panel, I look at several things. Number one, I look for that SCD 40L, CCL 5, VEGF pattern of vascular inflammation. And undoubtedly I'm going to, I'm going to find it. And there's different severities. And maybe they just have SCD 40L, like you said, at the beginning. Or, you know, maybe there's a little bit of lingering VEGF. That's the first thing I look for. The second thing I look for is the long haul index. And so, you know, if it's in normal range or as it elevated and how elevated is really important based on our new algorithms. So when I start searching for Lyme patterns, my three bullet points are elevated interleukinate plus elevated interferon gamma. Elevated interleukin 13 plus elevated interferon gamma. Or a long hauler index greater than six. Wow. Okay, that makes sense. 0.6. It's probably long COVID. If it's really high, I'm sending it off for Lyme testing. So I'm having this aha listening to you because I've been treating Bartonella, Obesia, Borrelia, forever. And what I know about Bartonella in particular is I'll use VEGF as a marker of activity. And I haven't because I haven't had access to your panel for that long been regularly using the other vascular markers and some of the new stuff you just mentioned. But it makes sense because Bartonella in particular is a vasculitis like it causes more vasculitis than any others. And again, I only knew about the VEGF, but this is making so much sense because what I was starting to see was my own little tiny one marker indicator of vasculitis, right? Which is what you're seeing in different ways with COVID. But you're able to now with machine learning and looking at these cytokine panels to put out this, we have the symptoms buckets. It's the same for Lyme and long COVID and chronic fatigue. And you're basically saying now we can actually look at cytokine patterns and say which is which. Exactly. And the latest in this is coming out in a new paper, which I should be sending off to a preprint server after the holidays. But we have a new Lyme index much like the Long Haller index. And the Lyme index, interestingly, in the numerator is TNF-alpha. Well, TNF-alpha, which we published in February in our outcome study with treating long COVID patients, TNF-alpha interleukin2 are the major drivers of fatigue. So now you can start to correlate which cytokines are actually representation, representation of those symptom clusters, right? Like migraines, this versus fatigue versus the brain fog. Fascinating. And you come up for a second, but did you say IL2 and TNF-alpha are the two that are more correlated with fatigue? Yeah, it's in our February paper in Frontiers and Medicine. But the most, you know, that was a 20 patient study, Moravrock and statins and long COVID. We did five different symptom scores, fatigue, dysautonomia, neurocardiac, and shortness of breath or dyspnea. And, you know, and then we looked at our entire panel and looked at those biomarkers and how they would respond to six to 12 weeks of Moravrock and statins. What we didn't, we expected, you know, the fatigue score to go down and maybe even dysautonomia because we've seen correction of those symptoms. All five symptom scores went down with statistical significance. But most importantly, as we didn't stop there, we told our bio statisticians to then correlate what symptoms correlated with reductions in what biomarkers. So we closed that loop of infection, inflammation, symptoms, treatment, infection, inflammation, symptoms, treatment. And that that circle, you know, I have not seen closed for any other marker in any of these chronic diseases where you say, oh, there's, you know, all this, especially early on in long COVID. Oh, there's this autoantibody and that autoantibody. And my first question was, okay, what symptoms does it cause? Yeah. Right. Right. And if you bring that autoantibody down with IVIG, for instance, does it, does the symptoms get better? No one closed that circle. And it was really important for us to close that circle between biomarker, symptom, and treatment of the, with a very targeted approach with our two drugs at the actual proteins that are causing the symptoms, not the symptoms. So, you know, for instance, here's a great example. This new paper that comes out, serotonin, and we did this clinical study, long COVID patients are responding to Prozac because it elevates serotonin. You know what, you know what the most important thing that lower serotonin levels are? Chronic inflammation. And you know what, cytokines lower serotonin levels, interleukin 1 beta, and TNF alpha. Yes. And we've seen in IL-6 too, all the studies on depression, IL-6, right? I don't know that that correlates with serotonin, but depression, absolutely in the studies that correlate with IL-6. Glad you mentioned them because from a mental health aspect, you know, in our 40,000 plus patients, I mean, the amount of anxiety and depression is, is incredible. And you know, their physician will throw them on this and that, this, this drug, that drug, at the end of the day, when you resolve the inflammation, it goes away. Yeah, I've been known to say, I think all depression anxiety is none, is, is, is organic in nature in the sense that there's some other cause of it. Now, I shouldn't say all because there's always exceptions and genetics and stuff, right? But I feel like more and more and more toxic load, infectious burden, cytokine, immune inflammation is really at the root, I would say 80% of my clinical mood disorders and, you know, any sort of psychiatric diagnosis frequently, if we get to that root cause, it's a game changer. It's amazing because we're starting to see, you know, I just read a paper the other day about dysautonomia and Lyme, you know, it's like all of a sudden, long COVID, we opened this Pandora's box for these chronic inflammatory conditions. And you know what, there was differences that allowed us to model that. But you know, there's also a lot of similarities. And you can see anxiety and depression in, in chronic Lyme, you see, and so all of this stuff is starting to come together under this rubric of, you know, an altered immune system and chronic inflammation. And here's another example, Pan's Pandas, you know, I probably have somewhere around 50 Pan's Pandas patients. And you know what the classic was, let's immunosuppress them and then give them IVIG. Well, you know what, the problem is, it's post-infectious. And you don't know if the infection is cleared. So, you know what, they always say Pan's Pandas is from strep and recurrent strep. Well, you know what, I have a handful of Pan's Pandas patients that all have a chronic herpes family virus that when it reactivates, it ticks, the symptoms, everything gets worse. When you press the chronic herpes family viruses, it gets better. But the other thing we found in Pan's Pandas and the reason why I think there was, it was hit or miss for IVIG treatment was that there's a chronic inflammatory component that nobody had ever identified before. And so just taking away auto antibodies wasn't doing it. And it wasn't doing it because there's also pretty significant chronic inflammation. But when you treat the chronic inflammation, for instance, with Morabroc and statins, and then you do IVIG at the same time, these kids are really responding. So, I love that because I think even we talk about IVIG, I have a lot of patients that are on that. They do well, but here's the deal. We think it's just that immune system, but the truth is it actually has a very potent anti-inflammatory mechanism as well. Same with the statin. It's kind of an equivalent. We're thinking about this cholesterol issue. That's really the side note, right? It's really this anti-inflammatory. And maybe you could talk briefly, because you alluded to this, but statins, your mechanism of action is much more directed to the endothelium. What is it that it blocks exactly? You mentioned it earlier with the statins. The protein called fractal kinase. It's made by themselves. And believe it or not, these pro-inflammatory, non-classical monocytes have a fractal kinase up there. And so, to keep them from binding to the blood vessels and causing inflammation, let's down-regulate statin, down-regulate fractal kinase. Well, statins down-regulate fractal kinase. And we don't use cholesterol lowering doses of statin. Yeah, you're using like 10 or 20, like quite low doses, right? I miss that. I'm like, no, we're not giving you massive doses of statins for the rest of your life. It's six to 12 weeks with a quarter of the dose that you would give for cholesterol lowering. And it's just an exquisite anti-vascular inflammation agent. So, great combination. We're making it into a single pill. Perfect. More avarok. And like I said, our RCT will... Which kind did you choose for the trials? We chose a tour of a statin. And the reason was when I was treating kids with long COVID, they responded so well. I mean, I would say kids, you always say six to 12 weeks. People with more neuro symptoms, maybe even longer than 12 weeks. But kids, I mean, some is as little as four weeks, and they're better. They're completely better. And four to eight weeks is about the standard for kids, because they probably don't have a lot of other comorbidities. But I was using a tour of a statin because there's studies published on the safety of a tour of statin in kids. They're getting better faster. So then I started to use a tour of a statin in adults. And with the SCD-40L be the main marker of that fractal kinin activation? Is there any correlation with one of your cytokines with knowing that the... I wish we had fractal kinin. Right. That's what I'm wondering. Like, how do we know for sure, even though we know the... Like we can understand the mechanism and see that. Is it that triad that you mentioned before? Okay. So the SCD-40L, the VEGF, and the RANTE, the CCL-5. Okay. Got it. And in that way, you know if someone has high on those, it's very likely they have the fractal kinin, the atypical macrophages. And again, this, I suppose, it could be another mechanism besides long COVID, but that mechanism is absolutely involved in most long COVID, right? Absolutely. And also involved in chronic Lyme and ME-CFS and maybe many others. You've had some significant success with Sjogren's syndrome. Yes, I've been seeing that too. So let me take the jump here because I'm in this functional world and seeing the diagnoses and obviously POTS dysautonomia is at an all-time high for all of these underlying reasons. Is that because of the vascular inflammation? Is that usually the link to that? Yep. When happens, when blood vessels are inflamed as they dilate. Okay. When they dilate, your blood pressure goes down. When your blood pressure goes down, your heart rate goes up. I mean, it's just, it's classic, you know, physiology. And then the other thing is these inflammatory cells, you know, I've seen infiltrates of the inflammatory cells around, you know, the vagus nerve. Yes. And we're going after these vagal nerve stimulators, which is a nice idea, but I'm like, that's not going to fix the root cause, right? I mean, and that's a thing, you know, there's so much out there on these different, what works, but most of them are just, are very transient. You know, hyperbolic, you know, vagus nerve stimulation, you know, there's this microclot stuff for a while. And I'm not really a big, big, big supporter of that, because really the anticoilins aren't, aren't work. And we tried Plavix a year or two ago with all of our protocols. And, you know, it just wasn't adding anything. And, and, you know, microclots are, are difficult to, you know, to look at when I see, I've seen pictures of microclots. And as a pathologist, I said, those look like epithelial mesenchymal transition cells for EMTs. I'm leaving tell under microscope, huh? Don't give me a microscope. Yeah, these EMTs are formed when there's tissue damage, of course, is an acute COVID. And then that makes so much sense, because really at the core, this is our immune systems damaging endothelium. And that's this whole cascade. And so how do we go? And the only reason the clots happen is because it's repair. It's our mechanism, right, trying to repair the damage to the endothelium. So that makes, so it's actually doing what it's supposed to do. But of course, and then. Absolutely. And so, and then these epithelial cells fuse with macrophages and cause an EMT. And you know what they express? CCL 5 and CCR 5. And so then they migrate to areas of inflammation. So macrophages actually expressing VEGF, or is that just a signal to get more blood flow? It would actually, do you know where express VEGF. And that's why we talk about the tumor microenvironment and tumors. Yes. And the inflammatory infiltrates that come into the tumor microenvironment. You're talking about producing high levels of VEGF, which allows the tumors to increase their blood supply. And you know what directly decreases VEGF is Maravarok. So all of this is just exquisite. And I think as I was sitting there in a hotel room in China, I was really thinking about the cancer literature and our work in cancer and and CCR 5. I mean, I initially started with some of the early trials of Maravarok and Vikravirac and others in the early 2000s for HIV. But then obviously, you know, we started talking about this more exquisite role in the immune system, basically as the quarterback, right? It's telling immune cells where to go, when to go. And it can be both good and it can be bad. So it's our job to exploit the good aspects of it. And the bottom line is it's not immunosuppressive. Yeah. Everyone's throwing on people on steroids, you know, yet again, another long COVID paper in nature with high cortisol. Well, you know what? Or no, low cortisol. I'm like, because everybody's on steroids. Yes. Yes. First, steroids and LDN is like, you know, the first like, it's like a reflex. Here's your LV, here's your steroids, you know. And we're not really going to the root. Now, is there anything, obviously in my world, I loved if I could use curcumin or lumbrachinase or any of these things. Is there anything that you've seen that has any effect even remotely close to the medications that you've been seeing success with that's on the realm of natural agents? You know, it's a good question. I mean, his patients come in with lists of those agents. And I mean, my first question is how's that going? And then my, but you know what, all kidding aside, I mean, we've looked at some of these agents with our panel. I mean, we actually, we have a non subjective means to test anything and everything for its anti inflammatory activity that would contribute to, you know, improvement in the pathology. So, you know, it's really hard to say. I typically tell patients, you know, don't stop, don't stop. I don't, you know, I, it's neither here nor there. But I mean, obviously the only one I talk about is turmeric, because turmeric, for some reason, increases blood levels of morale rock. So. Oh, interesting. So that's kind of just a nice synergistic effect with that makes wonderful sense. One other question that I know people are thinking, because we talk about mass activation, and that's obviously connected. Is this because we get cytokine activation, mast cells are part of our immune system, and they're becoming activated and prostaglandins and histamine are part of this. Can you correlate, like, how does that fit in at all? If, if anything, with the whole idea of mass activation? Having been in long COVID for so long, and some of the early theories, you know, mast cell activation was one of them. People took various agents, and you know what, they really weren't that effective, H1H block and that, you know, and you know what, to me, if there was really a lot of mast cell activation, I'd see elevated interleukin 13 everybody. Yeah. So, so. And you did say just with a lot of, with long Lyme, that was one of the patterns with, it was IFN gamma and interleukin. Yeah. Yeah. Okay. So maybe in that particular subset, there's more mast cells versus not. Fascinating. Well, what is the future? I mean, you, you and your lab are doing some incredible work. This is just game changer for those of us out in the field actually practicing medicine. What do you see as the future? What things are going to be coming out? What's next? So we've had so much good news, especially in this last, last quarter of the year. Number one, we're seeing really broad reimbursement. And that makes us extremely happy because now, you know, it's not just a long COVID test. Originally, we were coding it as long COVID. The fact is, now we have the new algorithms to detect chronic Lyme and have suggestions of ME-CFS that presented this meeting about a month ago that there may be five different immunotypes based on cytokine profiles that we discovered for ME-CFS. There may be five flavors at a minimum immunologically. I mean, we all know that it is very heterogeneous. We don't really know what the underlying cause is, but we're starting to map that out on an immune profile level so that we can use targeted therapy and ME-CFS that is independent of bacteria or whatever that could be causing it. That's exciting because I think sometimes a toxic load, infectious burden, which I'm dealing with on this level, it's so hard to determine exactly what, but if we can go straight to the immune system and say, this is what's happening and then we know what to target, it almost, it does matter, but it almost doesn't matter what the original cause was, right? I tell that to people frequently, you know, at the end of the day, you know, my initial thoughts are, I don't care what's causing this because it's the immune abnormalities that are causing you symptoms and I'm going to take care of those. So coming out at the end of year, reimbursement for the test, which is very, very exciting. The fact that we now have these patterns, which separate and define long COVID, Lyme, ME-CFS, even fibromyalgia, is all very exciting so that we can really treat them because they are treated differently. And then most importantly, great work by my team at InsultDX and in getting our trial design for Maravrock and Statens in long COVID, all that written up, all of that, all the additional information, all of it's been submitted to the FDA and we're really excited that 2024 we'll get our trial underway and get this hopefully at some point get an approval. The good news is they're already approved drugs so it's a different pathway where we're really looking at efficacy as a major focus. So it's going to be exciting year, but it's all been springboarded by the use of this diagnostic in chronic inflammation. And it's really resulted in great, great patient outcomes and that's the thing that gets me. I mean, I've gotten letters and calls and everything, but the most, I mean, this one girl is 12 years old, wrote me a letter on colored paper with colored pencils. Thank you, Dr. Patterson, for making me better. And you know what? You get one of those and you're like, okay, you know what? All that work that for me started in the late 80s in viruses was all worth it. I love that and that's just such a great way to end here because like truly that's why you and I do what we do is like to see the patients faces that, you know, see a change in their health and that's the reason I get up every day and I know for you too. And it's a long road sometimes, but I just want to say I've been in this role the long time in my little tiny window of functional medicine as an MD, but I see the value and that to me, this is not only this conversation, this podcast and all the work that you do is profound. Like this is a game changer. And if you're listening, you just listen to history being made and it's going to continue for you if you stay tuned to the studies that Bruce Patterson's work and group is putting out. So I just want to say on behalf of all physicians out there like me, thank you truly because this is the kind of game changer. These are kind of those pivotal moments like when the cell danger response came out and we understood that and some of these things are always game changer. So thank you. Thank you. Thank you for your work. Where can people find your work, your information, the lab, give us some websites and places and resources that they can find you and we'll list these. If you're listening or you're driving, we'll list them everywhere this podcast is shown. So www.covidlonghaulerswithins.com is the best place to get a hold of us, me. It's been a, it's a functional website, we're about to launch a physician's link so they can order the test directly for their patients and it's been, that's where all our information, all our publications, talks, etc. all reside there. And of course, if you search on YouTube with my name in long COVID, you'll find, I'll be just about everything we've ever talked about. Thank you. As always, here we are. We're recording around the holidays so thank you as always. Once again, here you are taking time right close to the holidays to share this great information, truly from the bottom of my heart. Thank you for your work. Thank you for your intelligence and your genius and curiosity and I hope I can continue to support the work that you're doing.