Ask Dr. Drew - What Causes COVID-19 Long Haulers? Dr. Bruce Patterson & Dr. Eric Osgood on Chronic Coronavirus – Ask Dr. Drew – Episode 63

Episode Date: January 7, 2022

What are the underlying causes of long haul COVID-19? Dr. Bruce Patterson & Dr. Eric Osgood reveal their research on chronic coronavirus infections and treatments. [This episode originally aired on November 22, 2021] Dr. Eric Osgood MD is a board certified internist and academic hospitalist, as well as the medical director of Mission Hospitalists at St. Francis Medical Center in Trenton, NJ. Dr. Osgood earned his undergraduate degree from Georgetown University, his medical doctorate from Tufts University School of Medicine, and completed his internal medicine residency at Seton Hall St. Francis Medical Center. Follow Dr. Osgood at https://twitter.com/EdoajoEric  Dr. Bruce Patterson is the CEO & Founder of IncellDx and covidlonghaulers.com. Bruce K. Patterson, MD is a leading researcher on the effects of viral pathogens on the human immune system. His pioneering technologies and findings have contributed to advances in detection, prognosis and treatment of patients infected with HIV, HPV and cervical cancer, COVID-19, and other diseases. Follow Dr. Patterson at https://twitter.com/Brucep13  Find out more about Dr. Osgood and Dr. Patterson's research at https://CovidLongHaulers.com/  Ask Dr. Drew is produced by Kaleb Nation ( https://kalebnation.com) and Susan Pinsky (https://twitter.com/FirstLadyOfLove). SPONSORS • BLUE MICS – After more than 30 years in broadcasting, Dr. Drew’s iconic voice has reached pristine clarity through Blue Microphones. But you don’t need a fancy studio to sound great with Blue’s lineup: ranging from high-quality USB mics like the Yeti, to studio-grade XLR mics like Dr. Drew’s Blueberry. Find your best sound at https://drdrew.com/blue  • HYDRALYTE – “In my opinion, the best oral rehydration product on the market.” Dr. Drew recommends Hydralyte’s easy-to-use packets of fast-absorbing electrolytes. Learn more about Hydralyte and use DRDREW25 at checkout for a special discount at https://drdrew.com/hydralyte  • ELGATO – Every week, Dr. Drew broadcasts live shows from his home studio under soft, clean lighting from Elgato’s Key Lights. From the control room, the producers manage Dr. Drew’s streams with a Stream Deck XL, and ingest HD video with a Camlink 4K. Add a professional touch to your streams or Zoom calls with Elgato. See how Elgato’s lights transformed Dr. Drew’s set: https://drdrew.com/sponsors/elgato/  THE SHOW: For over 30 years, Dr. Drew Pinsky has taken calls from all corners of the globe, answering thousands of questions from teens and young adults. To millions, he is a beacon of truth, integrity, fairness, and common sense. Now, after decades of hosting Loveline and multiple hit TV shows – including Celebrity Rehab, Teen Mom OG, Lifechangers, and more – Dr. Drew is opening his phone lines to the world by streaming LIVE from his home studio in California. On Ask Dr. Drew, no question is too extreme or embarrassing because the Dr. has heard it all. Don’t hold in your deepest, darkest questions any longer. Ask Dr. Drew and get real answers today. This show is not a substitute for medical advice, diagnosis, or treatment. All information exchanged during participation in this program, including interactions with DrDrew.com and any affiliated websites, are intended for educational and/or entertainment purposes only. Learn more about your ad choices. Visit megaphone.fm/adchoices

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please contact Connex Ontario at 1-866-531-2600 to speak to an advisor free of charge. BetMGM operates pursuant to an operating agreement with iGaming Ontario. And here we are, everybody. We are also out. Can you hear me okay here? Am I working? All right. Out on Clubhouse, where if you raise your hand, I'll bring you up to the podium.

You can ask questions of our guests in just a moment. And of course, if you agree to do so, you'll be streaming out on YouTube, Twitch, Twitter, Facebook, all the platforms that are available. We are streaming. Today, we're bringing back Dr. Bruce Patterson. And if you who has been with us through this pandemic will be aware that he has been an important voice researcher in terms of understanding and developing treatments for long hauler syndrome or whatever

we're calling it now. He is the CEO of InCellDx, developing new precision medicine paradigms for predicting, identifying, and treating long COVID. Again, Dr. Patterson is one of the leading forces behind COVIDlonghaulers.com. And, of course, Dr. Patterson is also a researcher on the effect of viral pathogens. He was very active in the HIV epidemic and unraveling that puzzle. And he's working together with Dr. Ram Yogendra, both of them. And Ram is on Clubhouse, so we're going to pull him up just so his voice can be heard

because we're going to have three people on the screen today except Rom is not on Clubhouse yet so hopefully he'll get there he said he is but raise your hand there you are oh you have a different thing now okay I see you okay you see with the hand up um and I will bring him up so he can bring you up in just a second here uh and I want to introduce our second guest who's a newcomer to the program Dr. Eric Osgood is an internist, hospitalist, academic hospitalist, medical director of Mission Hospital, St. Francis Medical Center. Oh, goodness gracious. My page just went away here. Hold on.

That was weird. All right. There we go. He doctorate from Tufts and medicine residency at Seton Hall. Our laws as it pertained to substances are draconian and bizarre. The psychopath started this. He was an alcoholic because of social media and pornography, PTSD, love addiction, fentanyl and heroin.

Ridiculous. I'm a doctor for f*** sake. Where the hell do you think I learned that? I'm just saying, you go to treatment before you kill people. I am a clinician. I observe things about these chemicals. Let's just deal with what's real. We used to get these calls on Loveline all the time.

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patterson welcome to the program thank you you, Dr. Drew. Thank you. Good to see you guys. And let's bring our friend Dr. Yo in from the clubhouse as well. So we've got a lot of voices here today. Dr. Yo, how are you doing, buddy? Dr. Drew, good seeing you. Good hearing from you again. Get it on.

Ram is an anesthesiologist who's been very active in, how shall I describe your role with the COVID long haulers? Are you a founder officially? I guess so. Dr. Patterson, Dr. Parikh, we're the co-founders and I guess co-medical directors, right Bruce? That's right. And we've recruited 11 physicians, Dr. Osgood, one of them.

So we're and we got three clinical nurses. So and we just tomorrow is our first day where we are doing our first telemed consultations in Europe, starting with the Spanish patients. So very excited about that. Very interesting. So where should we start the update? Last time we talked to you guys, we were talking about CCR5 inhibition. We were speculating about statins. Where should we go? How should we start this conversation, Rob? Yeah, I think, you know, there's a lot, you know, we've now treated or actively treating over 2,000

patients in the United States. We've got over 12,000000 patients in the United States. We've got over 12,000 patients registered in the United States in the program, and there are various stages, whether getting lab work, having gotten lab work, fighting for a telemedicine consultation with our team. So we're really, really excited about that. And one of the things that we are starting to do is really understand long COVID, what exactly it is, and then you start realizing there are other issues taking place. And there's no like magic drug or magic potion or this magic bullet or whatever you want to call it in clinical medicine. So we are now coming where we've now, you know, Dr. Patterson and I and our team for over 12 months now, we've been researching this, two papers. I think the second one, I think Bruce will mention a little bit about it.

It's kind of almost done with the peer review, so we're super excited about that. And one of the things we want to show is, you know, again, we're off labeling and repurposing things. It's sort of looking at tools in the toolbox that we have and one of the things we want to do is to be able to study and put this in a in a controlled in a randomized controlled trial and do some clinical trials and and this is where dr osgood has really had a lot of experience i'm super excited about him on the team he's so instrumental in that where what we want to do is to show what um what we're seeing clinically is that we can show this in a study design and control for all the other factors. And, you know, one of the difficult things in medicine is if you don't know what you're studying, you don't know, you can't define the parameters. Right.

What's a trial like? Yeah, I think you are swimming in the messy waters of a syndrome as opposed to a diagnosis, right? And you're trying to nail it down to a diagnosis, meaning a common physiology, a common presentation. But it's been such a new syndrome to have developed. You're still swimming in the syndrome waters. Dr. Osgood, how did you get involved with this group? Yeah, so I ended up meeting up with Ram. How did you and I start first talking? I think we did a podcast together when we really hit it off, and I think we had a lot in common as far as how we

approach disease and our clinical approach, our clinical thinking. And he, at one point, he and Bruce reached out to me to see if I wanted to join the Chronic COVID Treatment Center, start doing some telemedicine with them. So that worked out well. I've been working with them since about July. And then we've been talking more and more about how we really need to do a clinical trial, a proper, randomized, blinded, controlled trial, without which you're not really going to get buy-in from the general medical community. And you can never really know if your intervention is responsible for your patient improvement or if it's just this is the natural history of that patient's disease is it the placebo effect what have you

yet there are obviously going to be a lot of challenges and when you're in that syndrome those syndrome waters as you put it and you know you don't have a really clear definition and parameters so that's where we kind of brainstormed and i came up with a kind of a novel idea of how we could approach such a trial which i'm happy to talk about tonight please let's hear it let's do it yeah i'm gonna get to bruce to give me the whole i'm bruce i'm gonna have you bring me up to the present but i first want to hear from these two guys and then then i'll fill in the gaps as they say but go ahead dr osgood for me where i can sit back and um let it let the team talk for us as ron said we've got

three physicians to over 11 we've now launched in the eu we're up to three clinical coordinators we're going to continue to expand throughout uh mexico, LATAM, and as much of the world as we can. So, listen, I'm sitting back here like the proud father listening to everybody talk about this program. I just wanted to add that Eric's design of this trial was really quite innovative because, as I said at the International COVID Summit in Rome in September, this virus is a chameleon. And I'll tell you, every single patient that we've spoken to has a different story, different symptoms, what have you. And I think one of the biggest problems in COVID with getting treatments approved, not, you know, not to mention vaccines, getting treatments approved is having a properly matched

placebo group. I mean, when when everybody's different, it's virtually impossible to have a Debo's matched who doesn't get the treatment, who's in a similar boat, so to speak. So I think that's been incredibly difficult. I've never seen anything like it in medicine where that situation has arisen, that the patients are so incredibly different that you can't match them. And I think Eric's design has taken that into account and will be the first CCR5 antagonist trial with statins, of course, that takes into account biomarkers and matching patients appropriately. So I just wanted to add that in and I'm happy to let Eric expound on that. Yeah, Eric, I think I'm hearing Dr. Patterson say that rather than look at the

clinical presentation, you're looking at, you're matching with biomarkers. Is that how that's going to work? Somewhat. So a little bit of my background before, after I graduated medical school, before I did residency, I spent some time in the pain clinical research world, basically phase two, so proof of concept trials in the chronic pain world, and also doing like psychometrics and outcomes and really trying to best design trials that are not going to fail. So we're really looking at the, I guess, the construct of the phenomenon of clinical trial failure, specifically in chronic pain. Chronic pain is a very difficult condition to study because a lot of the study drugs are only going to work on maybe 30 or so percentage of that particular disease population. And then it is so prone to the placebo effect as well as to people maybe

not being that precise or accurate in the way that they report. And so there is a need often to do enriched designs or enriched enrollment designs in order to better demonstrate proof of concept. And one of the things we really focused on was recognizing that seemingly homogeneous and sort of monolithic conditions are often consisting of subgroups and subclassifications based on sort of the mechanistic input of disease. So take something like painful osteoarthritis of the knee, one might think of that as a pretty simple monolithic condition where you have degenerative loss of cartilage and you have the subchondral osseous tissue, which is heavily innervated,

touching it bone on bone, and you have pain and it's normal nociception, when it turns out that there's very little concordance between radiographic severity and pain, and it turns out that there's patients with peripheral sensitization, there's patients with wind-up, there's patients with loss of normal diffuse noxious inhibitory control, central sensitization, and these different mechanisms of pain have very different sort of potential pharmacological targets, where if you don't include the right patients, you're not going to see any benefit. And so, you know, when I started looking at COVID-19 and being a hospitalist in the hospital, seeing how this disease presented, and then later getting involved with chronic COVID, it became pretty apparent to me. strong hunch that we were treating likely a very heterogeneous condition that affects different people differently and has different, I guess, pathophysiological inputs as one condition. And I think that's led to a lot of the clinical trials being all over the place, like does

tocilizumab work or it doesn't work? Does this drug work? Does this drug not work? And I think it's because what we will ultimately find out, what my hunch is that there are probably multiple subtypes of severe COVID-19 predominated by different pathophysiological mechanisms. And I think that's where I really found sort of a connection with the way that Bruce Patterson is approaching this disease because he's doing that both in long haul and in acute COVID. So when it comes to COVID long haul disease, when you look at biomarkers, not everyone's the same. You have different forms of this, different ways you can land on the long-haul index with different types of biomarkers that will respond to different types of pharmacology. So I looked back and I drew upon my experience in sort of the pain research world and found a

lot of parallels to some of the challenges we might have in trying to actually study this in a randomized trial, where if we take sort of a traditional parallel arm randomized trial and try to put two groups together, likely the statistical power is going to be eroded by the fact that your effect is probably going to be overwhelmed by the placebo effect in the placebo group. You're going to have maybe only 30, 40% of people in your active treatment group who would even respond to your treatment if it does work. And therefore, without doing a massively powered study with a huge sample size, you're going to likely to have failure. And so one of the clinical trial designs that often gets used in the pain world is something called the enriched enrollment

randomized withdrawal, EERW study design, which I don't know, Dr. Drew, if you've heard of that. No, tell us. Yeah, so this is where you take sort of a predefined subpopulation that you're interested in in the disease model. So traditionally it would be chronic pain. Here it's going to be COVID-19. And we're specifically interested in patients with COVID-19 registering on the Long Island Index with a certain profile, such as elevations in C-cell 5-rantes, soluble CD40 ligand, interleukin-8, interleukin-6, low C-cell 4, what have you.

And we're going to start them off in an initial open-label phase where the entire study population knows that they're getting the study intervention. And what you do is after sort of a defined study period, you look at patients who start to develop a clinical response and actually start to feel better. Those patients then make it into the next phase of the study where they are then randomized to either continue on active treatment or go off onto a matched placebo. And what you're looking at is sort of a delta in effect size between do those patients in the active treatment arm continue to go on to do well and improve? Do those who then go on to the placebo go on to do worse? And we're going to look at, you know, we still have to decide on what our primary endpoint is going to be. Of course, we're going to look at different sort of validated scales for different symptoms, composite endpoints of activity and pain, you know, look at accelerometry.

And, of course, we're going to look at biomarkers to try to further validate. And of course, the weakness of this design is going to be generalizability. Like what about the patients that don't get better in that open label? The benefit is that I think it has the best chance to generate proof of concept so that we can show an actual clinical effect in a properly randomized and placebo-controlled trial to then go on and potentially do further studies that are larger. Right. It's not the absolute best design, but it's a good design for mandating further study or suggesting further study. Bruce, I know you're nodding.

Especially for this type of group, you know, a heterogeneous group like this. I mean, Eric's right. I mean, you know, with doing a standard parallel study, then you're guessing at what your sample size calculation should be because there's so many differences. There could be, you know, eight kind of sub phenotypes, if you will, that may have nothing to do with one another. And so I think this really does have the best chance of succeeding using the, you know, some of the outputs that and outcomes that the NIH has already mandated for potential long hauler studies, which we have.

And do we have any kind of standardized criteria for long hauler yet? Well, again, I think that's our published work that generated the long hauler index that came out in Frontiers in Immunology. I think that was a good start. I think actually what came out of that paper was kind of two things that we look for at the Chronic COVID Treatment Center. And that is, number one, the Long Hauler Index, which is really a composite of biomarkers that sets you apart from acute COVID, normal individuals, et cetera. And in a moment, I'll comment on other similar diseases. And then, of course, in addition to that, there's been this recurring pattern in our

panel that suggests vascular inflammation. And, you know, the vascular inflammation is characterized by, you know, four different markers and that are separate from the long collar index. And then, you know, about eight months ago, we asked, well, why is there vascular inflammation in long COVID? And that's when we started investigating and we found persistence of the COVID S1 protein in monocytes in the absence of replicating virus in those cells. In fact, we did whole genome sequencing to prove that there was no full-length RNA or RNA that was capable of making virus,

but it was distance of protein. And we used proteomics to really define that. And we've used that, you know, online, fibromyalgia, ME-CFS, and we're just about to submit an article that shows the similarities in these diseases, which have been actually lumped together because they have similar symptoms, fatigue, exercise intolerance, brain fog, et cetera. So there was always this question six to eight months ago. Well, are they the same thing? What are the similarities? Well, when we used machine learning and AI to look at the differences, they are indeed different.

But if you use a single algorithm to say, are they long haulers and non-long haulers, all of these register they long haulers and non-long haulers all of these registers long haulers if you use two out of the second algorithm which is a of all the inflammation and what's called a severity score that's where you separate acute COVID, long COVID, post-vaccination long haulers, ME, CFS, fibromyalgia, et cetera. So we're very excited about looking into the pathogenesis of all those diseases that had similar symptoms, but now we're finding that there are some similarities amongst the differences

in the immune system. Go a little deeper into that sorting, explain what the differences are if you can. So, um, I, again, I wish I had the figure that I could pull up, um, where we overlay. So we have, uh, on one X, the Y axis, we have the severity score on the X axis. We have the Wong-Holluler Index, which are made up of different composites of these immune biomarkers called cytokines or chemokines. And the severity index, which we use in acute COVID, which says how severe is the disease and are you going to become severe, uses more or less like six or seven of the 14 biomarkers we have in the panel. And then the long hauler index is made up of three. And for instance, ME-CFS, chronic fatigue syndrome,

and post-vaccination long haulers, which are patients who've never had COVID, who received the vaccine and developed long hauler type symptoms. And again, this population is very rare. It's a very rare side effect of vaccines. We're not, we are absolutely pro vaccine, but they do develop these immunologic abnormalities that resemble chronic fatigue syndrome. And then if you overlay ME-CFS with true long haulers, they actually have higher long hauler indices than even long haulers, which means they have a higher level of what we call type 1 cytokines,

interleukin-2 and interferon gamma. Yet they all kind of register as non-normal and non-acute COVID. So again, we'll be explaining a lot more in an upcoming publication, but it's fascinating to see that these diseases that have very common symptoms also have some commonality in terms of their immunologic abnormalities. Which makes sense. Do you have a sort of a hypothesis in your head about what the physiology is here? Do you have like a sketch or a favored kind of idea? Well when we looked into the literature,

and again, this is in our paper that should be out here pretty soon after peer review, we found that in post-Lyme, it's very common for the cell wall of the Borrelia bacteria, Borrelia burgdorferi, which is the best name in microbiology, is actually phagocytized or engulfed like Pac-Man by these monocytes that engulf the S1 proteins in long COVID. And then, of course, we also showed in this paper that these cells traffic all over the body, including through the blood-brain barrier. And they cause blood vessel inflammation because why?

They bind to the blood vessels through another pathway called fractal kind. The exact same mechanism seems to be at play in post-Lyme. And the cells, as you know, also carry Zika virus, dengue fever virus, and the intermediate monocytes are infectable by HIV. And then we showed in 2009 that these cells were infectable by hepatitis C. So they are really a wastebasket for dying cells and cells that may contain viruses and then they they process these proteins and either express them or carry them around the body and cause inflammation so it's really quite amazing that the body is capable of doing that in the absence at times of replicating pathogen which may be all totally who so i innovation and hope you don't mind a bunch of basic questions here i'm assuming these monocytes don't live forever

right i mean so why do they continue to have an effect or is that strictly the life duration of a monocyte that they have that effect? Actually, normally they have a very short lifespan on the order of a week. But when they're presenting antigen and carrying antigen, it blocks its senescence program so that they don't die. But if you keep them from doing what they're supposed to be doing, which is in the case of non-classical monocytes binding to vascular epithelium through statins, they die off. And if we follow serially S1-containing monocytes in long haulers following therapy with CCR5 antagonists and statins, it goes down. It goes down with therapy over time. And it's accompanied by, you know, improvement in symptoms. It's been pretty remarkable to watch that though.

The drop in the monocytes and the improvement? Yeah, the clinical improvement. And since I joined the practice and actually seeing people, and a lot of times I'll follow up and I'll see they presented months and months ago, you know, they're, they're all their cytokines are elevated, they're feeling terrible. And then there'll be in follow-up, they did, you know, a course of CCR5 antagonist statin, maybe a brief course of low-dose steroid or another, you know, immunomodulator or two. And then you see them in their labs, largely normalized, they're feeling better. They can focus and concentrate, generally not back to 100%, but just markedly different. And so it's been very fascinating.

And then actually, since I've been in the practice longer, I've actually got new patients who I've now followed for months. And then, again, you start to see them. You see the biomarkers improve. You see the clinical picture improve. It's been very rewarding to be a part of that and so you know getting a chance to now put that into a clinical trial is we're very excited about it so it's a big deal what are you using for the ccr5 inhibitor we're using a wrap which is a rack or cells entry Yeah, drug-manifestant, Mraviroc, or Celzentri. Yeah. Yeah, yeah.

And in fact— You guys were messing with that early on. You noticed something with that or a signal with that. So that doesn't surprise me. And once again, what is it the monocytes are doing normally when they bind to the endothelium? What was the purpose of that? It's really quite amazing. The non-classical monocytes express this receptor for fractal kind. Their main job is to patrol the vascular endothelium for for inflammation.

And and in fact, now all of a sudden they're carrying something that induces even more inflammation. And what was really interesting in going through the literature on the latest paper was that when the non-classical monocytes bind to the endothelium, they release type 1 cytokines, interleukin-2 and interferon gamma. Well, guess what? That's the numerator on the Long hauler index discovered by computer. So it's very satisfying to see, you know, at least this mechanism coming together. And by virtue of the fact that these patients have responded to therapy directed at that mechanism, at least gives us some great confidence that that indeed is a major mechanism of long COVID. And as Eric said, to see these people go from being bedridden to, you know, 85, 90%, 95%

better has been absolutely remarkable. And of course, you know, if they have, you know, this inflammation affects nerves, sometimes nerves take a little bit longer to, you know, this inflammation affects nerves. Sometimes nerves take a little bit longer to recover. But to see them going about their normal lives, exercising. We've had several in our program now, all of a sudden, they're climbing mountains and going on hikes and playing with their kids and running three miles. One gentleman told me on telemedicine a couple weeks ago he he was a little bit frustrated he was you know he was pumping iron again uh but he can only pump iron three days a week instead of six days a week and i said hey arnold you know you know so and he would be great rams rams sent over a graph did you see that true no show me can you

put it up on my phone put it up let's see what rom sent us a graph of oh this is the scatter rom this is a long hauler index versus severity scale these are the different syndromes and how they shake out right right rom you put yourself on mute again. Do it the other way. There you go. Go ahead. There we go.

Yeah. Yeah. So that's the scatterplot that Dr. Patterson was referring to. We just sent it over a couple of days ago. I think the dark blue, right, Bruce, are the ME CFS patients. Define the ME CFS for people. So again, you know, it's basically chronic fatigue syndrome. It's long thought to be caused by the chronic herpes family viruses,

EBV, CMV, varicella, herpes simplex, HHV-6, et cetera. But the hallmark is fatigue, brain fog, shortness of breath at times, exertional, malaise, etc., just like a typical long hauler. So what you see is from our paper that's about to come out in yellow, which is the, or no, the paper that already came out in yellow, which is the yellow is true COVID long haulers. The red dots are the post-vaccination patients who never had COVID, who have long hauler symptoms after three or four months. On the far left, it's hard to see to the left of the vertical dotted line, but that's where the acute COVID patients lie. And obviously, the higher up they are, the more severe their immune systems are.

And then, of course, in the lower dotted line in the lower left-hand corner are a bunch of normals and some mild to moderate acute COVID. So it's really fascinating how, you know, these different aspects of not only COVID, but post-pathogen immune disorders are really separating themselves out. They're similar, as we said, in terms of the fact that they would register, if you just did long hauler index, they would register as a long hauler. But using the two algorithms, you can see that the true COVID long haulers have a higher degree of inflammation than the post-vax long haulers and the ME-CFS. And indeed, the post-vaccination long haulers, two to four weeks of therapy, maybe six at the outset, they respond very, very well, very quickly.

COVID long haulers take a little bit longer, four to eight weeks, maybe some out to 12. And so there is a difference in the response. And the ME-CFS is that those patients, which may be a completely different etiology, in other words, not involving S1, also respond to meraviroc and statins. So, you know, focusing on precision medicine and treating the immune abnormality and then having that accompanied by symptomatic relief has been really gratifying and probably the most gratifying part of the program. And, you know, it's something that we continue to expand upon. Fibromyalgia will be added to this list, and we'll probably be looking at some point some of the autoimmune diseases.

Interesting. So I have a feeling this research is going to open up a bigger topic eventually, in that the lay sort of world is awash with descriptions of inflammation being an important part of health. And I, for a long time, thought that what people were really talking about was vascular information of some type, some endothelial something. Because we were not talking about synovial attack by neutrophils. We're talking about some sort of low level and i i've been had my eye on the fact that the lipid system particularly the apolipoprotein system and and insulin tended to figure in this as well seemed to be something that added to this whatever this

thing is we're starting to you guys are starting to look at this endothelial what should we call it what do we have a name for it yet endothelial inflammation you said vascular information i don't think that's specific enough because that's like it sounds like a vascular but that's not what this is what is it endothelitis we've been using that term endothelitis okay okay uh but but you know certain subsites, apolipoprotein metabolism, the effect of monocytes on laying down some of that inflammatory oxidized material, this is an important area of health. It's not a surprise to me that the statin would figure into this. How do you think that's working? Listen, I think Rahm will agree, and I think this is a little bit before Eric's time, but we added a statin into our program, I would say, you know, February, March of 21. And it was a real game changer. I mean, the COVID long haulers,

they got better quicker. They got the extent to which they got better was greater. And I think it all had to do with the fact that statins are instrumental in reducing vascular inflammation through this fractal kind pathway, which I think, you know, that's something we're also looking at to answer the question, why do some people become long haulers? Well, you know what? Just like other chemokine receptors, fractal kind receptors have mean polymorphisms, which are hereditary. They express different levels of receptors, much like a CCR5 receptor or other receptors. So they're looking into that as a mechanism. For instance, if you had a

some sort of defective fractal kind receptor, maybe you don't get vascular inflammation. You're protected from becoming a long haul or something, you know, from or a post-Lyme, for instance. So we've just, we're just at the tip of the iceberg and really identify how proteins can cause immunologic disease. I remember probably 10, 15 years ago when the first pan-veg called GeneShifts, which had all 2000 genes on them, which we used at Stanford developed by UCSF. We used it to screen patients.

We had no idea where to start. You couldn't validate it ever for We used it to screen patients. We had no idea where to start. You couldn't validate it ever for clinical use because you can't validate every 2000 targets, but we used it to steer us in the direction of FDA approved tests. And it was amazing what we found. But the fact is during that era, and that was the genomics era, everyone just slapped everything on the gene chip. I don't know what's going on. I'm going to put it on the gene chip.

You know, a lot of that was driven by the HIV pandemic. So one thing, having lived through now four, five pandemics and been involved in the research, what I've really noticed is HIV drove the molecular revolution in medicine and came up with great approaches to cancer where everything is precision medicine in cancer. You don't get a drug until they know that drug's going to work on you. to introduce proteomics and immunology into our daily lives in medicine, much like HIV introduced the molecular revolution. So we're getting ready. And cytokines as biomarkers.

That's the other thing. That's the thing that immediately started. Absolutely. Immune cell subsets, cytokines, all of it. biomarkers that's the other thing that's a that's the thing immediately started absolutely immune cell subsets cytokines um all of it and eventually we'll be able to uh uh you know put all that into machine learning and and and come up with even more signatures of of disease that are uh immune mediated rom is that you echo what what dr patterson mentioned about the fractal kind um yeah that was that truly was the you know a game changer for many patients you know it's very interesting there's some patients that are contacting us from overseas and they're long haulers or ones that are just having some

post-vaccine um symptoms some persistent symptoms after the vaccine. And what is very interesting is because they haven't gotten any lab work done or they're in a different country, a lot of times doctors will reach out to me and I just tell them, just start them on a statin, a very low-dose pravastatin or torvastatin. And while it may not get them, you know, completely resolved most of their issues, they do notice almost within a week some dramatic improvement in symptoms, especially the peripheral neuropathy. And the mechanism is if you look at the textbooks on the, of how these non-classical monocytes are binding, and as Dr. Patterson and Dr. Osgood mentioned

about the fractal kind receptors, it looks likecro and they almost stick like vel yeah when i remember looking at this going on this looks like velcro to me and and the way i describe it to my physician colleagues and especially to the patient so they understand what's going on it's almost like putting a piece of paper between velcro and what happens it doesn't stick and these non-classical monocytes another thing i explain to the patients and the physicians is that i look at it as garbage trucks and they're garbage trucks with garbage inside of it and if you put garbage sitting in a garbage truck for six months or 12 months or 18 months what's going to happen it goes bad smell yeah it's going to go bad you walk by and go oh my god it smells like crap and the cytokine the immune panel actually detects the smell in the long haul index it's it's almost

like it's got a this specific type of stench inside of it it's like rotting eggs and you know dead rabbits or whatever is in there and you go oh that's what it is whereas then there's a different immune pattern let's say for maybe cfs or some other pathology that we can then detect and use machine learning to identify that quote unquote smell. And the way I explain it is that our goal is to prevent the immune cells from sticking and then to immunomodulate and reset the immune system. Because there is a dysfunction of the entire immune system taking place here. And that's the overall goal of the treatment. It sounds like you also want those monocytes to die out, get their senescence back in gear.

It's where the CCR5 signaling is just, you know, like Bruce and I have been talking about on your show and many other podcasts, it literally is the quarterback. You knock it out it it's you know another thing i explain to patients uh drew is like it's almost like if you were on a street fight like you are in first and main street and you are about to get your butt kicked by someone so what you do is you text susan you text uh you know a couple other people like hey i need some help so all your friends come in like maybe maybe Susan comes in with like a bazooka

or, you know, Caleb is coming in with like a pocket knife. I like machetes. Oh, machetes, right. Susan comes in the machetes. The local favorite. Well, I don't know what you guys are doing over in Pasadena, but... It's just Los Angeles generally.

Oh, yeah. Well, so all of them come to this fight and now this one little fight between you and this other person has gotten worse. And that's what takes place in inflammation what a drug like maravarac does it blocks the text messages from um from being sent out so that text message you sent to susan she doesn't come but more importantly is that susan doesn't bring the machete to the fight so this is that whole downstream effect because now not only will be blocking ccr5 you're knocking out the quarterback you're knocking out the wide receiver you're knocking out the running

back so it has this dramatic effect also in the vascular markers or the vascular inflammation that's taking place and some of these inflammatory signals and then that's where where you're able to um you know decrease the inflammation and then, undergo apoptosis or program cell death of these non-class monocytes. Which is, you want them out. But let me ask this. I'm going to ask a couple of pushback questions. One was, Ron, when we first got to know you, you were talking about CCR5 as it pertained to loranumab, right? Yes.

Is it possible that the availability, heuristic cognitive distortion is affecting where you guys are looking? And you had already, in other words, did you already have a predilection to look at the CCR5 system because of your interest in loranlimab? It just seems weirdly coincidental to me that we have loranlumab and now

we have moravrec and it's both you know just so happened that this turned out to be a very important piece of it or is it just that this was a very important piece of the cytokine physiology that you were picking up a signal on and looking at yeah it you know i started studying ccr5 in the mid-1990s when it was a co-receptor for HIV and have been working on it ever since. We looked here the first one to identify CCR5 for instance in the female genital tract as a parameter for HIV transmission. And so it's been, and then also CCR5 on a variety of different immune cells, effector T cells, monocytes, T regulatory cells, which shut off the immune system.

So it's been, yes, it's been a pet of mine, but it's been a pet of mine since 1996, right? So it really happened. And actually, someone's writing about this. When I was in China the first week in January, I was there to talk about the immune system and some immune diagnostics that we had developed for CAR T therapy in cancer. When we started talking about, quote, immune virus that was coming out of Wuhan. Well, interesting story. I was about to go to Wuhan to visit a customer of InCell DXs the following week, which would be the second week in January. And they basically said, don't come, we're shutting down. And then that precipitated even more discussion. And when I looked at some of the data from this quote immune virus and then looked at some of the cells and plasma myself, that's when we saw this predominance of CCL5 or RAN-T's in addition

to elevated IL-6, in addition to elevated VEGF. And it was a natural, well, CCL5 and Ranty's is elevated. Let's block it with CCR5, right? Which, you know, I was involved in some of the early studies of Miraviroc and Vicroviroc, which was Shearing Plow or Merck's drug, and Icriviroc, which was GSK's. This was in the early 2000s when we were doing assays for the other CCR5 antagonists. So it was something that was just like, oh, wow, these three cytokines, CCL5, IL6, and TNF-alpha are elevated. That's just a setup for a CCR5 antagonist. And yeah, it happened. We had one that was right there, loranlimab, that was going into clinical studies.

We knew meravirac was around. We could always get that if we wanted to. And that's where it all started, was in, was in China. It's that, that it is an important piece of the system and it's a, it's just coincidence, serendipity that you happen to live there. Physician at a very, very prestigious university say,

why would you use a CCR five antagonist? They're immunosuppressive. And this is a viral infection. I said, excuse me, they're not immunosuppressive, they're immune modulatory. And that is the beauty of using CCR5 antagonists instead of, you know, potentially dexamethasone or other steroids, is that they aren't immunosuppressive. And in fact, they correct immune exhaustion. And, you know, that's why I think this is the next big wave in inflammation because we can actually modify the immune system without making you susceptible to other bacteria or fungi or some of the other things that just you know steroid blasting people with

um is going to make it acceptable that's my big fear in the hospitals when i get called from someone with acute covid um which i have a lot with delta lately and i said you know i know they're on dexamethasone i said said, personally, I don't think that's any good. And I push for Maraviroc and statins because they're both FDA approved. And you know what? Even in acute COVID? Oh, yeah. Why not?

You know, it's pathogenically. I mean, the cytokines are elevated would respond to that combination. And so I always lose the marabarock battle although some patients that they've grounded up and put it down ng tubes but at the end of the day i can at least get a lot of statin and there's actually a big paper that came out i think from mass general showing the efficacy of just statins in acute covid Now there's a safe and effective and approach to acute COVID that has very few side effects. What kind of dose, is it anyone, any statin and what kind of dosing? It's, it doesn't take a lot. You know, we use 10 to 20 milligrams of statins. We're not trying to lower cholesterol from 400 to 180.

So it really doesn't take a lot to see a profound effect on the cytokine profiles. I have to take a quick break here, but I want to ask you one other quick question. Last time we talked, you were toying around with the idea of sort of inflammation of the central nervous system, the elevation of the VEGF. What happened to that little theory? Is that still part of what's going on, or was that just an epiphenomenon that doesn't seem that important? No, I mean, the fact is, when you talk about blood vessel inflammation and you talk about cells that's what's so interesting about monocytes i mean they're you know you have this diversity of symptoms it's not focal like a rheumatoid arthritis you know where you can say well i got to get to the drug for the joint right

it's everywhere and that just that just smells of of a vascular type of inflammation. And yes, absolutely. Because what's key is when these non-classical monocytes bind to endothelium, they also increase VEGF, which is entry, which causes peripheral neuropathies, which long COVID patients have a lot. And it causes vasodilatation. Vasodilatation, what does it cause? Headaches and migraines and tinnitus. So when you correct that, that's when you see

a lot of that brain, and they say, oh, I have this pressure in my head. I've had so many patients, this is the call sign for long COVID. And when someone goes like that, you need a long hauler. Dr. Randall Bell, That's true. I do it kind of like, I felt the fog, I felt more in here, like the fog. Dr. Michael Lecce You have long COVID, no questions asked, because they feel this pressure. And the pressure obviously from vasodilatation and then the headaches and the migraines. And when you relieve the inflammation, obviously, from vasodilatation and then the headaches and the migraines.

And when you relieve the inflammation, a lot of it just goes away. It's like the Levine sign of long COVID. Right, right. So, okay, guys, I'm going to take a quick break here. This is a fascinating conversation. I've learned a ton already. I didn't get the joke. There are things you do that are classical moves like this and this.

And in medicine, they each have their own name. And now we have the long COVID sign, which will be the Patterson sign. So, okay. Okay, I get it now. So, thank you. We'll take a little break, be right back with more of this after this. I want to give a shout out to our good friends at Blue Mics.

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microphone to fit your budget and need i can't say enough about blue mics and once you try one you will never go back trust me to take your audio to the next level go to drdrew.com slash blue. That is drdrew.com slash B-L-U-E. All right, we are back with Dr. Yeo, Dr. Patterson, and Dr. Osgood. Dr. Osgood, back to you for a second, if you don't mind. This is all very interesting physiology, and I'm guessing as a hospitalist, it has sort of informed and changed some of your approaches to COVID. Yeah, definitely. I mean, pretty early on, we started giving statins to most of our inpatients.

And we saw pretty clear signals this was helping. Pretty early on, we were actually giving methylprednisolone as our sterative choice. We were doing really D-dimer targeted full-dose anticoagulation early on. Really, some of the intuitions we had early on were pretty vindicated. Some of the other things did not necessarily turn out to be borne out by the best evidence, but I think overall our protocols have been good. But really giving your attention to each individual patient, treating them individually, following biomarkers, as well as their clinical status has really been the most successful approach. I want to take a quick shout out and just give some recognition to the unsung heroes

of the pandemic in the hospital, the medical residents. And I've been privileged to be part of a teaching program with some excellent medical residents without whom we really could not have accomplished what we did during the waves of the pandemic. It's interesting. As somebody who did my residency during the darkest hours of the AIDS epidemic, it's interesting how these disease-specific pandemics affect our training and our outlook going forward. You know, in HIV and AIDS, oh my goodness. I mean, that was such a, we were in a war with that illness and people were literally being torn apart by it and just struggling to come up with something.

It was like being a surgeon at the turn of the 20th century with only limited things to be able to do and just struggling to find stuff. Yeah, it's quite a time to be in training, really. Yeah, yeah, it is. I hope it gives them a sense of desire to be very careful in their thinking and to be research-oriented in their practice and to be able to improvise and use their judgment in situations

where things look rough. I mean, a lot of what we've done has been the result of improvisation. I mean, Dr. Yeo and Dr. Patterson had some ideas about how this might work and started applying it and lo and behold, it did. I mean, if you hadn't tried these things, this is the part about this pandemic that I have found astonishing, that people have been unwilling to try things that might work that were based on good hypothesis, good physiology. And you guys did, Bruce. Yeah. Well, you know what? It wasn't easy, and it's still not easy.

I mean, I've talked to, like I said, a number of hospitals and, listen,, the hospitalists and incentive intensivists are under the gun and it is, it's unbelievable what they're doing, but, you know, part of it is they don't have time to think about what you're proposing and what, you know, and, and, and and or think about it mechanistically and you know and what they don't realize is that for instance if you used our severity score in acute patients and you had a a reasonable turnaround time of say a day to get your results not only would that allow you to manage the patient better but it'll allow you to manage your resources. What they're not recognizing is when you don't know where the patient is on this immunologic

continuum, you have no idea what the prognosis is. You don't know where they are immunologically in the cytokine storm or on either edge of the cytokine storm. And the problem is they're thinking about, you know, the next patient who is coming through the ER who is just as sick and needs a bed. And I get that. I completely get that. But what I insist to them is that you have to take care of that patient right in front of you right now. And you need to do the best possible job on that patient. I know there's patients waiting. Of course there are. And it's hard. I mean, sometimes they have to make difficult decisions about who gets resources and who doesn't get resources,

especially in, I would say, February 2020, when I was collaborating with physicians in New York City and doing some of our initial studies on acute COVID. They had to decide who gets dialysis and who doesn't get dialysis because the early COVID was really affecting kidney function and multi-organ function for that matter. But the fact is, you know, what they really need, and I've been talking about this, spoke about this at the International COVID Summit, is you need to correct the immune system and time. The problem is, and I just read an article that mimicked some of our early patients in 2020, where a patient was intubated and they were just about literally minutes away from pulling the plug and all of a sudden came to, and, you know, a few days later was out of the hospital. You know what? There's never been a disease like this.

And I saw that a lot when we were using, um, uh, CCR five antagonists under EIND in the February, March, 2020 timeframe, where, um, you could get them home. You could get them off ventilators. You could get them off ECMO. We've got five patients off, which is basically, you know, lung bypass. Right. But what they were given, the ones that did leave was time.

And you corrected the immune system with the ccr5 antagonists and they needed time and in fact ecmo was great because it gave their lungs didn't have to do their normal jobs all they had to do was repair themselves right or allow you know the inflammation to subside and and allow the the recovery to happen you know the problem inflammation to subside and allow the recovery to happen. You know, the problem is we don't have the luxury of time when there's just masses of people flooding the ER. And I get that, but that demands a different approach. And if that approach is restore the immune system to normal as quickly as possible,

then that's what has to be done. There's a time element here. And then also something like a severity score that can tell you where you are and how to manage those resources. There's some people in this severity score who were clinically severe, whose immune systems were almost normal, you could put them step down from the ICU, okay? Or conversely, someone with mild to moderate clinical symptoms who had a completely disastrous severity score and immune system that was very stormish probably needed a step up but that's how you could manage resources better while doing what's best for the patient yeah it's very difficult to try to go ahead eric please finish your thought i was gonna say it we have when when someone is in the process of crashing and you're worried about PPE and you're worried about, you know, gowning up and all that, it gets very difficult.

So being able to stay one step ahead, it would be incredibly valuable. And Dr. Drew, one thing you mentioned I really wanted to kind of expand upon, you mentioned kind of the rigidity of clinical thinking during the pandemic. And nobody thinks that it's appropriate to do anything until, you know, flawless randomized trials sort of spoon feed us conclusions about drugs. I mean, we seem to have forgotten that, I mean, the majority of clinical practice guidelines come from very imperfect studies. There's different grades and strengths of clinical recommendations. A lot of what we do, especially in infectious disease and hospital management, are based sometimes on retrospective studies, sometimes cohort studies. And it's been a shame to see this kind of new zeitgeist of this just incredibly rigid, protocolized approach to medicine. It's unbelievable. It's the biggest

shock to me of this entire pandemic. It's absolutely shocking. And I've witnessed firsthand a massive difference between those of us on the medical side versus the surgeons. The surgeons improvise. The shit goes down in the surgical field. They got to figure it out, not wait for a randomized controlled study. And early on, my surgical colleagues were trying all kinds of stuff. That's where I learned about things and how things were happening. The internal medicine side froze in place. I think it's because a lot of people are employees or have clinical pathways in their hospitals that they're required to follow. That's a catastrophe. People want us to use our judgment. That's why you see a doctor. You don't need a doctor if you're just following a protocol. You don't need us. Just tell somebody else to do that.

We're trained to use our judgment. When you don't know what right just tell somebody else do that we we're trying we're trained to use our judgment when you don't know what to do that's exactly where you want somebody making decisions that are that are uh that are improvisational that's just what you got to do the public is counting on us i don't know that's shocking to me shocking to me disgusting and shocking bruce and as long as we're still following the do no harm you know uh mantra that we all carry i mean you know it's you why not be innovative that's that's the hallmark of of everything that we do in life is is to be creative to be. That's why we became doctors. And then, but to be just a USB drive

and being plugged into some system is, for me, when the book is written about this pandemic, for me, that's gonna be my last chapter is that despite the creativity, despite innovation, you weren't allowed to be creative and innovative. And that's with FDA drugs that have a file on them, on their safety, and you can't repurpose them because it's not in some protocol that, like Eric said, that's been in some massive randomized control study where you don't get results for 18 months.

How does that help you with your current surge in cases? Yeah. I mean. Yeah, listen. Hollywood and the public valorized the Dallas Buyers Club. What do you think they were doing? They were just improvising, trying stuff. Now, the part of the story they didn't tell in the movie is they got in the way of actual treatment, ultimately.

And I had a ton of patients die because of Dallas Buyers Club. But we were supportive of them when there was nothing else to be done. People were trying things. Try something. Try stuff. And this pandemic, the exact opposite and it i hope i hope you will name that final chapter the the the in the biggest shock of the panda the what shocked me the most was was our behavior in this uh rom i was starting to ask you um something what the

hell was i getting into for you uh did you could you tell where i was going um no you couldn't tell um it is there's there's there's something actually i want to mention and i think it really maybe ties everything together because you you and you and bruce and eric were discussing about acute covid um and obviously a little shift from from long covid they they kind of, you know, there's a lot of things that we're picking up with long haulers and long COVID that I think really can, you know, ties in a little bit with the acute phase of the disease. And one of the things, you know, we're seeing is this immune dysfunction in a good majority

of the patients. But, and it goes to the first question you asked good majority of the patients. And it goes to the first question you asked, one of the earlier questions you posed was, you know, do we have a consensus or a definition? And even now, look, some people call it long haulers, long COVID, chronic COVID, PAMC. I know. We don't even have a consensus on what the pathology is. Or whether it exists. We don't even have a consensus on what the pathology is. Or whether it exists. There are people that insist that it doesn't exist, which I'm here to tell you is a long haul or it exists.

It's very unpleasant. So when you don't, when there's still discussion, we're still trying to define everything. And what Dr. Patterson and our group have done is really identify that immune dysfunction. But that does not mean that this is the end all be all this is the word of god right the clinical medicine doesn't work that way no and one of the interesting things that i'm sort of picking up and like i said this is from looking at over 2 000 patients now is there's a certain percentage i think it's probably anywhere from like 10 to 20 percent of the quote-unquote long haulers they're probably not dealing with an immune dysfunction these are patients i just personally

think they have they have some damage done during the acute phase of the infection yeah these are ones that whether it's neurological respiratory um cardiac or any one of the other systems in the body the acute phase of the of the viral of the disease caused destruction so we're talking about something a little bit different than the immune dysfunction now a good majority though of the of the long haul and i would probably say like 70 80 percent are what we've discovered with that immune dysfunction and the s1 protein and whatnot and that goes back to the clinical management and exactly what eric or dr osgood was talking about with the clinical design if you enroll those patients that had acute destruction and don't have an immune dysfunction the trial is going to fail maravarek and statin are not going to work for them or any of these

therapeutics that we're we're sort of looking at because for them there's something else that's going on um anyone in clinical medicine that says they have 100% success rate should be selling used cars. So, you know, so what this is allowing us to do with this clinical insight we have is to really start to understand the pathology. So you've got a certain group of patients that, and I say this, and I'll bring up one particular case, I'll try to keep it as general as possible. This is a young woman got definitely had an acute case um had definitely had a covid very mild case of covid started to develop neurological symptoms um back pain and really severe headache and and migraines while she had covid this is about day three of infection

very common by the way that's a very common symptom yeah she then started to develop you know she said like after she got over this acute phase of covid she started you know it just persisted and we looked at her cytokine panel she was normal she was on a clinical trial with another medication didn't respond we had her on marabrac ivermectin statins uh colchicine you name it she got it for weeks and weeks and weeks and weeks immune profile was always normal s1 came back negative what exactly is going on we work and this is the other thing people always think about what you know dr patterson me and the rest of our team they just think it's like marabarack or bust like that's all these guys we're interacting with hundreds and hundreds of physicians in the United States and now globally and again

It's what you told me several months ago. It's about physicians don't talk to each other and I I always tell you dr Drew I take it I took it to heart and they really have implemented that where it's a close collaboration And we're working with different researchers But we we have this patient work with a neurologist who's got a lot of experience with ME-CFS and a lot of chronic illnesses. And there's a test called a neuroquant. And it actually measures sort of the brain volumes. And it's almost like an MRI. I'm not too familiar with it.

But she had this patient who's a young woman. Young woman. She's 28 years old. We had a neuroquant. Her brain scan, and she shared these results with Dr. Patterson and myself, she looked like an early Alzheimer's patient. Yeah, I'm not surprised. I've seen other illnesses do something like this,

and I've always thought it was vascular-related. So it's literally, a lot of it's glial cell dropout, but it comes back, but it can also be irreversible. Well, we've also seen, you know, then it's a question of what was that Bruce? We found, we, we looked at, um, with, uh, Dr. Lalazari and his father, Dr. Lalazari, we did a, uh, a pilot study in Alzheimer's where we took brain homogenates and ran our 150 biomarker panel and found that interleukin-18 divided by interleukin-4 actually told you if you were mild Alzheimer's or severe. So the inflammatory component of Alzheimer's is very predictive and very interesting, and it's truly a part of the pathogenesis.

Interesting. That makes perfect sense to me. I never thought the plaques had anything but sort of incidental or consequential. It's like looking at gliosis and saying, the scar is the problem. It's like, hmm, I'm not so sure. Ram, I remember what I wanted to ask you. How's your friend, the anesthesiologist that I spoke to, doing? Tom's doing well. In fact, as Dr. Patterson sort of mentioned about, you know,

we're actually, somebody's actually writing our story. It'll be several months. And it's not about us. It's really about the whole program and how all these amazing people and how we're slowly transforming medicine. And Tom is doing well. Actually, just sent him a text message because his story kind of is the reason why I ended up meeting Bruce and really looking at this and from the whole acute phase of the COVID, he's doing wonderful. I'm really excited to say that he, you know, I don't want to say he made a full recovery,

but he's about 90% of where he was, still has a little bit of a foot drop. And but again, from where he was 51 days in an ICU to where he is now, it's pretty remarkable. But, you know, Tom was, um, Tom was so instrumental. Um, I think just changed the trajectory of my life if it weren't for him. And unfortunately getting sick, I would never have met Bruce. I would never have brain, you know, had all these brainstorming sessions for several months, uh, and formedlonghollows.com. The whole concept would never have started. I can't even put it into words how that changed my life. But it changed all of us.

I mean, changed Dr. Pat. I think he would probably agree. Like Dr. Patterson's life changed everyone. Well, by the way, for me, it's all the stuff I've been complaining about for the last 20 minutes, but it's been the one bright spot in terms of, for me, physicians doing the right thing, doing what we're supposed to do, what we know how to do well as scientists. I have to wrap up pretty soon. I have a couple of the monocyte function. Can PDE, not my brain, this is my COVID brain, the PDF5 inhibitors, the things like Viagra or Cialis, are those inadvisable in post-COVID? PDE5. You have to be careful with something that dilates blood vessels, you know, and people, you know, they have temperature, you know, insensitivity, both hot and cold.

And they're like, oh, my fingers are numb and my toes are numb or they're swollen. Everything's always swollen. Well, you know, all of that is vascular dilatation. So, you know what? I'd be careful with them while you have long COVID. Like exercise, we can bring them along slowly. And I never say never. We'll get them there at some point.

But let's take care of what's causing the bad vasodilatation. Right. And I think I also have a fantasy that as a result of all your guys' research that we're going to learn about how tremendously different the cerebrovasculature is, the endothelium is in the cerebrovasculature. I've always kind of thought that. And I bet you're going to uncover a lot of interesting, unique qualities in the cerebrovasculature. You agree with that? I think we're going to learn a lot about the effects of the blood brain barrier in these conditions. Yeah. It may be just permeable as well. So we'll see. Susan, I've lost my image of my friends here. I hope that's not what's going out.

We're good. Okay. Gentlemen, I got to kind of wrap this thing up. This is nerding out for me. I could kind of keep going. I can think of a lot of other things I'm interested in. One last thing. Fluvoxamine was something on the radar last time we spoke.

Is that just off now? It seemed to have helped me quite a bit. Somebody already on a statin. Curious. We're using a lot of it. A lot of it still, yeah. So that Sigma-1 system is a feature of all this. Interesting.

Eric, how long do you keep people on it? Again, we really let the clinical course drive. We don't really necessarily have any hard endpoints. We start to taper people off when we feel like they're ready. And generally, people are not big fans of polypharmacy. These are a lot of patients who have never been on a medicine, no past medical history. They want to get back to their lives. They don't want to be taking medication. But if you withdraw the therapy too soon, they can rebound. So we really keep a close eye on the biomarkers and we keep a close eye on the

clinical progress. And when it's time to start tapering we do it so it's it's there's really no one size fits all i i was i was really asking about what pertained to fluvoxamine as it pertains to the inflammation of the brain and we were talking about alzheimer's and the inflammatory component of alzheimer's and whether we're going to see some dementias down the road from covid and maybe some longer i've been ruminating whether or not a longer term fluvoxamine on a low dose would be something smart in people that have a long hauler. That's a very, very, very distinct question. I know you guys aren't looking at that, but any thoughts? I push long term, you know, statin use just, and I'm also pushing statins for people when they, when they get the vaccines, because I think

it's a non immunosuppressive way to just add a little bit of extra protection, you know, to the blood vessels if needed. Interesting. And finally, my last question, Bruce, any thoughts on the risk to pediatric populations? Can we, does anything keep you up at night there? We can't really give them statins. You can. So we are seeing a lot of, and both, there's great studies on Maraviroc in the pediatric population, which makes it unique amongst CCR5 antagonists. And also atorvastatin has been shown in clinical studies

to be safe for use in kids. So yeah, and indeed, we are seeing a huge uptick in the number of kids with long COVID or PASC. Yeah. Gentlemen, thank you so much for, first of all, for joining us, and more importantly, for all the work and the diligence and the ongoing work. And Eric, it's such a privilege to talk to you and to know you're part of this team. I agree with Bruce that your addition is exactly what the doctor ordered, so to speak. And I just look forward to it. I mean, so much has changed since the last time we spoke. It's really kind of interesting.

The last time we spoke, you were sort of saying, well, we found these S1 proteins in these classical, non-classical monocytes, and we think that might have something to do with something. And then you were sort of, we were also talking about CCR5 antagonists, and you were like, I just got a hunch there's something going on there. And I can't really say it yet, but we think there's something. This is a lot different now, a lot different. And I'm sure it'll be different next time we speak so uh please do keep it up gentlemen then thank you for joining us i appreciate it so much the pleasure thank you so

much thank you guys thank you guys and um rom you're still there on uh clubhouse i'll say goodbye to you thank you for bringing these guys to me and as always, being such an important driving force in all this. Thanks, Dr. Drew. Thanks to you and Susan, the rest of your team for the support that you provided us. But I think mostly, most importantly, the support and a lot of the advocacy you've done on behalf of the patients, the long COVID patients, patients having post-vax issues, many other chronic illnesses and pathologies. So I'm very grateful for your support, you and Susan, all the work that you're doing. And thank you very much. We're doing the light lifting.

You're doing the heavy lifting and we appreciate it. So, Ram, I'm going to end the Clubhouse Room. Thank you guys there. And thank you, Ram. And thank you everyone who patiently listened to us. And for those of you out there tomorrow, we have Dr. Lucy McBride. And Dr. McBride is a Harvard-trained physician who has been publishing a – she's been doing with a newsletter what I've been trying to do with this streaming show. And she's smart. She's got a lot of interesting ideas.

I just want to pick her brain a little bit. We have Dr. Bhattacharya in here on Wednesday. You know him well. He's been on this show before. Again, another brilliant person. Alex Berenson, who is the eternal gadfly to the COVID sort of response, the government, the COVID response. And then on Tuesday, that's on Monday, Alex. Then on Tuesday, Dr. Vinay Prasad.

I was listening to his podcast. His last four podcasts have been on fire. Oh, my goodness. I recommend them so highly. His latest one is talking to a virologist, vaccine expert about vaccines and kids and the things they're worrying about and having an honest discussion about this. And it's, these last four weeks have been the best sources on where we've gone wrong, what our concerns are to be,

how monolithic our, our thinking has been and the kinds of trouble we're likely to get into as a result. So we got a lot of really good people coming up and, and we're all heading into Thanksgiving. So we will let you go across the Thanksgiving holiday, but we have Lucy McBride tomorrow and Bhattacharya on Wednesday. Susan, anything going on with you?

No. I got to share with the Restream people and the locals people. We were on a local stream before we heated up here with the streaming show. I told them they were all very much impressed with your mom's house live on Friday night. And I told them you nearly threw up in the car. We were playing it in the car and Susan has to do everything in her power not to vomit. I'll be talking about that more on after dark because there was a lot of hysterical corollaries I want to save for the boys and Christina, if I can get her in there too

because they were the source of the extreme funny it was I was horrified I realized that's why Tom invented this thing was to torment his wife I think that's what this was all about but that was a particularly um tormentful uh live live uh YMH live well we were driving for an hour and a half from Pasadena Laguna. And I said, I paid for it. Let's watch it. Let's watch YMH Live. And thank God I was driving so I didn't have to look at it. I love that Christina was throwing up. She had to throw up too. Yes. Yes. And that's, I think Tom will start to lose it all of a sudden, but I, I really think it's the torment, his wife.

That's why he started this out. Yeah. Susan was particularly, was it the Brown or the vomit or which one got you the most? Do I have to talk about it? Yeah. That's why I said this with this all about, I can't really talk about it here. Right. I can't say what happened.

We'll get canceled. Okay, but was it, people were, the locals folks wanted to know, was it the brown? Was it the vomit? Probably the brown, right? A lot of the, yeah. The brown, yeah. The combo, yeah. Yeah, I got you. The vomit and brown.

If you don't know what we're talking about, it's your mom's house where I have a show called... There's a lot of it. I have a show called Dr. dar which some jokes and let's just say it as a very good going she going so soon caleb quit dicking around with the thing it's on the second screen okay i'm trying to fix it trying to bring it's over on the second screen now don't worry about it i'm fine i'm fine okay good i'm gonna wrap up anyway but i just want to say i accidentally like hit a button somehow and the screen went away and he's been moving it around. So that's why.

It's okay. All I see is the have a conversation. I know. Well, I'm trying to change the subject. But bottom line is. I didn't realize how disgusting. Was that actually live in front of an audience? Yeah.

Oh, no, no. It was a live in front of a live audience like us. Because I know they've done them live, live. No, no, no. no that's different that's very different yeah that's that's your mom's house i didn't think so in a theater i love how i love how joe started out with oh i can't believe you guys do this and he goes i'm so proud of you though yeah for making you know making this your thing right it was very funny and then he got But, but the, the bottom line is a very different emphasis than the, the time you've just spent with me. Very,

very different. That's sort of what I like about all these different things I do. They're very, very different. And I are different. The one I do by myself over there is different. This one is different. After dark is different.

They have different sort of cultures and qualities. All right, let's wrap this thing up. I will see you tomorrow. Tomorrow and Wednesday are at 3 o'clock. I hope you don't put those ones on your show. 3 o'clock. The next four are 3 o'clock Pacific time. So we'll see you tomorrow at 3 o'clock with Dr. Lucerne Pryde.

See you then. Ask Dr. Drew is produced by Caleb Nation and Susan Pinsky. As a reminder, the discussions here are not a substitute for medical care, diagnosis, or treatment. This show is intended for educational and informational purposes only. I am a licensed physician, but I am not a replacement for your personal doctor, and I am not practicing medicine here. Always remember that our understanding of medicine and science is constantly evolving. Though my opinion is based on the information that is available to me today, some of the contents of this show could be outdated in the future. Be sure to check with trusted resources in case any of the information has been updated since this was published. If you

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