181 - Dr David Putrino - The Multifaceted Approach to Long Covid Recovery

Dr. David Putrino shares his expertise on Long Covid, approaching it through the lens of comprehensive rehabilitation and personalized medicine rather than one-size-fits-all treatments. He explains how identifying the specific drivers behind common symptoms leads to more effective intervention strategies.

• Rehabilitation medicine encompasses far more than exercise recovery, including energy conservation strategies, mobility aids, and psychological support
• Different symptoms like fatigue can have various causes (sleep disruption, autonomic dysfunction) requiring distinct treatment approaches
• Techniques used for elite athletes to optimize mitochondrial function may benefit Long Covid patients through similar biological pathways
• Stabilizing symptoms through pacing apps and basic interventions creates a foundation for more targeted treatments
• Gender differences in Long Covid prevalence (65-70% women) may relate to protective effects of testosterone
• Treatments must be personalized based on precise understanding of underlying mechanisms rather than symptom categories alone
• Research is uncovering multiple drivers including persistent pathogens, autoimmunity, reactivated infections, and Dysautonomia

For those experiencing Long Covid symptoms, finding clinicians who understand these complex mechanisms and can identify your specific drivers is critical to receiving effective treatment.

Links: 
https://icahn.mssm.edu/research/cohen
https://longcovid.physio/
https://www.youtube.com/@CoRESinai

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

(music credit - Brock Hewitt, Rule of Life)

Chapters

• 0:00 Introduction to Dr. David Petrino
• 8:25 Redefining Rehabilitation Medicine
• 16:52 Energy Systems: From Athletes to Long COVID
• 26:17 Different Drivers Behind Common Symptoms
• 34:40 Targeting Persistent Pathogens and Inflammation
• 45:34 Gender Differences and Hormonal Factors
• 57:30 Unified Approach to Post-Infection Illnesses

Transcript

Jackie Baxter: 0:55

Hello and welcome to this episode of the Long Covid podcast. I am absolutely delighted to be joined today by Dr David Putrino, who doesn't need a lot of introduction doctor and researcher and all-round wonderful human. We're going to be diving into, you know, the what can we of Long Covid and how. That's informed by a lot of the latest research and what's showing up, I suppose anecdotally as well as research-ally I think I just made that word up. So a very warm welcome to the podcast today. It's so lovely to have you here.

David Putrino: 1:37

Oh, thank you for having me.

Jackie Baxter: 1:38

No, it's always great to chat with the community and talk about what's going on Amazing. So before we dive into all of that, can you just say a little bit about yourself and what it is that you do?

David Putrino: 1:49

Sure, yeah, so my sort of official title at Mount Sinai is I'm a professor in the Department of Rehabilitation and Human Performance and the Mount Sinai Health System, which is this sort of big hospital system in New York. They also call me their Director of Rehabilitation Innovation and in that role it's my job to identify new technologies, new treatment approaches, things that can help different communities and different populations of patients, and accelerate the path of those treatments or cures or approaches so that they can be used in common clinical practice as quickly as humanly possible. So my background before COVID was very much around implementation science for new technologies and new cures and new treatments. So we really, if there's something out there that can be helping patients, we want to get it into the hands of patients as quickly as we can.

Jackie Baxter: 2:54

Absolutely, and I think a lot of your focus at the moment is kind of around the sort of long COVID space.

David Putrino: 3:03

Actually so. At Mount Sinai I run six centres and each centre has its own specific clinical focus and we do everything from pediatric rehabilitation for kids with cerebral palsy and spinal cord injury through to brain computer interfaces for people living with ALS. We work with athletes, we work with people who are living with chronic pain and we do also have a center entirely focused on infection-associated chronic illness. So that's where we see folks with long COVID, with ME-CFS, with fibromyalgia, with hypermobile EDS, chronic Lyme and other tick and vector-borne illnesses. So it's a busy space but we, you know I would say that these days a lot of my attention is focused on these illnesses and trying to both do research and improve clinical practice strategies for patients.

David Putrino: 4:09

Yeah, that's a lot of hats to wear fortunate that I have this amazing team of really smart, motivated, passionate folks who really share the mission and try to get things out to our patients.

Jackie Baxter: 4:28

Yeah, absolutely. Now you, when you were saying your role or your job title, mentioned the word rehabilitation, and I think it might be a really good idea to just clear up what that actually means, because I think it can be misinterpreted in the way it's heard, but possibly also the way it's spoken, because I think to me initially I would have said, oh, rehab that's like increasing your exercise capacity after you've had a setback. But what I've learned while I was unwell was actually that rehab could mean that, but it also could mean a whole host of other things like breath, work or pacing and all sorts of other things.

David Putrino: 5:08

So I'd love to hear your kind of thoughts on that and and maybe if that's changed over time yeah, no, I think, um, rehab is a very broad field, and, and actually when I joined the team at Mount Sinai, we actually changed the name of our department from the Department of Rehabilitation Medicine, which it had been for over 100 years, to the Department of Rehabilitation and Human Performance, to sort of really put out there the idea that this concept of rehabilitation medicine should include a whole spectrum of activities, up to and including hey, I'm feeling fantastic, but I wonder if I could feel even better, I wonder if I could enhance my performance further. And so the work that we do runs the spectrum of some of the best athletes in the world who are working with us on actionable strategies and novel technologies to perform even better. There's not an injury, we're not doing sports medicine, they're just trying to, you know, push the limits of human performance, which I actually think, the more I learn, is highly relevant to long COVID, and maybe we will discuss that at some point. And then there are folks who are living with disability, and the role of rehabilitation medicine in that space is to either apply techniques that will help them to improve their functional capacity, so improve the sort of breadth and sort of repertoire of activities that they are able to perform independently, or teach them strategies to sort of avoid worsening of their illness. And so, you know, on the one hand, when we're helping people to improve their functional capacity, I want to be clear that that is not always the same as saying let's cure the problem.

David Putrino: 7:14

So often it's saying oh my goodness, you have an energy envelope and you burn through your energy envelope that much faster if you walk. How about we get you a wheelchair? You know, that is an example of something that can massively increase someone's functional capacity without focusing on rehabilitation exercise, et cetera, rehabilitation exercise, et cetera. Also, you know, in the domain of preventing people from getting worse, we have things like pacing, strategies like pacing, where we try to understand okay, well, what is your energy envelope actually and how can we equip you with techniques that will help you to. You know, stay within those boundaries.

David Putrino: 8:03

This also involves a multidisciplinary approach. So we work with psychologists and psychotherapists who will help patients with coming to terms with the emotions that come along with being newly disabled and helping just go through the adjustment of um, coming to terms with the fact that you have a diagnosis that means that you have a recognized disability under the americans with disability act, or at least for right now. That is the a true statement, and you know um and what that means for you and what that means for your identity, and you know and how you navigate that and move forward. We also have neuropsychologists who will help with techniques, such as cognitive remediation therapy, that can help you acknowledge OK, my cognitive capacity has changed, has changed, but if I apply these techniques I can often function at a near to the same level. You know um and and and work through that.

David Putrino: 9:08

We have nutritionists to help people address, uh, new onset food sensitivities and allergies, issues of that nature. We have social workers who help with loneliness and social connection and social isolation and introduce folks with long COVID to one another so that they have a little sort of support group, often in their neighborhood. We try to match people up by zip codes so that you know you've got a few folks who you know. If you're COVID conscious, they're also being COVID conscious. If you're not up to hanging out, they're not going to hold that against you. They're going to say, yeah, I get it, you know you're in a crash, let's just text, or you know something like that. So all of this falls under the umbrella of rehabilitation medicine and helps us to help folks with different diagnoses live full lives, or as full as they can, you know, given the severity of the diagnosis.

Jackie Baxter: 10:13

And I love this idea that you know it's putting supports in place, do the best you can for each individual person, which isn't always the same because everyone's different but you're able to do this with all these kind of different branches of your umbrella of rehabilitation. I don't know if umbrellas have branches, but right now they do um.

Jackie Baxter: 10:36

So I I think that's great that there's you know it's this broader approach rather than the traditional kind of I don't even know if it's the traditional model, but I think it is what a lot of people who don't know, um understand traditional rehabilitation to be.

Jackie Baxter: 10:53

Um, so you know this, this is, this is awesome. Um, I'm I'm gonna jump on something that you said quite early on because I thought let's, let's just do it. Um, where you said that the sort of the upper level you know, of what people can physically do, you know your athletes that are, you know, rather than wanting strategies in order to get well, are wanting strategies in order to hit those pbs and break those records and, you know, run further than anyone's run before. And you know these things that, when we're unwell, seem like, you know, not even completely out of reach, just kind of like insulting that people can actually do that sort of stuff while I can't move off my bed, kind of thing. And you said that that does have relevance to the long COVID world. So I would love to hear what you kind of mean by that, because I think this is fascinating yeah, you know.

David Putrino: 11:46

I just mean that often, when we're working with these extremely high performance athletes, um, uh, where we're often looking for ways to extend the capabilities of their energetic systems. So, okay, what are we trying to do? We're trying to make their mitochondria more resilient to overexertion. We're trying to make their mitochondria more efficient, um, we're trying to eat up reactive oxygen species that cause oxidative stress in the athlete, meaning that they produce all our waste products, um, and so a lot of the techniques that we do for that. So, things like oxaloacetate as a mitochondrial support, coq10, nad, plus all of these um technologies that enhance the krebs cycle, uh, in our mitochondria and make our mitochondria more efficient and help to take out the trash a little bit. Things like hyperbaric oxygen therapy you know that make oxygen more bioavailable and improve the sort of capillarization. Improve the sort of capillarization, so you know, get more capillaries and more blood vessels to to be created and and um, supply tissue with resources. Um, these are all things that have been used in athletic communities for decades. Um, and as we start to think about this, and and also as we butt into longevity science as well, and we look at people who are taking things like mTOR inhibitors at low dose like rapamycin.

David Putrino: 13:27

What does rapamycin do? It makes your cells more efficient at generating energy. It boosts your immune system so you can fight off pathogens. These are interesting topics. As we learn more about long COVID, as we learn more about these infection-associated chronic illnesses, we start to see maybe a framing for these illnesses is that they're illnesses of accelerated aging. They're illnesses that accelerate cellular aging.

David Putrino: 14:39

And so some of these techniques that people are using and have been using again for decades metformin, low-dose rapamycin these are things that many people in the long COVID community who may be listening to this and nodding their head going oh yeah, metformin did give me a little boost. Rapamycin has been helpful for my friend down the road. So it was an unexpected sort of discovery that what we've been feeding these athletes for so long actually makes some sense here. But the more we learn about the physiology, the more I learn from absolute genius researchers like Rob Wust, who again has just worked in elite sports for a lot of his career and understands muscle physiology and the generation of energy so well. You know, we start to see that they could be two sides at the same point.

Jackie Baxter: 15:34

So, even though these two groups your elite athletes and your people with long COVID, elite athletes and your people with long covid are so complete ends of the spectrum, um, it's, it's still about those little tiny margins, those little tiny gains, um, you know, making the most of what you have and and all of this sort of supporting the body as much as you possibly can in all these different areas. Um, so, yeah, they seem very disparate, but there's an awful lot, as you just can, in all these different areas. So, yeah, they seem very disparate, but there's an awful lot, as you just said, of those parallels. Yeah, I mean, I say this day after day after day. You know, breath work is my area, but you know, we learn these breathing exercises because we have to, in order to help us to get better, to be able to function better, to feel better day to day, but they're tools that will help us every day of our lives, and I live and breathe that every day. So all of these things that we're doing are, you know, things that are, or can be, certainly applicable to many, many people, not just people with long covid.

Jackie Baxter: 16:45

Um, and, yeah, I think that's amazing. Um, so you mentioned, um, you know all these sorts of different areas and you must be seeing this kind of day-to-day with the work that you're doing, that all of these things are are helping people to either see a bit of improvement or to stop them from getting worse. And is there, you know, you mentioned these two categories the seeing improvement and the preventing backslide. Are they the same things that people are doing that do the going forward or the stopping going backwards, or are they different? Or is it different for different people?

David Putrino: 17:28

I mean, I think you know, from our perspective and from the perspective of our clinic, we think about long COVID as a diagnosis, where people have many common symptoms but many different drivers that are pushing those symptoms. So if you read any paper that's been published in the last five years about long COVID, where symptoms are being catalogued, the symptoms that are at the top. Now this is not saying that everybody has these symptoms, but it is saying that these are the most commonly reported symptoms. You'll get fatigue, usually number one. Post-exertional malaise. People talk about a sort of a racing heart rate. People talk about headaches and migraines, people talk about GI disturbances and then you know, as we know, there's over 200 different symptoms, but you know those are invariably sort of the top five and what we know to be true is that those symptoms can happen for a number of different reasons and often we actually need to delve in a little bit deeper because sometimes, when somebody tells you that they're fatigued, what they actually mean is that they have post-exertional malaise. Sometimes, when someone tells you they're fatigued, what they actually mean is that they're sleepy all the time. Tells you they're fatigued, what they actually mean is that they're sleepy um, all the time and you need to sort of tease those apart, because someone who tells you that fatigue is their most disabling symptom, well, you know, we've, we've seen some great work and and I know that you had, like, um, the incredible david joffey on the podcast at one point, who I love, uh, and I love the way he explains things and you know, but, like you, look at the work that I love and I love the way he explains things and you know, but like you, look at the work that he's doing and he's seeing, you know, really disrupted slow wave sleep in a lot of folks with long COVID, and if you fix that, you know, if you fix that with something like ProVigil or you know, or a medication that is often used for narcolepsy but you know, can be used to stabilize short wave sleep, a lot of these folks who are having crushing fatigue, they're back to normal, they're feeling actually pretty good and you know this is the phenotype of, you know I can't, you know I can get to sleep just fine, that's what they usually tell you. But then a couple of things that usually sort of tip me off. That we're dealing with something like this is usually very vivid dreams and lots of dreams can sleep, as long as you'll let them sleep. You know, like, if you know, like, if you let them, they'll go all the way into the afternoon and then, no matter how long they sleep, they feel unrefreshed and that's the pattern. And that's the pattern where they're skipping the slow wave sleep, they're staying in REM and, no matter what, they're just not getting to that restorative slow wave sleep. So that can be one form of fatigue that you know can be treated in one way.

David Putrino: 20:46

Other people can have fatigue because they have autonomic nervous system dysfunction, you know. And so now we're seeing an overactive sympathetic nervous system, which means that their heart is racing. Their heart is racing. If they push themselves beyond a certain point which triggers, you know, an overactive sympathetic nervous system response, then they will click back the other way, after that exertion, into their parasympathetic nervous system, their rest and digest part of their nervous system, and they'll just crash, you know, and that's all the work that they're going to do for the rest of the day. And then sometimes you'll even see, despite this extreme fatigue, folks with dysautonomia will experience the tired but wired feelings. So they've crashed, but their sympathetic nervous system still isn't letting them get to sleep. You know, they're still full of adrenaline and that's where things like breath work and using parasympathetic breathing techniques have been so instrumental in bringing things down.

David Putrino: 21:50

So, again, we said at the beginning we could probably go for 10 hours, but we could go on forever with all of the different rabbit holes. But I think the main thing to remember is what clinicians need to do is understand the symptoms, catalogue the symptoms, listen to the symptoms, but also understand that there are going to be different drivers that are causing these symptoms, and so the true, you know, the real important piece is is less about. You know, I often get. I often get asked like how do you treat pm? You know, um, what's more important is what's driving the pm? What is the cause of pm? Why, you know, why does someone have fatigue? Why do they have gi issues? Let's figure that out and then there'll be a treatment.

Jackie Baxter: 22:48

Yeah. So it's kind of understanding what's going on underneath, what could be causing this to happen. Because, as you say, you know, sleep, we know that sleep is super important. You know, sleep is super important for everyone, you know, and before I became unwell, I did not get enough of it.

Jackie Baxter: 22:59

But I could have a rubbish night's sleep, have an all nighter, um, you know, and the next day I would be grumpy, um, and I would probably eat far too much, but then I would get a good night's sleep the night after and everything would be fine, whereas, you know, when you have long covid, that is not the case. You get a rubbish night's sleep every single night. You never feel refreshed and it makes you feel worse and worse and worse, and the cycle continues. So, you know, by being able to even improve that sleep just a little bit, um, you know, is is absolutely huge for someone who is really struggling with sleep, um, you know, and and still, going to help someone who's struggling a bit with sleep, um. So, as you say, you know that that will then probably have a knock-on effect onto all sorts of other things too. Um, you know that maybe their fatigue isn't quite so bad, or some of their other symptoms, maybe, even if they're not improved, then maybe a little bit easier to handle.

Jackie Baxter: 23:55

Or, you know, what happened to me was that I found something that helped me and then suddenly I was able to see the wood for the trees and see a little bit more of what was going on elsewhere. So I think, yeah, you know, just because there isn't one cure doesn't mean that there's not so many things that can be done. And the more you kind of clear the decks a little bit, the more you can kind of see those little whack-a-moles that you have to go after. That, isn't it exactly?

David Putrino: 24:24

I'm full of the analogies today absolutely yeah, and I think our strategy early on was we really wanted to. We wanted to focus on things that we could help with. So, you know, like, one of the first papers that we put out, you know, after identifying long covid as a symptom in 2021, we said, you know, we're noticing that people with long covid have, like hypocapnia, low levels of co2 that they they shouldn't have, you know like. So that's's where we started to talk about breathwork at that point in 2021. Then we started to notice, you know, pots was extremely prominent. So we started to look into autonomic rehabilitation. We started to publish papers about drugs like ivabradine, peridostigmine you know, all of these POTS drugs that can sometimes help.

David Putrino: 25:26

And now, as we've learned more about persistent pathogens, as we've started to publish on chronic inflammation, autoimmunity, reactivation of old pathogens as well as persistence instance, we're moving into clinical trials of medications that can maybe address these, these, these issues. Now the problem that we're running into with these approaches is these are, you know, these are complex issues and what? What we're learning is, you know, we're running into this problem of for the last hundred years, people have really sort of said, hey, you know, we know that EBV sticks around your body. You know Epstein-Barr virus, but it's no big deal Like everyone has it and don't worry about it.

David Putrino: 26:21

Don't worry if it reactivates Now we're learning, oh it probably kind of does matter in some people if it reactivates, but we don't have good drugs to address pathogens that have become chronic in the body Because those pathogens, unlike acute pathogens which are in your bloodstream, they're very available to your physiology. These pathogens hide, they hide in tissue, they hide elsewhere, in immune privilege sites. They're very available to your physiology. These pathogens hide, they hide in tissue, they hide, you know um, they hide elsewhere in immune privileged sites. And so we did run a clinical trial of pax lobed in collaboration with um, yale university and akiko osaki and harlan crumholes, who are amazing collaborators, and it failed. Um, uh, we are still doing subgroup analysis to understand who it helped and and hopefully why it helped a small percentage, because a small percentage did experience benefit.

David Putrino: 27:40

But also, when we were looking at paxlovid, it was, you know, it's known that paxlovid does not penetrate tissue. You know it's it. And so, even though we were trialing it out and we wanted to see because there is a percentage of folks who have circulating spike in their blood and we want to try and understand what's going on there and whether or not this could be a subset that benefit from something like Paxlovid we also know that if your persistent SARS-CoV-2 is hanging out in your gut, or it's hanging out in your muscle or breast tissue or lymph, paxlovid isn't going to do much to address that. And so now, in addition to up-leveling our understanding of persistent pathogens, reactivated pathogens, so on and so forth, we also need to start thinking about okay, how do we target these things in folks where it may be an issue?

Jackie Baxter: 29:11

So it's bringing this all together, isn't it? Because you say you know there's all sorts of different stuff stuff being a technical term going on, sort of underground that you know we can feel in the symptoms that are presenting themselves, but we can't really see what's going on, certainly not in our own bodies. Um, what's actually causing that? Um, and you were talking about, you know, obviously covid itself, or a vaccine, or a previous infection, if it's someone with mcfs or you know whatever it is that caused that.

David Putrino: 29:24

But it was the, the sort of acute infection, the acute insult um, I like it because it can be exposures, it can be trauma. Lots of things can trigger these disease states.

Jackie Baxter: 29:37

Yeah, yeah, absolutely so. It's not, not even just a, a disease of itself, that the acute trigger, so the assault good word, um, that that happened has set off all this technical, scientific stuff. Um, you know, and there's all these different things going on underneath um, some of which you've mentioned, and you know there's all sorts of other sort of things out there, um, and I think there's some overlap as well. You know, some people have dysautonomia plus persistent pathogens and some people have, you know, some other collection of things. And I'm quite sure where I'm going with this.

Jackie Baxter: 30:24

I'm almost thinking, you know, in some ways, yes, it is important to know what's going on, because then you can target certain things. But also is there a sort of space for more broadband stuff that, if it's done appropriately and gently, that we know is going to help, um, like eating well, you know, eating appropriately, breathing, again, so long as it's not going to stress the person. You know we're not talking Wim Hof. You know all sorts of other things nervous system support, so that people can just sort of start doing that. We know they're going to help on some level, even if we're not totally sure what all the deeply scientific stuff underneath is is going on I.

David Putrino: 31:20

I absolutely think that there is a lot of space for more generalized techniques that we we know to be helpful. I still think that the goal of a clinic should be pretty quickly to try and understand, even amongst you know. Like I could throw 50 things at a person with long COVID, you know that may help, right, but these are folks with energy limiting disease. So you don't want to say do these 50 things right away because you know that is going to be, um, that's going to be overwhelming. But certainly, you know, our general general approach tends to be if someone comes to us and and this is often the case, you know they've been sick for a couple of years um, completely feel very, completely out of control with with regard to their symptoms, um, step one is we throw as many mitigation techniques as we can toward them to stabilize their symptoms. So it's not even about like, let's reduce your symptoms, let's just get to a place where you know when the symptoms are coming and you know why those symptoms are coming, right. So that's where we like to start, and pacing is a really good example of a strategy that can help folks get there, and we also. You know these days we talk a lot about using computerized forms of pacing. So there's like the Visible app, there's Guava app, there's, you know, like there's lots of these chronic illness apps that allow you to log your symptoms and give you a little bit of analysis. They're not perfect for everyone, you know. I think a lot of people can sometimes become very fixated with, like logging their symptoms and if that's you and that makes you feel uncomfortable, I'd say you know, don't use the app. But if you're someone who's very data-driven and it helps you to know, oh my God, I ate a tomato and then I started getting reflux and a racing heart rate, which we know to happen because tomatoes are nightshades and they have a lot of histamine. That is something that can be helpful to some people. So, stabilizing symptoms, then general strategies to see if we can start to reduce symptoms. So that's when we bring in, you know, um, uh, different rehabilitation techniques. That's when we're starting to talk about things like vagus, nerve stimulation and and ramping up the breath work a little bit. You know, like there's there's breath work for stabilizing symptoms, then there's breath work. That is, as you know, I don't need to tell you, like actual work. You know it's hard to do. You wouldn't give it to someone with unstable symptoms because it's pretty tough stuff and but it can actually get them feeling better and having reduced symptoms if they commit to it. Um, and this is where we also pull in a lot of different supplements, you know, this is where antioxidants can be really helpful.

David Putrino: 34:36

This is where working with a nutritionist not just to cut out, you know, go low FODMAP, you know, or whatever it's really to not just identify the food's trivia, but also build a meal plan where you're getting adequate nutrition.

David Putrino: 34:55

Um, we see so many folks who, when they start working with our nutritionist and they actually start getting enough protein, they actually start getting enough calories in a day because they know what hurts them. So they know instinctively, okay, I'm not going to eat that, I'm not going to eat that. That leads them with like three healthy foods Well, three, sorry, safe foods, you know. And so by the time they get to our nutritionist, they're malnourished, you know, and they're not getting enough nutrients and that can lead to all sorts of problems. So then, working with a nutritionist to actually get them enough, you know, um, uh, enough protein in their life, enough, uh, you know, carbs, etc. Is is extraordinarily helpful. So I and I do think that, as we're waiting for all of these more precision targets to come out you know, as we're running clinical trials on some of these targets there's a lot that we can be doing in the meantime.

Jackie Baxter: 36:02

Yeah, I think so, and you know, you just sort of alluded to it. You know there's a million different types of birth work, right? And I think you know expanding it beyond birth work. You know there's a million different types of strategies, of diet plans, of pacing plans, of ways of pacing, of ways of doing all of these different things, and it's, you know, the right strategy for the right person at the right time, isn't it?

Jackie Baxter: 36:28

You know, if you start talking about certain things, when someone is, you know, rock bottom, they're not able to access that. Um, so it's finding, okay, what is going to work for you in that situation, whereas once things have stabilized a little, maybe symptoms have reduced, maybe they've seen a little bit improvement in their functional capacity, um, you know, then different stuff is available to you, isn't it? So it comes back to that. You know, okay, what can we do in this moment? Because, even if it's a tiny, tiny, tiny bit, it may then level you up, even if it was 1%, to the point where you then can access some of those different things. So it's, yes, there's so much that can be done, yeah.

David Putrino: 37:12

Absolutely. And then again, we don't want to get too far into the weeds, but you know, but we can also. You know, it's also the point where once you start to stabilize symptoms, once you start to sort of do some of the safe things that you know are kind of generalizably good for everybody and can give a little bit of function back, starting to delve into the symptoms with a little bit more precision, starting to just try and understand why someone is feeling a certain way, becomes very important, because some of the more active interventions can also be harmful if they're misapplied. So you know, for instance, we, we sort of generally, you know often, or all too often, we generally just talk about pots, but we generally just talk about dysautonomia. But you know, there are some folks who have pots and their pots will take the form of if you have them lying flat on their back, they'll be hypertensive, they'll have high blood pressure and if you get them going from lying flat on their back to sitting, to standing, their blood pressure will drop. And then there are other folks who are the exact opposite. These are the folks with what's called hyperadrenergic POTS. You have them laying down flat on their back, their blood pressure is pretty stable and normal. By the time you get them standing, their blood pressure is just increasing non-stop, um, until you get them laying back down again.

David Putrino: 38:45

So understanding that, like, just because the doctor says that you have pots doesn't mean that necessarily you know you should be overloading yourself with fluid and taking one particular drug. Understanding that you know you should be overloading yourself with fluid and taking one particular drug, understanding that you know there's specific approaches to the different type of pots that you have and a good clinician is going to help you figure out, like, what is your physiology doing when we're moving you about? That can give us a clue as to the interventions we should apply, rather than again just saying oh, pops, okay, everyone gets Iverdine, everyone gets, you know, an IV bag of saline. That's not necessarily going to be helpful to everybody and you know these are the sorts of things that not only can be harmful to patients in a clinic but can also be harmful to the science.

David Putrino: 39:41

When you know there's a sort of hey, let's just run a clinical trial on iVabradine and give everyone who meets POTS criteria iVabradine, like that's not a good idea. Like that's not a good idea, that's, you know that's going to lead to a failed clinical trial where you then say, well, iverdine is not a useful drug for long COVID parts, when it actually is. It's just for a subset, you know. And yes, if you find the wrong subset it makes people a hell of a lot worse or it does nothing, you know. But in the right subset, subset can be life changing.

Jackie Baxter: 40:20

Yeah, so one umbrella term, many different presentations and it comes back to, doesn't it? You know whether it's a doctor or a practitioner, or a nurse, or you know whoever you're seeing, you know it's that practitioner, that doctor should be looking at each person individually rather than coming in with assumptions, I suppose, doesn't it? You know? What are you bringing to me today and what are we going to actually do about you? Not about what I assume is going on with you, whether it's dismissing their symptoms entirely or saying I read about POTS, this is what we do with POTS and, as you say, maybe it is for some people, but it's not for everybody and that person is an individual.

David Putrino: 41:09

Exactly, and you know we could say this for all of medicine. Of course this is an obvious and a general statement, but when it comes to complex chronic illnesses, I think it just becomes much more evident that our health system is not set up for precision, it's not set up for thoughtfulness, it's not set up for personalized medicine. What it is set up for is very sort of skin deep, algorithmic medicine. So it's like someone comes in the doctor, takes a look at them and exactly within a few seconds makes some assumptions about what they're looking at and says, oh, you fit in this box, which means you get this, this and this. That's how we want medicine to be, and one of the things that I'm always advocating for when it comes to complex chronic illness is we need to look at other complex illnesses that have been managed well. So you know we, you know the HIV world is an incredible world. To take some knowledge and take some wisdom from the world of cancer and cancer rehab is and sorry, not cancer rehab cancer treatment is a really good place to take some inspiration from.

David Putrino: 42:39

You know, I often sort of bring up the the example of when we were in the late eighties, early nineties in cancer. Um, the sort of level of understanding that that that the medical profession had of cancer was was, you know Susan Sontag, who's a, you know, wonderful author and a poet. You know she wrote about this in one of her books. But she was diagnosed with bowel cancer and she was told that she had the cancer personality and she got her cancer because of the way she lived and her personality. And so she then, being the brilliant sort of incisive person that she was, she went on to write this whole book about how we metaphorize illnesses that we don't understand. And so she was told she had the cancer personality because the medical establishment didn't understand cancer, so they were just like you've got it because of how your personality is. So that was cancer in the 80s and 90s.

David Putrino: 43:40

Now, cancer in 2025 is you get a personalized treatment based on the type of tumor, your genetic background, your past medical history, your gender, your race, your age. All of these are built in to the computational algorithm that determines the drugs that you get. That's where we need to get to with complex chronic illness and, unfortunately, for the last 50 or 60 years, these are illnesses that have been largely held in the domain of psychology and psychotherapy and psychogenic illness, and so we haven't been able to make this progress big increase in the amount of research that is being done across the board in these illnesses, these complex, chronic illnesses that are triggered by infection or, you know, other sort of physiological insults. We're really starting to see that these are biological illnesses. We're really starting to see that multidisciplinary approaches are um and very highly personalized approaches are needed yeah, and I think you know that the personalized is so important, isn't it?

Jackie Baxter: 45:04

because you could do? You know you were talking about using ivermectin for pots earlier and that you know, depending on which subset of pots you have, that will work beautifully or it will be a total disaster, um, and, and possibly a whole spectrum in between. Um, for all those other subsets, um, you know, and, and any intervention or treatment has got to be personalized, isn't it? Because every person, as you said, is a different gender or a different race, or a different weight, or their presentation is different. So whatever it is that you're doing or taking or whatever, has to have that kind of personalisation.

Jackie Baxter: 45:50

And I think this is what you were kind of alluding to earlier about the sort of very structured box, like nature of um of medicine. You know, you go to your doctor, you have whatever it is, they give you this pill and you take it, um, you know, and that's a very simplified version, but what if you had one person who was a totally different race, gender, weight and something else? Um, surely even just that one very simple drug that they're taking is going to have different effects on two different people, um, with with differences in them. Um. So you know, I would have thought even just down to very simple, you know, taking your ibuprofen out of the cupboard. Surely, even just with something like that, these nuances are still going to be felt.

David Putrino: 46:44

Absolutely. You know, and and that's you know, I feel Again, in, in, in almost Every aspect of medicine. You can, you can really go down this rabbit hole and be highly. You know, we should be striving to be as highly personalized as possible. Um, we know that, uh, you know for decades and decades. This is not, this is not an opinion, this is documented fact. We know that, um, uh, women were more likely to uh have adverse reactions to drugs because, uh, the drugs were tested in uh disproportionate amounts of of male research participants, even male animals. You know, like, even when they were doing the rodent studies, they were doing them in male animals because, because, ironically, they didn't want the, the noise from the menstrual cycle of the rats to influence the outcomes of the drugs. And I was like, yeah, the noise is the point right, like, that's where you understand.

Jackie Baxter: 47:55

Like you know, um, and heaven forbid us women should make things difficult for a man and exactly.

David Putrino: 48:04

And in addition, you know it's like, even though some lengths are being taken to improve inclusion of women, inclusion of female animals, etc. If you were to walk into a doctor's office and ask about most medications not all, because they do have this information, but for most medications if you were to ask, is there a particular point in my cycle where I should take this drug, most doctors will look at you like you've got three heads, when it's actually a very fair question. Are there points where estrogen surging through my body is going to cause this drug to be more or less effective? And should I be aware of that in some way? And the reality is we actually just, due to years of neglect, we don't have answers to those questions.

David Putrino: 49:02

And now take that statement that I just made about women and multiply that for communities of colour, for other historically excluded groups in healthcare, and we have, you know, an enormous amount of diversity that we need to be actively accounting for and we need to stop pretending like it's not there. We need to embrace the complexity, but not to sound overly cynical. But every time you ask a drug company to embrace complexity, they're like okay, well, how much is that going to cost and how long is it going to take me to get this drug to market? If I embrace complexity and you know honestly, to me it's pretty straightforward calculus that's the reason that a lot of these things are taken out of the equation, simply because they're bothersome and they stand in the way of medications making money.

Jackie Baxter: 50:00

Which is pretty shit. It's pretty shit, isn't it?

David Putrino: 50:04

It's pretty shit yeah absolutely, we can say that.

Jackie Baxter: 50:08

It is. But it's also highly relevant to long COVID because, you know, I'm pretty sure the stats say that women have a much higher, much higher proportion of women have long COVID than men. And that's not to dismiss the men who are having the experience, but I think when I saw it before, it was five out of six people with long COVID are women. I don't know if that's the up-to-date one, but it's pretty skewed, isn't it?

David Putrino: 50:34

if that's the up-to-date one, but it's pretty skewed, isn't it? It does appear to be askew, I think. The literature I'm familiar with points 65% to 70% of long COVID cases. And you know, akiko and I have a paper under review right now looking at the role of hormones in presentation of long COVID symptoms. And, lo and behold, it appears to be related to testosterone and it appears that testosterone may be in some ways protective from people experiencing severe, uh, long covid symptoms. And again, this is not to say that there are not men out there who are experiencing, um, extremely, uh, severe long covid, because of course there are um, but you know um, when you look at similar trends that have been seen in fibromyalgia, similar trends that have been seen in pots, similar trends that have been seen in fibromyalgia, similar trends that have been seen in POTS, similar trends that have been seen in ME-CFS over the years, it's all been explained by well, women have a higher propensity for anxiety and depression and these are not my words, these are published literature in systematic reviews.

David Putrino: 51:54

When asked, you know, when leading experts in this field were asked why are more women being affected? And the thing that always blows my mind is, if you ask the sixth grader who just started health class, like, hormonally, what's the difference between men and women? They would say testosterone, um. And yet it didn't cross these scientists minds to say why don't we look at testosterone levels? And also, in men, the lower estradiol went because as men, because we don't have ovaries, we produce estrogens through conversion of testosterone, so it can also serve as a sort of relative marker of our testosterone levels. The lower those hormones went, the worse symptoms were being reported. So you know there are, are you know, for those who are sort of intellectually curious and willing to listen to the community, that there are clues everywhere as to what's going on and how these illnesses are affecting our bodies. Um and um, you know, and these are the sorts of dots that you need to try and put together if we're going to come toward, you know, actionable treatments yeah, I mean, that's huge, isn't it?

Jackie Baxter: 53:22

like the, the sort of testosterone stuff and the hormone, um, and the hormone fluctuations, um, you know, because it's been documented, certainly since very early in long covid and, and, I'm pretty sure, since you know, many, many years before in the ME-CFS community, that fluctuating hormones and fluctuating symptoms are, you know, very much a thing that goes side and side, side by side, sorry. So, yeah, it's like, okay, well, why, why is this happening? And let's dive into that kind of thing. So I think, yeah, that's something that's amazing, that that is is now happening. Um, I feel like we, we need to talk more about that to do it justice and don't have time, um, so I think, just just maybe.

Jackie Baxter: 54:11

Finally, you mentioned earlier in your, I think, six different hats that you wear, um, that one of them was the sort of the long COVID, the ME-CFS, the fibromyalgia, all of the sort of infection associated chronic illnesses, um, you used a much better word than that, um, and they all sort of fit under the same hat. And you know, we, we know that there's a lot of commonalities in presentation. It's a lot of commonalities in terms of some of the things that help. So, under your sixth hat. Are you sort of treating all these illnesses as the same, with these myriad different triggers, or are they very separate? What's your kind of approach in there, um, and is all this research that we're doing in long covid also going to help all of these other people who have been suffering so much for so much longer?

David Putrino: 55:11

yeah, I, I think again, it's uh, we, we to. It was very intentional to study all of these illnesses and treat all of these illnesses under the one banner, and the reason for that is these are still not well-characterized illnesses, and when I say not well characterized, I mean that, you know, when someone receives an ME-CFS diagnosis, just like somebody with long COVID, their symptoms may be driven by a myriad of different things. It can be driven by mold exposure, all the way through to persistent enterovirus infection. It can be driven by chemical exposure and heavy metals in their blood, you know. So these are all things that can drive symptoms in an ME-CFS diagnosis. Similarly, in folks with long COVID, sure, covid was the trigger, but we're starting to see some really wild things in the blood work that we're studying. So again, everything from autoimmunity, which requires autoimmune drugs, to reactivation of bacteria and parasites, babesia, bartonella these are things that we're seeing in our research to POTS and autonomic nervous system dysfunction that requires blood pressure medications and fluids and salt and and and things of that nature. And so I think that certainly what we're going to learn over time is that there is a precision approach for everyone and the person who has long COVID, because they have persistence of SARS-CoV-2, that person is going to need, you know, a combination monoclonal SARS-CoV-2 antiviral.

David Putrino: 57:11

That probably won't help anyone else in this bucket of conditions, right, it's just going to help that person with long COVID.

David Putrino: 57:18

It's not going to help someone with ME-CFS who's been sick for 30 years, someone with chronic Lyme disease, but the person who has long COVID because they got COVID and it reactivated an old Babesia infection that is now chronic I'm really glad that we've got chronic tick and vector borne illnesses in the clinic who are going to say, oh, give that person this antiparasitic drug so that their symptoms will clear up. And what we need are specialists who have that level of understanding, are specialists who have that level of understanding. And again, my mission in life, I think, is to make it the problem of GPs and PCPs, because they have done such a good job of managing complex illnesses like HIV, which is similar where you sort of say, okay, well, you're infected by HIV, but you have all of these other problems going on. So this is going to be the medication. You know, this is going to be the medication regimen for you and you know that's where I think we need to get with complex chronic illness in general.

Jackie Baxter: 58:29

Yeah, so it's bringing together all of these specialists in their own area, but in this collaborative approach. So you've got them all under one roof, I suppose, so you can literally bounce them around the break room.

David Putrino: 58:41

Um, exactly yeah, yeah, and then people can start to. People can start to do what a lot of these uh uh clinicians are craving, which is start to create the more algorithmic approach to if you see this, then do this, if you see that, then test for this, and then either do A, b or C, because we do need that, we do need clinical pathways, but first we need to understand the problem better.

Jackie Baxter: 59:12

Sort of like following a map of the wrong area is not going to help you get where you want to go. I think I should put that on like a little quote bubble somewhere, and that was quite good or looking, looking for your keys under on the lamp lamppost, because that's where the light is.

David Putrino: 59:28

You know that's.

Jackie Baxter: 59:30

That's not going to get you anywhere either so true when they've actually fallen down the drain just behind you Amazing. Thank you so much. This has been an absolute pleasure chatting. I feel like I've learned so much. I will try to reference all these studies and things that you've mentioned in the show notes as well if people want to follow them up. And yeah, thank you so much for giving up your time and energy today to chat with me and for all that you're doing.

David Putrino: 1:00:00

Thanks for having me and thank you for putting this podcast out. It's so important and I really appreciate it.