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Jill Brook: Hello, fellow POTS patients and marvelous people who care about POTS patients. I'm Jill Brook, your horizontal host, and today we are discussing the new and super valuable yet somehow free long COVID treatment guide created by my guests, Dr. Jennifer Curtin's team and Charlie McCone's team. Dr. Curtin is Chief Medical Officer and co-founder of the RTHM Clinic in California. You may remember her from past episodes where we have discussed some of her team's amazing and innovative creations, which she'll remind us about. If you haven't already, you really must check them out. Dr. Curtin was once a complex chronic patient herself and now she has a private clinic, a telemed clinic, some online services for gaining access to common medications and my favorite, the RTHM Intelligence platform that she'll tell you more about.

And our second guest is Charlie McCone from the Patient Led Research [00:01:00] Collaborative, who is a superstar patient advocate with extensive experience in nonprofit work. His long COVID advocacy efforts have been featured in the Washington Post, the Atlantic, Time Magazine, PBS, and he has written pieces in The Guardian, San Francisco Chronicle and Stat News. So, wow. What a team, Dr. Curtin and Charlie, thank you. Thank you for being here.

Charlie McCone: Thank you for having us.

Jill Brook: So maybe for starters Dr. Curtin, we have had you in past episodes, but maybe you could just kind of remind everybody what you do. And you're, you're unique. You don't like, just only do the normal doctor thing. You do some cool things. Can you just sort of like remind people who you are?

Jen Curtin, MD: Yeah, sure. So, I am, I'm first and foremost a patient. I've got a lot of the stuff that I treat, so I'm hypermobile, I have POTS. I've got a primary immune deficiency. I had ME/CFS for nine years. I like, just thankfully went into [00:02:00] remission from the ME like in 2019. And I know, you know, at any time that may come back. So I, you know, grateful for every single day I don't have those symptoms. And yeah, so I basically co-founded RTHM after the the lockdowns lifted during the pandemic. So I was really just worried that so many people, I mean, I had gone through the whole diagnostic odyssey of trying to figure out all the things that were wrong with me.

And in part, you know, my going through medical training I went through as a patient and I was getting worked, like, so I was getting worked up as I was going through training. So I kind of saw this system from both sides. And I realized, you know, a lot of these conditions just aren't taught. And so I was very, very worried with this pandemic spreading everywhere, that a bunch of people were gonna end up with all these conditions that are often triggered by infections or worsened by them and end up in a medical system that really wasn't ready for them or wasn't trained to work with them in a, you know, a useful, positive way.

And we all saw that unfold. [00:03:00] And so we've expanded. RTHM has a telehealth clinic that operates in multiple states. We keep adding additional states there. We've got medication access, which is a much lower cost option to access certain medications at like a lower reduced price. And then we also have our free HIPAA compliant AI platform. You can like sync your medical records with it. Use it to brainstorm ahead of clinician visits. Use it to kind of chat and think through things, look into research on your condition.

There's so many things you can use it for. Drafting things like disability letters, accommodations letters. And then, you know, most recently is this the long COVID treatment guide that we did with with PLRC, and Charlie was a massive part of that. And you know, to try and just give like a short guide to people for free, just let's get this out there, of things that, you know, have at least some evidence behind them for the treatment of long COVID. Many of them are also used for POTS, for ME/CFS, [00:04:00] for MCAS, for many of the overlapping conditions. To try and have like a quick guide that people could like take to a primary care appointment and have a meaningful discussion with their clinician who may not be familiar with what to use, to try and see if they can, like, get access to some of these treatments, have the discussions around them to make those clinician visits maybe a little bit more productive.

Jill Brook: Yeah, you guys keep just coming out with so many cool things. I'm excited to hear more about it. But first maybe Charlie, on this podcast we haven't yet discussed the Patient Led Research Collaborative. Can you maybe tell us about it, how it started, what kind of work you do, and how did you end up collaborating with Dr. Curtin and the RTHM Clinic.

Charlie McCone: Yeah. I'll just briefly tell my story and how it segues both into RTHM and PLRC. But yeah, so I was in 2020, perfectly healthy, 30-year-old biking, you know, 10 miles back and forth to my job in San Francisco. March, 2020 comes [00:05:00] around and I get an infection and everything changes. And so I had a pretty mild, moderate case, but you know, after three months, you know, I all of a sudden started having this thing where my heart was beating 160 beats per minute when I stood up in the kitchen. And a couple months later I heard about this thing called POTS. And so, that first year I was in kind of, I, I say stuck in Kaiser system and I was bouncing around 30 to 40 different doctors and couldn't find, you know, really any good answers.

And kind of throughout this process, I kind of came to the realization, if I'm ever gonna get better I'm gonna have to start advocating beyond the medical system. And so I kind of jumped online in Twitter and plugged into this amazing patient community who was trying to raise awareness about what was happening with long COVID, you know, while this information was completely void, you know, from our public health, and, you know, medical professionals. And so kind of throughout that process, I [00:06:00] met kind of the folks who started PLRC. Patient Led Research Collaborative was founded by four patients, and they were the first to publish on long COVID.

And so they have a couple of major kind of landmark studies that were in very high profile journals that kind of helped change their narrative around long COVID. And so that's how I originally became familiar with them, and eventually became friends with some of the co-founders, Hannah Davis, Lisa McCorkell, Gina Assaf, and now Leticia Soares, who's the other co-lead at the moment.

Also throughout this process, came across a doctor at One Medical who was actually trying to help patients. And I had seen 30 or 40 doctors at Kaiser. They wanted nothing to do with me, nothing to do with this. And then through kind of just discussions online, I came across a doctor named Stuart Malcolm and he's like, hey, I'm trying to figure this out. If you get out of Kaiser, [00:07:00] I I'd be happy to see if I could, you know, help in any way at One Medical. And so, lo and behold, that summer, I switched my insurance. I go to One Medical, and I line up with Stuart Malcolm. And I have, you know, the luckiest, best doctor you know, I've ever had. And he helped me alleviate some of my worst symptoms immediately by kind of trialing some of these medications that were coming out from the literature based on the physiology that was going on.

You know, we started to hear a lot from the researchers, from people like David Putrino, is it takes 17 years for these findings, you know, to translate, you know, into a clinical setting. And here we are like fighting for our lives, being like, hey, like I can't breathe, I can't work, I can't do anything. And this is happening to millions of people. And here's this paper that says 20 outta 20 people benefited from this medication. Or here's this new finding that's saying that there's a coagulation or immune issue and you're not gonna do anything about [00:08:00] it. And so this was a rude awakening for I think a lot of people with long COVID to realize how the medical system works and kind of just how dismissive society kind of generally is to people with chronic illness and disabilities. And from that point, you know, I became more involved with advocacy and I joined Patient Led Research Collaborative as a member, helping with some of their advocacy efforts. And in general, I consider PLRC to be the most trusted voice, both on advocacy issues and research in the space.

And so PLRC was the organization to, you know, fund the breakthrough in post exertional malaise that just happened in the Netherlands. They were the organization who is the thought leader behind the long COVID moonshot advocacy in Congress. And so that kind of just gives you an idea of the spectrum of work that they're involved with and kind of the quality of the work, at least, you know, from my opinion as a patient and now as a member, which is, you know, volunteer. And also throughout [00:09:00] that process, Stuart Malcolm met Jen, and they, they formed RTHM. And I was lucky enough to join Malcolm's, you know, list of patients to join to join RTHM. And I've had just an incredible experience at RTHM getting to know Jen and also co-founder Ryan and the team there.

And throughout this process, I've kind of come to the conclusion I consider RTHM to be kind of the most trusted voice on the clinical side. And I, and I consider PLRC to be the most trusted voice on the patient research and advocacy side. So I kind of had this thought, like, what if they teamed up together and we put out, you know, a guide on treatments. So whenever I have people reaching out to me, which is happening around once a month, about what to do 'cause they have this condition, we can send them one place and not 12 different links, you know, with all this overwhelming information. And this is both, I think a little bit outside the scope of both organizations, but I [00:10:00] think they both realized the need was there.

And I think there are a lot of great guides out there, but in my opinion, not for the purposes of people who are new to this and necessarily don't have a lot of time, both on the physician side and on the patient side. And as we've kind of come to know that if we want any chance at improving our quality of life like we have to trial medications.

And one last story I'll share before we can move on is, a couple years ago there was a great patient advocate named Julie Rehmeyer, from the ME space, who I was kind of like, in this place where I'm like, I don't want a trial on these medications until they're proven. You know, like, we need clinical trials, we need you know, hard evidence. And I'm, and I'm sick of doing this, you know? And she's like, dude, the only way you're gonna get better is if you try things. And I kind of had this moment, I'm like, gosh, like, she's so right. And [00:11:00] one other kind of thing that came to, you know, to my mind, and we can talk about this later, is I developed migraines and I started realizing there's all these FDA approved medications, but the process of trying these medications, exact same what I'm complaining about with long COVID.

And so that's kind of, you know, a meandering way of kinda telling my story a little bit and how I connected with RTHM and PLRC. But I'm just so grateful for both of their work. I'm so grateful that they partnered together to put this guide, which I, I tried, my role was kind of corralling these, you know, mini geniuses in all these places.

I didn't, you know, contribute much of the content, but I'm so happy that it came together, and the feedback we've gotten from patients so far about how it's been helpful feels great.

Jill Brook: Well, I would like to say what I love about it, and I'm not even a long COVID patient, I'm just a person who has a lot of the same comorbidities since long before COVID, but this guide was like the greatest thing. And by the way, for listeners, the link is in the show notes, so you can be looking at it right now if you want [00:12:00] to.

But it's like a catalog for treatments. It's like going shopping. It's like every page is one treatment and it's just really clear and succinct about what it is and then what the data says. You know, how many people with long COVID or something similar improved, how many didn't, maybe some details. And it's just so nice and succinct like, like I know that there's so much to understand with long COVID OVID that I don't have the brain power to, to really understand. So when you want to kind of just get down to the brass tacks of, okay, what are my choices for trying to feel better? And, and then what I loved about it too is that it also was a lot of stuff that applied to Mast Cell Activation Syndrome and POTS and things that, that those of us who didn't necessarily get these problems from COVID can relate to too.

But did I describe it? How, how would you guys describe it? And what did you intend, like what made you even think to do this?

Charlie McCone: I love that description. Jen, why don't you go and then I can, I [00:13:00] can follow up.

Jen Curtin, MD: I actually love that description too. That that really hits right at it. It's just there are some really wonderful guides out there, I mean, for, for ME, several for long COVID. They're really wonderfully done and, and groups have put so much work into them. I think the, we just kind of wanted to focus on more of like prescription medications.

We added a few other things. So a few lifestyle, a few supplements, a few procedures just to kind of show the breadth. But the focus was just kind of like, okay, what are kind of like a core set of, I think it ended up being like 24 medications that you can just kind of like, here's like a good just place to start your look, your research, your conversations with your primary care clinician. Because especially as a lot of long COVID clinics, academic clinics in particular, are closing. We've seen the articles, you know, 80% of them have closed.

That means that a lot of people are going to their primary cares for help. And so those primary cares may not be familiar. So we [00:14:00] wanted something, like a short, concise little blurb that's just like one medication is is one page. Typically. There's a few that ran over, but what can you take in and just have a conversation in a short, you know, 10, 15 minute appointment with your primary care to really kind of, that's all the time you have, what's succinct and, and able to be done there, that's not like insanely overwhelming as well to try and review.

Charlie McCone: Yeah, I would just add that, I think one other thing I was thinking about with what PLRC and RTHM have in common is, I think their feelings around the evidence base of treatments and what, you know, what is actionable and and, and what isn't. And I feel like they're very aligned on that. And for a lot of the guys that are out there from like bigger, more esteemed organizations, I think they tend to be very conservative.

And then some of the more in depth guides, I think they, for a new patient, you know, they can be maybe a little overwhelming or they would need like a, a [00:15:00] clinician who's really dived into it to really help them sort through it. And so I think with this guide as well, it, I think serves the purpose of somebody who went to their doctor, went to a long COVID clinic and they're still not satisfied, you know, with what the kind of results were.

And now, you know, they can look at this guide and see that there's actually, hey, you know, around 30 different interventions that they can try. And I would say that, you know, a lot of different people may have different feelings about the evidence base, but I feel like it meets the need of somebody who's in that position of saying, well, hey, there's a compelling case study here. There's an early clinical trial here. And it also relies on one of the biggest, you know, surveys done on treatments with long COVID and ME patients to date, which was led by Dr. Martha Eckey and other colleagues at Stanford and Harvard. And and so there is, I think, robust, you know, data out there and what treatments may be helping or not.

And I think the more, you know, this information gets in front [00:16:00] of, you know, a physician that shows, you know, not just one study, but you know that it's listed in other guides and that there's a separate survey that's, you know, also backing this up, all on one page. I think it makes the decision for the doctor and the patient very easy, you know, saying whether they want to do this or not.

And so they don't have to sort through, you know, and dive through, try to find this information, you know, in all these disparate places.

Jill Brook: Yeah, I agree. I think that's great. And some of them have more data than others, and some of them, the data's pretty slim. But my feeling has always been like, as somebody who's had some of this stuff for 30 years now. Yeah, I started at the top. I started with the stuff that had the most evidence. But as you know, things gradually either failed for me or I, you know, didn't work for whatever reason. Unless you're gonna give up, unless you are, you know, lucky that you're feeling good enough, that you can just wait until there's more, you know, randomized control [00:17:00] trials, you have to keep going on slimmer and slimmer evidence until you get to a point that you can just kind of like live with yourself.

And so I really appreciate that you guys included some treatments that didn't have tons and tons of evidence, but they had some. And, and for, for people in a position, you know, where they've tried everything else, that that's huge.

Jen Curtin, MD: I think, you know, one other thing too is you know, obviously it's gonna be up to the discretion of like the clinician, the patient, hopefully just having like an a little bit more informed conversation about, hey, what's your, you know, what's your evidence threshold? What's your risk tolerance? Are there any contraindications, drug/drug interactions, allergies, et cetera. Having those conversations, but this can at least just be something to point to, like, hey, there is some evidence that this works in at least a subset of patients. And yes, we know that there's not strong RCT data backing this up, right? This is to kind of, I, I would say fill the gap because there are [00:18:00] RCTs being done, there's a lot of trials going on, but it's gonna take time before those results are out. And several RCTs that have been done, you know, usually what we've been kind of seeing is either they're quite small, and so you can't really determine if it, you know, a lot of them have failed, a lot of them have been negative, unfortunately. And part of that may have to do with just like patient selection, how heterogeneous the condition is, are we selecting the right people for that particular drug trial? Is it really gonna be that we actually need, you know, sequential trials, we need actually combinations of therapies that you have to use together. And those are much harder to kind of like, you know, get groups together to do.

And so it's like, as this plays out over the years, it's like, what do we do for the people right now? Because there are folks who have been suffering with this for five plus years at this point, and it's like, you know, the, the [00:19:00] trial process, well there's some amazing efforts going forward and, you know, I'm really excited about like, the VIPER project for the, the diagnostics and multiple different trial structures that are going on right now. There's still, it's gonna take time before that reaches the evidence threshold and it's like, this is kind of a here's at least what we've got till now. And it's gonna be a dynamic thing. Like this stuff is gonna be outdated in probably, you know, another six to 12 months, right? The evidence is there, but then there may be trials that finish, and it updates.

So it may be something that we update in the future as well going forward. But it's just a, hey, here's a snapshot as of like, kind of the end of 2025. Just what's out there, what could you potentially consider discussing with your clinician until we have these, you know, more powerful treatments or combination therapies coming out from these trials. You know, fingers crossed. I really [00:20:00] hope they, they succeed.

Charlie McCone: I went to the long COVID symposium conference last year in Santa Fe, New Mexico, which is kind of the premier long COVID conference that happens every two years. And with talking to the UCSF team, who I consider probably some of the leading, if not the most, you know, high quality leading researchers in the field who are trying to really break headway on, on diagnostics and treatments and are kind of legends in the HIV field. Dr. Steven Deeks and Mike Peluso, he's like, this is what we call a 10 year problem. And says, you know, we're looking at 10 years here, you know, to really make significant headway on understanding, you know, having diagnostics and treatments and you know, some people may disagree or agree with that, but like, that feels about right to me with kind of the pace of how things are going.

You know, it's only been five years and, and two of these medications have made a significant difference in my life, you know, before I started this. One was LDN, which I [00:21:00] think at this point, if you're a determined patient, you go to a long COVID clinic, you might be able to get access to this. And there's probably a 50 50 chance whether it has some difference, you know, in your quality of life.

The other one was Plavix, and it really alleviated my shortness of breath. Which my shortness of breath was so bad the first two years, I told myself, if I'm still like this in five years from now, I'm gonna jump off a cliff. It was that debilitating. It was that awful. And after 30 days of on Plavix, it started to improve.

Jill Brook: And that's an anticoagulant, right?

Charlie McCone: It's the antiplatelet. And I remember you know, I asked so many doctors whether they would try this and they were like, no, we're not gonna try this. My cousin, he's a doctor in the army, and he is like, why, why don't you just try it? I'm like, well, they're saying it's too risky. He's like, he's like, I don't think it's that risky just to try it.

And so like, I think there's different, you know, incentive structures. You know, he's in the army, he can't be sued or whatever, but I think there's just different incentive structures for doctors in different positions. But [00:22:00] it was so infuriating to me that it was so hard to get that drug that made a difference to my life. And so many other people are in this position. Meanwhile, one in five drugs in the US, or one in five prescriptions in the US are already prescribed off-label. And, and so from my point of view, and I wrote an op-ed about this with a, my colleague Julia at PLRC is, I think, you know, do no harm to me at this point means giving us access, you know, to, to drugs because we can't wait 10 years for, you know, the evidence base that the medical systems feels very comfortable with.

And, and so I hope you know that this guide helps, you know, grease the wheels and all of that a little bit easier about, you know, there is some evidence, and, you know, there is, you know, good rationale as well.

Jill Brook: Yeah. Could we name a few more of the specific treatments that are in here, just 'cause I'm sure people are very curious.

Charlie McCone: I'll [00:23:00] add two more things. Going through this guide as somebody who's in the weeds every single day for the past five years, I found two drugs that I was like, why haven't I tried this? You know, because getting into the evidence base and be like, whoa, there was this trial, there was this case study, and that to me is like, this could also be bene, this will also be beneficial to patients who have been in the trenches for a long time and seeing everything in one place.

And so I started both low dose rapamycin and low dose Abilify. And so those are two drugs that have been on it that are, you know, purportedly are going to help with, you know, my kind of global symptoms, specifically post exertional malaise and cognitive issues. No, you know, specific verdict on that yet, 'cause they've served them recently. But those are just two examples, you know, of two drugs that, you know, are fairly common, but even me, who's been in this every day, you know, reading that evidence base in one place made a difference, you know, in me trying to pursue them.

Jill Brook: Yeah. One that got my attention was hyperbaric oxygen therapy, because when I've tried that a couple times, it makes me feel [00:24:00] better instantly. So the idea that doing like 40 sessions over several weeks could be beneficial and then also have the, the hours that I just feel better right after seemed kind of, really hopeful to me.

Charlie McCone: How and how long have you had POTS?

Jill Brook: About 30 years.

Charlie McCone: And are there any medications in this document that felt new to you, that generated your interest?

Jill Brook: That's what was exciting to me is there were absolutely things that were new to me that were exciting to me. Like one of the ones that's intriguing to me was the nicotine, because I, whatever it is about my particular kind of POTS, I'm all about having too much vasodilation. For whatever reason, I cannot vasoconstrict very well. And so seeing that nicotine had you know, been okay for some people it, it made me a little bit more likely to think, okay, well maybe that's something that I should really talk to my doctor about considering. And the low dose naltrexone, I was [00:25:00] happy to see that there. I was already on that. The rapamycin was very intriguing to me because that's one where they talk about it in the longevity space. And so I'm always liking seeing drugs where it's like, oh, well maybe the side effect is that you also get to live longer.

Charlie McCone: Right. I get something out this. If it doesn't work, I least get that right?

Jill Brook: Yeah. And then, let's see. You had five different supplements in there, none of which I had tried before. You had four lifestyle approaches. Yeah, there was a lot of new things for me.

Charlie McCone: Can I ask a question for Jen? Jen, I'm kind of curious, like one question I still have about this and I'd be interested to get your perspective too, is for me, like the value to patients feels like very evident and I hope that, you know, that will pan out.

One aspect of this, I'm still curious to see how it pans out, is how receptive have some of your colleagues been to this guide who are maybe less familiar with the evidence base, are familiar with [00:26:00] the evidence base, and how receptive do you anticipate kind of the, the, the lay PCP to be with, you know, a patient or a colleague, you know, bringing this to their attention?

Jen Curtin, MD: Yeah, so I mean so far, so we had several clinicians take a look at it. All of them are familiar with long COVID. And so that group kind of took a look at this first and you know, they had some feedback on it, but honestly they were, they were pretty positive and supportive and just like, yeah, these are a lot of things that I use in the clinic every day. And they're like, this is great. I know there's certain folks who are actually using it in their clinics, like as a handout for patients and things like that. So, you know, I think we're gonna have a couple of those folks on a webinar probably sometime in June to talk about their experiences.

I haven't really talked to as many folks who are, who are doing straight primary care who maybe weren't as familiar with long COVID, so I'm not sure how it's gonna go over with that group yet. But it is a really interesting thing. I did reach out to a [00:27:00] colleague who's got ME/CFS experience, does direct primary care, waiting to hear back from her. So yeah, I think it's really, we're still kind of waiting to see like how that goes. I know one thing when I earlier on in the pandemic when I was talking to various clinicians, anywhere from primary cares to neurologists to cardiologists. As you know, long COVID was kind of emerging as something people were just beginning to recognize, some of the things that I thought were interesting was, especially from the neurologist, 'cause neurologists tend to be the people who use like pyridostigmine, Mestinon the most out of any specialty, 'cause it's used primarily for myasthenia gravis. But you know, it was interesting to hear this person who was very open-minded about this early on was saying, hey, you know, I just am not sure how to dose it for these specific conditions.

They're like, I know how to dose it for myasthenia. I know how to dose this for hypertension. I know how to dose this for these other conditions, but I'm just not sure how to dose [00:28:00] pyridostigmine for ME/CFS, for long COVID with ME, for POTS. They're like, that's the thing I'm just not sure of. And so that was something that I was, you know, we, we try to include start low, go slow. When in doubt start with like a quarter of the dose that you would typically use for any other indication and taper up very, very slowly, like every one to two weeks and just watch how the person's doing.

You know, that's kind of always like a, just a general trend in dosing is start lower, go slow. And we try to put in sort of like general ranges of dosing. For instance, like low dose Abilify, you know, that is dosed starting very, very, very low. That's like much lower than the doses you would typically start anyone on Abilify at, for like the typical kind of psychiatric indications.

It's much, much, much slower. And so I, I was hoping that this guide would be kind of the guidance around [00:29:00] like, hey, here's kind of where you usually start. Like, yes, it may be really, really tiny doses, and then here's kind of how you move up and here's like the dose that most people may end up on, and it may still even be lower than the lowest dose you usually put someone on this drug for other indications for. So I hope that that part is helpful and that that clears it up and just gives people a little bit more comfort to use drugs that they otherwise have prescribed many times for other indications.

Charlie McCone: Right. One cardiologist spoke to you at that conference in Santa Fe was kind of talking about this, she's like, there's all these drugs out there. I'm not familiar with them. And she's, she's at the Long COVID clinic, I believe UCLA. And she's like, I don't really know, you know, what to what to make of them. And I'm like, well, would it make a difference if you saw, you know, all the evidence, you know, in one place and that other, you know, people were using them, you know, say other associations and other, you know, groups. She's like, it absolutely makes difference if I know I'm not the first person doing this.

And [00:30:00] so I don't know how much weight that carries and, you know, and a one-off conversation, but that was just one other, you know, affirmation that, you know, having you know, both the, the dosing guidance, the evidence base, and then also the fact that of the links to everybody else who's also doing this. Like the goal is just to eliminate as much friction as possible, you know, for folks who are, you know, trying to get access to these drugs.

Jill Brook: Yeah. And the fact that you, you do a nice job summarizing and citing the sources. And like a lot of the, the data comes from the Harvard/Stanford Treat Me trial, so, you know, it's really credible researchers. I feel like the whole thing is just so high quality that if anything's gonna inspire confidence, I, I think this would do it.

Jen Curtin, MD: Thank you. And I think, you know, we are limited by the quality and the amount of evidence for these things. You know, basing it on like a treatment survey is not always like the [00:31:00] ideal thing, but it's like we're kind of doing with what we've got and it's like, hey, let's summarize what we have and you know, just try to put it in the condensed format so you can see, okay, here's things, you know, that are, here's kind of what we're seeing right now. Here's like the sources if you wish to like look them up and read it in more depth. And yes, we acknowledge this is not a perfect evidence base, but it's what we got right now. And until that evidence is created, like this is what we got, here's how you can do something with it if you so choose.

Jill Brook: Yeah. Yeah. No, I appreciate that, that it always shows that you are thinking so much about how to help today's suffering patients. And I, I don't blame a lot of doctors for thinking about just like how not to get sued, but like it's, it's like sort of clear where one's attention is focused and I am just so grateful that, that you guys are doing stuff like this and I'm wondering if you can maybe talk [00:32:00] a little bit more, you, you said that there would be more data coming in, hopefully, but then you also said that some of the long COVID clinics are getting shut down. How's it looking for long COVID treatment and research going forward?

Charlie McCone: I'll give my patient perspective and then maybe Jen can give her clinician perspective. I feel both, I feel like it's both bleak and optimistic. I feel like the treatment landscape, the long COVID landscape, getting care, like, to me it still feels bleak.

Like I still hear from patients every day who are getting gaslit by doctors, who are having, you know, kind of lukewarm experiences at long COVID clinics, you know, and the, the ones that do exist are shutting down. And so it still feels like the quality of care out there for long COVID patients is pretty low.

I think probably the general information around long COVID is higher than it was five years ago. There's probably, you know, a few more doctors who are willing to try things, a few more doctors who are familiar with this. But I feel [00:33:00] like, I still feel very nervous walking into, you know, a random PCP or a random specialist and being like, I have long COVID. Because I have no idea how they're gonna respond still, you know? However, I feel very optimistic about kind of the quality of research that's being done. Like, I think we have some of the smartest minds in the field, like focusing on this problem. And to me the problem feels more like, it's like political and funding rather than kind of, knowing what to do, where to go, what to trial, you know, everything.

I think all of that feels so clear and exciting and I think, you know, the quality of clinical trials, you know, are continuing to improve and increase. So I feel like the problem, to me, feels bleak as well on the political side, on the funding side. But for the research and the people involved in the field, it's, it's so exciting.

You know, the treatments that are being trialed, the ideas that are happening. [00:34:00] It's just a question of how much, how fast will that all happen? And I feel like that's just a question of, you know, politics, unfortunately. Jen, what do you, what do you think?

Jen Curtin, MD: You know, honestly, I've kind of got a very similar view, where it's like, you know, I know this is gonna take a while. I hope there's like something that accelerates super quickly and that like, just, I think the, I'm really excited about the VIPER program and I think there are some really, really wonderful researchers doing some incredible work.

And this isn't just in the us like the US. Europe just got some funding, I believe, I can't remember if it was Germany or the Netherlands or, but they're putting research towards it. There's some really awesome research being done in the EU as well and in other countries too. Like, we keep seeing interesting things coming out of China.

I am so glad that the world is working on this. You know, obviously the, the US government is a, in a ton of debt and we've got a lot of things going on where it's like pulling funding away from other [00:35:00] things. And so it's like, I just really hope that it doesn't lose steam and I hope you know, there have been some really amazing people who have funded out of private funding a lot of research especially in the long COVID space. We know in the ME space. In all of that. And I think, I think there's gonna be an element of public funding, but I then I think really these people stepping up on the private funding side and filling the gaps there is absolutely critical and I am so grateful for them doing that.

And I just hope that that momentum keeps driving forward. I think there's some really exciting initiatives going on. I think there's some amazing trials already going on, several that are planned that I cannot wait to see the results of. And as I've met various people who are doing this research, and I'm just like, I, I think we're in good hands there.

I think it is just going to be that it will take time. And I just [00:36:00] am like, okay, what do we do until we get to these tests, to these drugs, to these answers? And especially if it turns out that the clinical trials need to be much, much, much larger to capture the heterogeneity, if we're not able to better subsegment and choose which subsection would benefit from a treatment, or if we're not able to gather and do multi treatment trials.

So this is all stuff that's being worked on by like really smart and motivated people. So I have hope there. And I think, you know, the thing I really am just kind of focusing on, I think is, is sort of one of my personal missions is just like, okay, my hope, like my genuine hope is that there is like a cure or at least a, a treatment that works really, really well for a, a good chunk of people.

But my, my gut instinct having come [00:37:00] from the POTS, ME, you know, all of this world is that I suspect it's going to be that there's gonna be treatments that generally work better for a subset of individuals and we'll need to be able to figure out how to match people with those treatments or those combinations of therapies.

And it's how do you predict who's gonna respond to what? And what do you do for the people while we're waiting for these things to happen? And so that's kind of where my thought is, is like, okay, how do you get the care scaled up as the clinics are closing so that when these trials, when we do get some stuff that succeeds, how do you get it out to people very quickly and easily? Make sure that that structure still exists. And then the other component is, anticipating that it is a heterogeneous group, stuff may only work for certain subsegments. How do we develop the prediction algorithms to figure out who's gonna respond to what.

Charlie McCone: One other thing I'll add to that is when I, I think that the thought process for [00:38:00] some of the leading researchers in the field is we've had a lot of clinical trials fail over the past few years, and I think the qualm there is, we're not subgrouping adequately. And so I think a big focus, for instance, at UCSF now is they've just launched this VIPER program and their hope is once we validate diagnostics, two things are gonna happen.

One, we're gonna be able to subgroup people better in clinical trials. And two, the moment they get what's called a surrogate diagnostic, which means if you can move a marker that correlates with improvement with a patient, the flood gates will open on the pharmaceutical industry side.

And they said that's exactly what happened in the, in the HIV world. And that's exactly the map that we're trying to replicate with, with long COVID. And so I think that is kind of the 20,000 foot view on the landscape of that. However, you know, the other thought process that I've had is there's over 30 FDA approved clinical trial backed drugs for migraine.

And there's no [00:39:00] cure. And I've tried, you know, multiple of these drugs and I'm still trialing them but I still have migraines. A few of them have helped a little bit. And so I think my thought process has come, yeah, and the next few years, I think it's very plausible we get a, we get an FDA approved drug for long COVID.

I'd be surprised if, if something like LDN fails, you know. And if it does, like that's gonna be very concerning to a lot of us, you know, because that's a drug that, that, that seems to work for some people. It may be we get LDN, you know, and a few other drugs that are proven to improve the quality of life for some patients.

My thought process is as a patient, like why not start trialing these promising drugs now? Especially if the safety profile is solid. And if there's, you know, 30 or so drugs I'm gonna have to get through, and it takes like three or four months to figure out if a drug actually works, I get to try three or four drugs a year.

You know, it's, the math starts mathing in a, in a very daunting way that, you [00:40:00] know, I might as well start now, you know, trialing these drugs. Also, just because something has worked in a clinical trial doesn't mean it's gonna work for me, which I've learned with migraine, that a lot of these FDA-approved drugs have not worked for me.

And so I think to Jen's point that I don't know as well that we'll have a silver bullet for a complex chronic condition like long COVID. I hope we do. And I think there is some exciting avenues that could point in that direction. And as a, as a patient, I'm gonna continue, keep advocating, and that's a big focus of what PLRC focuses on, is just trying to strengthen the breadth and depth of clinical trials and working towards that. But I think to Jen's point the landscape is such that, if things pan out, we're still going to likely be in this situation where the approach is having to trial these drugs and figuring out which works for which patients, and hopefully as technology and science advances we can figure out who needs what faster. But my [00:41:00] mindset has changed that, you know, this will be, you know, a few FDA approved drugs will drastically change the landscape. I feel much more pessimistic about that now, even though I think that will be critically important.

Jill Brook: Okay. Yeah. Yeah. If you don't mind, I would just like to quickly name the drugs that are in the long treatment guide simply so that they show up in the search results for this episode. So anything I pronounce incorrectly, please just shout out the right way. But low-dose naltrexone, beta blockers, Ivabradine or Corlanor, midodrine, mestinon or...

Charlie McCone: Pyridostigmine.

Jill Brook: Oral ketotifen, cromolyn sodium, antivirals against herpes virus reactivations like Acyclovir. Do you wanna say the other ones? Valacyclovir.

Charlie McCone: Valganciclovir and Acyclovir, maybe.

Jill Brook: Yep. Okay. And then antivirals against SARS CoV-2, which are Paxlovid or Ensitrelvir.

Maraviroc, clopidogrel [00:42:00] or Plavix, intravenous immunoglobulin and subcutaneous immunoglobulin or IVIG or SCIG, rapamycin, Abilify, Provigil, Guanfacine with or without NAC, Trazodone, the GLP receptor agonists. The supplements are nattokinase and lumbrokinase. Then antihistamines that are H1 blocking, like cetirizine, fexofenadine. Famotidine. I'm not gonna pronounce this one right, oxaloacetate. Nicotine patches. And then in your lifestyle section there's pacing, salt and fluid loading, compression garments, lymphatic drainage massage. I've never tried that, but that's another one that's on my list, 'cause I mean, what is there to lose, right. Procedures, Stellate Ganglion or sympathetic field blocks, hyperbaric oxygen therapy.

[00:43:00] And so I just want that to come up. If people are searching for information about these, I want them to know that the long COVID treatment guide is the place where they can probably get the information that they're looking for. We just have a couple moments left. I know I need to let you get back to your day, but do you wanna give any little updates about what else is going on with your organizations? Dr. Curtin, I know that you had said that you were gonna be working to be kind of like collecting information from users to find out like what worked for them.

Jen Curtin, MD: Yeah. So, we like basically ask people how they did on different treatments and we kind of, we anonymize that and, and like share it with everyone who uses the platform. So it's kind of like you can kind of see like an aggregate of what treatments have worked for other people. We're working on adding the filtering so you can see like, okay, of other people who, let's say, have POTS and MCAS, did, did it work for them? Or for people who have long COVID, did it work for them, et cetera, and like what were the, the top symptoms that it helped improve? What were the [00:44:00] top side effects that they had and how many had side effects?

So those sorts of things. So we're we're basically working on including that data. The other thing is we just finished up the the Mayo Clinic Platform Accelerate program. So we had access to Mayo Clinic's data, and so we're analyzing a lot of that and we're hoping to include certain information on potential outcomes and what's generally recommended at Mayo Clinic as well.

And and then we're looking at other data sources in addition to try and like just gather as much as we can to kind of get it all in one place for people. And then, you know, something we are working on right now is, so we're trying to add these sort of consults that are, they're a little bit more like, you kind of work with our AI. You work with it to say, okay, here's my case, here's what's going on. It kind of helps you formulate, well, what are my big next steps that I need to do and what would be the key, like top two to three to four things that I'd like a clinician to review. [00:45:00] And if you don't really have access to a clinician, we're working on like, being able to do like a consult on those key things like asynchronously or potentially synchronously in the future with someone on our team.

And so that's something we're kind of rolling out like a beta test for shortly. We're also looking at what are some interesting laboratory tests that we can give people access to through the platform, 'cause you know, you can pay cash for a lot of different labs, but there's still some kind of ones that are harder to get ahold of, and certain ones that are really interesting. We're working with a company that uses whatever wearable device you have, there's like four of them, four companies of wearables that may work where they can do like a version of autonomic testing to at least get what your parasympathetic versus your sympathetic nervous system are doing in relationship to each other from home.

And so we're actually working with them on a pilot to, to see if we can start using that, 'cause I [00:46:00] think, you know, when we try to figure out what people respond to in terms of medications and procedures and things, I think that the autonomic state that you are in is one of the big predictors and I almost see that as a missing vital sign.

And I'm like, I would love to get that information more accessible to people. Is that actually predicting what people are responding to? Because if you're in actually heightened parasympathetic state and then you have parasympathetic withdrawal and sympathetic overshoot, it's a different treatment strategy then if your parasympathetic is blunted and you have sympathetic that kind of overshoots.

So like the ratio and how they dynamically interact with each other may actually change how you respond to medications and the strategy you would use to manage those symptoms. So we're looking at a lot of different tests like that, including, actually we're about to sign a pilot with one of the groups that is [00:47:00] actually in VIPER, and also another group that's spinning out of Stanford that is I think, looking to join VIPER. And so we're working with that. We're gonna be, we're working on trying to like just get access to really promising early testing, treatment, all of it. Like what can we get for people, put it all in one place and just give them access to it while we wait for the trials and everything to, to roll forward. So those are, those are some exciting things on our end. And I know I ramble when I get excited, so, but...

Jill Brook: That's super exciting and I've never heard anybody talk like you did about how your autonomic state might determine how you react to things. So that's exciting too.

Jen Curtin, MD: Yeah, 'cause I mean, there's a lot of stuff around vagus nerve stimulators and we know that, you know, there's some negative studies, some positive small studies. There's people have very differing effects from this. And it's like, to me, I'm like, well, it would make sense that , you know, a vagus nerve [00:48:00] stimulator would work if your parasympathetics, let's say are a bit blunted or they're, they're down.

But if you actually have high parasympathetic, would that actually make you worse? Things like that. And stuff like a Stellate ganglion block where you're kind of, you're blocking the sympathetic. How, how would that be influenced by the state your autonomics are in? And so I, I am just, I'm very curious to, to get this data. I'm actually, I have to do my demo test tonight for it. But it's like, what are the pieces of information that we are missing from everyone's case. You know, and can we narrow down what the most high yield testing is to predict how you're going to respond to treatments? And I think that autonomic type testing, I think that looking at better ways of detecting what kind of viruses you may have reactivated [00:49:00] or persisting, that is also gonna be key. Looking at different aspects of coagulation that are off in different ways than kind of a lot of the standard stuff that's available now. There's you know, several other categories of these kind of key things where it's like, we're just missing this data in general. And could this data be what actually determines how you respond?

Charlie McCone: Right. So overall the main focus from my understanding at PLRC is really trying to improve the breadth and depth of clinical trials at the moment. And so they're doing a lot of work with the NIH to try and provide a lot of feedback to, to improve the drug selection, which, as a lot of people in the patient community know that the first stab of this was not, you know, very exciting or satisfactory to most patients.

I think the second round at CLC has improved quite a bit. I think there's still a lot of room for improvement. So I think that work is really [00:50:00] invaluable and that's really where the bulk of all the funding's going to come from. So being able to get our best, you know, bang from our buck by putting, you know, the best minds at the table from the patient community side and helping select the best researchers, I think that's been incredible and that's a huge focus of PLRC.

A few other things is they continue to publish, you know, very, you know, high quality impact papers. They just had a piece in the Lancet recommending that long COVID papers should require a patient review panel on most of them, which, you know, would, I think would be amazing and, and vastly eliminate a lot of bad research that we see every day, that continues to be problematic.

Another area that they're focused on is just improving access to care. And one exciting pilot project that they ran last year was in Brazil and it was basically working with community health workers in low income neighborhoods to identify long COVID in the community where people are not familiar with what's going, that it's happening, and they can be [00:51:00] pointed to the right area of care.

And as we know, there are so many people walking around throughout the whole world, in our neighborhoods in the United States who have long COVID and do not know it. And I know there are some initial conversations of trying to replicate that program in other places, you know, in the world and hope and maybe even in the US.

And they also just published this amazing fact sheet, which is 20 facts on long COVID that goes over kind of the epidemiology, key research. And it's an incredible resource for anybody who is trying to get their facts right, trying to give information to other people who are looking for it. And that's very cool. And so that's kind of just a brief overview of what they're, of what, you know, they're working on at the moment.

Jill Brook: Wow. So many great things. You guys, you guys bring me great hope. We'll put links to your organizations in the show notes, but do you wanna just say quick where people can find you online?

Jen Curtin, MD: Sure. Yeah. So, ours is just RTHM.com and yeah, you can access [00:52:00] the, the AI platform just kind of on that homepage for free. And then there's a clinic page if you're interested in the clinic or the medications.

Charlie McCone: PLRC's website is patientresearchcovid19.com. But they're also very active on Twitter, Blue Sky, Instagram, and LinkedIn. And so you can find them there at, @PatientLedResearchCollaborative.

Jill Brook: Thank you for everything you guys are doing. I'm, I'm just so grateful that there's people like you really making a difference and and I just can't wait to see what, what you do next. So, thanks a million for being here.

Charlie McCone: Thanks so much for having us.

Jen Curtin, MD: Yeah, thanks for everything you do.

Jill Brook: My pleasure. Okay, listeners, that's all for today. We'll be back again next week with another episode, but until then, thank you for listening. Remember, you're not alone, and please join us again soon.