#29 Long Covid: what has six years taught us?

How far have we come in the understanding of this illness? I think we've come in awfully long way. A lot of experts, all of the very specialties are really pivoted towards studying on COVID. We've worked with thousands of Lankovia patients who are incredibly grateful for their time and energy that they've given to research. We decided to try to work together with the advocates to the greatest extent possible. We vow to do no harm. I think that the medical establishment is doing more harm by not trying some of this interventions. Welcome to Make Visible, the podcast shining a light on complex chronic illness. I am your host Emily Kate Stevens. Welcome back to Make Visible and welcome, Jez. This is a kind of special episode for us because this actually marks for both of us our six-year anniversary of having long COVID. Thank you. I feel great. Happy anniversary. Please still be here. Let's look at the winds. I am still here. I'm going to kick the can down the road because the long COVID anniversary, how technical you're going to get with it because really the initial infection versus when you clocked you had long COVID, there might be any webbed you've been for in eight weeks or something in that. Yeah, yeah, yeah, that's true. Longer than 13 months until I got diagnosed or some months, yeah, you've got to pay for our consequence. But I kind of take it from when I felt that virus hit or when I know I contracted that virus for the first time. Do we get a cake? Like a cake just got nothing in it because we can't tolerate anything. I'll send you one made out of cardboard. Great. Perfect. That's very good. Today is bringing an episode that is the review of the last six years in some respects and an overview of where we have got to in those six years. And so what we're bringing you is multiple different voices and experts to tell us about the state of research, the state of studies, the state of healthcare systems and how far we've come in our understanding of this illness, how far have you come in the understanding of this illness because you have been on this journey as have I interviewed people talking to people for over five years now. Tell me about that trajectory. You know what? It all depends on perspective. And this is something that's going to come out in the interviews that we share today about how the patient perspective is different from the research perspective and the science perspective and the different timescales on which stuff happens. Research happens on a geological timeframe and unfortunately our patient experience happens on like what do you call those flies that have an entire lifetime in a day? Free fly. Free fly, yeah. And yeah, that's the timeframe we're on where every minute is gruesome and each day that goes past can be brutal and every week that goes past without maybe new symptoms or the same symptoms and with no treatment on the horizon feels horrific. So that clash between the two timescales between research and the patient's experience defines almost I wouldn't say conflict but there is certainly a clamoring of patient voices of frustration screaming out from the void. Maybe that's hard language, but I think it's fair at this point in time and our understanding in the condition has greatly improved but we've got such a long way to go and I think that's the frustrating thing. The fact that the long-coded handbook which got published in October 2022 isn't really out of dates. 9C to 95% of that book is still bang up to date. If I was doing a second edition now, I wouldn't have any new chapters that just add some new trials that have filled in a few blanks here and there. We've got a few more pieces on the jigsaw board that we didn't have before but we still don't have agreement yet on what the picture is that the jigsaw is trying to draw when we get all the pieces down and everybody's putting the pieces in different places and saying it's this, no it's that. It's tough. And I think that's the thing. What I reflect on on this is right back at the beginning as early as beginning of 2021 we had these theories emerging of what might be driving long-coded and we had brilliant, I have to say absolutely brilliant researchers and doctors operating in this space and some real ingenuity. But those things that were identified early 2021 some of them actually in 2020. We have then spent quite a lot of the following five years saying yes, our suspicions were correct, not us, the researchers have been saying yeah, we can prove that this is correct. And in terms of treatment, in terms of approved drugs, we haven't really moved forwards. However, that's not to say that these people have not been doing incredibly important work because we actually needed to have that proof, we needed to have that evidence base. And this is again something that will come up as we listen today. This idea that we are all clamoring for those results, we're clamoring to reach the next stage. But we have to also still do it safely and following the scientific rigor because I do still worry that some treatments five years down the line, we will see that there are repercussions just in the same way that I think we will see five years down the line that there are still repercussions from the fact that everyone had COVID. A couple of things I wanted to say about this topic generally. One is let's take a metaphor of building a house and it's like I want to move into my new house. What does it take before you can do that? The metaphor here is that effective treatment for the condition as opposed to symptoms is the new house that you can move into and that's the goal that we want. But before you can build that new house, you can't just whack up some bit thing made of cardboard, put it on the beach on the sands, it's going to fall down pretty quickly and your house isn't going to help you when it falls on your head. You've got to spend a bit of time digging out the ground, you've got to spend a bit of time putting in the concrete for the foundation and you're still looking at longer to eye level. You still can't see anything, you can still see no house. But the critical first stages of building a proper house have been put in place. Yeah. That's where we are at the moment, which is that we've got the foundations down, the ground's all flat and we're ready to start building the house now, which we weren't 3, 4, 5, 6 years ago. Where I say there's still quite a long way to go, yes, the walls have got to go up, you've got to work out what the house is going to look like and the rest of it. The metaphor is probably running out of steam at that point. But in terms of the hypotheses we had, the floated out from the start about here are the five things that could be causing long COVID. It could be persistent virus, it could be persistent debris, it could be auto munitose, it could be reactivated, latent viruses, it could be microbiome, it could be all of this stuff right. Not only have we not said it's this one and chosen one and got everybody to agree that's the one. We haven't even knocked any off the list. They're all still up in the air and up for grabs because they've got evidence for all of the house. They're all still in play. Yeah. So this is what I'm in about the foundations. We'd learnt enough to know that we were right in having those hypotheses in the first place, but we haven't yet been able to nail them down enough to say, okay, it's two, four and six and they interact with each other in this way in 64% of cases and in the other 36% of cases, it's three meets two meets one or whatever, right? This is how complicated the picture is. But what we do have using that analogy is we do actually have all of the multiple different contractors on board because we have got an incredible number of people working in this space and I am humbled to speak to the majority of these people. There has been this surge in incredible charities and nonprofits that have been operating in this space in terms of research and in terms of helping people, but actually every single one of the healthcare workers of the doctors of the researchers, no one is doing this for making fast money. Everyone is doing it out of a genuine interest in furthering things for the patient. I truly believe that from the people that I've spoken to, I was privileged to actually attend multiple long-haven and MECFS conferences, actually at the back end of last year and there's some amazing groups coming coming together on this and I had the opportunity to talk to Vindranath who is a neuro immunologist and he's the clinical director for the National Institute of Neurological Disorders and Stroke at the NIH. He's done deep phenotyping into MECFS and he has a particular interest, in viral impact on the brain. This was his take on what he saw coming out of those conferences in terms of the way that the research was shaping up. (upbeat music) - Over the five and a half years since you made that first call, there's been so much work that's gone into it. You actually spent two days at the third international long-covid conference in Boston. Can you give me your opinion of what's really exciting that's coming out of other labs, perhaps that you saw at the conference in terms of our understanding and our development of treatments for long-covid. - So one is that I'm absolutely gratified to see that a lot of experts in infectious diseases and rheumatology, all various specialties, are really pivoted towards studying on COVID. They have really invested a lot of their own expertise and they are very driven to really try to get to the bottom of it. So seeing those, which was very hard with MECFS, getting these experts to actually study MECF was very, very hard, but now we have the best of the best minds that are really studying this. To me, that's actually very gratifying. And I'm starting to see them come to all these conferences. Before that, we had one in Santa Fe, which was a keystone conference that I helped organize and it was broader than long COVID. It had MECFS and other post-infections and drums in there. And a lot of them were there and then they came and you can see progress already within a few months they're showing here. To me, it's very exciting that people are finding residual antigen and RNA in patients with long COVID, but they also caution us that sometimes you can find that people have fully recovered. So trying to figure out, okay, is it really causing the symptoms or not? I think it does it people. It's not just the presence, but how your body reacts to it, that probably is more important, right? So, and then people are thinking about disease-modifying therapy. A lot of studies out there doing symptomatic treatments. And that's all we have. - That's all we have. And their good trials being done for symptomatic treatment. All those things are important, but I think what you really need is disease-modifying therapy. And I saw some good data being presented. There was data being presented on metformin. People are trying to see if these antivirals, like plavix and other things will make a difference or not. Those data are still not available. They're getting close to coming to an end. So the data would get analyzed soon. The people looking at stimulating the immune system, there was one on looking at IL-15, for example, to see if they were stimulated and do something. And so I think there's a lot of excitement in the field. For a relatively new infection, new field, only five years, five years, a very short period of time. - For you, it's an absolute need for the people. - The people who are infected, of course, it's very long. - They feel like it's a long time. - But if you look at any disease, look at Alzheimer's, for example. I mean, what do we have there? What do we have for Parkinson's where we can make a, you know, disease-modifying therapy. We've been studying those for decades, right? And so to be getting to disease-modifying therapy within less than five years here, comparatively, that's a huge, yeah. - It's remarkable. - Yeah. - And the way that everyone's come together. When you say, "Do disease-modifying therapy," can you give us the titles, not necessarily the specific drugs, but are we talking about monoclonal antibody therapies or are we talking about IVIG? What's the type of therapy that? - They're all out there. So there was a trial that's been to cover, is doing a trial with IVIG, it's a multi-center study. And there is the monoclonal antibody study has also, people have tried that also. - There was a big presence from the UCSF team, the conference. - Yes. And the UCSF guys are starting a study with IL-15, as an immune stimulant. So there are people who had done studies on metformin earlier, giving it in the acute phase, and showing that actually it decreases the chances of developing long COVID. - That kind of preemptive idea is tricky, isn't it, because people don't necessarily know if they are going to just develop a long-term consequence of it. - I think people were actually questioning why it has an entered practice guidelines, so far, where the data was so overwhelming, and it holds up from repeated studies. - Yeah. - So people thought there was underutilised for treating. - So there are trials definitely coming through, which are more about treatments, because I was actually at another conference that was organised by the Alliance of the Missing Millions. And that was still much more focused on us trying to find the biomarkers, which is all, as we've just been saying, completely valid. But it is important for us to have this balance between what are we treating, and how are we treating it. We have these multiple groups. I know that there was some criticism of the third long COVID conference that it was two NIH-focused, and you've almost got this splinter group of people who are real international group of people, and you've spoken to a lot of them. You're talking rich, praterious. Rob Vurst, but you've got Mike Van Aal's, like, "David Sistrom, there are so many people in this space. There's some really, really incredible minds coming together." I had the opportunity to talk to Benita Cain, who is a consultant respiratory physician in the UK, and she's a founder of the Long COVID Clinic, and this came about from her respiratory physician work, but also because her daughter got very sick with Long COVID, and she was trying to find a way through. She's a huge advocate for multiple-long COVID charities. She sits on parliamentary advisory committees and is an advocate for therefore me. And here is her take on how far we've come. (upbeat music) - I think we've come an awfully long way. An awfully long way. There are some incredible researchers out there who've talked about some of them already. You David Petrino's, and you Rob Vurst, and Amy Pro-Al and Danny Altman, and there's many, many more people around the world who are doing this incredible work. And Danny, actually, is making a real effort to get people together and pool the research and say, "Let's come up with some sensible biomarkers "that we can all look at and start to really join things "up across the world." And there was a global conference in Santa Fe last year, where that's the conversation they've had. I think the frustration for patients is that it's not translating fast enough into treatments and that's just a direct result of a lack of investment from governments. And so I think there's a big policy piece here as well that needs addressing, because we've got the scientists, we've got the researchers, we've got the patient community, we've got all the skills we need to do this, but it needs funding and research is not cheap. - Yeah, and so many people that I've spoken to is all coming from private funding. There is obviously a large amount coming from NIH grants for various programs, but the majority of people are reliant on private funding. So do you think that we have the patient power or expert power to put any pressure on governments? - One of your papers, 400 million people globally with Long COVID. How many people is it gonna take for government to do something? - I think one of the reasons for us founding the International Society of Long COVID, it's got a very long name, International Society of Long COVID and post-accute infections in drones. That society is a bunch of research and scientists more around the world, which have come together. We are originally sort of connected through the world to help network, but this is being set up separately. One of the reasons we're setting this up, and it's still in the very early stages of being set up, but it is around being able to influence policy. That's one of the goals, as well as coming together as a global scientific community to try and join forces, 'cause any individual country at this moment in time when we're not really getting traction, probably the state's is doing, was doing the best, but the Trump administration coming in through a few spanners in the work there. And the UK is definitely behind, and I think now we've got Germany who's just announced its decade of research and put half a billion euros in next 10 years into research and to post-infectious illnesses. I've got a huge, huge hope that Germany's going to lead on this on the global stage. (upbeat music) - What was really interesting about what Benito was saying was about not just finding government money, but also joined up thinking between countries on how we deal with this. And so I spoke at the EU Parliament in Brussels at the tail end of last year, and that was an initiative that brought together a large number of speakers who were involved in long COVID research work in each of these different countries and were connected to whatever degree of coordinated program there was in France, Germany, Italy, Spain, another EU countries. And one of the things that was really interesting that came out of that was at that point of time. The lack of every single country was struggling for funding and struggling for government recognition and Dust money to actually get trials off the ground. They were all kind of It's hard to use the word "bodge" but I think it's sort of fair Bodging together their own way of dealing with the challenges of researching it with the resources They had available to them in terms of the clinics the universities the labs and whatever way they were approaching the problem from whichever angle They were coming at it, but what there really wasn't was this joined up thinking Between the countries. I mean what it really needs was the EU to come together and say okay We're gonna put together a task force of the top 10 minds in Europe onto this and we're gonna create an agenda The uses all of our resources in the most intelligent way to divide and conquer and Really bring it together so that we We're not just doing this scatter gun approach We're actually coming into it in a concerted sensible way because this is a problem that's gonna need that if we're gonna crack it And one of the the figures that jumped out from that session and from that discussion was that Germany alone is losing 65 billion euros a year just in lost salary So that's essentially GDP loss and that's completely ignoring the healthcare costs the support costs the social welfare costs of the condition So in the light of that 65 billion euros a year the half billion euros in the 10-year plan They've just announced feels like a bit of a drop in the ocean when you compare it to the 650 billion euros But it's gonna cost them in just out lost salary productive workforce that's out of the equation, but it's a start, isn't it? And at least it's a recognition and I'm really hoping that half billion euros can Go somewhere into actually creating a bit of joined up thinking and Create a model for the rest of the countries in you to get behind as well because obviously we'll have to see what happens in America and whether we get N.I.H. Stage 2 and what happens from this point on but we are making progress Far faster and far better than we ever did in the face of MECFS 30 years of that but from a patient's perspective It's still very frustrating to watch because it doesn't feel like the problem's being taken as seriously as it should be I have a bad habit of being devil's advocate and I'm just gonna throw a little idea in there which is why the hell aren't the fast money people here too? Because surely if you've got 150 million people suffering worldwide with a condition that's this serious Why is why are the big farmer not on this and again? That is what I said the words big farmer Let everyone goes there evil in the rest of it. That's what we need But we need some proper investments some commercial investment to actually get the wheels turning faster because the governments at the moment are very slow to react In principle the governments have been broadly slow to react and the problem is bigger than the government's reaction We need something to fill that gap and that either means that Governments and health bodies need to step up or we need more commercial funding to come in to fill that gap Yeah, and I actually think that it's a combination of the two if we are talking about governments one of the things that we should refer It's that the US did have a huge amount of investment. I think is it 1.15 billion dollars I'd believe that was the figure that gets bandied around my Corpication on that would be I haven't seen the accounting for the fact that all actually got spent If I went through the trials a little while ago and tried to add up which ones have been allocated what funding and I couldn't get anywhere near a billion dollars I would say 10% of that now I want to be corrected on that I want someone to sort of write in and say yes, here you go This is the 1.1 billion has all been spent on this is what we've got out of it But the funding that I saw for individual trials that was connected to the NIH recover project didn't come to anything like that So I don't know how much governments get the benefit of announcing a huge figure and going Hey, we're going to do this but actually how much do they actually then spend that's a big question And I don't know if the most recent American administration has challenged some of that too And I think that is a huge problem because a lot of the funding into this space was actually via a lot of the US University systems and obviously we have seen what has been happening to funding of a lot of those projects a lot of the grants But I had the opportunity to meet with Joe Brin who is the Section Chief of Adaptive Community at the NIH He's the National Institute of Alligy and Infectious Disease And he actually heads up the TransNIH and ECFS Working Group He's has a huge history in Lyme disease and he is co-chair of the recover TLC Which is this second impetus from recover that was actually to start putting money into Trials and here is Joe Brin talking about the work that they are doing So obviously we had this initial a billion dollars of funding that went into the recover program And then subsequently what you you've been very heavily involved in is this recover TLC It's one of the main things that has come into the renewed effort with the recover TLC Bringing in the lived experience and bringing in that patient experience They recover, I'll call it 1.0 clinical trials They also they had patients involved in the protocol development They had patient advocacy groups, they still do today TLC was an opportunity to try and do it even better more inclusively Have it driven even more with patient partners I think it's imperfect TLC was an opportunity to do that from the start recover 1.0 was truly in the middle of the pandemic It was a different time and place and we could leverage lessons learned You as part of that recover run these workshops where you've actually led to of them now that you bring together people and you sit down and you talk about the prioritisation You talk about the way in which the things that we need to do to be able to move forwards In the recent one in September 2025 you revealed four new studies, is that correct? Can you tell me what we are looking at in those studies or what are those priorities that you've identified from bringing together all of this information I want to be clear I work in a really exceptional dedicated team at NIAID who are clinical based You co-chair the meeting, this is where I come to you to ask for your overview of the work that all of your team are doing and actually the other very interesting point to mention about the work that you do for long-covid and for MECFS is it's this ability to have this trans working groups across the whole of the NIH and across multi-centres isn't it? It's the collaboration that is enabled by your position Just step back a second for MECFS we didn't always have such a great relationship between advocacy communities and NIH and it's beenachromonious when there was a chance to reset this trans and NIH effort about a decade ago we decided to do it differently and to a great extent led by Vicki Whitmore and Walter Korshets at NINDS and as well as our institute and others we decided to try to work together with the advocates to the greatest extent possible and I think that's really proven to be a good model Is that just turning it from being a sort of top-down approach to being a more inclusive or collaborative approach? I think so I think a researcher who has an idea that's like truly molecular they may do that in their laboratory but more and more laboratories actually make connections with patients and communities also some of the advocates that we've worked with always say like this process is more difficult when we work together but it's better and you know one particular patient doesn't represent an entire community so you have to weave a little bit but it's a better picture it's a more complete picture so TLC the point of the September meeting was really to be as transparent as possible here's where we are we had a public portal that we launched the year prior and took in ideas still are taking in ideas and then evaluated those again with experts as well as members of the public who's you know in some case submitted the ideas in some cases were just people that volunteered their time with lived experience in the end we came up with four really three plus one therapeutics that are we're planning to move forward with one was actually a drug that's already started in clinical trials in a pathway that we also thought and through this process where we solicited outside experts the jackstat pathway we really we think we need to look at this pathway and it turned out there was a group that was when we were sort of making this decision that wasn't enrolling yet but they were going so it just made sense to try and combine efforts to try and help them increase that enrollment and get to the get to the answer sooner if this drug is going to be beneficial if we turn up the volume and the number of people that are recruited in the period of time will get there faster so that's that's one of the four And is that called reverse? Reverse LC, right, which is being led at a Vanderbilt. And so TLC's contribution there is adding sites to increase their ability to recruit. The others are low-dose now-track zone. Which again, it's something that has been anecdotally used because it is FDA approved for other things. So it's being used off-label. And it's being run in a couple of other trials. There's another trial that is-- With David Sistrom. Or is that part of the follow? He has a trial that's actually-- I think it's low-dose now-track zone and-- Mestanon. Yeah. But there is a trial in British Columbia that is low-dose now-track zone in adults, which is enrolling, but it's not yet complete. Because that is ongoing-- and frankly, we received a lot of feedback from the community that low-dose now-track zone is already readily available. And the community wants something that's going to give them relief in something that's perceived a higher throughput than low-dose now-track zone. But as you said, this has not been tested for a long COVID in a clinical trial, at least outputs. I mean, it's being tested now. And the other thing is, since recover 1.0, started their trials two plus years ago, there were no pediatric trials. Yeah. So we assembled groups that included pediatricians to help us with TLC. And we thought pediatricians really were in a tough spot. There's nothing approved for adults and nothing approved for kids. We decided that we would undertake low-dose now-track zone in-- In pediatric. In pediatric's adolescents and ultimately young adults. Because we felt like there were still in need in the community. The others are, I'm sure, the GLP-1 fear is not escaped. They're very interesting, popular class of therapeutics. There's actually a trial that's recently launched for a particular GLP-1 drug sponsored by Scripps. And there's a lot of discussion about dosing. But again, based on our portal, the feedback, trying to dovetail that with potential mechanisms and symptom burden in Long COVID, we thought we really probably need to address GLP-1. So we're planning to do a trial. For our audience, can you explain what-- I think this is your area of expertise, the pathway that that's addressing, or what the GLP-1 possibly does in something like our patients? I think, honestly, they are pleotropic. And so I don't think we can say one for one, what is the driver. We know, for example, that markers of inflammation decrease with that class of drug. We know that that is something that's often increased in Long COVID patients and in research studies, also. So I think there's a lot of crosstalk in the pathways. And there's so much, frankly, safety data that we think we can test this in a safe manner. And there's enough overlap in the mechanism and, frankly, a lot of interest and anecdotal evidence in the patient community. And that together really drove this into something that can be done safely, quickly, to really help to see whether this is beneficial or not. And we're clearly-- and IH not the only one, as I mentioned, there's an independent trial that's already underway. And we would likely pick a different-- GLP-1. It's interesting, isn't it? Because each of these Ole Miss targets are different. And there are a lot of drugs that we use in a lot of conditions that we don't necessarily understand the exact mechanism or pathway that it's using, but it works. And it's worked historically. Right. There are lots of likely things. Hopefully we'll learn from a trial like that, too. Looking at exploratory endpoints, looking to see what pathways are changed in the GLP-1 treatment, and how does that relate to symptom burden. So that's the other piece of it that we hope to benefit from study like this. Yeah. And these studies-- each study that you do is going to give you more of an indication in terms of the way that it alleviates the symptom burden as to what is actually going on in the body. Because it's the LDN. Actually, it more targets the neurological impacts of the disease. Possibly the GLP-1 impacts the inflammation. And then the fourth study is at the Stunt Ganglia. It's really-- the fourth study is a pilot study. It's really an experimental study to get more information about the Stullet Ganglia in block and the benefits that really are pretty astounding for people who are suffering and then have been treated with that procedure. And that's something that's used in migraine sometimes. So what does the Stunt Ganglia-- So I think-- I think-- So there's two main ideas there. One is that you're blocking obviously a pain pathway. And there are people that do have a good deal of pain with long COVID. But there's 200 symptoms. So it's very plagiarics. The other is that there's an idea that you're blocking a pathway and not allowing it to amplify. And so there may be other things going on where these folks are benefiting. And so we, again, through the portal, even talking to some of the recover sites where clinical work was going, we heard really pretty astounding stories. Again, this is anecdotal. This is why I think we need a study to do this. And it's-- again, we assembled experts as well as patients and reviewed this idea. And we think it needs testing. It's not the kind of thing where it's going to be large enough to do statistical efficacy. We may have to think about it in a bigger sense if it looks promising. But that's an exploratory-- So this is a very preliminary exploration. Yeah. And of course, we hope to get data from exploratory type analyses to help understand. There are multiple trials into the same things going on globally. And actually, you start to see research papers that you almost think you've seen before. Even you and I, who almost read scientific studies for a living, I find it impossible to keep up with the volume. An integrated international approach is definitely, absolutely essential for us to ensure that we are moving forwards. We're not covering ground that someone has already covered there. So yes, it requires exactly as you described it, an international task force to ensure that we're not covering all ground, to ensure that we are moving forwards. Now, that recovery LC workshop that we referenced, one of the incredible nonprofit organizations that is operating in this space is PolyBio. And Amy Pearl was present at that workshop and really pushed Jay Brin on why they weren't investing in monoclonal antibodies. And there is criticism from some camps about where the money is going. I think that he, in that interview, presented a good case of that they had gone out to the patient's and sourced information. And we are always going to have this lack of cohesion in terms of what some people want us to work towards and what other people want us to work towards. What do you find most exciting at the moment, Jay, is in terms of what we are repurposing or what we are trialing? What are you most interested by in terms of those trials that are being undertaken? I'm talking about treatment trials, in terms of the treatment trials, in terms of some that are repurposing and some that we are developing. So if you'd asked me this question a few months ago, I'd have said monoclonal antibodies are the thing for me that make the most sense. Over that few months, however, I have had two doses of supervibe arts, which is being trialed in the US. I think Nancy Climath and the team that I spoke to there are looking at the efficacy of that. Yes. And I have to say I've seen no improvement from it. And I know two or three other people who are similar to me in terms of moderate to severe severity who also saw no improvement from it. So it's a difficult one. There are reports of people who respond very well to it. Unfortunately, I just wasn't one of them. And this is one of the things for me personally is I just keep going to keep throwing mud at the wall of any bit of mud that I can get the hands on, I'll throw it at the wall and I'll see what sticks. There's all sorts of stuff I haven't tried yet and some of these treatments are being trialed. A lot of the ones which are first symptomatic relief are maybe less interesting. The stuff that sort of gets me excited is the stuff that might actually take on the mechanism of the condition itself. And I don't really think that even on the research side because we don't understand what is actually causing the condition exactly, we're still being a bit random about the kind of drugs we're throwing at it. And we even heard in the interview regarding the GLP1 drugs that it might kind of vaguely work if the mechanism kind of inflammation, okay, right. Yes, let's do it. And I'm all for that. I'm all for that. But that's still the place we're at. We're not really at the place with the solid logic. And that's for me, that's where monoclonals were exciting and may still be exciting for me. many people because there's a solid logic there. You've got a theory, persistent virus, what did you do to get better, kill the persistent virus? How do you do that? Monoclarinated bodies. That is a through line that is dead straight and makes perfect sense. The GLP ones, for example, is harder to draw that through line. Now that doesn't mean they're not going to be effective, maybe they will. But it's frustrating that we're still at the stage at the moment where we are, even the researchers are throwing mud at the wall. Yeah, that was going to say that that's what everyone's doing. You say that you haven't reacted positively to it, but some people have. And I think that that is the space that we are still in because we have so many different phenotypes or so many different buckets of this disease that until we are able to identify which type you have, it will be almost impossible to determine which treatment option. And that is something that these researchers that I have spoken to have said is a huge problem in the trials because you actually need to make the trials relevant to the phenotype of the disease. And it has caused huge problems in the results. I had a fascinating conversation with Mark Fahee who is a professor in clinical exercise physiology at the University of Lafbre and he is an expert in respiratory physiology. Again, he is one of those people who is on so many different long-covid boards and non-profits. He has this apparently super basic explanation of how our body works and I love this analogy that he presents here. Any physiologist will know that the way we view the body and the different systems of the body is a set of cogs. And what we are trying to do is to understand the limitations of each of those cogs, how they are being impacted by the virus and through that long-covid scenario. Because if we can understand how they are being impacted, how they are working together or not working together, we can have a better understanding of what we can put in place to kind of resolve that, but we are very much still in that understanding phase. And the brilliance of exercise physiologists is we like to dismantle the body bit by bit and piece by piece. And if we have that understanding on a single system level and then look at the interaction between those systems, we feel like we will be able to build the understanding that we require to do effective treatments rehabilitation in the future, but we are not there yet. It is one of the most amazing analogies that I have ever heard this system of cogs. It was amazing how all of these component parts are so independent. Yep. And it's a physiologist bread and butter the cogs. It works perfectly for how I approach and how we approach our understanding of what's happening and what we're trying to do in developing that mechanistic understanding. And you have done a lot of work with a lot of different teams looking at multiple strands of this because you have looked at the mechanisms, you have looked at the need for this integrated approach to healthcare in Long COVID, but I think that felt a sound more generally. And you've even done a systematic review of the biomarkers. Can you tell me six years into awareness of Long COVID? What are the primary areas that we have gained understanding in over those six years? And where do we need to go right now? Yes. That's another brilliant question. Where I think we've made progress is having an understanding of the multi-system nature of the condition, the individual nature of the condition and how it affects different people in different ways. We've worked with thousands of Long COVID patients who are incredibly grateful for their time and energy that they've given to research because without them, we wouldn't be able to do this. And we have a better understanding of the condition and how it affects people, but what we don't know where we are at the moment is why this is happening. We're starting to put the pieces of the jigsaw together. But I feel like we're actually at a really important time in kind of the six years. And I have to be very honest and say six years in research is not a long time. We've made some incredible advancements in the knowledge, but I always ground myself in the patients and think about what the patients think. And this is six years of their lives that they've not been able to engage with their families, their friends, their employment, their lives. So that's an incredible amount of time if in that context. So whilst I think we've made some amazing progress and very conscious that we still need to be accelerating and research and accelerating the understanding because without truly understanding what's driving the condition, we can't really start to think about the interventions and the kind of the treatments that we can put in place to be able to do that. And that's complicated by the fact that it affects different systems in different ways and in different magnitudes. So it's a real crooks point. But I think there was a large volume of activity in the kind of the immediacy of the pandemic, so from 2020 to 2023. There's a lot of research activity. The rate of publications was beyond anything I've ever experienced before for a particular condition. So I feel like at the moment it's a really good time to consolidate what we've learnt. So bringing together the understanding that's happened in these areas and then driving forward with an agenda that's really refined. What have we learnt? Where do we go next and how do we find the certain solutions to be able to do that? And I think we have to be honest that with the volume of activity that was happening in the rate of publications, it was practically impossible to keep up with the literature. It moved so fast. So we need to consolidate that. We don't want to repeat things that have already been done. We don't want to be treading on our ground. We need to bring together that understanding. I know there's a lot of activity happening globally in the minute to to review where we are and shape the direction moving forward. And I think that's where we are. And do you feel that it's happening in a collaborative way? Do you feel that the researchers, the scientists, the doctors and the government are beginning to come together in a cohesive way? Yes, so let's go through them one by one. I think researchers have learnt from the early stages of the pandemic that the only way we're going to be able to affect change is by working together. It's not going to be marked far here in the team from Lafara, formerly Derby. It's not going to be Robin Amsterdam. Shory, weren't me saying that we're going to have to work together. We're going to have to work across disciplines. We're going to have to bring together the skill sets. One of our philosophies as a team is that we don't make room at the table. We make the table bigger. So if there's something that we don't know or don't have the expertise for, somebody will have it. We will find it and we will bring them into the fold and we work with them collectively. So researchers, I think, are working more collaboratively from my experience than my previous experience, pre-pandemic. Healthcare is also acknowledging that there's a period of transition and a period of change. People are having to look outside to bring expertise in. I think that's created and afforded some wonderful opportunities for us to collaborate with healthcare practitioners, you know, or nearly wouldn't have done. Still some work to do there. There's some old thought processes that we kind of need to refine and to improve. But that will take time. But even on a government level, there is a recognition that this is creating challenges across society in different areas. And we've seen governments in the UK and overseas now starting to proportion money into long-covid research and to make that available. You know, that hasn't happened in the last few years. And it wouldn't be forthcoming if there wasn't the recognition that there was a challenge that needs to be sorted or addressed. And I know that's multinational, that's not just the UK, because governments around the world are looking at this. So one of the things I'm most interested to hear from Mark Fahey next is the results of his Rundezavi trial, which has got a lot of us quite excited. It's one of the only antiviral trials that's happening in the UK. I don't know exactly when they're due to publish, but that's been running for about 18 months now. And I think all of us have got our fingers crossed that they pull something out of it that is meaningful, rather than just a mixed bunch. One of the things that we have to be, like you just said earlier, having the right phenotype of people in the right trials is going to be key. If that trial is full of people who don't have viral persistence, an antiviral isn't going to do much to them. If it's got a lot of people who do have viral persistence, then it could. But we don't yet have the ability to identify who doesn't, who doesn't. So how do you put the right people in the trial in the first place? So all of these questions are still floating around with these sorts of treatment trials. And I think one of the other sort of the helicopter view of all of this, which has been said by some of the people in the interviews today, is six years feels like a long time, but in the world of research, it's a blink of an eye. And I think we have to look at that in the context of where we are. And to think you have to extrapolate forwards from that. It's taken us six years, as Mark Fahey said, to do the consolidation without the consolidation phase. And it's going to be another six years, I think, before we take another big step forward and are in the position where the ground has shifted enough in terms of our understanding that we can really have a completely new discussion about where we're at on this front because we will have had enough trials that have been released to give us a fuller picture and enough research done into the biomarkers. And Simulta, what's really going on? That time as well to see how effective has that been, not just in the initial response to it, but a year down the line, someone who's had that treatment, does it give you lasting relief? Because as you know, I'm someone who it's not one thing that helps me improve. It is multiple things. I think that I had viral persistence and then a huge cascade effect and have had to deal with all of those different things. But even now, a yes, since I started to get better. I still have. relapses. I still have times where a crash essentially. So I think that point out from actually having had some amazing wonder drug is going to be really, really telling in whether there is prolonged effect of us having had this viral persistence or whatever it is in our systems for five years, six years and whether the treatments are actually cures. You know what, the word cure is a tough one in this space, isn't it? It's not something we ever say, is it? Yeah, I tend to avoid saying it because it's too glorious a word to feel reasonable. I'd look for sustained recovery rather than cure. It's tough. Language is so difficult in this space, isn't it? And even recovery is tough. So sensitive. Yeah. It's a super sensitive word. And what does recovery look like? I know I'll never have my old life, but I was talking to a chap yesterday and I'll mention to him, I'd had long COVID and he says, oh, that's funny that because I used to be an average cyclist. I was very, very fit. And now I know I just can't get back to those same levels of fitness I had anymore. And I don't think it's age. And I said, yeah, there's a lot of people out there who are in that position. But if they weren't pushing themselves to those levels before, they wouldn't notice the difference now. But COVID is affected so many more people than are just registered in the long COVID quotients. But it's at a level of severity that is just dismissed. Oh, it's just getting older. I've just got this problem where I just get it out of breath now or I get more headaches than I used to or my stomachs being funny for the last couple of years. Yeah. And not even to mention all of the people who have now heart conditions, lung conditions, serious repercussions that we actually don't classify as long COVID because they are separate identified conditions in their own right. But I know a lot of people who got them as a direct response to a COVID infection who were fine before. Just on the points on that interview with Professor Farhi, consolidation is not a sexy word. It's not a word that you want to hear as a patient, but it's actually a really, really important word. Because if the next six years are going to be spent well, we have to do this consolidation phase rights because that's going to determine which trials we go into and how we shape the research going forwards. And it absolutely should not be scat gun at this point. It ought to be a concerted, intelligent, calculated effort based on best probabilities. And that requires consolidation. It's building the house again. You need to be able to get the foundations down before you start building the house. Or more, he's talking about there is getting the foundations down and making sure that you design the house right in the first place. Rather than just throwing it up and then finding that it falls down. So I think it's incredibly important. Yeah. I think one of the problems with this idea of consolidation is it feels like you're going nowhere. But what it enables you to do is to then make progress faster and more sustainably. And that's why it's so important. And this is time for my film slash TV movie reference. You've been waiting for this week. So I don't know. Emily, if you've seen the Apple TV show, Pluribus, have you seen it? No. Okay. So it's sort of a sci-fi black comedy show about story of a woman who's an author, but it's in a world where scientists discover this signal that's being beam to us from space. And they go, Oh, great. What's this signal? And they work at that. Oh, look, it's a DNA helix. So they go into a lab and they build the DNA helix. It promptly infects one of them. And then it affects everybody. And all but 11 people on the planet get infected by this alien DNA. And what it does is it turns them into a hive mind. They lose their old brains and personalities and they become part of this new hive mind. But any one individual of this hive has access to all of the knowledge and experience and everything that any person on the human on planet earth knows. So you can go to literally any of the people in this hive. And they are the most knowledgeable person that's ever been times six billion because they have everybody's knowledge. And one of the fun things about the show is that this hive are desperate to try and persuade the 11 remaining people to join them. So they're jumping over themselves to do anything for the 11 remaining humans. The fun thing about the show is that it puts you as a viewer in a position where you're going, what would I do in this world where I essentially had infinite power, all of the resources of all the humans on the planet to satisfy my every whim? And I just thought, Hmm, if I asked them, solve long COVID, how long would it take that hive mind to do it? And the reason why I bring up this reference is that it's a really interesting thought exercise. If you brought all of our existing knowledge from all of our experts together and shared all of that into one place, what would be the right way for that ultra intelligent hive mind to go about solving the problem once it got all brought together? And that's what we should be doing. How can we get our coordinated nature of all of these different bits of tentacles and spiders web of research? How do we hive mind it's all in a way that enables us to make that best step forwards? And what I said earlier about that international task force is almost the best way we might have of doing that. But to do that requires political will and the momentum. Yeah. And I think we've got the will and the momentum in the researchers, in the experts in this space. But what you're saying is that we actually need the governments, the bigger bodies to come together to form a task force. It's like the UN of long COVID. If we go back to the house analogy, it's almost like we bring everybody together to say, what should this house look like? Everybody comes together to design a house that's going to meet everyone's needs and everybody gets the input as opposed to what I've got at the moment, which is lots of shanties getting chucked up all over the place. With no town planning. I will not allow you to call the work that these people are doing in this space shanties because honestly it is completely phenomenal. I agree. I agree. Please don't take that the wrong way. If any of those people are listening, they are doing incredible work, but they're doing it with a degree of isolation and with a degree of a lack of funding and a lack of resource that is hindering their ability to do what they would be able to do otherwise. Absolutely. For the people listening here who have said, well, that's great. You've just told us a load of things that are still years down the line. What we've been trying to do is we've been trying to give you an overview of actually what is happening out there because it is hugely exciting, some of this research that is being done and some of it does have the potential to change our lives. But I don't want people to think that you actually have to wait for all of that to come in to even make small improvements in your life. There are things that people can be offered. Maybe you simply refer to it as symptomatic treatment, but there are things that can improve the quality of lives for a lot of people with long COVID. One of the most striking conversations that I have had in recent weeks is with a really inspiring lady, Dr. Alva Azola. She heads up the MECFS and related disorders program at Johns Hopkins University. She's a rehabilitation physician. She's done a huge piece of multi-disciplinary framework guide for clinicians in how to treat the symptoms that your patient presents in front of you. And she is repurposing drugs and using different things from her arsenal to make improvements in close conversation with her patients. Listen to what she had to say. I adopt things that most people are wooden adabbed. Absolutely fascinating. I've spoken to a lot of people and there are drugs that you are using to treat patients that I have never previously had adopted telling me that they're using because there are various treatment strategies that multiple people are repeating. Your treatment strategies are what's the word for it? Well, I just think it seems like you're thinking outside the box. I guess there are things that you're repurposing from other situations because you know it has this effect. Absolutely. I found myself in this fringes of medicine, right? Where the repurposing of medications, the trial of things of label, became kind of increasingly common. And there were early adopters and later adopters and there's different people in that spectrum, right? I consider myself midway to early adopter I had good mentorship from people that were doing this for a long time. That helped me understand how this particular cohort of patients or this type of patients responded to certain medications and understanding when to use it and when not to use it. And I always, I would say probably my close relationship with patients and the communication is keen. Like when I started using, for example, messing on or a period of stigma, I was scared because it doesn't does have kind of quite a wide side effect profile. So I wanted my patients to report to me, even with middle drain, I did this. Like I would ask them to send me a message every week to see what their blood pressure was doing. Yeah, they were feeling. And I learned a lot from that. And it became kind of a partnership. I'm willing to experiment, but we need to talk to each other so that I can really understand how it's helping you. And that's the way I learned a lot. And I think it benefited the patients later on as I became more comfortable. I didn't need to be communicating so closely. And I kind of started learning about what to expect and what not to expect. Yeah. But it's a fascinating approach, because it only takes one person to start to try something. And now you've got a mess in your trial taking place, people taking that step to try something with patients, and also patients taking the step to trust their doctor. That doctor is trying something with in their best interest, in both of them's considered best interest. Is the only way we can step forward. Right. We vow to do an all-harm. And this is something that is really close to my heart. I think that the medical establishment is doing more harm by not trying some of this interventions, and specifically by not listening and by minimizing the patient experience. That's why I try some of these medications, because I think that we have to find a way to help them. And I think responsibly within the context. And I think if you have those mentorship, that's why we wrote this guidelines. We will help you start using these medications. We will guide you on who would benefit from them, who wouldn't. But it is the best way that we can continue to do what we sign up to do and help patients. Yeah. I think one of the things that Dr. Azola said that patients will particularly respond to is this idea of do no harm. But in a world where harm is being done by not treating the condition and harm is being done in not listening to the patients. And that will be the sort of expression that makes most patients punch their fists in the air and go, "I've been saying that for six years. harm is happening right now in not having any treatments and not having any doctors listening to me." And whilst it's a very noble sentiment that is appropriate for doctors, do no harm, I think it also has to be assessed in both directions. I think what she brought to it and assessing it in both directions there is incredibly valuable. And I think most patients wished more doctors will like that. And we're a bit more open-minded about the things they might be able to do off-labeled that could help their patients. Yeah, I am hugely privileged to talk to these people who have these incredible, sometimes relatively simple strategies. But because these people know how to deal with complex chronic conditions, they really approach with such a degree of sensitivity and the way that they listen to patients. And I have to say that that is not at all my experience out there in the world. I have had almost no medical help over six years of this condition. And the majority of things that I have bought in have been things that I have found and researched for myself. I do celebrate the incredible minds that we have out there working on it. We need to work out how we can get that information to primary frontline care so that the people listening to this can actually get help. I completely agree. Thank you so much for joining me, Stages. Thank you so much, all of you for listening. We hope that this has given you a little bit of information of what's going on and perhaps a little bit of hope. (upbeat music) Thank you for listening to Make Visible. Please do like, follow or subscribe to listen to our next episode where we'll be uncovering more insights into complex chronic illness. This was brought to you by the team at Visible, a group of scientists and engineers whose lives have been affected by energy limiting health conditions. We're building wearable technology that's helping 100,000 people measure and manage their complex chronic illness. To find out more about what we're working on and how Visible could help you, visit our website at makevisible.com. [BLANK_AUDIO]