120 - Dr Mark Faghy - Research update & first Long Covid anti-viral trial in UK!

Episode 120 of the Long Covid Podcast welcomes the wonderful Dr Mark Faghy back to the podcast for a long awaited catch-up on all the research he's been involved in at Derby Uni, but also info on the first anti-viral Long Covid clinical trial - in the UK, if not the world!

https://www.derby.ac.uk/research/showcase/long-covid-research/

Episode #103 with Amy Proal on Viral Persistence

Episode #36 with Mark when we first spoke, back in early 2022.

For more information about Long Covid Breathing, their courses, workshops & other shorter sessions, please check out this link

(music - Brock Hewitt, Rule of Life)

Transcript

Jackie Baxter  
Hello, and welcome to this episode of the long COVID Podcast. I am absolutely delighted to welcome back Dr. Mark Faghy, who has been on the podcast before, we think it's about 18 months ago. And I will drop the link to that episode in the show notes if anyone wants to listen to our first conversation. But we are going to kind of catch up on the results of what happened before and then what has kind of happened in between. So a very warm welcome back. It's wonderful to see you again.

Mark Faghy  
Hi, Jackie, thank you so much for having me back. And apologies we've not managed to do this sooner. But as we're about to discuss, we've been quite busy, but hopefully all for good reasons.

Jackie Baxter  
Yeah. Well, it means there's more to talk about now. So hopefully, it's a good thing. So would you mind just giving a sort of very quick intro to yourself and what it is that you do? 

Mark Faghy  
Yeah absolutely. So yeah, I'm Dr. Mark Faghy, I'm an associate professor in respiratory physiology at the University of Derby. I'm a clinical exercise scientist, by training. And prior to the pandemic, I was researching actively in clinical areas, trying to understand people who have acute respiratory infections, why they don't recover as soon or as well as we would hope and why there's go into those long standing issues associated with recovery, and almost trying to figure out what we could really do about it. 

And we finished a portfolio of activity in 2019, which we now refer to in the team as BC, before COVID. And what we were trying to do was just trying to understand how we could develop the research and push that forward to secure additional funding etc as the pandemic hit in the latter part of 2019 into 2020. 

But very quickly, the clinical team that we work with, were obviously pulled on to the forefront of the COVID pandemic response. So providing urgent care treatment for patients admitted to hospitals. And then you know, when we spoke last time, we talked about that kind of patients coming back with that reoccurring persistent symptom profile. Not achieving that recovery that we were possibly anticipating or expecting, they might have, rightfully or wrongfully we know the evidence was there for post viral issues. But nobody really thought it would probably be to the severity that we're experiencing at the moment. 

So yeah, we established a series of projects, to try and better understand the profile of recovery. And what we mean by the profile of recovery is like, what does that look like to an individual in relation to their symptoms, into their abilities to undertake daily activities. And one of the big things were really keen to do was to learn about what called the lived experience. So that being in the shoes of that person on a day, and as I'm sure as we'll discuss that's provided some incredibly moving, powerful data. But that's actually really allowed us to hone in and focus on and develop projects that are specific to those challenges, so that we can help to understand. 

And that's until now, that's been our approach for the you know, for the whole, almost four years now, which is unbelievable to say. But that's what we've been trying to do is just understand, because if we understand, we think we can affect, rather than, you know, just oh, well, let's try this. Let's try this and hope something sticks, just throw stuff at it and hope something works. We've never been kind of along that process. And again, that precedes the pandemic. So, yeah, really trying to understand so that we can be informed and make improvements.

Jackie Baxter  
Yeah, no, I totally agree. Like, even if you don't understand the full picture, then once you understand some things, then you're then able to be like, right, well, at least I have now something I can start to throw things at, you know, some sort of an idea, some sort of underlying something. You know, I think, yeah, as you say, that's so important.

Mark Faghy  
Absolutely. And we're not in a position to say that we fully understand, you know, long COVID Yet. I think we're not, as much as I wish we could say that we're absolutely not. But we do have an increased understanding, we are now in a position where we can make informed decisions about things that might work. And you know, we'll come to that with some of the work we've got planned a little bit later. 

But, you know, that's not just on a hunch that this might work. It's based on evidence that we've collected through the research trials, empirical trials that we've been conducting. And it's, you know, that increases the chance of success, and how we, you know, might be able to help people. 

But even the ones that, you know, that we're going to be trialing you know, that's not necessarily going to be a one kind of fit all intervention or treatment that we can run, it's going to be part of, well has to be part of a broader intervention to support that kind of real complex pathophysiology that we've seen in Long COVID.

Jackie Baxter  
Yeah, definitely, I mean this is something that I've come to understand more, as I've been speaking to doctors, as I've been speaking to researchers particularly, is that it's not like you do one research study and suddenly you have all the answers. Like it would be lovely if it were that simple. But it's just not. 

And I think - I'm not a scientist or a researcher. And I've never been in this world before. So it was a bit of a surprise to me when I started speaking to people, and suddenly it was like, oh, okay, so we do this little study, and then we do that little study. And then we do that little study. And then we start on the next level. And it's like building up this kind of like pyramid of things, like some of them don't work. But it's still useful, isn't it? 

Mark Faghy  
It's knowledge, because we know whether is active or not? And, yeah, we talk very openly in the group, about a successful research project generates new knowledge, but generates more questions, because it should give you more questions to do, which means our jobs are never actually done. So I don't know what we're chasing in relation. I don't know what success is now in research, because actually, we should finish a project and go, Oh, now we need to do this, this, this this. 

And that's kind of, you know, definitely where we are in the sphere of the long COVID research, and very fortunate to work with some academic groups around the world. And yeah, we all have that kind of constant requirement to answer another question. And, you know, some people might look at that and go, Oh, crikey. That's really exhausting. It's been challenging. It has, you know, on multiple levels, but that just pays to the complexity of the challenge that we need to understand. 

And, you know, there might come a day where we might not have as many questions to answer, we will still have some, I'm sure. But then that means we've made progress. And by progress, we're going to help people. And that's obviously where we want to get to. 

Jackie Baxter  
Yeah, definitely. And I loved what you said, as well about, you know, the involvement of the lived experience, because like, of course, you know, I think a lot of science and research and everything, you know, you have to have data, because that's what you use to then do your projects and to find your results and everything. But I suppose it's probably quite easy to forget that these are people, not just numbers. And I think by involving the lived experience, you're very much involving those people as people, rather than just like data points, I guess.

Mark Faghy  
Yeah, and this is something we did before the pandemic. And you know, so it's not that we've been, we've just started doing it in response to the pandemic, we were. I learned an awful lot from a trial that I took part in, you know, prior to the pandemic. And it stemmed from the fact that I was given a CRF, so a case report form, which is like a data collection sheet, where you write the date on the top, and then you write in the data that you've collected. 

And this patient had so much to tell me in terms of how it had impacted this, or how it had done that, or there was a day where they were feeling better, a day where they were feeling bad, or they did this and it had a knock on effect. And I had nowhere to write that information, because it wasn't in a box, or it wasn't quantifiable to fit in this CRF. 

And I remember just scrawling it in the margins around all the text boxes, and took it back to the clinical team, and was like We're missing something here when we need to actually, you know, this is really important to understanding what we're testing, and you know, in terms of the presentation, and maybe we should do something around that. 

And what we did was we actually gave, you know, subsequently submitted an amendment, gave all the patients on that trial a diary and just said, tell us anything. It's a little bit more guided now. But at that point, it was if you want to write something down, and you want to tell us something about your you know, your illness, your recovery, or how this is impacting you, then we want to hear it. And you would be very surprised how much interconnected data comes through in that qualitative method, you know, just scrawling down notes on people, and how people feel. 

And some people filled it in, religiously, and some people didn't touch it. And, you know, again, that's part of knowing, you know, and learning about individuals, but giving them the opportunity was what was really powerful. And that's something that we've carried forward into, you know, the long COVID work, and I honestly can't tell you how moving and powerful and emotive some of the stories have been. 

But I think it's really changed and directed our approach with the research because we're actually getting insight into the people who are living with this condition at home as they are living their lives. And I can caveat that by saying that they're not living their lives because of the way that it's impacting them. 

And, you know, I have to, you know, acknowledge that, you know, these chronic illnesses such as long COVID, they aren't new, they aren't a spawn from the pandemic, as you know, as we know it. They've been around for decades previously with the MECFS community, who have largely felt ignored and kind of frozen out of society. So actually giving a voice to the patients and giving them the opportunity to tell us so that we can learn from them, but also engaging them in the process of we think this is something we want to look at, as a research study. What do you think? 

And we have a phenomenal PPI group who we meet on a monthly basis. We talk about Projects, we share ideas. We discuss hedgehogs because someone in the group has familiarity with hedgehogs. So that's number one on the agenda item every time we meet. But it's a concentrated amount of time because they don't have the energy to dedicate too much. But we also have like a WhatsApp group where if they do have something they want to say outside of meetings they can. 

And I cannot tell you how valuable that is to shaping and making sure that our research stays current and addresses the real challenges. I think it's very easy, or could be very easy for an academic clinical exercise science team to go, Oh, we're just going to go and do this. And historically, that might well have been the case. But we go, oh, team, what do we think about this, is that? And it's amazing, because it doesn't necessarily always change something dramatically. But it gives us a different layer of context to how the research is important. 

And, you know, we published some of the findings from our lived experience work that we've done, which is the diaries, the surveys and stuff that we've done. And the response from the patient community has just been so moving, so powerful, in terms of providing the data, but also when you publish the findings and present them in a way that they can read them. So we only do it in open access, so anyone can read it. Because I think that's important. It doesn't need to be behind a paywall. You don't need to be an academic or scientist to read something. But publishing and they just go oh, my gosh, this is me, I feel heard. And it's so so, so powerful. And it has been such a brilliant, fantastic addition to the work,

Jackie Baxter  
I think, yeah, as you say, that's so powerful for you. And I think probably for them as well. And, you know, to feel like they're being involved in the research, but also that they are improving it, you know, it's not just that you're paying lip service to them, it's that actually you are listening to them. And they are making the research better as a result of their involvement. And I think that has to work both ways.

Mark Faghy  
Without a shadow of a doubt. And yeah, we do, we are now in a position where we do pay for our PPI representatives to be on trials and support us with trials. And they also find kind of - they don't hold back is what I'm trying to say. They're quite happy to tell you if something's not quite right. And I love that. I love that we have that, you know that ability to challenge and to say, well, actually, no, this is, this is what we need to do. This is how we should do that. 

And we have to facilitate and acknowledge that. We don't want our patient participant engagement to be tokenistic. So not we've got a patient involved, and we've talked to them once or twice, they are a key fundamental part of what we do. And kind of the research movement that we're on. And I know that's, you know, really well regarded within the patient community, because it's just ingrained, a central figure of what we do. And I know that it's improved the quality of our research over the last few years. I know fundamentally.

Jackie Baxter  
And I think this brings us quite nicely on to the research that you were doing before, which you kind of just alluded to, as well. And we talked about this in much more detail in the first episode. But maybe you could give kind of like a quick recap, and what the sort of results that came out of it. Because I think at the time, it was still ongoing when we spoke before it, wasn't it? 

Mark Faghy  
Yes. And we actually decided to extend it a little bit. Because the data we were getting was really powerful, actually. So the biggest study that we've done over the last few years is what we call in practice a cohort observation of patients that had either been admitted to hospital and discharged, or who had been referred to a long COVID service. 

So the idea behind the study is that you you track them and follow them over a period of time. And you know, there's no necessarily endpoint of what that should be. Some of them are for a few months, few weeks, some of them are for a few years. But really, what we wanted to do was to be really knowledgeable, but provide insight into the daily changes of living with long COVID. Because it was very clear very early on, in the pandemic, that it was going to be hugely episodic, that no two days were going to be the same. 

And we did learn that from our kind of pre pandemic research again, to have to draw those, you know, over - one of the differences between the study that we've done and others that are out there, because there's some massive national cohort observations been done by some great groups around the country and around the world, is they take the baseline, and then they see them again at six months. And then they see them again at 12 months, or they see them at 12 months and 18 months or whatever the configuration is. 

And that's okay, because that gives you an indication of how that person has progressed or relapsed or, you know, even stay static in that timeframe. But what that doesn't do is actually give you an indication of what it is like to live with a chronic disabling illness such as long COVID. And so what we intentionally did was we worked with them for four months, but we had weekly interaction with them. 

So we do daily reporting of their Symptoms, you know, reporting of more of the broader outcomes on a weekly or bi weekly basis, phone calls inter-dispersed with home visits to reduce the burden on the patient. But really wanting to understand the day to day changes, the week to week fluctuations. And then to tie that to the lived experience. 

So, yeah, we got all the sciency stuff, which we needed to kind of show that and I'll come onto that in a moment. But it was really focused around increasing the understanding, again, of what a day to day experience of long covid was like. And because it was going really well, we decided to extend it, which the team I'm sure were delighted about when I realized that they've got so much more work to do. But we worked really closely. 

And one thing to say, again, it's not the biggest cohort observation in the world, because of the intensity, because of how many times you have to engage and interact with the patient. Had we reduced that dramatically or increased the time period, we could have seen more, but we got over 100 people through that process. And that taught us an awful lot about what actually was happening on the ground on a daily basis. 

And, you know, one of the key findings was, and you know, the context of long COVID being an episodic condition has been touted for a long period of time. And I know Darren Brown, etc, have done some fantastic papers on you know, the episodic nature of long COVID. But we can actually see the undulating process in the graphs and the figures that we've drawn with the data. You can see the individual changes and day to day, week to week changes in patients. And how drastic that can be from being today's a really good day. And today's a really awful day. And we could be talking about 48 hours. 

And you know, that for us, in terms of developing the interventions, and the support mechanisms that we can wrap around those patients is so so insightful. And from my knowledge, we're the only study that has demonstrated that kind of intricate changes in symptom presentation, symptom profile. But it's so so important to make sure that the services that we develop are appropriate for the patients when they come to access them. 

So we have to acknowledge that there has to be fluid changes, and it has to be flexible to allow them to accommodate for today be in a really good day, or today be in a really horrible day. And I don't think some of the other cohort observations that are looking at their longer periods of time can reflect that. I think they can show that there might have been a gradual improvement or a gradual reduction or that they've been static. But it's in that moment in time. 

So if I was to go for an assessment next Wednesday, I don't know what next Wednesday is going to bring or what the rest of this week is going to bring, you know, I could be having a really good day. Well, that will influence my performance on those assessments. And conversely, if I was to have a really bad day, I would perform worse. But those judgments are being made on that one point in time. 

Where I think our conclusions and the data that we've draw really does highlight that, and it's across multiple levels as well. So yes, we've got the symptom presentation in terms of severity and intensity. Okay. But that's one part of what we know is a really complex condition. So we've also got the physiological data to underpin that. We've got the cognitive data, we've got the mental data, the biological data. So we're trying to pull together a really robust insight that is multi dimensional, and multidisciplinary, to increase the understanding of how we can support that. 

And we finished the data analysis for that, strangely on the train home from Liverpool, because we've been up to see Binita Kane in and her clinic in Liverpool, and we finished it at the start of the data analysis and start in December. And we're going to be putting out lots of kind of communications around the findings for that, and the impact of that. 

But it tells a really compelling picture of how sensitive Long COVID is as a condition and how susceptible it is to change and how that change can happen so quickly, but so drastically. And I think, you know, it's great to have that data and to have that visible as we will be able to present you know, in the coming weeks or months. 

Jackie Baxter  
Yeah, I think that's something. I mean, I've said this before that I you know, before I got sick, I had a couple of friends who had things like ME and chronic fatigue. And, you know, I thought I understood them, you know, I thought oh, that they're just a bit tired some of the time and sometimes they're a bit more tired. I suppose, you know, it's just something that until you have, I suppose a more intimate knowledge of it, or that experience really, then you are not going to be able to understand it. 

But also because it's not.... it's quite difficult to describe, you know, these fluctuations, as you say how quickly, how dramatically, things can sort of go down the plughole, so to speak. Or indeed how sometimes you can see dramatic improvement, only to then have the rug taken from under your fet the week later kind of thing. But, you know, it's very, very difficult to understand that. And I suppose if there's some actual data that can show it, then that will help. 

But I'm just, I mean thinking personally, as well, you know, I lived through my experience, and I, you know, not everybody's experience is the same. But you know, I have an understanding of it, having experienced it myself. And even my partner who has lived through every day of this with me, still doesn't understand a lot of it. You know, he'll understand a lot more than many people will from having seen it, but because he doesn't have the actual experience of it, he still doesn't really get it. 

And I guess that's what makes these conditions so difficult for other people to understand. Yeah, even someone who's literally watched it for three and a bit years, still can't really get it. And that's where they can be so misunderstood.

Mark Faghy  
Absolutely. And I don't think we can truly develop resources or interventions or mechanisms to speak directly to every individual response to that. And again, you know, from our data, or our experience of even working with patients, you know, over the last four years now, we don't have any patient profile, which is identical to another presentation. They are all completely unique. And we have to acknowledge that. And I think we have to be aware of that. 

Now, I don't think we have the infrastructure in the NHS or the health services in the UK, and even broader, further afield than that, to provide, as it currently stands, 1.9 million interventions to support, you know, improvement in quality of life and virtual status, that's not feasible, nor is that achievable. But we do have to create flexibility within the models that we do create, to cater for and to allow those fluctuations to be assessed and addressed and acknowledged. 

So we can't create rigid plans of this is what you're going to do. And this is going to make you feel better, it's just not going to work. And we have to be truly interdisciplinary and you know, flexible in our thinking to be able to do that. 

And what we've also learned is that it has to - and you hit the nail on the head a moment ago, Jackie - it has to acknowledge the friends, families, partners that go around it, who are also living that experience, and are probably in a state of pure confusion as to what is happening, or how to address a day which is really bad, or a day where it's improved. 

Because if you feel great, the temptation might be to just go out and oh, let me go and live my life and then two weeks of crash follow, and then you know what that was, you know. So we have to manage expectation and improve the knowledge and awareness more broadly, not just for the patients, but also for the like, you know, the supporting constructs that are around that. And that's friends, families, and I'm gonna throw employers in there, because I know, that's a really contentious aspect as well. 

And there's work that we can do, and there's work that we're starting to do to do that. Because it's so, so important that we have that increased awareness and understanding of how you know, because we are unfortunately, rightly or wrongly, we are in a position where we are being forced to live with COVID and live with long COVID. So it's inevitable that people will get it, because that's what the powers that be have decided, rightly or wrongly. I'm not gonna go into that, that's a whole different podcast. 

But, you know, we, we need to have the support constructs around that, so that if we are to live with it, and I don't agree with the phraseology of that, but that's what we've been given. So if we are to live with it, we need to be able to support it. And at the moment, we are doing one, but we don't have the other. So I'm really hopeful that we can improve the kind of knowledge and understanding and the support mechanisms for the patient, but also for the supporting constructs that allow that person to have an identity, wherever that's employers, family, friends, partners, loved ones, children, I don't know, all of them

Jackie Baxter  
Yeah, absolutely. Something that I suppose I understood, maybe more through the experience than at the start, because, you know, you're just all consumed by it. You know, it's all about me, because I'm sick. And it was kind of as, I suppose, as I started to see some improvement and as I actually was able to think about somebody that wasn't me, just some of the time, you know, and kind of realizing how much of an impact this all does have on the people around you. And it didn't affect my partner in the same way that it affected me, he was still able to do things that he wanted to do, whereas I wasn't. 

But that doesn't mean that he wasn't massively affected by it. You know, it had a humongous impact on his life, you know, that that you wouldn't wish on anybody. So just because my experience was worse doesn't mean that his isn't worth kind of considering in its awfulness, kind of thing. You know, and I think people do forget that sometimes. 

Mark Faghy  
They do. And we've you know, we've seen a lot through the lived experience data, the pressures that is put on relationships, of different magnitudes, you know, friendships, loved ones, etc in different ways. The stress, the pressure  that puts that is unexpected and also how to cope with that. And you know, we've seen people who have almost like, resented their loved ones because they can have a normal life. And it's not because they just miraculously decided that they disliked them. It's like, No, I want to do that, I can't do that, why? That's not fair. 

And that is a completely reasonable and logical thought process when your identity has been changed or altered by a life limiting condition such as long COVID. And that, for me is where the kind of the lived experience aspect comes forward. Because, you know, we still acknowledge, we might not be able to recover everybody to the where they were pre pandemic, that's a reality, unfortunately, you know, it's heartbreaking in that sense. 

But we still have an opportunity and the possibility to improve people's outcomes. And if we can improve that, and from the data we're seeing, provide some aspects of stability, we might be able to improve some of those kinds of more social impacts that we're talking about with the pandemic as well. 

So this is where, you know, you don't really get that insight from a clinical data set that says, oh, today, you perform this well on this, or you didn't do very well on this, you don't get that. And that's where I think adding in this lived experience has really enriched our understanding of the pandemic, and the kind of the, you know, the legacy impacts of that. And there's still lots more to understand, you know, but it does really shape how we think and how we approach the development of the services that we kind of want to do moving forward.

Jackie Baxter  
Yeah, you know, it's understanding what is important to people. And that is not going to be the same for every person, I suppose. But you know, it's still important to know.

Mark Faghy  
That was a really important point you just made there. And it just taught me to an example that I had before Christmas, because I was delivering a session to our clinical exercise science students. And I put a scenario, two scenarios on the board, and asked them to tell me what was the most important impact of chronic disease. 

And one of them was an Olympic standard athlete who is trying to get to the next Olympic Games, or an 82 year old gentleman who likes to walk to the shop to fetch his newspaper in the morning. And I asked them to discuss and critically evaluate which of those is important. And it's not a criticism of the students at all. But they says, obviously, we've got to help the Olympic standard athlete get to an Olympic Games. Olympic Games is a once in a lifetime opportunity. 

And I was like, it is. But in a context and social identity of an individual who has to go and has a routine of fetching newspaper and collecting his paper. And that informs an important part of their day. Where do we have the most impact in what we can actually achieve, you know, overcoming some of the mechanistic patho-physiological challenges of our COVID. Whooft. That's gonna take some time. But can we restore that person's ability to collect their newspaper, which, you know, has mental, physical and kind of cognitive impacts alongside it? For me, that's more powerful. And also, in the short term, probably more realistic.

Jackie Baxter  
And that's going to be different for different people, as you say, you know, the athlete would say, Well, I'm the most important whereas the, you know, 80 year old person who wanted to walk and get their newspaper would say, Well, I don't care about the Olympics, I just want my paper. 

Mark Faghy  
Exactly, because I want to do the crossword, or I want to read what's happening in this area, or you know, that the things that drive the narrative, is the context. And the context is so important. And, you know, you said you was going through your recovery, you know, with, the difference between your partner was like, Well, I want this, or I can't do this. And we've seen it a lot in the things... and we do, we look internally when things aren't going to the way that we would expect. And often we do sometimes forget the broader picture. 

And I think that's where we have to, you know, not change that mindset, because that would be wrong, because you have to live the experience, and you have to learn from them. But can we provide the support for both parties in those conversations to say, this is the reality, this is what we're doing. And this is how we can support everybody in the process. 

And this is where it has to become much broader than the "I" to recognize the "we" and again, that's come through the lived experience data, tremendously, you know, the impact it has on family units, and friendships, and relationships, etc. And we definitely wouldn't have got that had we not included that live experience aspect.

Jackie Baxter  
Yeah, which it just goes to show its importance, doesn't it? Yeah. So you kind of touched on this a moment ago, you know, about how can we use this to inform either the next bit of research or the services or, you know, because data is useful only if it can actually lead to something that is useful for the people that you're trying to serve, I suppose? You know, which in this case is for people with long COVID who want to get better. So I think that's the next sort of step in your research, isn't it? It's putting it into more kind of practical research.

Mark Faghy  
Yeah. So on the off shoots, you know, we had three projects close just before Christmas, which was extended and derived from that kind of cohort observation work, and that was more honing in on the mechanistic pathophysiologic side of that. So, you know, we've got two PhD students, Rebecca Owen and Callum Thomas who are absolutely incredible. So I had to get their names in here, because they're just so brilliant. 

And they were finishing up a series of projects, one was looking at the limitations of the physiological systems, the interrelatedness of the physiological systems to achieve submaximal, cardiopulmonary exercise tests. And I know that's a really contentious word in the world of long COVID. But it was prescribed relative to an individual's capacity. So we took an awful lot of time to consider, what is their kind of point, and we never went beyond the kind of the crux point to prevent induce crashes, it was screened for post exertional malaise and everything. 

There's a lot that went into that it took us 18 months to design that study, before we even launched it. That's how much time we spent and our patients, again, were central and pivotal to the whole design and success of that study. And I have to say that because it was a really successful study. So that was really trying to look at the integrity of the cardio respiratory pathways. 

And we coupled that with, measures of tissue oxygenation, to see how well the tissues could receive oxygen from around the body and how well that was being used by the muscles. So we've got some really important data that we're analyzing at the moment that it's kind of showing it's impaired, but along the chain. So from the respiratory, cardiovascular muscular systems, it's not just a one point where it all falls down, it's actually incremental as it progresses through the body. But the knock on effect, or the end product is what we see at the muscle is heavily heavily impaired. So our potential for performance is reduced. 

And what we saw through that, just sharing kind of initial observations from the data, is that the high anaerobic contribution, so the inability to use the oxygen, either because it's not there, which we've seen, but also because we don't have the infrastructure mechanistically or architecturally within the muscle to deliver the exercise. 

So that, you know, was was really important. And we finished that, again, over 100 patients, which I'm incredibly grateful for, because there was risk associated with those studies. But we worked really hard to get the kind of the programming, the planning for that, right. And the uptake for that was to do you know, repeat CPET tests, so two day CPET. So yes, we can observe the differences in the systems. You know, day one, what happens in day one, but also what happens when we ask you to repeat that 24 hours later. 

And the differences again, quite emotional, some points when you look at the data and the differences in the capacity. But we know that we're doing it objectively for the right reasons. And so to learn from that. 

What we've also cobbled in there is we've, you know, working closely with some of our collaborators from the UK and around the world to understand the kind of the biomarker profile associated with that. So we've collected over 500 samples in six months at the back end of last year, from patients trying to look at the biomarker profile. 

But not just look at it, and take a sample and analyze it, but understand what's happened around it. So if they're having a good day, then we know they're having a good day. But we've been using the wearable stuff, using the Visible apps and stuff that we've been collecting with patients, you know, for, you know, nine months leading into Christmas, really trying to understand where they are in their journey or within their presentation at that time point so that we can infer that learning into the interpretation of the results. 

And you will know and you will have heard through your conversations, communications over the last few years - that my test results were normal. They might well be but if you asked me to return up to a clinical appointment, well rested and not do anything in that day, that's going to have an influence on the date. 

And this is where the kind of the pulling of the external physical stimuli. And there's still work to do cognitively and emotionally I know, but to change things. And to understand where the differences are. What we've actually realized is that some of the reference values that we currently use clinically to make decisions around treatment pathways, they don't account for the changes and the differences we're seeing in long COVID. 

Because the change might only represent, you know, a 5% or 6%, swing relative to normal, whatever normal is - a lot of viewers aren't gonna hear but I'm literally just raising my hands and putting it in quotation marks. I don't know what normal is! In normal contexts that that might appear okay. But the actual thing, when you add the context and the narrative to that it actually shows that it isn't! 

We're actually co-authoring a paper at the moment that basically says there's no such thing as normal, because there is no such thing as normal. Everybody's responses is very different. And we need to be more acknowledging of you know what that patient presentation is, and that time point that might be okay. But in a normal, everyday situation, it might actually be very different. And our ability to interpret needs to be better informed and more objective so that we can do that well.

But all of this learning which we've been doing, and you know, we've been incredibly busy, and I'm incredibly proud of every part of the team that we have, which stems around the world it does, we're very fortunate. But it has led us to kind of be at the next phase of our researches, where we now starting to look at, you know, potential candidate targets for medicines that we can use to address some of the underlying pathophysiology, which we'll come on to in a moment. But that won't alleviate or eradicate completely long COVID. Because it's much more complex than that. 

Jackie Baxter  
I love what you just said, talking about with the normal thing. Because what even is, you know, if you were to go to your doctor and get your bloods taken, and they put it into, like, what is it called the normal range. But the normal range is massive! And like normal for one person isn't necessarily anywhere near normal for someone else. So actually, you know, when you're comparing people to people, it's not that relevant, What's better is to compare yourself to yourself, are you coming within your normal range?

Mark Faghy  
And I did a keynote discussion with Binita Kane, in September, and we discussed the principle of normal and, you know, even whenever I'm teaching or presenting, I always put it in quotation marks, because I don't know what it is. But you know, if you're comparing one person's data to another, you may as well be comparing apples and pears, bananas and oranges, because what are you actually comparing it against? There's so many mitigating factors that could influence that data. 

And the the ranges are often quite extensive. So then it doesn't account for a person's small change, because it's still within that reference range. It's still within what we consider to be normal. And, you know, it's not a disservice, I can see the value of those, in some cases, and in some contexts, I can. 

But they haven't evolved in recent times, either. They're quite old reference ranges. And, you know, has the research actually adhered and changed with society? Like, you know, because society is a different animal to what it was 20 years ago, and it's a completely different animal to what it'll be in 20 years time. So, you know, is it contemporary? And I don't know the honest answer to that. 

But medicine, and this is something I speak to Binita about all the time, is medicine has to evolve. Medicine has to go with the times. And to know that it's not just about Okay, well, there's a population demographic, we have an increasingly varied demographic within the population, within society, relative to ethnicity, whether to health status, you know. 

So how do you draw a line between what is normal and what is not? And it is absolutely, as you say, about understanding that person's profile, to understand what their normal is, and then detecting any deviations fluctuations or changes within that, and responding to that. And that's where we're trying to develop a bigger picture. 

And as a collaboration that we're, well we've proposed, with the University of Nottingham, our big partners, is to actually develop a way where we can remotely monitor everybody's own presentation, for long COVID, in a way that we can then make informed objective decisions. Not - Oh tell me what you've done for the last three months, you know. 

So when, you know, when patients come into a long COVID clinic - Oh, tell me about your case history? Well, no, they should have the case history and the data that goes with that before so they can make, Okay, well, this is what we're gonna do in response to it. And these are the kinds of things we're thinking around in terms of the development of the service plan is how does you know the role of technology and I, my team will laugh when I say this, because I'm the biggest technophobe there is like, I can switch my laptop on, my students love it when I can turn the computer on. 

But there are people who out there are much more expert than me. But there's technology that we can use, and we can incorporate into our everyday life, that creates a passport and not just for long COVID. More broadly, that creates a passport of normal for that person. 

And then, if and when something goes wrong, which is normally at the point we end up with the doctor or the GP, we can actually assess what's happened. But we can do that in an objective way, data driven way, and not a subjective Oh tell me what problem is. Because health service practitioners, you know, GPs doctors, they're all under increasing pressures, if you're lucky enough to get a GP appointment, you get eight minutes, and it's like, right, okay, figure that out.

Jackie Baxter  
It would take me like two hours to tell you my last three year's history like...

Mark Faghy  
Chapter one! *laughs* And then keep turning the page. Exactly. It's incredibly challenging, but I think we have to acknowledge that, you know, the pressures that the health service is under, the sheer difficulty of the challenge the amazing people within the health service have to do, without the kind of the resource and the support to do that. 

But that's where we can be smarter in how we inform that process. And that's kind of almost actually what's driven us - I'm gonna bring it full circle back to the kind of the next trial that we're kind of going to do. Because it was through some of the data that we saw, you know, that viral persistence. And I know you had Amy Proal on, which was one of the most amazing podcasts ever, by the way, like, I literally listened to that 15 times. But I was just like, I can listen to it again,

Jackie Baxter  
She was amazing to speak to,

Mark Faghy  
Ahhh isn't she just?! Honestly, but just the value in that work that they've been doing. And we've highlighted them, and they've, you know, Amy Proal's team have highlighted the role of viral persistence. And it was just at, it was at a networking meeting that I was at, where I was introduced to David Strain, who's a doctor down at Exeter. And so you know, and he was like, Well, why don't we just use this antiviral medication? I just thought, oh, is it that simple? There was one available. 

And you know, through that, what we are able to do is to bring to the UK, the first antiviral trial for long COVID patients, you know, starting this year. And I'm incredibly proud to be heading up that team and sort of be leading that project. And the first phase is what we call a phase four trial, where basically, we need to test that the patients are prepared to come in five consecutive days for an antiviral infusion, because we're delivering it via infusion. 

When we did the press release for that the state of my inbox probably could have answered that question of whether patients would be willing to come in and do it. But we have to do it through the scientific routes, because we had 1200 responses in a weekend. And we were talking before, about having half an hour to do your emails in the morning. Yeah, that went out the window, I spent two days replying, because, again, I care about individuals, I don't copy and paste email responses. I'm not that person. 

So I responded to every single email personally. And it was, but incredibly valuable. And people feel valued when you do that. And you don't just go, Oh, here's a link. It's much more about the individual and the people. And I want people to feel valued and heard and not that they've been dismissed, because a lot of that's come from the learning that we've seen in the lived experience. 

And I did foolishly make the mistake of kind of responding to Oh, I see you're interested in this, tell me about that. And then you end up in a conversation. But that's fine. That's, that's my own personal flaw and my character flaw. 

But, you know, we have a candidate medication that is licensed for use in the UK, and it's treated, used during acute admission to the hospital in COVID-19 patients. So the data suggests that that reduces the risk of developing long term issues. But it's not been trialed in the context of long COVID. And because we know viral persistence and the reservoirs, not going to do any service to Amy Proal, maybe stick the link to hers in there as well, because her explanation of it is brilliant. 

But what I think, you know, we can actually start with, well, if there are those reservoirs, can an antiviral medication, actually, you know, eradicate those and remove those from the body. And one of the big things - and I'm slightly biased, because of the angle that the research is taking - is that the viral persistence can lay dormant. So even if you clear the active virus away from the body, it can still persist in the body. When you then get in contact, or you know, have contact with an acute infection again, it can reactivate those reservoirs, and then the symptom profile and presentation is much worse. 

So what can we do to actually reduce the size or the magnitude or the volume of those reservoirs in a way that will have an impact on the symptom presentation downstream. Now, viral persistence is only one of several mechanisms that underpin long COVID. So again, have to be balanced and say it's not going to eradicate long COVID completely. As much as I wish that was the case. I wouldn't have a job but everybody would be healthy. So winner. But you know, can we add one part of the jigsaw to doing that. 

And we've been very lucky to secure the funding from pharmaceutical company, Gilead, who funded the trial to, you know, the first stage to 1.25 million. But we're already in active conversation with, Okay, if people are willing to come in for five days, we need a national trial. We need to do this everywhere. And you know, the response we've had, it's just been incredibly positive and receptive from the long COVID Community. It's born out of some desperation, because people just want to be themselves, and get back to being themselves as they call it. But also, because, you know, there's just a desperate need to have these answers and these resolutions. 

So we know there's a big national need to do this. And we're having those conversations already. And a lot of the groundwork that we've done for the last six months, is so that we can go from Phase four to randomized control trial very quickly. As soon as we know there's efficacy, we should able to progress straight into a bigger national trial, which will be opening the doors massively. But first, we've got to show that people are prepared to come in and out five days, because that's what the regulatory people say we need.

Jackie Baxter  
I suppose for people that are extremely unwell, that is quite a big undertaking. So if they are willing to put themselves through that, then that means quite a lot, doesn't it, about what you're trying to do?

Mark Faghy  
Absolutely does. And it's, you know, you say, it's five days, IV infusions, the first one 60 minutes, the second to fifth one are 30 minutes in duration. And in an ordinary context, that doesn't sound like a big time commitment. But the energy that is required and expended in getting to and being part of the trial and getting home again, the accumulation of that over five days is a big ask. And we fundamentally know and appreciate that. 

But from the data that we've got, in terms of the impact it has on the symptom profile, the presentation, it's kind of almost worth the investment. But we need to show that it's tolerable to patients, because we don't want to cause any harm, don't want to do it in a way that, you know, will set patients back, we want to help. And we have to find the best way to do that. 

And, you know, it's not to say that the next phase won't use a slightly different treatment regime that is slightly maybe longer, a little bit more sparse in terms of the day to day contact. It could be that it's what you know, maybe once a week over a period of time, and we've got teams looking at that at the moment, to work out what the best treatment plan is. 

But at the moment, and again, it comes back to that generating new knowledge. At the moment, what we know is that this is the most effective one. But we are very open to discussing and having anybody's input into what that looks like. Because we just want to work for the patients. So if that means working with everybody and anyone, fine.

Jackie Baxter  
Yeah. And that comes back to you know, the importance of listening to the patients. Because it's all very well, you saying Right? Well, we have this five day trial, you have to come in, and you have to sit here for however long each day for five days, and it's gonna cure you. 

But actually, if those patients aren't physically able to do that, then you've just basically spent a load of money on something that's not really that useful, which is completely pointless, isn't it? So that's why it's so important to work with those patients so that doesn't happen. 

Mark Faghy  
Completely pointless. And you know, Lindsay, who is our patient representative on this trial, and is somebody I respect so much, she's just an incredible human being, and again, wouldn't have met Lindsay if it wasn't for the pandemic, I know we were talking about that before we started recording. And, you know, she's actually too unwell to take part in the trial, she won't be able to take part in this trial because of the intensity associated with the visits, etc, and the requirement. But Lindsey is at the more severe end of the spectrum for long COVID. 

And, but what that means, then is that, you know, this trial might not be accessible for Lindsay and others that are at a similar presentation. However, that means we have a job to do to find a way to make this accessible to her, and others within that cohort. 

And what we're doing with that then is, well, that's my responsibility and the team's responsibility to find alternative ways to do this, whether that's with an altered treatment strategy treatment regime, in a way that is, you know, can we get to a point where we can deliver these in the houses? These are the kinds of the questions we're having with all the relevant parties and organizations at the moment is, okay, well there's 1.9 million people in the UK. Let's think - we're not gonna be able to get everybody through this first trial. I wish we could, but we can't. But with the second one, how can we speak to the most of, or if not all of, the 1.9 million people and offer some insight of opportunity. 

And have to be balanced, and it won't be 100% effective in everybody. We know that. But if we can offer some form of improvement or some form of, you know, reduction in the presentation that has an impact in broader areas, then it again becomes a candidate for helping people. 

Jackie Baxter  
Yeah. And it comes back to this, you know, level of improvement doesn't it? You know, of course, you know, the ideal is that everyone clicks a button or takes a pill and is 100% back to everything. And wouldn't that be wonderful. But, you know, the reality is that actually it takes time, and it may take more than one thing. 

And you know, some improvement is better than no improvement. So if you can take part in your trial or something else, and it helps a bit, and this person is able to do a bit more, maybe they're able to go back to school or maybe do something that they enjoy, then we still have work to do. But that's a step in the right direction isn't it. 

Mark Faghy  
Exactly yeah. And that's, you know, we've been spending a lot of time going back with the regulatory bodies and the people designing the trial to make sure that it's, you know, gives us the best opportunity to show this as a candidate intervention. But you know, the first phase of that which we'll start later this year. At Easter. You know, but then we've kind of gotta go, right. Okay, so that's worked. So now let's get on to the bigger trial. 

This is probably one of my biggest frustrations is that we have to go through that process and I'm not frustrated by the process, I'm frustrated because of the time that it takes to help people. And what we want to do is to help people as much as we can. But we have to adhere to the governance structures that are in place to make sure people are safe. And so I completely respect and am, you know, adhering to those processes as the, you know, the team that we're working with. We just wish we could do it quicker so that we can help people faster. 

So it's like, Ughh yeah, it might take us another, you know, 18 months to two years to have the randomized trial completed. And at that point, then we can go through the licensing agreements for it to become available to people. 

Some people that have been living with this for four years already can't think of anything worse than having to wait another two years, potentially three years. And I fully fully respect that. But we have to kind of go through the right structures and processes to make sure we do things that are safely and, again, you know, be innovative with the treatment strategies to make sure that we can improve as many people as we possibly can as well.

Jackie Baxter  
Yeah, absolutely. And I will make sure that all the links and studies and reports and everything that you've mentioned today will all go in the show notes, if anyone is interested in reading up or when the antiviral trial does go live, then I will stick the link to that in as well.

Mark Faghy  
We're trying to be incredibly public facing with all of the research that we're doing again, you know, making sure that we disseminate journal articles in open access. So it's not hidden behind paywalls. But also providing, you know, non academic, non medical summaries of those papers so people can engage and interpret that. And, yeah, obviously, got new website in development at the moment, which will kind of house all of that. So, yeah, more than happy to share that. 

And, you know, for anybody that's listening, and is kind of has, you know, ideas and suggestions. We will collaborate with anybody, like we're not in it for our own personal individual gain. It's not about us or the "I's". It's about helping people as much as we can. And some people might have ideas and suggestions. And whether they're from patient backgrounds, or clinical backgrounds, academic backgrounds, we're more than happy to work together to help as many people as we can. 

Jackie Baxter  
Well, thank you so much for joining me today. I feel like it's been - we've packed a lot in. So it's been amazing. It's been so lovely chatting to you again, and hearing about all the amazing things that you've been up to and those plans for the future as well. So thank you so much, and we can catch up again when you've got more results to share. If you're up for that?

Mark Faghy  
absolutely. Thanks for having me, Jackie. Thank you

Transcribed by https://otter.ai