Long Covid: what has six years taught us?

Emily Kate Stephens (42:36): It's one of the most amazing analogies that I have ever heard, this system of cogs. That's what we do, amazingly depict how all of these component parts are so interdependent.

Mark Faghy (42:47): And it's a physiologist's bread and butter, that 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 different mechanistic understanding.

Emily Kate Stephens (42:56): 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 health care in Long Covid. But I think that filters out more generally. And you've even done a systematic review of the biomarkers. Can you tell me, six years into our 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?

Mark Faghy (43:39): 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 1000s of Long Covid patients who are incredibly grateful for the 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 the patients again. 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 in that context. So whilst I think we've made some amazing progress, I'm very conscious that we still need to be accelerating the 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, but affects different systems in different ways and in different magnitudes, so it's a real crux 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, you know, there was 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 learned so bringing together the understanding that's happened in these areas, and then drive forward with an agenda that's really refined. What have we learned? Where do we go next, and how do we find the 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 way 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 at the minute to review where we are and share direction moving forward, and I think that's where we are.

Emily Kate Stephens (45:59): 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?

Mark Faghy (46:09): Yeah, so let's go through them one by one. I think researchers have learned 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 Mark Faghy and the team from Loughborough, formerly Derby. It's not going to be Rob in Amsterdam. I'm sure he won't mind me saying that we're going to have to work together. We're going to have to work across disciplines. We 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 sort of opportunities for us to collaborate with healthcare practitioners, you know, ordinarily wouldn't have done. Still some work to do there. There's some odd 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, hasn't happened in the last few years, and it wouldn't be forthcoming if 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 too.

Gez Medinger (47:43): So one of the things I'm most interested to hear from Mark Faghy next is the results of his remdesivir 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 does and who doesn't. So how do you put the right people in the trial in the first place? So all of these questions still floating around with these sorts of with these sorts of treatment trials, and I think one of the other sort of, the helicopter view of all of this, which 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 Faghy said, to do the consolidation, the consolidation phase, and it's going to be several more 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 going on

Emily Kate Stephens (49:21): And simply that time as well, to see how effective has that been, not just in the initial response to it, but a year 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 helped me improve. It is multiple things. I think that I had viral persistence and then a huge cascade effect, and I've had to deal with all of those different things. But even now, a year since I started to get better, I still have relapses. I still have time where a crash, essentially. So I think that point, a year 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.

Gez Medinger (50:31): You know what that word is a tough one in this space. 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 cures. 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 just talking to a chap yesterday, and I mentioned to him I'd had Long Covid. And he says, oh, it's funny that because I used to be an avid 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, 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 has affected so many more people than are just registered in the Long Covid quotient level of severity that is just dismissed. Oh, it's just getting older. I've just got this problem, or I just get a bit out of breath now, or I get more headaches than I used to, or my stomach's been funny for the last couple of years.

Emily Kate Stephens (51:48): 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. 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.

Gez Medinger (52:14): Just on the points on that interview with Professor Faghy. 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, right? 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 scattergun 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. And what he's talking about there is getting the foundations down and making sure that you design the house right in the first Yes, rather than just throwing it up and then finding that it falls down. So I think it's incredibly 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, so I don't know, Emily, if you've seen the Apple TV show Pluribus. Have you seen it? No. Okay, so it's a sort of a sci fi black comedy show about a story of a woman who's an author. World where scientists discover this signal that's being beamed to us from space, and they go, Oh, great. What's this signal? And they work it out. 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 access so 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 6 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 if you were 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 planets, to satisfy my every whim. And I just thought, 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, 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 spider's web of research, how do we hive mind it all in a way that enables us to make that best step forward? So 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 momentum.

Emily Kate Stephens (55:40): 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.

Gez Medinger (56:03): 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 we've got at the moment, which is lots of shanties getting chucked up all over the place. No town planning with no town planning?

Emily Kate Stephens (56:21): Yeah, I will not allow you to call the work that these people are doing in this space shanties, because honestly, it is completely phenomenal.

Gez Medinger (56:31): 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.

Emily Kate Stephens (56:45): 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 Alba Azola, she heads up the ME/CFS and related disorders program at Johns Hopkins University, and she's a rehabilitation physician. She's done a huge piece of multidisciplinary 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.

Alba Azola (58:28): I adopt things that most people wouldn't adopt.

Emily Kate Stephens (58:31): 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 a doctor telling me that, because there are various treatment strategies that multiple people are repeating your treatment strategies are, what's the word for it? Wow. I just think it seems like you're thinking outside the box. I guess there's things that where you're repurposing from other situations, because, you know, it has this effect,

Alba Azola (59:02): Absolutely, I found myself in this fringes of medicine, right where the repurposing of medications, the trial of things off label, became kind of increasingly common, And there were early adopters and later adopters and and there's different people on 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, you know, type of patient, responded to certain medications and understand when to use it or when not to use it. I always, I would say, probably, my close relationship with patients and the communication is key, like when I started using, for example, Mestinon or pyridostigmine, I was scared, because it does have kind of quite a wide side effect profile, so I wanted my patients to report to me. Even with midodrine, I did this like I would ask them to send me a message every week to see what their blood pressure was doing, how 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, you know, the patients later on, as I became more comfortable, you know, I didn't need to be communicating so closely, and I kind of started learning about what to expect and what not to expect?

Emily Kate Stephens (1:00:41): Yeah, it's a fascinating approach, because it takes one person to start to try something, and now you've got a Mestinon trial taking place. People taking that step to try something with patients, and also patients taking the step to trust their doctor, that their doctor is trying something with them in their best interest. In both of them, considered best interest is the only way we can step forward,

Alba Azola (1:01:08): Right? We vow to do no harm. And something that 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 you 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. You know, 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 signed up to do and help patients.

Gez Medinger (1:02:20): 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 treatment 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 were like that and were a bit more open minded about the things they might be able to do off label that could help their patients.

Emily Kate Stephens (1:03:15): Yeah, I am hugely privileged to speak 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 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 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 today. Gez, thank you so much all of you for listening. We hope that this has given a little bit of information of what's going on, perhaps a little bit of hope. 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 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.

‍