 Hey folks, welcome to the podcast. So we're doing a special series of podcasts which I'm recording over Google Hangouts. So we're doing audio and video because for some unknown reason people don't want to come see me face to face right now. But there's always opportunity and the cool thing is I'm able to now podcast with people from all over the world. So we're going to get an amazing eclectic mix of people from different industries, different perspectives to share their story and tell us their thoughts and feelings on what's going on right now and all of that cool stuff. Hope you enjoy it. Please subscribe in all the usual places and enjoy. Awesome. Folks, welcome to the podcast and so it's video and audio and it's been recorded over the internet. So apologies if there's any delays or anything like that. Looking forward to getting back to real life podcasts very soon. So through lockdown and Covid there's been an awful lot of discussion around prevention. So the masks, social distancing and rightly so. But I'm really interested in our immune system and the very thing that will help us fight these things. So I've been looking for someone to come and speak to me and I'm really pleased to say that Professor Adrian Martino from Queen Mary University has kindly agreed to come in there and speak with us. So he's a clinical professor of respiratory infection and immunity and one of his primary areas of interest is the effects of vitamin D on human health. So absolutely perfect and let me patch Adrian in. Adrian, thanks for joining me. It's a pleasure. Thanks for inviting me, Lewis. Pleasure. How has lockdown been for you? How's it all been going? Not too bad. I think harder for the kids than for me as I've been able to get into the hospital and get away from, I think, get a bit of fresh air. That's true. So you're a key worker? I guess I am. And whereabouts are you? Well, I'm at the Marlend hospital today. My primary interest is actually in tuberculosis, so I've been keeping the TB service running while my colleagues are firefighting at the Royal London. Okay, brilliant. So you're doing a mix of research and hospital-based? That's right. Yeah, primarily research but keeping my hand in the clinic. Nice. So what's your background? Do you mind giving us a little overview? Sure, yeah. So I'm a respiratory doctor. I've been interested in respiratory infections really since I graduated and went to work in South Africa for a couple of years, where I got interested in TB. And my interest in TB sparked an interest in Vitamin D because Vitamin D was historically used to treat tuberculosis before antibiotics were discovered. So I did my PhD on the effects of Vitamin D on the immune system. And then I discovered that Vitamin D can also boost immunity to other respiratory pathogens than TB. So I got interested in viruses. And here we are, COVID came along. So we're working now on Vitamin D and COVID. Wow, it's crazy. How was your experience in South Africa? Well, it's fantastic. I love to work there. And in fact, we've got a big clinical trial going on in Cape Town at the moment. And 1600 kids in the Cape Flats who randomized to Vitamin D or placebo, that's for TB prevention. But we're going to look at COVID outcomes as well. Amazing. Okay, well, I know you're doing a lot of studies and you're doing one currently as well, which we need to promote and make sure people sign up for. So we'll speak about all of the studies. Maybe let's start with why is a strong immune system important? Maybe let's start with that. Well, that's probably best illustrated by looking at people who don't have a strong immune system. So there are people who are born with genetic defects in particular branches of the immune system. And they tend to succumb very early in life to infections, which most of us will just rush off. And in fact, it's observations from these people who have so-called Mendelian knockouts or mutations in genes that are of key importance to our immune system that have been really important in telling us about which immune responses are protective against which pathogens. Another key area of immunosuppression is what happens when we give patients medicines which suppress the immune system. We've learned an awful lot from giving people who have autoimmune disease medicines to suppress the immune system that then succumb to particular infections. And we can then work out, oh, well, that cytokine is obviously important for protecting against this infection. So it's a common story that we can learn about what's important for our immune system by studying people who've got defects in particular pathways. Okay. And so having good or strong immune system, is it partly genetic, partly good dire, exercise, sleep? But what can we actually do? One of the most things, Lewis, it is, as you summarize, a heavy combination of nature and nurture. I mean, these sort of genetic defects are quite extreme. They're extremely rare as well. So when you have one, then you're rendered extremely susceptible to particular infections. But they're very, very rare. And for most of us, there are genetic influences on our immune function that they tend to be pretty subtle. And there's a lot that we can do in terms of our lifestyle and diet, which really will overshadow any subtle effects of genetics on our immune response. Okay, right. So we can actually improve it? Absolutely. I mean, to take a look at COVID, there are very clear and simple things that we can do to reduce our susceptibility. If you're smoking, you must stop smoking. If you're overweight, then it's good to shed a few pounds because we know that if you put on a few pounds over lockdown, as most of us have, that's associated with worse outcomes of COVID. So these are simple things that we can do just by tweaking our lifestyles to reduce our risk from COVID and indeed, other infections as well. Yeah. So we have seen, I think, in intensive care and stuff, and correct me if I'm wrong, because I'm not going to get these stats right at all, but most of the people that have found themselves in intensive care have had underlying health conditions, right, obesity, diabetes, and so forth. I would say, yeah, probably a majority, but there are people who don't have obvious risk factors who've also had severe disease. It may be that in these cases there are genetic factors or there may be other environmental factors which we don't fully understand yet. A bit of indeed efficiency could be one of them that could explain the susceptibility. So I think it would be a mistake for people to go around thinking, well, I don't have one of these big ticket conditions like diabetes, hypertension, heart disease, so I'm going to be okay. I think that would be a bit of a whole hardy approach. We need to be super careful because this bug is not one you want to play around with. Yeah. So really the things that you can control, I mean, because you can do what you can with the masks and social distancing, you still might catch the COVID. You might catch other stuff too, obviously. So the things that we can do that we can control, good diet, regular exercise, and good sleep, and I think they're the three cornerstones, right, of a good immune system that we can control. What you're getting at really lies at the heart of this research project we're doing that you alluded to at the beginning of the show, Louis. So this COVID-19 UK study is a national questionnaire-based study. We're trying to recruit people age 16 plus from all over the UK to answer questions about their lifestyle and so we can work out which of these factors really are protective. I mean, from a common sense perspective, yes, you might think that if we cut down on our drinking, cut down on our smoking, try and get a good night's sleep, et cetera, it should help. But there isn't actually a strong evidence base for that yet. And there might be some surprises as well. So what we're doing with this study is trying to work out which of these lifestyle factors can affect risk so that we can actually modify those in time for the winter that's coming. Eventually, of course, a vaccine is going to be the way out of this, but a vaccine is not around the corner and when it does come, it's unlikely to be absolutely perfect. If flu vaccines, anything to go by, you know, people who are older or people who've got underlying conditions like diabetes may not be able to mount protective responses as well as others. So in those people, those lifestyle factors still going to be really important. Yeah, yeah. So this study, how can we get people involved and where do they need to go in? Yeah, well, the way to sign up is to go to our website, which is QMUL, that's Queen Mary University London, where I'm based, dot ac.uk forward slash covidance. The study is called Covidance UK. You can just type that into your search engine and it'll come up as well if you look on the QMUL link. And when you go onto the website, there's a button that says more information and sign up and that'll take you to an information sheet that spells out in detail the nuts and bolts of what's involved. But to summarize, it's an online questionnaire. It takes about 20 minutes to complete. It's pretty detailed and it needs to be in order to have value. So we ask in detail about people's diet, exercise habits, sleep habits, medications, underlying conditions, age, sex, gender, and ethnic origin as well. And then we take that information and we put in our database, we've got 10,500 people signed up already. And we also ask about any symptoms people might have had of Covid since the first of February, which is essentially when transmission started in the UK. What we can do from those symptoms is we can run an algorithm or essentially a computer program that calculates a probability whether or not somebody's had Covid. And then we take the people who have had probable Covid. We look at their risk factors, compare them to people who probably haven't had it. And then just on the basis of that questionnaire, we can start to get clues. There's a second phase of the project just getting underway called Covenants UK Biobank. We're starting to roll out a collection of samples of small blood samples, which we can get DNA and serum from. And this will tell us whether people got antibody responses or self-mediated immune responses. So then we'll be able to get a more objective and precise handle on who's had it and who hasn't. How accurate are these though? I mean, I hear people, I spoke to someone the other day, her antibody test came back positive last month. It came back negative a few days ago. We hear stories of maybe the antibodies not lasting so long in the blood. I mean, how accurate would this actually be? So it's hard to say for Covid-19 at the moment because we just don't have the longitudinal data. We don't have the follow-up data yet because that's a new pathogen. We can get a hint, perhaps, from looking at other coronaviruses, things like Versailles virus or MERS-CoV, which is a Middle Eastern coronavirus, much more virulent than this one. And also, from coronaviruses that have been circulating in the community that might cause common cold symptoms. In general, the emerging picture is that immunity can be robust, but it's not necessarily that long-lived. Antibody responses maybe six to 12 months long. We know that people who have more severe disease develop more robust antibody responses that last for longer, but there's an emerging picture that perhaps antibodies aren't the best thing to measure and that looking at what's so called cell-mediated immunity or T-cell responses might give us a better clue to future protection. But what we're hoping to do with this biobank study is collect these samples. Some will analyze straight away. Some will put in the freezer when people are working full-time on immunology as opposed to doing public health studies, come up with a good biomarker. We can then take the samples out of the freezer, run the biomarker, and then look at our own database, see did the presence of this biomarker confer or associate with resistance over the long term. So this is like a bank of samples that we can use not just to evaluate the tests that are around at the moment, we'll be able to evaluate the better tests that are going to come out in the future to look at what really are the best correlates of protection. Great. And just for those of us that don't know, what's the difference between T-cells and antibodies? Okay, so your white blood cells are divided into several groups, but one particularly important group are called lymphocytes. And these lymphocytes are important for the branch of the immune system which called the adaptive immune system, and that's the sophisticated part of the immune system that learns from experience and that has memory. In other words, it's the part of the immune system that is affected by vaccines and that vaccines can stimulate. Now these lymphocytes very broadly come in two main flavors. You've got B-cells and you've got T-cells. The B-cells are the cells which pump out antibodies. The antibodies are like these Y-shaped protein molecules which can bind onto a virus and neutralize it. They're like the effector molecules if you like. The T-cells are a different kettle of fish and they can help the B-cells to make antibody. So they basically secrete chemicals which encourage the B-cells to pump out the antibodies. So what you need for an ideal protective immune response against COVID or indeed any other respiratory virus is a family of T-cells that can recognize the virus and that will multiply in response to the virus. That will help them to pump out chemicals which then affect the B-cells. The B-cells in turn pump out the antibody which then neutralizes the virus. Awesome and then depending on your diet, maybe your genetics will be dependent on how effective your immune system is at fighting these diseases. That's it. We think that there are a whole range of environmental factors that can interplay with the basic sequence of events I just described to affect how efficient they are. Great. Moving on to Vitamin D, why is it important for a good immune system? Well we know that in the lab Vitamin D has two really key actions which help immune responses to respiratory viruses. The first is that they can boost what we call innate immune responses. So this is the other branch of immunity, the branch of immunity that doesn't learn from experience but which you're born with. Right. And this is an important branch and often a neglected branch of the immune system and we know that what Vitamin D can do is it can boost that part of the immune system quite effectively. One of the key mechanisms by which it does that is by supporting production of these substances called antimicrobial peptides which are essentially like natural, antiviral, antibacterial substances that come in white blood cells and lining of the lung that can have damaging effects on a whole range of respiratory pathogens. Right. So we know that the Vitamin D boosts those. So that's part one of the Vitamin D immunity story. The second part which is particularly interesting in the context of COVID is that Vitamin D is also anti-inflammatory. Now we know that the drug that's really shown the most benefit in people with COVID is a very potent the anti-inflammatory steroid drug called dextamethasone. And the success of that drug in treating patients with COVID basically illustrates the importance of the immune system and particularly overactivity of the immune system in causing adverse effects of COVID. Early COVID is characterized by having virus around but actually the people who are doing worst with COVID are not those who've got virus in the bloodstream, it's those who's immune system is overactive and it's the overactivity of the immune system that's causing the problems. So the second key activity of Vitamin D is to dampen down these harmful overactive immune responses. So one could think of it in theory is almost like a designer drug that's on one hand with a left fist is hitting the virus with innate immunity and then with the right fist it's coming in and it's dampening down harmful excess inflammation. Interesting. So Vitamin D sounds like it's acting in a few different ways for your immune system? Well that's in the test tube. What we won't want to find out is what happens when you give it to people. Right. And so that's another goal of the COVID study is to form a platform to do clinical trials where you can randomize people to get different amounts of Vitamin D and see whether or not that might confer a benefit. And so we've put in grant applications to try and get funding for these trials and we're waiting for the answers to those grant applications to see if we can get some cash to get these studies off the ground. I heard that there's some studies already being done on Vitamin D. Has there been any interesting findings? Yes, so there's a number of studies that have been done. Primarily what we call observational studies. So they're not clinical trials. This is what sort of study that I was talking about. Right. There's studies where Vitamin D levels have been measured and then they've been correlated with people's response to the virus. So at a basic level some studies have measured Vitamin D in people who do and don't have antibody responses. And they've found that Vitamin D levels tend to be lower in those who have antibodies, suggesting perhaps they were more susceptible to infection. A second family of studies have measured Vitamin D levels in patients coming into hospital. And those studies have tended to show that the people who've got lower Vitamin D levels when they come into hospital tend to do worse. They tend to need intensive care. They tend to be at a higher risk of dying of COVID. And their Vitamin D is really low? Yes. Now that doesn't necessarily prove a causal relationship. It's an association but there are reasons, there are non-causal potential reasons why the association might be there. So for example we know that some infections can actually reduce your Vitamin D level as a way of subverting your immune system. It could be that COVID is one of those. Right. We also know that for example being overweight is associated with having a low Vitamin D level. So it might be that the Vitamin D levels are bystander and it's actually the overweightness that's causing the problem rather than the low Vitamin D level. Now there are statistical ways to kind of tease this out. But ultimately it's always hard to prove cause and effect with this observational study design. I think those studies are important to do because if they didn't show signal then you know we'd be pretty sure we were barking up the wrong tree. Yeah. When they do show signal it's basically a pointer to encourage funders to support clinical trials to see whether it really is reasonable there or whether it's just association. So what's a good number of participants in a solid clinical research study that can be relied upon? So that depends on the question that you're asking. So very broadly the types of trial that people are thinking about with Vitamin D are treatment trials and prevention trials. So treatment trials are when you're giving Vitamin D to people as they come in through the front door of the hospital to stop them ending up in ICU. And those trials can be smaller and that's because the event rate of interest, so the outcome of interest which is primarily ICU admission or the need for ventilation is more common. So around perhaps a third quarter to a third of people coming through the door might end up needing more intense care. If you want to demonstrate an impact on an outcome that is that common statistically you actually need fewer people to show that effect. By contrast if you're trying to do a prevention study the risk of somebody getting ill with COVID in the population is a lot lower than the risk of somebody who's at the hospital front door of needing ICU. And the statistical consequence of that is that for a prevention trial it's got to be a lot bigger. So we're talking between five and 10,000 needed to detect about 20% protective effect with 80% power and alpha 5%. So we're looking at maybe a few hundreds for a treatment trial but several thousand for a prevention trial and that's what Credence is trying to do. So you've already got 10,000 people signed up. We're aiming for 20 and in particular one groups of people that are underrepresented are people of Bangladeshi, Pakistani, Indian, Black, British, African, Caribbean, African, ethnic origin. We know those groups are underrepresented in the study and between them they make up around 6% of our participants, around 14% of the population nationally. It's particularly important that people from these ethnic backgrounds take part because one of our key reasons for existing is that we want to try and understand why they're at higher risk. So we can get more people from those backgrounds to take part. We're going to be underpowered to answer that question. Yeah, so there's been conversations that they are at higher risk. Is that linked to Vitamin D? So that's a working hypothesis. It's one of many hypotheses. Just to wind back just before, so are they actually at higher risk? Have their studies done and the statistics over the last four months indicate that they are definitely higher risk? Yes, that's uncontroversial. So studies across numerous different international settings have come up with this similar finding. So in the United States, people of African American origin at higher risk in the US, in the UK were seeing it among South Asian communities, Black communities in the UK. So that's a replicated association. Most of the data relates to severity, but we're actually seeing it in confidence UK as well. We're able to take a slightly, we're taking a different perspective. We're looking at the population levels. We're looking at susceptibility to infection as opposed to severity and risk of death, but we're seeing increased susceptibility to infection as well. Now the reasons for it, I like to be a single factor that explains it. There are a lot of environmental factors that I like to contribute. In the UK, we know, for example, frontline workers, NHS staff, people of Black and Asian ethnic origin are overrepresented in that group. We know that other occupations that are at higher risk, so public transport, working in catering, shops, people of Black and Asian ethnic origin are overrepresented there. That explains part of it. Some of our early data suggests that housing may be a factor, so overcrowding. But indeed, maybe part of the mix. So it's going to be a multi-factorial affair. And who knows whether visibility will turn out to be one part of it. It's certainly a possibility. Interesting. That'd be really interesting to delve into. Do typically ethnic minorities have lower vitamin D? Yes. There's good evidence to suggest that from national surveys of vitamin D status, people of Bangladeshi, Pakistani, Indian, Black, Afro-Caribbean backgrounds do have higher rates of deficiency. Right. Interesting. Well, I'm really looking forward to the results of the study. So if anyone is listening or watching, please sign up. We'll stick the link to sign up for the study in the show notes and also on the communications we do to publicise the podcast. So it's really cool. And once the study's done, we'd love to have you back in and you can go through the findings, which should be really interesting. Yeah, thanks. So we're hoping to, if we can get a real boost in numbers in the next couple of weeks, we're hoping to get some preliminary results out by the end of August from the data that's accumulated so far. So end of August, beginning of September, hopefully I can come back and share our findings. That'd be awesome. What's at the moment then, obviously without the results of your study and stuff, what's the link between the vitamin D and fighting COVID, if we cover that? So the link primarily comes from the laboratory story. So the data suggesting that on paper, vitamin D is doing the right things to the immune system that will help us against COVID. The clinical story comes from these observations linking lower levels to poor outcomes. And then there's a third piece of the puzzle, which relates to clinical trials of vitamin D that my group and others have been doing, looking to prevent other respiratory infections. So a couple of years back, we pulled together data from 25 different clinical trials done all around the world of vitamin D to reduce risk of other respiratory infections. Obviously, they weren't due to COVID. That wasn't around then. They were due to pneumococcus, rhinovirus, influenza, a whole host of other respiratory pathogens. We did show overall a protective effect. And interestingly, that protective effect was stronger when people had lower levels of vitamin D to start with. So maybe the source for the goose is source for the gander. It might work. But it's a case unproven until we can actually get the clinical trial working. Fine. And so how do you actually get vitamin D? Like what are the sources? Yeah, so vitamin D, as you probably know, is called the sunshine vitamin. And what sets it apart from other micronutrients is that we're really designed to get it from the effect of sunshine on the skin rather than from the diet. And you can get it from eating oily fish. And indeed, oily fish get it from eating plankton. And the plankton make it from UV themselves. So the original source of vitamin D either be it from the diet or from our own skin is always going to be the action of ultraviolet B on molecules called 7D hydrocholesterol. So that's where it comes from. In the UK, because of our relatively northern latitude, the intensity of ultraviolet B in sunshine is insufficient to stimulate synthesis of vitamin D in the skin for about six months of the year. All right. And the half-life of vitamin D, that's the amount of time it takes for us, the level in our circulation to drop by 50%, is around about a month. So vitamin D status in the UK peaks around early September at the end of the summer. And for every month thereafter, it halves. So you could have a really good level of, say, 18 animals per each in September. And you're down to 40 in October, down to 20 in November. And you've got vitamin D levels in your boots right through December, January, February. And that's a good sign with when we're at highest risk of respiratory infections. I mean, there are other factors. But no, no, no, no proven link yet. Well, there is proven link from these clinical trials of other respiratory pathogens, because we know that when we supplement, we are seeing lower risks of these other respiratory infections. But you're right to say no proven link with COVID yet. No. Okay. Okay. So, okay. So sunlight, oily fish. What other sources can we, can we supplement with? And I guess the follow up push is would you recommend supplementing? Sure. So other sources start to get a bit esoteric. If you enter your shiitake mushrooms, that's quite a good source. There are certain foods that are fortified with vitamin D. People might have seen slightly sinister sounding irradiated mushrooms in supermarkets. These actually aren't irradiated with X-rays. They're irradiated with ultraviolet, which interestingly can make vitamin D in a mushroom just as effectively as it makes vitamin D in a human. Amazing. Some other foods are fortified, some flowers, some breads, some juices. But really, if you want a barn door way of making sure you're getting enough, taking a supplement is a pretty effective way to do it. The Department of Health recommends that we all take 400 units or 10 micrograms of vitamin D per day over winter and spring. What does that mean in terms of how many cans of sardines should I be eating to get that amount per day? Or should I go down to the local health food shop and get my little tablet I can dissolve in my water? Well, if you want to get all your vitamin D from oily fish, you need to do what the Scandinavians do. And you need to really eat oily fish most days of the week. Every day. I was in a hotel in Norway recently and I saw the breakfast buffet, people taking shots of cod liver oil. That's how they're doing it. You can get the cod liver oil tablets. You can get the little tablets. You can get the tablets. That's an effective way. That gives you a bit of vitamin A as well, and that gives you some omega-3s as well. So there's other goodies in cod liver oil. Obviously, it's no good if you're vegetarian or vegan. You want to avoid that. And in fact, deficiency is a lot common in people who are vegetarian or vegan because meat and fish do provide a bit of a bit of the vitamin. So in general, taking a daily supplement of 400 units as a pill is an effective way of getting it. And the vitamin D in those pills actually comes from sheep's wool. So it is suitable for vegetarians, if not vegans. If you're a vegan and you want to get your vitamin D, then you need to get it get a form of the vitamin D called vitamin D2 or ergo-calciferol. That is available in some supplements. It's a bit less effective at boosting levels, so you have to take a bit more of it. That's the one that's available in mushrooms or yeasts. But the vitamin D3 comes from sheep's wool. So it's okay for vegetarians because the sheep lives to fight another day. And that's vitamin D3. That's really the best form because it's most effective in boosting levels of vitamin D in your circulation when you take a pill. Okay. I get like a little, there's a little tablet you can get from. I think it's Holland and Barrett and they do, they brand it an immunity tablet, which is interesting. And you can get it's a vitamin D, vitamin A, vitamin C in a tablet and you can just dissolve it in water, which is quite effective. Yeah. Yeah. I mean, I've got a tonal vision when it comes to micronutrients. Vitamin D is my favorite, but there's some good evidence that other ones are important, particularly zinc might be important for antiviral immunity. There's a story around vitamin C. It's quite controversial. There's a story around selenium. There are other shows in town and if you're taking something that's got a bit of some of the others, then that's good. I think the one thing that sets vitamin D apart is that it's not, even if you eat a balanced diet, you're not going to get enough of it. Things like vitamin C, et cetera, you should be able to get if you're eating enough fruit and veg. But the vitamin D is one that is quite hard to get in diet. So that's why you might want to consider taking a supplement off the shelf. Well, unless you like sardines, I love my sardines, but my wife doesn't like, doesn't love me having them every day. But the tablet's great. Can you can you overdose on vitamin D? Is there any studies done that, you know, the effects start to weigh in after a certain number? Yeah, so you can overdose. Vitamin D is what we call a fat-soluble vitamin. And the consequence of that is that it can build up in muscle and fat if you take too much of it. So you certainly shouldn't take more than 4,000 units or 100 micrograms per day. That's a maximum safe dose. That's 10 times what the government's recommending, which is 400 units or 10 micrograms. In terms of whether the effects weigh in off the more you take, I guess in the vitamin D enthusiasts world, a lot of people think that more is better. But we just did a big meta-analysis of another 30,000 people in clinical trials. It's just on the internet a couple of days ago. That showed actually that the most effective dose for reducing respiratory infections was somewhere between 400 and 1,000 units. So I don't think it's necessarily the case that more is better. I think a modest dose and what's really important is a daily dose. So taking it every day, not taking these weekly or monthly mega doses and then forgetting it the rest of the time. Little and often is the way forward. So during that night now, the summer months, would you get enough from a daily walk, I don't know, an hour of sunshine? Or do you still need to supplement right now? So it's hard to be dogmatic about how much sunshine is enough because there's so many effect modifiers in place. So many variables in the mix. It depends on the time of day, which affects the angle of the sun and the intensity of the ultraviolet. Cloud cover, how much clothes you're wearing, whether you've got a sunroof or not. All of these things can affect how much sun you need to get in our vitamin D you need. In general, during the summer, most of the UK population get enough from the sun. That's not true of everyone. It's not going to hurt if you take 400 units a day through the summer as well. But certainly taking it through the winter from between October and April makes sense because you're certainly not going to make any significant amount from the rather watery sunshine that we are blessed with during that period. Yeah, definitely. So to be safe supplement, I'm really looking forward to the results from your study as well. It sounds like you've got a lot of people. You'll end up with your 20,000 and there should be some really interesting results from that. So looking forward to that. Thank you. Thank you so much for coming on the podcast. It's been really interesting. I've wanted to speak to someone about this for a long time. I wanted you to say, you know, exercise, be healthy, and you'll be fine for fight disease. Obviously it's not so simple. But for me anyway, I've been really focusing on really good quality diet during lockdown, good exercise and good sleep. And I feel, I feel pretty, that's all I can do to make sure that I am able to fight off these things effectively. Yeah, absolutely. I hope I didn't get the impression that exercise isn't important. No, no, no. There's early signal from our study indeed that exercise is indeed protective. I hope to be able to confirm that if I come back next month when we've got the final data in. So 100% agree with you, Lewis. Lifestyle can be so important. Stopping smoking, losing a few pounds if you can, if you need to, good exercise, sleep if you can. I've got Colin Somney and myself. It's hard, you know, a lot of people are anxious and worried about what's going on and stuff. So yeah, a lot of people aren't. But I think it's just, you know, those three things, certainly cornerstone of a good, healthy life. And it's what you can control, right? And I think it's important. So thank you so much for coming on. I'm looking forward to getting you back on to hear the results. Yeah, thank you very much. Great stuff. Thanks for having me.