 And really thank you so much to Professor Kingston Mills from Trinity College Dublin for stepping in at the last minute. Kingston is a professor of experimental immunology in the School of Biochemistry and Immunology in TCD. He's head of the Centre for the Study of Immunology at the Trinity Biomedical Sciences Institute and he's the theme champion for immunology, inflammation and infection in TCD. Not content with being one of Ireland's best known and leading scientists. Kingston, a lot of you will also know him from his athletics career. He has a marathon PB of 213, says here 213.55, but we say 213. A half marathon PB of 63 minutes and he is also represented Ireland in the marathon at the 1987 World Championships in Rome. So thank you very much, Kingston. Thanks very much, Brian, for the introduction and thanks to Merck for the invitation also to Greta Hickey and Eamon Tierney who recommended me to Merck. So thanks to all of you. And also to Jerry Kearn and Jerry was running around the same time as myself and we ran together in many, many races. I actually roomed with Jerry in a couple of international competitions with Ireland. So Jerry was a great friend and also always the centre of attention and the hub of the party. And he's sadly lost and it's great that the foundation has been set up now in his memory and I wish it great success. So if you're coming to hear me and expect to hear how to run faster, I'm sorry to disappoint you. I know little about the science of running. I'm an immunologist and what I'm going to talk to you about is some of the sort of risks you like around running and but also some of the benefits in terms of issues related to immunology and infection in particular. And I think I'd start this by telling you how wonderful it is that you're runners and the benefit this is having on your health. This is some statistics that I dug out from a paper which showed the risk reduction in various diseases all mortality for people who exercise, especially who have exercised with objective measures of fitness that would include running of course. 45% reduction in risk of all case mortality, cardiovascular in particular, but also things like cancer. And type two diabetes, which is a very much a obesity related disorder and on an exponential increase globally. It is, you know, you don't see too many of these runners. So runners are much less instance of all type two diabetes than the general population. But other effects, benefits as well, including neurological, psychological wellbeing and also cognitive function. It's known that this is influenced by the anti inflammatory effect of exercise. So helping to fight infection is something I'm going to come back to. But that's the sort of the good side of exercise. And it's well known that as your, you know, exercise training volume increases, the benefit is actually greater. But it comes, there's a law of the finishing returns. So when you go past a particular level, especially for cardiovascular diseases, overtraining can result in loss of benefit of the exercise or reduced benefit of the exercise. And there's a number of reasons for this. Excessive exercise can result in cardiovascular problems, arrhythmias in particular. And even sudden cardiac deaths on syndrome have been associated with extreme exercise. So this is a cautionary note about over exercising infectious diseases. You've heard of sudden adult death syndrome and you've heard of athletes and sports people dying on the playing fields without any known cause with no underlying health condition. Sometimes these can be caused by underlying infections that haven't been diagnosed. So that is really important that if you do have an infection that you don't compete in, especially something like a marathon. Also, most of us, 60% of people in this room have a virus called Epstein-Barr virus in their circulation. It causes infectious mononucleosis or glandular fever. Mostly it doesn't cause us any problem. But if we're stressed and that stress can include working for examinations, it's very common in undergraduates leading up to exam time to get glandular fever, but also athletes. I suffered from myself from glandular fever when I was in my final year of my undergraduate and I was a runner at the time. And I tell you, for three months I really couldn't run. So exercise exacerbates chronic viral syndrome. Herpes is another one as well. The immune system is there to fight infection. And luckily we get infected, but luckily the immune system can deal with it. And these include viruses, bacteria, fungi, and not so much in iron but parasitic diseases. We've got an array of immune mechanisms, cells immune system, antibodies of the immune system that deal with these infections. So in a normal course of events, if we get infected with one of these microbes, we can deal with it if we're healthy. And exercise helps that. So exercise, frequent exercise can enhance the immune surveillance against pathogens, against disease-causing bacteria and viruses. And this is partly due to the redistribution of immune cells from the central reservoirs in the lymph nodes and the spleen into the circulation, making them into the tissues where the infections occur. So there's a reduced incidence of viral and bacterial infections or reduced effect of them in people who exercise. It also heightens your response to vaccination. And it limits the aging of the immune system or our bodies, all parts of our bodies age with time, including the immune system. But regular exercise has a huge impact on many aspects of aging, reducing aging in terms of neurological diseases in particular, but also the immune system. So it's really beneficial, the effect of exercise. But excessive exercise, and in particular, people who run marathons or ultramarathons, they very often get infections. And I know myself from the time I was a runner that at times of extreme training leading up to a competition before tapering down, I would often get sore throats and colds. And this is as a consequence of stressing the immune system and producing, and it's explained by the production of hormones, in particular cortisol, which suppresses the immune response. So overtraining and going into sort of a state of stress as a result can affect the immune system and our ability to deal with infection. So that's the sort of cautionary note. Listen to your body is the key thing to remember. I'm going to talk now about COVID, which is an area that I know a little bit about. And I think it's important for you to maybe think a bit about what has happened and also to say that it's not all over yet, and the effects of it are not all over. And that's what I want to say in the next couple of slides. First of all, a little bit about the disease. A lot of people get infected, don't have any symptoms, about 50%, in fact. But these people can transmit it. So that's one of the issues that we had when the COVID pandemic was at its peak. People didn't know they were infected. They weren't being tested and they were passing it on to others. And that resulted in the escalation of numbers of cases, et cetera. During the early stages of disease, it's not so much the case now because the Omricon and other variants that we have at the moment are not as pathogenic disease causing as the original ones. But the original ones, we had very serious symptoms of fever, fatigue, coughing, muscle aches and pains, and then severe disease. And I'll come back to this in the last slide. I want to talk about long COVID, you know, multi-organ damage, not just in the lungs where the infection occurs, but the kidneys and even the brain can be affected. And one of the big issues is you get the immune system responding to the virus is what's calling the problem. So the hyperinflammation and these what I call these cytokine storms are what can cause severe damage to the system or indeed can result in death. And 20% of people early on that were hospitalized with the early variants and 2% ended up in ICU and around 1% of these people died. But Omricon is 1% hospitalization and less than 0.2% in ICU and 0.06 have died. It's a little bit different now that was January statistics. The risks factor are aged, people over 70, underlying medical conditions. And I would include in that obesity, which is a medical condition, type 2 diabetes and cardiovascular disease. So normal healthy runners are unlikely to be affected by the severe effects of COVID-19. That's not to say there are risks which I will come back to. Just a few statistics now, we think it's all over. But this is the world map taking from the New York Times of yesterday of where we're at worldwide with COVID right now. I mean, Ireland is a pretty good place. We're at the lower level of it, still some countries in Europe, Italy, for example, Greece in particular, but it's still pretty high levels in Russia. In Australia and New Zealand, two countries that adopted a zero COVID policy, which I have to say I was always skeptical about. And they're now paying the penalty for this in that they're having a surge that they didn't have in the first two years of the pandemic. So trying to keep it out by closing the borders didn't really work. It was almost impossible to do it. North America is still raging in the US. The US has had sort of ambivalent, a very good person Tony Fauci in charge of advising government, but the measures in place weren't nearly as effective as they were in Europe or Ireland and other countries. In terms of Ireland, we're pretty low levels now. This is the number of cases, although the case numbers now don't really reflect the real case numbers PCR testing has more or less been abandoned and antigen testing, which is very effective. And I was one of the advocates for it early. But the thing is people are not reporting the tests results. So these levels are probably a little bit higher, but the bottom line is we're in pretty good place right now. And the debt rate, of course, is much lower. It was a severe problem early in the year, which was even more problematic than the middle of 2021. Of course, the debts occurred with the early variants, even though the numbers were smaller. And now the debt rate is still there. I mean, we can't trivialize this. There are still up to 50 people a week dying from COVID, which is extraordinary. And it sort of seems to be forgotten about. Currently in hospital, we have quite low numbers, about 200. A lot of these are people who are admitted with other indications and then get tested when they go into hospital. And so they're what are called incidental cases of COVID-19. And it's around 200 to 300 at the moment. The number in ICU is also pretty small now. I think it's around 20 people in ICU throughout the country. So the problem, the acute problem we had is at least for now resolved. But look at the age profile of those who are infected. You see that in terms of case numbers, it's the middle age group between 15 and 44. Are the dominant numbers of cases? This is cumulative throughout the whole pandemic in Ireland. If you look at the number of hospitalized, it's very much due to the end at the older end. So over 65, over 75 are the dominant ones. But I point out to you that 2,000 people between the ages of 15 and 24 were hospitalized in Ireland. So it is younger people are not, were not immune to getting severe disease. So it's not just the older people. In terms of deaths, it very much was in the older cohort. But having said that, there were 100 people between the ages of 25 and 44 that died from COVID-19 in Ireland, which is quite extraordinary. What has changed everything is the emergence of these variants. So we originally had the Wuhan strain and then we had the Alpha strain and then the Delta strain, Omicron and then sublinages of Omicron, BA2, BA4 and BA5. Right now the dominant strain is BA5. This is very distinct from even from Omicron and incredibly different from Delta. And also there is no resemblance to Alpha. This is a very variable virus, much more variable than influenza. The good news is that these variants are less pathogenic. This is natural selection. They're more transmissible. And the upper respiratory tract infection is dominant over the lower respiratory tract. And that is natural selection where a virus is surviving that can transmit more effectively, but doesn't kill its host. A good pathogen doesn't want to kill its host because then it can survive longer to transmit to the next host. So this variant now, one of the big issues with even though it's less pathogenic is that the vaccines don't work as well against it. This is the some statistics from the US and I think Qatar show it's a little bit out of date now, but it can give you the general picture. So these are unvaccinated people, the number of cases compared with vaccinated. So you can see the benefits of vaccination, but it's still a significant number of people that are vaccinated are getting infected. But if you look at deaths, the unvaccinated make up the vast majority of people that have died from COVID-19, but those that have a vaccinated very few have died from the infection. One of the problems because of the change of the virus is that the effectiveness of the vaccines is dropping off. So this was the effectiveness against Delta over time. This is months after vaccination. Even after two doses with against Delta is pretty good against Omicron. It's not great. So bottom line here is the vaccines are good at preventing deaths and serious illness, but not at preventing disease infection. And what is happening now is that the two major companies that are leading the vaccine market, Moderna and Pfizer, have a new strain of the vaccine in regulatory approval at the moment. And it's already approved in the UK and expect to be approved in Europe in the coming weeks. And that will be available. I don't know when Ireland will get its share of the allocation, but if you're going to get a booster, this is really what I would recommend. So I'm just going to finish on this because this is a particularly important for athletes and runners. 30 to 70% of people with COVID report symptoms of between 12 and 24 weeks. Now that was largely on statistics based on pre Omicron. It might be quite as high as that with Omicron because this is a very mild infection in most people, especially younger people. In terms of exercise after COVID, this is just taken from the UCLA website and the advice is that people should wait at least two weeks after the cessation of symptoms before they start exercising again. And I think that's very, very, very good advice. I wouldn't go out and run the day your symptoms if you have COVID disappear. COVID pneumonia is a big issue and this occurs in some people. You can see that the red spots on this long are areas of inflammation caused usually by secondary bacterial infections that occur in some people that get COVID-19. In terms of long COVID, the instances are reckoned to be about 10%. So 10% of all people who get COVID-19 have longer term symptoms. In Ireland, the statistics from the HSC in January put this at 100,000 people in Ireland. Now, since then, we've probably had another maybe 2.5 to 3 million people infected since January. So that estimate is a serious underestimate. It's probably excess of a quarter of a million. The main symptoms of long COVID are fatigue, weakness, tiredness, 60% of people showing this, shortness of breath, muscle aches, all the sort of things you don't want to hear about if you're a runner because if you run with those symptoms, you're going to exacerbate them. More severe complications including cardiac dysrhythmias, heart attacks, pneumonia, and reduced lung function. It's not clear what's the cause of long COVID. There is tissue damage from the residual infection. Actually, the immune response against the virus may be partly responsible causing excess and prolonged chronic inflammation. In terms of treatments, treatments for COVID that work very effectively and we only found this out sort of into the middle of the first year of the epidemic was simple cork of steroids, dexamethasone, antitrombotic agents are very good in severe COVID. These are not indicative of people with long COVID and there's no real specific treatment for long COVID other than rest, unfortunately, and managing the symptoms. Indications for runners, excessive exercise may exacerbate the symptoms of long COVID, but slowly introduced mild exercise can be beneficial. So the real take home message from my talk and I'm going to finish now is that exercise but listen to your body and if you have infection, wait for it to recover before you start exercising again. Thanks very much. Thanks very much, Kingston. I think we may have time for a couple of questions. If there are any, I know, I know I have one. Just, I mean, I'm in the age category that's allowed get the third booster or is it the second booster? I can't remember what one we're on now. So I was almost first in queue, but it seems like we have a lot of booster fatigue at the moment. Is that possibly related to what you're showing about the fact that it may? Yeah, I have to be very careful answering this question because I put my foot on it with the HSC a few times already, but I'll battle on anyway. So personally, I've had two vaccines and then a booster and I've had COVID. So I'm well immune and I didn't get a second booster. I'm going to wait until the new vaccine is available to get my second booster and I'm not saying that's advice for everybody. If you're over 65, you should certainly get the fourth booster because the second booster, the fourth dose, because it will reduce your risks of getting a very severe disease or hospitalisation, but it won't stop you getting infected. Whereas the new vaccine is a good chance it will stop you getting infected. Okay, great. Thank you very much. Another question here. You'll have to shout. That was a fantastic lecture. Thank you. You mentioned about going back to the health effects and running. There's a co-optic thing going on in excess of running. Is that what you're suggesting? I'm afraid so, yeah, and I'm no expert on this now, but I think when I was a runner, I was obsessed with training and I couldn't bear to miss a day. I thought it was going to have detrimental effects on my performance. Looking back now, if I'd taken more rest days, I think I would have been a pressure performer. So that's not really answering your question, but it's all about listening to the body. And if you're tired before you start going out and doing your running, you shouldn't be running. I know all of us that are, well, I'm not a runner anymore. I haven't run for years. I cycle these days. But I know that when I was running, if I was tired before I started my run, I knew there was something wrong. So this is not very scientific answer. I'm sure the scientists will find a better way of answering it, but listen to the body. If you're tired and you're exhausted before you start your run, you shouldn't be running. Thank you. I think that's what you always say to us, Murt. Thank you very much. Thank you.