A mucosal perspective on pandemics

Clare Taylor: 0:15

Welcome all to ESWI Airborne. This is your host, Clare Taylor speaking, and this is the place to be to meet the members of ESWI, the European Scientific Working Group on Influenza. Folks, we are going viral. Today's episode is all about COVID vaccines, with ESWI member Peter Openshaw in the studio. Peter is a pulmonologist and mucosal immunologist and professor of experimental medicine at the world-renowned Imperial College in London. Welcome Peter.

Peter Openshaw: 0:45

Well, thank you so much, Clare. Thank you for that kind introduction.

Thanks a lot for taking the time to be with us today. Now, Peter, first, I am really curious what does a mucosal immunologist do?

Well, I mean, throughout the history of immunology you've rather wondered about, you know, the different sites where the immune system acts. But I think it's very clear that the main sort of battalions of the mucosal defense system are lined up on the moist surfaces of the lung and gut and genitals, and it's those surfaces which are the focus for mucosal immunologists.

What motivated you to specialise in this area and work with these battalions?

I think I was always interested in infection, from childhood actually. It was one of the things that motivated me to go into medicine and go into research is that I was fascinated by these viruses that so frequently afflicted myself and my schoolmates.

And you've worked on RSV, or respiratory syncytial virus and influenza, for quite a while now, since the mid-1980s. You've even received a Lifetime Achievement Award, the Chanak Prize in 2012. And over the time you've been active in the field, how have you seen the research challenges evolve?

I think the biggest change has been from a focus on what the virus does when it gets in and how it damages cells to the way in which the immune system responds to the virus and is a real participant in causing disease. And it's that involvement of the immune system in causing disease as well as defending against pathogens which has been my work for the past 30 years.

But how does the immune system cause disease? Does that not protect us against disease?

Yes, it does, but part of that protection is to mount a response which is sometimes described as inflammation. Inflammation is part of the defence against viruses and sometimes the inflammation just becomes too much and causes a lot of the problems that we see in terms of swelling of the mucus linings and expelling a lot of mucus and even preventing the lung from working properly as a gas-exchanging organ. So all of that inflammation is part of the host defense response.

Thanks for explaining that. Now, as I understand it, the coronavirus pandemic was not your first pandemic. In fact, you were working in an active research capacity during the influenza pandemic of 2009 to 2010. What was your role here?

Well, it was a surprise to me that we had that pandemic of swine flu in 2009. I'd actually just been funded by the Wellcome Trust to set up a centre, to direct a centre on respiratory viral infections, and we put in the grant application that if there was a pandemic, we would down tools and focus all of our attention on responding to the pandemic. So when it actually happened, it was a bit of a surprise, but we did have all the parts in place to respond and we were able to coordinate a big national study in the UK with 45 co-investigators and hundreds of research staff all studying different aspects of influenza during that pandemic, which I think really was trailblasing in terms of setting up big research cooperatives very fast to try to solve all the different aspects of a pandemic together.

That's extraordinary, the coincidence that you were ready. You were pandemic ready.

It was extremely fortunate we had, in particular, all the administrative staff that we needed to really get going, and also some very, very wonderful young researchers who were prepared to roll up their sleeves and just crack on day and night collecting all the information that we needed and all the samples we needed in order to do a comprehensive study of influenza.

And to give our listeners some idea of the scale of this project, how many people were working on it?

Well, all in all it was close on 300 people. I mean, they weren't all working on it full time, but we basically assembled a whole range of talent, all of which was brought to bear on the virology, the immunology, the epidemiology, the clinical aspects, and we all pulled together to try to make one giant jigsaw and get a complete picture of what was going on by piecing together all of that different type of science that we could muster.

That must have been a very valuable experience to have had then, when we came to 2020 and had to deal with the coronavirus pandemic. What was most useful to you?

I think the most useful thing was to understand all the things you needed to have in place in order to respond fast. It's no good assembling the best collaborative consortium in the world if you can't do it within weeks really, because pandemics won't wait. It's like trying to turn back a tide. You need everything in place very, very fast. So I think what we learned primarily was that you needed all the protocols in place, you needed all the legal agreements in place, you needed people signed up to submit patients to the consortium and you needed all the consent forms. It was all that mechanics that was necessary in order to get the samples and to bring people together into that coordinated, focused effort. And some of the people who worked with me some of the young investigators who joined the consortium back in 2009, actually went on to lay down all of those documents and to keep them ticking over in what you might call peacetime, so that we were actually prepared and ready to go within hours of hearing that there was another threatening virus on the horizon.

So you had a strong sense of the machinery that was needed and were you surprised at the outbreak of the coronavirus pandemic? Can you remember where you were and how you first heard about it?

I think what surprised me was how unconcerned some people who really should have been very concerned were at the time. I mean, we were, you know, our breath was being taken away by the threat that we could see and we knew that in the original SARS outbreak in 2002, you know that was a very near miss. It was only by a hair's breadth and a lot of effort in terms of the epidemiology and the good, sensible precautions that were put in place, that SARS was defeated. You know it spread to Canada, it was spreading person to person, it was spreading in intensive care units and it so easily could have turned into a devastating pandemic with a very high mortality. And we had seen that. We'd lived through it. We knew what coronaviruses could do and it was just surprising that some people were still saying, oh, come on, you cried wolf in 2009, it wasn't that bad. You know, we knew that this could be a really bad one.

So you may not want to name names here, Peter, but this is interesting to explore a little that not everyone was immediately alarmed at the outbreak of the pandemic. Do you have any insights to share with us on the reason for this? Is it ignorance perhaps, or fear of causing general panic? What's your, what's your take on this?

I think it's so difficult to generalise. I think people had many reasons not to want to think that this was going to be a really bad one um, including people who had worked in infectious disease for a very long time. I remember actually writing out some of the things which I thought were really scary about this and presenting this list to a friend of mine who's an infectious disease professor as we had supper together. And as he was leaving I said look, you need to read this. It looks really bad. And he smiled at me and said oh, come on, Peter, it's not going to be that bad. And he left it on the side in the restaurant. So that's a vivid memory for me. I mean, I don't think that I would particularly want to say that there were people in the political arena who didn't take it seriously. I think that, you know, once the advice was coming up from the advisory committees and being passed to those in government, they did actually take it quite seriously in that early phase and were quite responsive to the advice that they were getting. But it was difficult to respond with the swiftness and energy that you need in order to contain a virus of this contagiousness, really difficult to really get it home. Just what you needed to do in order to stop this virus spreading.

The speed of the response. Indeed, especially at the start, a critical aspect and I'm sure we can all sympathise with policymakers who find themselves confronted with a situation as the time we have lived through. Also something that happened at speed it seemed to me that the COVID-19 vaccines were developed and deployed at incredible speed. Is this unprecedented, would you say?

It is extraordinarily unprecedented. When I first came into the field of testing vaccines and helping industry to develop vaccines, we were looking at timelines of maybe 12, 15 years from concept to actual launch of a vaccine. And to be able to see the vaccines being first thought up and then developed and then launched on a mass scale in under a year was absolutely breathtaking. We didn't think that was going to happen. I remember the first report we wrote for the Academy of Medical Sciences. We were pretty dismissive of the idea that vaccines might in any way play a major part in controlling the pandemic, because we just didn't think that we could operate at that speed. And I take my hat off to those who were central to that effort because they did amazing work and I think you know I remember when I first heard the news that vaccines were achieving protective efficacies of over 90%, I just couldn't get the smile off my face for days because that was absolutely not what I'd anticipated at all.

And you can say that as an expert in your field. For me, as a an every woman or a very ordinary person, I would say I remember the joy of being getting my first vaccination and realising I could travel to see my family once again, that it was a real prospect, so an extraordinary achievement, and one that we must remember and also be grateful for. However, although I was double vaccinated, I was still briefly sick with the coronavirus several months after being vaccinated. So I must ask again, now that we have you here, how effective are the COVID-19 vaccines?

Well, I think this can take us back to the whole question about the mucosal system, mucosal immunology and why it's important. You know. What these vaccines do is they go in through the muscle in your arm and they teach your immune system generally that there's a bad thing here that needs to be recognised, namely the spike protein of the coronavirus. Now, what it doesn't tell the immune system is actually, and another thing you need to focus on the mucosal system in order to defend the surface against infection. And that's the real weakness of these vaccines is that they go into the muscle and there's no sort of label on the message to say you know, and head into the mucosal site in order to protect. So viruses can still infect the mucosal site and cause an infection and cause a degree of illness. But what these vaccines do brilliantly is they stop them spreading outside from the mucosal site into your systemic circulation. So they generate a lot of antibody in your blood but not in your mucous membranes. So you know they do work really well at stopping you from getting very sick, stopping you from needing to go on a ventilator or go in intensive care or from dying. They're really good at that, but they're not very good at stopping the virus gaining its first foothold and exploring your mucosal lining.

Indeed, and as we are moving forward, will I, will people generally continue to need booster shots of the COVID-19 vaccine?

It's difficult to know because we're in rather uncharted territory. I mean, we know that there are a number of coronaviruses which have been around for probably decades, possibly centuries, possibly millennia, which cause common colds, and we first encounter them as young children and we continue to encounter them throughout life. They cause about 15% of common colds and we don't know what would happen if you first met one of those coronaviruses as an adult, let alone as a frail elderly person. So it may be that what we need to do is to build up the sort of lifelong experience of COVID-19 and SARS-CoV-2, starting in childhood, and that then you know it will behave more like an ordinary coronavirus. We just don't know. We're rather speculating at the moment. I think it's likely that we're going to need some more booster shots. That doesn't mean to say that there's anything, you know, gone wrong with the vaccines. This is, you know, we're feeling our way and testing things out as we go, and I think, you know, the prospects for getting pretty solid immunity are actually not that bad, given the range of vaccines that we now have.

This is interesting, that this is really a new frontier, as you describe it, uncharted waters and I was wondering can you tell us there are these different variants Omicron and Delta and so on that I hear about? Are there specific vaccines against each one and are there more in development, or what's the state of play here?

Well, so it's again, it's been fascinating to watch the way in which the virus has evolved over time. We've never had these powerful molecular tools that we've been able to use to really work out just where the virus is going in evolutionary terms. And Omicron came out of what you might call left field. It was a mutant which developed from an earlier variant which had gone almost underground and which was not circulating particularly frequently, and then it suddenly came to the fore and spread very widely around the world because of its high transmissibility.

So, so far, the evolutionary steps, each little baby step or giant leap that the virus has made in evolutionary terms, has been towards being more infectious, you know, infecting more people, making more virus and hasn't been particularly adapted towards escaping the immune response. I think as immunity builds up, then the pressure on the virus will be to evolve more in terms of escaping from the immune response, in addition to being highly transmissible. But we don't know where it's going. You know Omicron, as I said, came out of left field. It could be that the next variant which arises is going to be, you know, something where we haven't expected which could be a more serious infection and which could totally evade the immune response, for all we know is so difficult to predict and you know we're really learning as we watch the virus evolve.

So a huge amount of experience gained in rapid development of the tools to deal with this situation. Of course, vaccines are not the only tool we've had. We've all learned much more about NPIs or non-pharmaceutical interventions, wearing masks, limiting social contacts, these kind of precautions. Is this something we should just forget about now?

No, I think it's something we should learn about and go forward with new information. I think maybe something we haven't touched on is just the vast amount of research that's been done on every front, focused on COVID-19 over the past two years, and there's been vast learnings about not only how to make a vaccine, but how to test a vaccine really fast when the rate of infection is quite high, and that's been a major factor in the speed at which vaccines were developed. It's not that corners were cut, it's just that it was very easy to do large scale trials. And, the same way, you know, large scale studies have now been done on very difficult interventions like mask wearing and limiting social contact, and we know that these things do actually work now and I think we need to take that learning forward and be more tolerant of wearing masks and kinder to each other in terms of not exposing each other to our viruses. When we know that we've got a viral infection, we should do all we can to not spread the infection around, because it may only be mild for us, but it could be much more serious for other people.

So do you have any numbers you can share with our listeners about how effective it is if I wear a mask if I'm infectious, or how much that protects me, or protects the people around me?

Well, it depends how you wear it. I mean, there's masks and there's masks. There's the very, very effective masks which have been developed for medical use, which are quite expensive and which do filter most of the small particles of spittle and of nasal mucus. You know that you might call spiticles and snoticles and these little particles are the size of particle that needs to be filtered. It's not that they're filtering out things the size of a virus, because the virus is associated with clumps of mucus. So that's really their function.

But they need to fit well and you see so many people who are wearing a mask under their nose, for example, or which is bunched up around their ears and obvious gaps in fit. So the mask needs to fit well, needs to be well designed and it needs to filter out these particles of mucus and spittle. So that's really what masks are doing and if they are worn properly, then they do reduce transmission by over 50% I would say. In most of the studies they are really effective and that sort of reduction is of great significance in terms of preventing transmission. You don't need to get transmission down to zero necessarily in order to drive the contagion down in society.

So a sort of harm reduction. That's what an individual can do to contain their own spiticles and snoticles, which is quite a marvellous. I must use this again. Now let's talk about what's happening at the level of the system monitoring the spread of the virus, testing, contract tracing, surveillance. Where are we at with system level interventions at the moment?

Well, I think it's another remarkable step forward that we're all now familiar with these rapid tests. These have been around for many decades. We've used them in clinical settings to try to triage patients coming in, to see whether they need to be isolated in containment rooms and stop viruses spreading in hospitals, for example. The general experience has been pretty disappointing because I think they've not been very well designed, they've not been very well used. But the huge amount of research and development that was done in producing these rapid lateral flow tests that really do tell you how much virus protein there is in your mucus, in your throat and your nose, you know it's very, very informative to have that information. But I think what you mentioned about a sort of systems approach is so important too. It's been described as layers of Swiss cheese. Each of the layers has holes in it. So you can have a layer which is vaccines, you can have a layer which is masks, you can have a layer which is keeping two meters away from people, you can have a layer which is working from home. And if you bank all those layers up, even though there are holes in each of them, the total net effect of that whole system approach is to make it very hard for the virus to spread.

I'm very curious. There's a point I'd like to pick up on. You were talking about the rapid tests and saying that we have not perhaps used them so well. Could you expand a little on that?

So, we've had these for a long time, they haven't really been optimised in the way in which they have in the past two years. And, I think, going forward it's likely that other viruses that we encounter in accident emergency departments or in GP surgeries, like influenza and respiratory syncytial virus, you know these will be worth diagnosing using a rapid test at the point of care or even self-administered in a pharmacy, because we're coming into a new era now where there are going to be specific antivirals, not only for COVID-19 but also new antivirals for influenza and for RSV. So you need to know which virus it is and you need to know quickly which of these antivirals might be the most appropriate, because antivirals only work if they're used very early, almost before the train has left the station. Once the disease develops, the train is off down the track and it's not very effective at that stage to actually do something about the virus. You need to intervene very early and these rapid tests have that great advantage of telling you within minutes whether you have a particular infection or not.

This new era, where we understand that early intervention is absolutely critical, and the body of scientific knowledge and experience that has been built up over the past two years. How do you see this translating and feeding into government policy?

Well, it now goes into the field of political negotiation and of cost appraisal. You know, is it worth doing a test in terms of the quality of life improvement that results from that test being performed? Is it worth giving an antiviral for a disease which is normally self-limiting and from which people mostly recover? Would it be better to use that money to fund something else, like hip replacements or kidney transplants? So, you know, it isn't a given that these tests will be transformative in how we manage respiratory viral infections in the future. But I think, with the cost coming down so much, it's now come into the range when it may be cost effective to test and treat specifically according to the results of these tests in the next few years.

Indeed, politics being the art of the possible. But for the researchers who are working on vaccines, is there a holy grail? Is there some kind of big objective that people are reaching for in the field?

Well, I would say that the things which we absolutely need in the field of vaccinology is to have vaccines that not only educate the immune system systemically throughout your body, from the muscle, but also direct it to the mucosal site. So mucosal vaccines that contain that information are very, very important, and that primarily means using some sort of live attenuated vector that infects the mucosa and instructs the immune system at the same time as directing it to the mucosal site. I think the other obvious holy grail is a more universal approach, for example with influenza vaccines being able to protect against different strains of influenza, including future pandemic strains and all the circulating strains, so that it's not so much of a guessing game each year what we put into the flu vaccine. So universal vaccines which have broader protective ability and, in the case of coronaviruses, maybe coronavirus vaccines that protect against coronavirus colds as well as against potential pandemic threats.

That's quite a holy grail, all right. Peter, what would you most want to see happen next in how we manage viral infections?

Well, that's a very big question, isn't it? I mean, I think what I'd really like to see is what happens in terms of ultimate health benefit if we're able to control these common viruses better. You know, we have learned a lot during the past couple of years about, you know, the post-COVID syndromes, the post-viral syndromes, the increase in diabetes, the potential effects on the central nervous system in some people, the adverse effects on the heart, on the blood vessels, on clotting. All of these, you know, unexpected, often rare, but quite severe effects of COVID have become evident. So how many of these conditions that we don't understand the cause of are going to be potentially prevented by new vaccines or new ways of controlling these common viruses and preventing these uncommon but long-term effects? I think that's going to be so fascinating and so important medically.

And so valuable to the people who are suffering from long COVID and the other effects. Peter, you've been a wonderful guest at ESWI Airborne. Thank you so much.

Well, thank you, Clare. It's been very interesting talking to you. I've really enjoyed it.

Folks, keep on tuning in to ESWI Airborne, the viral podcast series, for all the latest on pandemics, vaccination, influenza, visualising viruses and more. Direct from the members of ESWI, the European Scientific Working Group on Influenza. Until next time, dear listeners, stay safe.

Aida Bakri: 29:57

ESWI Airborne is brought to you by ESWI, the European scientific working group on influenza and other acute respiratory viruses. These episodes would not be possible without the team's efforts and we would like to extend special thanks to our ESWI secretariat, our technical and IT teams, our arts team and our host, Clare Taylor. The podcasts are recorded virtually and we thank our guests for their participation in this inspiring series. Talks are adapted to a global audience and are intended to be educational. For any specific medical questions you may have, these should be addressed to your local general practitioner. Many thanks to our sponsoring partners and thank you for listening.

A mucosal perspective on pandemics

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