Wrap up - Unpacking intervention strategies for acute respiratory viruses

Speaker 1: 0:16

Welcome to ESWI Airborne. You're listening to the podcast of the European Scientific Working Group on Influenza, otherwise known as ESWI. We have a very ambitious goal for today's episode an overview of intervention strategies for dealing with respiratory viruses, including HMPV, as well as the more familiar SARS-CoV-2, rsv and flu viruses. What's the big picture for how we deal with these viruses? Here, to paint that picture for you, I'm very pleased to welcome to S-Suite Airborne Colin Russell. During this episode we're also going to hear from two very distinguished experts, professor Catherine Vial-Olivier and Dr Barbara Rath, and I was lucky enough to speak with both of them previously and get their insights on this important topic. But first the man of the moment himself, esri chair, dr Colin Russell, professor of applied evolutionary biology at the University of Amsterdam, colin's work focuses on the evolution of pathogens and the host responses that control them A deceptively simple description. Thanks a lot for joining us here today, colin.

Speaker 2: 1:30

Thank you very much, claire. It's always a pleasure to sit down with you and I agree we have an ambitious task ahead of us today.

Speaker 1: 1:37

Ambitious, but so far I've really enjoyed this series on intervention strategies. This series on intervention strategies. Some highly recommended listening in this series, folks, for a wild ride on vaccine production platforms, check out the S-Week Airborne episode on flu vaccines. This one features a very lively debate between global experts. In another episode we walk the long and winding road towards an RSV vaccine and then in another one it's testing testing. One, two, three. Sars-cov-2 is still with us and changing all the time, so be sure to get the latest on intervention for COVID-19, probably the most famous virus in the world and finally, the most important virus you've never heard of, the human metapneumovirus. I'm so pleased I can finally say that correctly, you can listen in to a discussion between the scientists who first identified the virus more than 20 years ago and how this discovery changed their lives. So there is really a lot to be said and a lot to be learned about intervention. But first, colin, in a nutshell, how would you define intervention strategies?

Speaker 2: 2:54

Gosh, that's a challenging question all by itself. Intervention can mean many things depending on the context that we're using it. So a lot of time we think about intervening when someone is already sick. But from a general health perspective, intervention starts at prevention. So ideally we stop people from getting sick in the first place. And you know, one of the best ways to do that is vaccines, and we will come back to discuss vaccines at length, because they remain the best way to keep people from getting into hospital. But you know, there are other elements to prevention too, like when you're sick, if you can stay home from work, don't go to work. It reduces transmission. If your kid is sick and you can keep them home from school, keep them home from school. That also cuts down on transmission.

Speaker 2: 3:41

And then, you know, during the pandemic we all became very familiar with the idea of masking and social distancing, and really all those things I was just mentioning are extensions of that, where we're really just trying to reduce the probability of transmission and stop people from getting sick in the first place. But let's say that that stuff hasn't worked. Let's say that someone is now sick. The next best way to make sure that people don't end up in hospital is detecting the disease early and making sure that people can be diagnosed and, if there are good drugs available, making sure that they get those drugs. However, this really requires that people seek testing early, and this is something we'll come back to later in this episode too. But diagnosis is the basis for understanding burden and it's also the basis for our capacity to intervene when somebody is already sick, and that's really where we get into the sort of treatment space. But ultimately, all of these things combine to talk about sort of basically how we approach public health for respiratory virus diseases in general.

Speaker 1: 4:40

Okay, that is really helpful because I think intervention it sounds quite dramatic, but the way you describe it there I can really understand that, even though you know, okay, some of the treatments and diagnostics can get quite complex, a lot of it is about practical and simple steps and in this series we took a different virus for each episode and so we treated intervention for each virus separately. Why do you think it's important to do that?

Speaker 2: 5:10

Some of the things that we were just talking about, particularly when we talk about non-pharmaceutical interventions and social distancing and staying home when you're sick. We know that that works for virtually all respiratory viruses, in large part because we're reducing our contact with other people and so we're reducing the probability of transmission, and in no place was this clearer than during the COVID-19 pandemic, when we basically saw seasonal flu not completely disappear, but seasonal flu became very rare during that time, largely because people were just staying home. But when we talk about why we focus on each virus separately right now, when we think about prevention in the context of vaccines, right now we only have individual vaccines for each virus and there are different groups of people who are at most risk for severe disease with each of these viruses, and so we have to target those campaigns carefully to make sure that the people who are most at risk are the ones who are most likely to get the vaccines.

Speaker 1: 6:04

So, colin, you were just talking there about how there are different high risk groups, but something I noticed during this series was that there is also an overlap with some very similar high risk groups that were mentioned. Right, we're talking about the very young, the very old, typically those with underlying conditions. So there are similarities, there are differences, and how does this feed into the design of an intervention strategy to protect people most at risk?

Speaker 2: 6:35

So when we think about how we define risk groups, you know it's really thinking about who's most likely to end up in hospital if they get infected with these viruses, and the easiest one of the viruses that we've covered in this podcast series so far is RSV.

Speaker 2: 6:52

So RSV is a risk to everyone, but the people who are most at risk for ending up in the hospital with infection with RSV are children under the age of two, which requires that we really focus a lot of attention on pregnant women and also on infants shortly after they're born, and so there are immunization strategies and vaccination strategies that we can use to target those groups, but it's really important that they are the primary recipients in the first instance.

Speaker 2: 7:20

Along those same lines, though, one of the reasons we haven't thought a lot about RSV from a historical perspective in the context of vaccination is it has taken us a long time to get to the vaccines that we have now, but we also don't really have a good understanding of burden of RSV in older adults, and that's still something that's being resolved, and now that we have a vaccine, it really does create opportunities to reduce disease there as well opportunities to reduce disease there as well when we think about flu and COVID and RSV, the flu and COVID and HMPV. The range of risk profiles there is much more heterogeneous, where both the very young and the very old and healthy adults with comorbidities all are at risk for disease there, and so we have to think more broadly about how we target those different groups and when you're thinking more broadly about them.

Speaker 1: 8:04

I mean, does this come into the idea of combining vaccines, at least in time, even if you're not actually able to make a sort of integrated vaccine, so that people don't have to keep going back to the doctor or to the pharmacy?

Speaker 2: 8:20

You know, combination vaccines raise a whole host of interesting questions. So certainly in the next couple of years we're going to start seeing combination vaccines being used, and on the one hand, that creates really important opportunities to reduce the number of clinical interactions that are required to get someone vaccinated against these viruses that we know they should be vaccinated against. At the same time, these vaccines are likely to be expensive, and so we're still going to rely very heavily on the vaccines for individual viruses as well, and so it's not like when combination vaccines come along, they're going to push out all the other vaccines. All of the other vaccines are still going to remain very valuable for a host of different reasons. But it does present an interesting opportunity, moving forwards, to think about ways that we can help increase vaccine uptake.

Speaker 1: 9:09

Thanks so much for that. Now we're going to hear from someone who has done so much in her lifetime, very distinguished career to encourage vaccine uptake and is still working extremely hard on this topic. This is Catherine Valle-Olivier, the Honorary Professor of Pediatrics at Paris Cité University, france. Catherine has been working in the vaccine field for over 30 years and for this episode, catherine came to speak to us representing the Coalition for Life Course Immunization. This is a not-for-profit network which includes public health experts and associations, academics and patients all of these people working together, bringing the message that the benefits of vaccines are an important part of daily life at all ages and stages. So let's hear this message from Catherine herself. It's a critical aspect.

Speaker 3: 10:05

When we are searching a prevention method, we are obliged to know better about who in the population we need to target first in this prevention domain. It could be the very young children, it could be pregnant women, it could be those people with chronic diseases and it could be pregnant women, it could be those people with chronic diseases and it could be just aging. And the more we go and it is one of the focus of CLCI is the continuum of measures all along your life, depending on your status.

Speaker 1: 10:42

So there was another point that I wanted to bring in from Catherine, because it really echoes what Colin was saying about the focus on RSV, focusing on pregnant women because of the danger for young children.

Speaker 3: 10:56

So let's hear what Catherine has to say about protecting pregnant women, because it has been an incredible increase of interest in immunizing pregnant women with large success, and it has to go deeper, in maternities, all kinds of maternities, in order to promote this strategy and to make young women, or less young women, understand that it's for their own benefit, the benefit of the fetus, the benefit of birth, the benefit of their newborns, and explain so. There is a very specific need for information. That is crucial if we want to add protection in the youngest infants, in the youngest infants, and it has been extremely demonstrated for the last pertussis epidemics, where suddenly we jumped from 30% to 40% coverage up to 80% coverage in the pregnant women. So I consider it's a very dynamic field and we need to make people aware that at any moment of their life they may require and benefit from any kind of immunization. But it has to be explained and we need to take time for education, for the lifelong course immunization. That's.

Speaker 1: 12:19

Catherine talking about lifelong measures, lifelong immunisation. It's really interesting the example she uses from pregnant women and obviously a time of expecting a lot of. There can be fear there could be vaccine hesitancy there and, colin, like this is essentially a non-scientific aspect but nonetheless very real the risk of vaccine fatigue and, as we're talking about this and you're saying, could there be five vaccines per year, where is the balance between what the science is telling us and what's really possible in practice, given that there are constant advancements in vaccination platform technologies?

Speaker 2: 13:07

You know it's hard to priority order these viruses in terms of oh, this one is the most serious and you really need to worry about that, but it's okay to not worry about these other ones. They are all really substantial contributors to disease burden. And so when we think about the addition of the RSV vaccine right, because for at least the last few, for decades now, we've had flu vaccines and in the last few years we've had COVID vaccines. In the last couple of years we now have RSV vaccines it seems like we're just sort of stacking them up, but what this is really is the very real march of progress, because we now have the opportunity to reduce the burden of these diseases. So part of this has to rely on education, and this is about making sure that clinicians and the people who are really on the front line nurses and pharmacists as well have good information about vaccines and they're communicating that to their patients, because these vaccines really can help to save lives.

Speaker 2: 14:11

You know we mentioned a moment ago things like combination vaccines that could reduce the number of vaccines that people are receiving and yet, for reasons that will boil down to patient preferences and doctor's views and things like that, they might not want to use all of the things that are in the combination vaccines and instead won't want to pick and choose, and those are realities that are going to be very difficult to overcome, but it's part of why we make sure that we emphasize that the most important thing is that people get vaccinated, regardless of what they're getting vaccinated with. So if it's several individual vaccines or combination vaccines, regardless of the platform, the most important thing is that we still end up with needles in arms.

Speaker 1: 14:53

Now we're going to hear from Barbara Rath. Barbara is a paediatrician and infectious disease specialist with decades of experience in clinical trials, public health and virology. One of her many accomplishments is that she is a co-founder of the Vaccine Safety Initiative. This is an international think tank focused on new avenues for the individualized treatment, communication and prevention of infectious diseases. So when we were talking, I asked Barbara how could healthcare professionals bring more awareness to the patient on the uniqueness of the different respiratory viruses? And this is what she had to say.

Speaker 4: 15:35

So I think the steadiness of bringing up vaccination as the most important way to prevent disease, the reliability of that happening, has a huge impact which we as healthcare professionals often underestimate. We've done some work looking at how aware people are of the importance of vaccines and it looks like, for example, tetanus vaccine is in the front of many people's minds. Why? Because with any injury, you're being asked by your surgeon have you had your tetanus shot? This is not happening enough with respiratory viral illnesses and the communication gap there needs to be closed.

Speaker 1: 16:14

Comprehensive testing was also a recurring topic throughout the series. So I asked Catherine should we move towards a broader testing approach covering multiple viruses at once? And this is what she had to say.

Speaker 3: 16:28

The question you raise is fundamental, both on the practice, for the patient, for the doctor and for science. We need to know better about the circulation of viruses, the co-circulation of viruses, the co-infection of viruses and the large number of viruses. It happens that we benefit now on point-of-care testing and I would insist on the early testing, as early as possible. How long do you take to go to the doctor or be able to be tested? And this is a fundamental point because in some cases you will have different treatments and it's really useful to know that. On the scientific aspect, the more we know about viruses, the better it is how?

Speaker 1: 17:14

about antiviral treatments? What are the main barriers preventing more antiviral treatments reaching patients?

Speaker 2: 17:21

So right now we primarily have good antiviral treatments for flu and for COVID, and these drugs can be substantially effective in helping to keep people out of hospital. So they're really more about reducing severe disease than they are about preventing disease in the first place. But these drugs really only work well when they're given very early an infection, so on the order of one or two days after you start having symptoms. Now, one of the key problems with that is that if I'm sick, if I have a respiratory tract infection, I don't generally go running to my doctor. But what that means is that things are going to have to get very bad before I start to seek attention. But once things are already very bad, these drugs are no longer nowhere anywhere near as effective as they could be had.

Speaker 2: 18:11

I sought treatment early in infection, and so for otherwise healthy adults, I think there's going to be an uphill battle towards getting them to go see their doctors very quickly. But when we think about people who are in risk groups so you know we talked a lot about age earlier, but we didn't talk enough about people who are, you know, cardiology patients, for example, or people with diabetes, or people who are obese, you know these people are also at very real risk, regardless of their age, at risk of severe disease, and there needs to be much more communication to these groups about the importance of seeking diagnostics early, Because if they do seek clinical attention early and they get tested, there are then the options for them to receive drugs which can really go a long way to helping reducing the probability of them ending up in hospital. So you know in very short the main barrier is not the drugs themselves, it's not the tests, it's really a lot about the importance of seeking testing early, because without seeking testing early, we really restrict the options for the use of these drugs.

Speaker 1: 19:13

Thanks a lot for explaining that, because it's quite a subtle point. I mean, timing is everything when it comes to antiviral treatments. Another thing I wanted to know about was in relation to monoclonal antibodies, because, as I understand it, these have shown promise for RSV and COVID-19, but how are they used? In what ways do they differ from antivirals? So when I was talking with Catherine, I asked her whether these are actually considered prevention or treatment. This is what she had to say.

Speaker 3: 19:47

You have to distinguish what is a monoclonal antibody against COVID when the disease is here and the monoclonal antibody given to RSV, which is a totally preventative measure.

Speaker 3: 20:00

It is an IgG given as early as possible at birth and that will prevent bronchiolitis, which is the major phenotype of RSV. And people know about bronchiolitis. They know it personally because they have other kids or they have their neighbors or cousins or members of the family and they know about bronchiolitis. And this is the simple way we know that bronchiolitis is not always RSV, but this is the scientific part. It's roughly 70% of cases. But for people we have to translate our discourse. So not to be abstract, we have to be totally practical. The no bronchiolitis. Speak about bronchiolitis and then we will explain that the major agent is a virus and the virus we can identify and we know better about it. And now we have the capacity of a specific treatment. That is the monoclonal antibody.

Speaker 3: 21:03

And you have to explain that monoclonal antibody against RSV is not a vaccine.

Speaker 3: 21:09

And I speak for French people and you know the hesitancy plus the fatigue after COVID and people don't like very much vaccination yet and especially in flu our uptake is lower than the previous year.

Speaker 3: 21:28

But when you spoke about preventing buccalitis with a shot people accepted, and then you can explain that it's a way to give antibodies directly to the babies and he will be protected within one or two days at best, and so the experience was there and it worked well. So it's the reason why you have first to explain, at least for the healthcare professionals, that there is an immunization One is active and you contribute with your immune system. One is active and you contribute with your immune system and the other is passive and you give directly antibodies here to the baby. So I don't want people anyway the public or public health professionals to be fact that monoclonal antibodies, in the mind of doctors was mainly for biotherapies in immune diseases in the adults, and this one is totally different and it had to be explained very simply, that's a very elegant example of, indeed, what she called translating our discourse from Catherine, and I wanted to bring in Barbara's experience here, because her work is directly connected with translating our discourse.

Speaker 1: 22:54

The Vaccine Safety Initiative is all about how to better reach patients reach patients, and so I asked Barbara about the best strategies in her experience that she had realised to improve education awareness for all major respiratory threats.

Speaker 4: 23:08

I think what in the general population has been very confusing and I think that's one of the things we work on with the Vaccine Safety Initiative when we talk about the communication of vaccine-preventable or soon-to-be vaccine-preventable diseases, is that we always call them flu-like illness, or the flu in the popular language. Working with translators, that actually applies to any language I've dealt with so far that there's sort of this general term in the general population that encompasses a number of very different virological and other organisms that may be the underlying cause and that makes it very difficult for people to sort out how these strategies could be built. And then we have some pathogens, some viruses for which we have both prevention and treatment options available and relatively advanced diagnostics, some of them to be used at home. For others we have nothing much or they only get detected if you have complicated diagnostics used in the hospital. Sometimes there are delays because people look for those viruses only when all the other ones have been testing negative.

Speaker 4: 24:41

Huge issue in how we communicate these respiratory viruses as we develop complex intervention strategies which usually consist of some personal protective equipment behaviors, then vaccination if available. Sometimes there are immunotherapies or immunizations available. Then you have the idea of transmission in the household, which can happen more with some than with other viruses. And then there's this whole journey of the patient, which we've been working on for the past 10 years. That needs a lot of different intervention points or I would call them decision points that determine how you will get out of this episode.

Speaker 1: 25:21

That's a very timely reminder from Barbara that there is always a person at the center of any complex intervention strategy and the experience of this person which could be you or could be me is what the patient journey is. Barbara set out for us what the ideal patient journey could and should look like and gave some best practice examples where the information is available to the person, to the patient, all the time. Let's hear from Barbara.

Speaker 4: 25:58

I think there's one very practical example where we work with people in very poor neighborhoods in the United States over the years.

Speaker 4: 26:08

You know these are clinics that look like a barbershop or a piece of a strip mall and they're usually governed by a nurse practitioner and maybe an MD in a distance.

Speaker 4: 26:18

It's a very low-key community care and we help them sort of totally revise the way they arrange their clinic so that if somebody comes to the reception desk and says I feel crammy, I have some flu-like symptoms, they were immediately taken to a separate room where there was a rapid test available for the key players, where there was a testing and also use of an app to measure how severely are you affected right now, so that by the time they saw the nurse practitioner or the healthcare professional, there was already the key data in place for a very personal, tailored conversation and consultation. That didn't take longer than it would have otherwise. It was usually faster and also the time to treatment was faster. So that's why I keep talking about exactly what Colin just said. The healthcare system has to catch up with the scientific advancements in a way that we use the tools we do have at their very best moment and their best peer group.

Speaker 1: 27:18

so to say. So you can hear from Barbara there that there's obvious, very clear practical advantages from paying more attention to the patient journey. So to wrap up what has been really quite an adventurous episode with many stops on our speaker journeys, I'm going to ask each of our speakers what's the single most important change you'd like to see in how we approach respiratory virus intervention, say, in the next five, 10 years, over the next decade? Barbara?

Speaker 4: 27:55

Example I think we, rather than just talking about rocket science right here is how can we bring these different elements together in a way that people understand what the positive PCR test means in the absence of symptoms, and how we can make sure we don't constantly defeat our own message by not bringing these elements together in a way that makes sense. When do we need testing? What do we say when we do testing before and after? When do we need testing? What do we say when we do testing before and after? When do we vaccinate? What do we say before and after? When do we treat? And what do we say before and after? And how do we close these communication loops so that somebody isn't reliant on their neighbor happening to be a physician to provide some clarity in what just happened.

Speaker 1: 28:38

Let's hear from Catherine.

Speaker 3: 28:41

I will have two major messages.

Speaker 3: 28:43

The first one is a scientific hope that we will have a mucosal impact on our immunization, because we are talking of respiratory viruses, we know they are transmissible and we need to cut the transmission. So the next decade we should work more on mucosal capacities because it's fundamental If we want to have a global impact on our population, individuals, whatever their vulnerabilities, and both the public health and we will prevent super infections and we haven't talked about that. But viruses induce infectious bacterial disease and we know to be aware of that and try to work more on this aspect. On a more pragmatic way, I would say that we need a feedback of our actions. Feedback of our actions. So we should make available not only for public health, not only for professionals, when they have to search on a specific site the results to the public every year. We should inform them of what the epidemic has been, what was the uptake, what was prevented, what we should do better for the next year, because otherwise people are too far from the results, and so the feedback for me is something extremely important.

Speaker 1: 30:21

I absolutely loved Catherine's proposal for the annual respiratory virus weather report, so I'd just like to take note of that, in case someone out there is listening and wants to do this and they need a host. I'm ready. Colin, back to you. What do you wish for in the next decade? Is it mucosal? Is it the patient journey? Is it testing? What do you long to see happen, colin?

Speaker 2: 30:48

You know, there are so many good suggestions that were just presented there, and so, on the one hand sure, I want all of that. I think I have a slightly simpler but possibly even more ambitious wish, which is that, on the one hand, it's easy to get excited about the new technological innovations that will create more opportunities for reducing severe disease so, you know, this could be better vaccines or better drugs or better ways to reduce transmission but I think what's really critical, to my mind, is that we don't lose sight of the fact that we already have effective tools right now, and in some cases we are making really good use of those tools, but in some cases, we're not more consistent and better education about the risks that all of these viruses pose and the benefits that can be derived from either being vaccinated or making sure that you seek treatment quickly if you are sick. And what I really think this boils down to on many levels is education, and so this is making sure that people who interact with patients, and that's throughout the patient journey these are doctors, it's also nurses, it's pharmacists that they have good information about the risks that these viruses pose and about the options that patients have in the context of reducing their likelihood of severe disease. And so one of the languages that I've heard used about all of this is making every interaction count. Languages that I've heard used about all of this is making every interaction count.

Speaker 2: 32:28

If you have someone sitting in front of you who you know is at risk for severe disease, just ask the simple question have you been vaccinated against flu? Have you been vaccinated against COVID? Have you been vaccinated against RSV? And at some point that can all start to sound like a lot, but yet, at the same time, a very short conversation, even lasting just a couple of minutes. And, believe me, I recognize that everyone in these positions is very busy as it is, but because of the simplicity of the intervention around just making sure that people are vaccinated in the first place and the true value that has been demonstrated for that over and over and over again, that time investment is worthwhile.

Speaker 2: 33:05

But that requires that people in these positions are really aware of both the risks and the benefits, and, on the one hand, we would hope that that's already true. On the other hand, we see that there is this need for continual need to re-inform people about all of this just because, on the one hand, we hear that the landscape is changing and yet, on the other hand, the risks have remained the same and the benefits of existing vaccines have remained the same, and so I think it's really about making sure that we make best use of the tools that we already have and making sure that everyone who is an important stakeholder in that space knows about all of them.

Speaker 1: 33:41

And that is really the last word there from SWE Chair Colin Russell. Well observed, colin, and, as Catherine also mentioned, a very dynamic space in which people's minds and public opinion, and of healthcare professionals, does change quite rapidly. So lots of food for thought there. Some take home messages Vaccines are an important part of daily life at all ages and stages.

Speaker 1: 34:12

That's life course, immunization, the patient journey. This really totally changes the perspective of interactions with the health care system and the people who work in it, along with very exciting new tools like antivirals and monoclonal antibodies in the Intervention Strategy Toolbox a magic box indeed. So thanks to our guests Colin, barbara and Catherine for their time today. A reminder, folks, that this episode you're listening to is just one of a five-part series on intervention strategies. I highly recommend that you tune in to the others in the series that tackle each of the four acute respiratory viruses separately. Stay tuned to SWE Airborne and keep getting your news, insights and up-to-date information directly from the scientists and clinicians in the SWE network, because these are the people that know the most about viruses, vaccines, intervention and a whole lot more. Until the next time, dear listeners, stay safe.

Speaker 5: 35:31

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, claire 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. © transcript Emily Beynon.