Activity Transcript

William Schaffner, MD: Hi, everyone. I'm Dr William Schaffner. I'm a Professor of Preventive Medicine at the Vanderbilt University School of Medicine, and we're here to welcome you to this Medscape program entitled Respiratory Syncytial Virus: It's Not Just for Kids -- A Review of Data Clinicians Need to Know. I'm very pleased to be joined today by my colleagues. First, Dr Charles Vega, who's Clinical Professor of Family Medicine at the University of California Irvine in Orange, California. Hi, Chuck.

Charles Vega, MD: Great to be here. Thank you.

Dr Schaffner: And also joining us is my colleague and friend, Dr Ruth Carrico, who's Director of Research Operations at Norton Infectious Diseases Institute at Norton Healthcare in Louisville, Kentucky. Hi, Ruth.

Ruth Carrico, PhD, DNP, APRN: Hey, good to see you again.

Dr Schaffner: So we're all together and, over the next 30 minutes, we're going to be discussing patients at the highest risk of severe RSV disease. We'll be talking about RSV testing and management and RSV vaccines that are in development. But first, let's start with a little background on the current circumstances regarding RSV.

First thing we should note is that many of us, when we went to medical school, were taught that RSV is a pediatric disease. And of course, among us, every family doctor and pediatrician knows that RSV is a cause of bronchiolitis, a respiratory disease of children, particularly young children. However, over the last, I would say, about 20 years, the data have accumulated such that we now know at the other extreme of age, RSV is also a very serious pathogen.

If you look at this pyramid on the right of your screen, you'll see that about 14,000 deaths are an estimated, year in and year out, in people age 65 and older, associated with RSV infection and over 140,000 hospitalizations easily occur each year as a consequence of RSV. For many of us, that's new information. RSV, a disease not only of children, but also particularly of older adults and, as we'll see, older adults with underlying illnesses. We'll get to that.

In this slide, you will see that the RSV season begins rather early in the winter, extends through January and February and beyond. And if you'll note, it just about duplicates the season of influenza. They are both out there, often circulating concurrently in our population and they're difficult to distinguish. Now, in the most recent couple of years, RSV has done some unusual things and that's because, obviously, of all of the COVID precautions, masking, social distancing, that we have taken. We've suppressed RSV during its normal season, January, February, and that period of time, and it's come early. And we all know that it came early this year and it's still out there as we all are recording this.

So the next thing we'd like to talk about is, of people who are older, are there people in that population at especially increased risk of RSV infection? And Chuck, why don't you start addressing that question for us?

Dr Vega: Thank you, Bill. That's a great summary looking at the epidemiology of RSV. And we are in this triple-demic phase right now where we've got influenza, RSV rates very high, and COVID-19 rates are also rising now across the United States, certainly in my area they are. And so real challenging for the clinicians, real challenging for folks who are at high risk. And so who are these individuals?

The list of folks who are at high risk for complications of RSV is not that different from what we've been experiencing with influenza and COVID-19. So if you look at those folks who have those especially chronic underlying conditions – but oftentimes, not just one condition. I see, in my practice, mostly older adults with five or seven chronic health conditions. And unfortunately, when you have obesity, plus diabetes, plus chronic kidney disease, plus COPD and heart failure, those are the ones who are at particularly high risk. Generally, these risks tend to be synergistic, tend to be additive.

I think frailty is a very important factor, as well, because it's not just about mortality, you did a really nice job of sharing that sobering statistic regarding mortality of RSV among older adults, but it's also about morbidity and loss of function. So take an individual with those seven chronic illnesses. They get RSV, they are hospitalized because they are hypoxic and they need support, but in the hospital, they get weaker, maybe they develop acute kidney injury or a nosocomial infection. And that person consequently is no longer able to live independently. These are big life changes and they could be as a result of an infection like RSV.

And then, of course we see difference in viral virulence. It's not static. And you can certainly see a difference in immune response. And I think that that's something I'll call out, that we can contribute to that problem by freely using drugs like systemic corticosteroids, for example, can have an effect on immune function. So we want to be careful with those. This is a study that looked at 756 adults retrospectively and who was admitted for RSV from a large Medicare database. You can see some of the risk factors, and I think this falls into the range of the usual suspects when we think about heart failure, when we think about history of chronic kidney disease. Those are known risk factors.

Why, in this study, weren't folks with stem cell transplant or solid organ transplant at a higher risk for complications of hospitalization with RSV? I think it has more to do with the sample size. I would certainly be very wary about someone with a transplant who gets RSV. That is a known risk for complications. Particularly nosocomial and secondary bacterial infections rates are high among those individuals. So this isn't a comprehensive list, but I do think that, if you have major dysfunction that's chronic of a major organ, generally, you're going to be at higher risk for complications of RSV.

Another thing that a lot of folks don't realize, certainly my patients don't, but I educate them about, is that these viral infections are cardiovascular risk factors. They are direct risk factors for cardiovascular events, such as heart attack, such as stroke. This is a great study by Kwong and colleagues where they patients acted as their own control. And you can see that the period where patients are in this post-infectious period strongly with influenza, but also very strongly with RSV, with a statistically significant increase in the risk of acute MI in the period following infection with RSV versus the other 50 weeks per year.

And so this is my closing argument for a lot of folks about why they should get vaccinated against influenza and, for that matter, COVID-19, because you may think this is just a bad cold to you, but if you have two stents in your coronary arteries, you have a TIA, this could be something that prevents a heart attack or a stroke by getting vaccinated. You can make an argument that the flu vaccine is actually a pretty decent cardiovascular intervention.

As I said earlier, and Bill also enumerated, age is a major risk factor. You could see that the annual incidence of RSV, these are folks who are diagnosed among hospitalized adults. We tend to under-recognize RSV among hospitalized adults traditionally, but you can see that age is, in of itself, is a major risk factor. The other thing from this slide that stands out to me is, why is Rochester having lower rates than New York City? I have a feeling that has a lot to do with the population served and probably some social determinants of health, that the folks in New York City, maybe there's higher rates of poverty, less access to care, less access to vaccinations, more chronic illnesses, and that's what puts more folks in the hospital in that denser urban environment.

And then, of course, if you have both infections, influenza plus RSV, you're more likely to be admitted, as well. So we know that co-infections do happen. You mentioned how the seasons for influenza and RSV overlap. So if, at any time, you combined RSV with another infection, whether it's another viral infection with influenza or we're thinking potentially about a bacterial infection, a super infection, such as Streptococcus pneumoniae, those patients have worse outcomes, unfortunately. Unfortunately, it's very concerning stuff, but it also speaks to a lot of my practice and, I think, a lot of different practices for primary care physicians where we have a lot of vulnerable patients, and we have to do more to protect them against infections such as RSV.

Dr Schaffner: Excellent. So Ruth, come join this conversation, and I'm going to be giving you a tough question. These are all respiratory infections that we're talking about. Is there a way, as clinicians, for us to be able to have a patient in front of us and to distinguish one respiratory viral infection from another? And how should we address diagnostic testing? Would you like to get into some of those questions with us?

Dr Carrico: Sure. Well, if only we could. If only I could look at a patient and have them describe then how they are feeling, what they are experiencing, and then be able to pinpoint the cause, but unfortunately, I can't, that we still have a variety of initially respiratory symptoms with both influenza and COVID and now RSV, where we're bringing all of that together as part of our respiratory pathogen discussion. So we may have an individual that presents with some very mild symptoms. As we begin to, or as they delay perhaps, seeking care, we begin to get into a little bit more depth with what a patient with RSV may be experiencing.

Generally, it seems that, with those upper respiratory types of symptoms, we will have individuals coming to us with symptoms that make us suspicious for RSV when they include things such as voluminous rhinorrhea, a lot of respiratory secretion, sputum production, cough, nasal congestion, and headache. They may not have some of our typical influenza symptoms with the myalgias, body aches, and so forth. So it's not very easy to discern, but some may give us a little bit more of a clue.

Certainly, we become concerned when we have individuals with fever or wheezing that take advantage, as you have said and Chuck said, now they begin to take advantage of some of those underlying medical conditions. Then we begin to see a few more problems and then it becomes particularly more important to begin to figure out exactly what we may be confronted with, what we need to do in terms of testing. Is there something then that we can treat and then that helps us perhaps with COVID or with influenza?

It may not be as much of a help with RSV because of many of our lack of treatment options, but it may help us, though, in terms of understanding how to adequately address the sequela in our individual patient that both you and Chuck mentioned then, that RSV, just like COVID and influenza are not just diseases of the respiratory tract, but they certainly then will present in many other ways. And oftentimes, there may be a decompensation or exacerbation of that underlying health condition or underlying comorbid condition.

So anytime we see a patient that experiences a change or a decompensation of a health condition, then we need to be continuing to think, respiratory pathogen. We figured that out some years back with influenza. We certainly have seen that occur with flu. Now, we've got then this consideration with RSV. We may be seeing the same thing. So I think, eventually, what we're maybe getting the hang of, a respiratory viral illness may present in many different ways. And so it is very important for us then to be thinking with our patients, what is it that we need to be doing, especially in our older adults, as you have mentioned, that we may then begin to have a patient that experiences some severe consequences of illness and may not present in some very typical ways that help us actually pinpoint.

Dr Schaffner: I hope you'll accept a friendly amendment because I would really like to reinforce the notion that you have just made that older adults with underlying illnesses may present with an exacerbation of their underlying illness, but particularly with RSV, they may not be febrile. And if they're not febrile, then we can be snookered because we won't think principally of an infection, but often in this respiratory viral season, when they present with a deterioration of their underlying illness, even though they're not febrile, we need to start thinking about particularly RSV, and flu can do that also and older adults can present without fever. So we have to be careful about that.

You didn't mention testing. Now, are you testing in your shop, generally, your colleagues? In our shop, the emphasis really is on patients who are admitted and there really is an encouragement of testing patients who are admitted to the hospital because they're seriously ill. In the ED, it's kind of plus minus. In the outpatient department, I have to tell you, not so much. Well, rapid tests for influenza, but we haven't been doing that much multiplex testing, which would include RSV, in the outpatient department. Ought we to be testing more broadly?

Dr Carrico: Well, I think your point is well made. And many of the times, it's really availability of testing that, if somebody is in the ED or they're hospitalized, then we have the ability to take advantage of that multiplex testing. I might be doing a respiratory pathogen panel that will give me a number of options, not just RSV, not just flu, not just COVID, but give me a much broader basis for consideration. On the outpatient side, then I'm very limited. And in fact, your thought process sometimes is guided by the testing that you have available.

So for example, we may be thinking influenza, or influenza and COVID in the outpatient side, and then, if both of those are negative, then we think, "Okay, the two top considerations are negative," so have the person then go home, treat more just the symptoms, and we fail then to recognize what else may be a problem, whereas someone that is more acutely ill in the hospital, we have more diagnostic capabilities, then our thought process shifts a little bit. And I think that that's something that we need to think about, as a clinician and as we become better versed in how RSV may present and, as you mentioned, how we can get, unfortunately, lulled into that false sense of security and think that there isn't a problem, and absence of fever is an excellent example.

But I think that, over time, that we're learning that our index of suspicion certainly needs to be higher when we are dealing with the older adult, when we are dealing with individuals with underlying comorbid conditions. And also, and I think both you and Chuck mentioned this, that there is an element of understanding the social determinants of health and understanding that we have individuals that either haven't accessed care, don't access care, and that we may need to, again, shift our way of thinking and then understand then some of these disease states that are present, but unrecognized in our populations, particularly those of color.

Dr Schaffner: So Chuck, I would like your opinion a little bit about this. How do you test and how do you approach the diagnosis of respiratory infection in this population?

Dr Vega: I'll gladly represent the outpatient sector, where most patients are seen, of course, by far the most. So proud to be an outpatient-based clinician, but I do think that you're absolutely right, the strategy of testing, testing is most important for those who are hospitalized. The more severe your illness, the more you should get tested. I also recognize, Ruth, you're spot on with the issue around availability of resources. It's highly variable, not just from region to region, but from month to month, even in the same area.

But I do think we carry a bit of an austerity complex from COVID-19. This comes from wearing trash bags over our clothes and our scrubs, back when there was no PPE available, to people lying quite a lot to get vaccines early. And so that's just become such a part of our healthcare culture over the past couple years. And I think, if we have testing, we should use it. I'm generally pro testing, even in the outpatient setting. Why? Because we have two pathogens here. When we think about influenza and COVID-19, yes, they present very similar clinically, but we have effective treatment options for them, particularly for those individuals at high risk of complications. So we want to identify that versus RSV, where we don't really have that therapeutic option.

And I think even, if nothing else, when we think about how we might isolate and report on these illnesses where we're thinking about epidemiology and we're thinking about keeping the loved ones in the household, contacts safe, I take a different approach with RSV and flu and COVID-19. So I think it's important to know. And so I'm generally very pro-testing for those reasons.

Dr Schaffner: Great. I like that a lot. Now, here, we've talked an awful lot about this illness, this viral infection and its seriousness in this older population, but at the moment, other than supportive care, we don't have any direct therapies, nor do we have any preventive modalities. However, looking down the road a little bit, and not too far down the road, there's an awful lot of research currently going on related to RSV, therapeutics of various kinds, and really, at the forefront, vaccine studies that are ongoing. Vaccines directed at people age 65 and older, vaccines directed at women who are pregnant, whose antibodies then could get into their babies and protect the babies for a period of time, and then later on, vaccines against children also.

But for truer, these vaccines have made substantial progress. There are any number of companies that are working on vaccines of various kinds. And I think that that is an exciting development, makes it even more important for the average physician, I think, to start testing more broadly because, when every doctor starts testing and seeing how much RSV there is in their own practice, that will become even more real to them

Not to go into too much detail, but the breakthrough in vaccine technology had to do with the nature of the virus and the way it interacts with its host cell. It has a critical protein, which is analogous to the spike protein of COVID virus, which is called the fusion protein, that interlinks with the cell membrane and allows the virus to enter the cell. Now, this fusion protein is an unstable protein and, when investigators were able to actually stabilize that protein, then vaccine manufacturers were able to develop vaccines against that pre-fusion structure of the protein. The antibodies could glom onto that pre-fusion protein and prevent its insertion into the cell membrane, thus preventing infection.

So beyond the basic science, once that was established, investigators began translating that science into clinical work and phase one, two, and now phase three clinical trials of vaccines are underway. Chuck, would you like to talk a little bit about these trials?

Dr Vega: The trials that I think we'll focus on today are the ones that are most advanced because we want to maintain clinical relevance here, but it is exciting to see, across different age ranges, even in maternal cases, that there are vaccine trials underway. So we're not going to go into the details here, but the slides do detail who the trials enrolled, how they were run, and some of the outcomes they were looking at, generally looking at lower respiratory tract infection, so really looking at the complications of RSV.

So good studies that support one another. One, I think really important because we want to support particularly our older adults at high risk of complications, but two, it shows that there is a protection against getting infection in the first place associated with this vaccine product, as well.

Dr Schaffner: I just wanted to get Ruth's impression quickly. We don't want to get ahead of our skis, but how does that sound? Are you encouraged?

Dr Carrico: I am excited about seeing this because we've experienced a disease that is caused by RSV in the adult. And so to have the option of a vaccine or having a vaccine option on the horizon, I think, is exciting. Our challenges are going to be, how do we figure out what to do with that? One of our many issues that we deal with in the adult patient is trying to figure out who owns adult immunization. Our pediatricians have done a fabulous job in maintaining vaccination and vaccination schedules in children and adolescents. We need to learn from them. How are we going to do that as adults? Because now, we're just really beginning to, I think, get a little bit better at influenza and pneumococcal vaccine.

Now, to have RSV vaccine, how are we going to get this done? When are we going to get this done? How are we going to look at this? Are we going to look at this as a seasonality sort of issue? Is this going to be an annual vaccine? Is this less frequent? There's so many things that we will have to figure out from the implementation side. And then who does it? How do we make sure that it's done consistently? And then back to, how do we make sure then that all of our patients have equal opportunity for best practice care? How will we make sure that that happens? And then how to do this implementation with that same sense of urgency. When we have a vaccine that may prevent disease, may prevent serious illness and death, how do we incorporate that well into our process?

So we know that it's going to take a variety of people on our team, that it's not only going to be the clinician, it's going to be their entire team, our pharmacy colleagues, IT, that may be helping us figure out how we do this as part of a systematic approach. How do we use in decision support in our electronic medical records systems, but that it really points to the notion that vaccinology is a specialty, and how are we going to really hone those skills and then make sure that they are integrated and embedded into care across the board for our adults?

Dr Schaffner: You've given us our challenges, there's no doubt about that. So as we bring this to a close, I'd like to give each of you an opportunity to give us a summary statement. Where are we going? What's important to you? Chuck, why don't you start, please?

Dr Vega: Right. Well, I'll go back to the fact that, like you, I was taught in medical school that RSV is a disease of children. And certainly, that was reinforced. Anybody who's done pediatric wards in the months of December through March knows this really well, but it really makes its impact in terms of serious consequences, morbidity and mortality among older adults. So I'm very excited. Of course, when we think about how do we manage it, we don't have great tools in terms of antiviral treatments for RSV, but we do have some vaccines that look very promising and I hope that's on the near horizon and something we can incorporate into our armamentarium.

Dr Schaffner: Excellent. Ruth, please.

Dr Carrico: Each of you have mentioned the importance of understanding the current epidemiology, what is happening in your community, what are you seeing, and then how do you use then not only the abilities for clinical assessment, but appropriately using testing? And that is, whether or not you are a small clinic with very few resources, whether you are a larger center or part of a health system, to figure out how do we make sure then that, when we have testing abilities, that we're able to implement that across our patient population? And then what are we going to do when we decide and find out about vaccine options? What will we need to be considering on implementation and integrating that into our practice?

So a lot of take home messages, as you've mentioned, a lot of bringing home the great points that you have brought up today. Give us opportunity to think about how will this challenge the current way we are doing things and how do we look at improvements in our future and in our patient's future?

Dr Schaffner: Excellent thoughts. I would just add to all of that, the challenges and the opportunities that are before us regarding these respiratory viruses and to have, in the near-term future, the possibility of having vaccines against RSV I find very, very exciting. But translating that, even if it were in hand today, translating that into effective practice at the local level in each doctor's offices, in pharmacies, in public health clinics, that's difficult because some of that trust in public health, in prevention, in vaccines has been lost. So we'll have to work on that once again to extend the benefits of prevention to a larger and larger proportion of our population.

So on that note, Ruth, Chuck, thank you both for your great discussion and thank you all, participants, for participating in this activity. Please continue to answer the questions that follow and complete the evaluation. Thank you very much.

This transcript has not been copyedited.