RSV in Pediatrics in the Vaccine Era

Podcast Transcript

Release Date: May 22, 2024

Expiration Date: May 21, 2026

Estimated Time of Completion: 45 minutes

Frank Esper, MD

Description

Welcome to a special series by the Respiratory Exchange Addressing the Impact of RSV and Vaccine Hesitancy. In this series, we explore the efficacy of RSV vaccines and discuss preventive strategies aimed at reducing the occurrence of severe RSV respiratory illness in infants, children and older adults. 

This episode will focus on RSV in field of Pediatrics in the Vaccine Era,where our expert, Dr. Frank Esper will discuss the impact of RSV on children. He will review the burden of RSV infection in children, the history and challenges of RSV vaccine development, and the recent breakthroughs and innovations in RSV prevention. The episode will conclude with recommendations and resources for RSV prevention and surveillance.

Learning Objectives

• Describe the burden of RSV infection in children and its impact on healthcare systems.
• Review the history and challenges of RSV vaccine development, and the recent breakthroughs and innovations in RSV prevention.
• Identity the two strategies available for RSV prevention: active immunization of the expected mother and passive immunization of the newborn.

Target Audience

Geriatricians, infection disease physicians, intensivists, nurse practitioners, nurses, obstetricians/gynecologists, pediatricians, pharmacists, physician assistants, primary care physicians, pulmonologists, and other prescribing and non-prescribing providers.

Accreditation

In support of improving patient care, Cleveland Clinic Center for Continuing Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Credit Designation

• American Medical Association (AMA)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

• American Nurses Credentialing Center (ANCC)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.75 ANCC contact hours.

• American Academy of PAs (AAPA)

Cleveland Clinic Center for Continuing Education has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.75 AAPA Category 1 CME credits. PAs should only claim credit commensurate with the extent of their participation.

• Accreditation Council of Pharmacy Education (ACPE)

Cleveland Clinic Center for Continuing Education designates this knowledge-based activity for a maximum of 0.75 hours. Credit will be provided to NABP CPE Monitor within 60 days after the activity completion. Universal Activity Number List:

- Pharmacist UAN: JA0000192-0000-24-481-H06-P

• Certificate of Participation

A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

Cleveland Clinic Planning Committee for Addressing the Impact of RSV and Vaccine Hesitancy Series:

Cecile Foshee, PhD
Co-Activity Director
Director, Office of Interprofessional Learning

Steven Gordon, MD
Co-Activity Director
Chairman, Infectious Disease Department

Kaitlyn Rivard, PharmD
Co-Activity Director
Department of Pharmacy

Nichole Brown, MSN, RN, CHSE-A, PhD(c )
Nursing Institute

Neal Chaisson, MD
Department of Critical Care Medicine
Department of Pulmonary Medicine

Frank Esper, MD
Pediatric Infectious Disease
Cleveland Clinic Children’s Hospital

Debra Kangisser, PA-C
Director of Education
Physician Assistant Services

Aanchal Kapoor, MD, Med
Department of Critical Care Medicine
Department of Pulmonary Medicine

Steven Kawczak, PhD, CHCP, FACEHP
Co-Medical Director, Center for Continuing Education

Neil Mehta, MBBS, MS
Center for Technology-Enhanced Knowledge and Instruction
Associate Dean of Curricular Affairs, Cleveland Clinic Lerner College of Medicine

Anne Vanderbilt, APRN
Senior Director, Advance Nursing Practices
Center for Geriatric Medicine

Hannah Wang, MD
Director, Molecular Microbiology & Virology

Faculty

Frank Esper, MD
Pediatric Infectious Disease
Cleveland Clinic Children’s Hospital

Host

Steven Gordon, MD
Cleveland Clinic Chairman of Infectious Disease Department

Agenda

RSV in Pediatrics in the Vaccine Era

Frank Esper, MD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Nichole Brown, MSN, BSN,
Cecile M Foshee, PhD, Steven Mark Gordon, MD, Debra Kangisser, PA-C, Aanchal Kapoor, MD, Steven Kawczak, PhD, Neil Mehta, MD, and Anne Vanderbilt, APRN.

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC, AAPA, ACPE Contact Hours, OR CERTIFICATE OF PARTICIPATION:

Go to: http://cce.ccf.org/ccecme/process?site_code=main&activity_session_code=EHCE05704

to log into myCME and begin the activity evaluation and print your certificate. If you need assistance, contact the CME office at myCME@ccf.org

Acknowledgement:

The Cleveland Clinic Center for Continuing Education acknowledges an educational grant for support of this activity from ModernaTX, Inc.

Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.

PODCAST TRANSCRIPT

Dr. Raed Dweik:

Hello and welcome to the Respiratory Exchange Podcast. I'm Raed Dweik chairman of the Respiratory Institute at Cleveland Clinic. This podcast series of short, digestible episodes is intended for healthcare providers and covers topics related to respiratory health and disease. My colleagues and I will be interviewing experts about timely and timeless topics in the areas of pulmonary, critical care, sleep, infectious disease, and related disciplines. We will share information that will help you take better care of your patients today as well as the patients of tomorrow. I hope you enjoy today's episode.

Dr. Steven Gordon:

Welcome, everyone. My name is Steve Gordon, and I am Chairman of the Department of Infectious Disease at the Cleveland Clinic and I'm excited about our guest today, Dr. Frank Esper who is going to be talking with us in particular about the new RSV vaccines focusing on children and infants. I have known Frank for a while since he has been here. He is a remarkable colleague. And as he taught me way early on with my other colleague Johanna Goldfarb, kids are just not small adults. So, Frank, welcome and I'm wondering if you could tell our audience just a little bit about your background and how you got here.

Dr. Frank Esper:

It’s great to be here, Steve. Thanks a lot for having me. It’s funny, I kind of fell into respiratory viruses when I started doing my fellowship. I thought I was going to do something really interesting like pathogenesis of salmonella and E. coli but go figure. And it's funny because I started with respiratory viruses fairly early on, now, going on 20 years ago. And I really was interested in newly recognized pathogens and so that's kind of how I found myself in this is that I recognized some new viruses as PCR and molecular technologies were just coming to the forefront of diagnostics. And I was able to use those to find some new germs and I found I was just riveted by it. So, I've always had a keen interest in my research and in what I do on newly emerging and newly recognized respiratory viruses. So, I've had my hands in a bunch of different topics whether it's RSV. I was doing coronavirus research before it was cool to do coronavirus research as I tell everyone, and I have been studying a lot of these pathogens. And obviously, with the most recent COVID pandemic, we have been doing a lot of work on that as well.

Dr. Steven Gordon:

Well, thank you. And we have all benefited from your expertise in managing the pandemic and for our patients. Let us pivot now. So, I wonder if you can set the scale, when we talk about respiratory viral season, what that means to you as a pediatrician in terms of how you approach the potential onslaught of morbidity and unfortunately some mortality each season. And then we can get into things now that may be changing that curve.

Dr. Frank Esper:

If we are not just specific to a particular germ, there is a respiratory virus season that people talk about basically from the late fall to basically the early spring, but it really isn't a single respiratory virus season. In fact, when you ask what is the respiratory virus season, it depends on what respiratory virus you are talking about. The majority of them like to show up in the late fall through the winter and into the early spring. It isn't like all these viruses are jumping into the pool at the same time. It is actually a very well-choreographed movement of specific viruses happening in a very specific sequence, that has been one of the reasons why we think that there's some sort of interactions between some of these viruses that it always seems to be virus A comes before virus B, virus B before virus C. And it's well-standard even though there are minor shifts each and every year. Some seasonal variation each and every year. They always seem to follow that same pattern. But there are viruses that love to show up in the late spring. There are viruses that love to show up in the summer. But when we talk about what the respiratory virus season for most doctors and most families out there, they know that coughs and colds and flus usually start up a little bit after kids go back to school in the fall and they keep going on until the weather starts to get a little bit warm in around March and April, and then things kind of die down. But where it's really a series of multiple viruses happening not just one big viral party. So, you really have to follow these very carefully and there's some really good work being done looking at how these viruses circulate, when they circulate and how they're dancing together.

Dr. Steven Gordon:

Well, thank you for that. Frank, so as we set up now, I like to think of it as the big three although there's obviously more that can cause respiratory viruses in adults and children, but I wonder if you can walk us through the big three before we focus on the one topic today that we're going to do which is respiratory syncytial virus or RSV.

Dr. Frank Esper:

Yes. You call it the big three. I go by the big 15 in my neck of the woods. But, certainly RSV, COVID and influenza are the three viruses that seem to be associated with most significant morbidity and mortality in children and in adults. Not to belittle those spunky little adenoviruses and metapneumoviruses that are out there. But those three have been long associated with a lot of disease especially in compromise people who, who are at risk for getting really bad lung disease. So very, very young or very, very old people who have underlying lung problems. People who have underlying heart problems and immune problems. Those are the ones that really seem to have to bear the biggest burden. And those three also do... We are still learning our COVID, but they do seem to also all show up around the same time specifically the December through February is usually when those big three have their biggest peaks. Although, COVID can be found anywhere during the time. And even flu and RSV have little sporadic times that they circulate. In addition to that, I want to just go back to respiratory virus season. Not only does it matter about what virus you talk about, but it also depends on where you are at, because the respiratory virus season is very different down south in the tropics than they are up here north, if we call Ohio North where the respiratory virus season is very constraint to a couple of months. Whereas down in the tropics it's spread out over an 8-month period of virus circulation. So, it's also a little bit different depending on where you are at.

Dr. Steven Gordon:

Thank you and as you pointed out the astral versus the North, we generally know what's coming or try to predict what's coming by what's going on down under in terms of either selecting strains to including the vaccine or maybe a harbinger of what's coming our way.

Dr. Frank Esper:

We assume that what happens in the Southern Hemisphere is going to then switch on over to the Northern Hemisphere and sometimes that is right, sometimes it's not. We’ve gotten pretty good at predicting. Most of that prediction is based on influenza and we have been doing that for decades. We don't do as much for RSV, surprisingly. Now, that we have vaccines we might do it a little bit more but for the most part we don't really look at RSV circulation and in the types of genotypes and the types of subtypes that are going down in the Southern Hemisphere like we do with the variants of COVID and the subtypes of influenza. But that may change. We will see.

Dr. Steven Gordon:

So, I'm wondering now if we can pivot to, as a parent of a kid with a “cold.” Can you tell us is there any way to distinguish between these respiratory viruses that we talked about? And if not, then what is the typical course when you see children that get into trouble? I wonder if you can kind of lay that scenario for us.

Dr. Frank Esper:

The short answer is no. You really can't tell the difference between one virus, and another based on symptoms. There is a lot of overlap. And because of that overlap we never know. That is why we try to test, and we like to know what we're dealing with. Some viruses, the ones that we are focusing on right now are a lot of the ones that we have medicines that may help. So, we really want to know if you have flu because you might get some flu medicine that will help you get better. COVID the same way. But all these other viruses really don't have a lot of treatment options. But trying to tell the difference between influenza, RSV, COVID and all these others still has some importance to play. People want to know if you are COVID positive. We actually now, after the last three to four years, know what it means to be COVID positive. We know that we want you to stay home and although we recently changed the guidelines for how long you want to self-isolate, it was important to know if you had COVID or not. 

Influenza is also important because there is a lot of people who can get really sick from influenza disease. The difference between the two are subtle but to a lot of astute clinicians such as yourself and all these other pediatricians and family doctors that are out there, they can kind of gauge influenza. The fever is much, much higher than a lot of these other viruses. It has a lot more GI problems, a lot more vomiting, a lot more abdominal pain in influenza than it does with some other viruses.

RSV in the smallest children has a very characteristic finding of bronchiolitis where they are wheezing. Now, it is not unique to RSV. There are other viruses that do that too. Even flu can do that. But when we see a small baby wheezing, we think, "Oh, this could be RSV." And then COVID obviously can lead to a lot of lower respiratory disease, a lot more pneumonias that we have to watch out for and people can get very sick very quick, especially if they're at risk and they they're a type of person who can get very sick from a virus like that.

But one thing that I always tell my colleagues as well as the patients and the families is that there's actually really good surveillance on a lot of these viruses. And if you want to know what is going on in your neck of the woods, you can actually just go on over to Google and type NREVSS, N-R-E-V-S-S. That is the National Respiratory and Enteric Virus Surveillance System. And a lot of these viruses are out there, and you can actually see what's up at the time. So, what is going on in January versus my child is sick in November. What viruses are circulating in November right now? And you will say, "Oh my God, it's a parainfluenza. It's croup." Right? As opposed to an influenza that might be at the peak influenza season in January. And a lot of people can actually feel like okay at least now I know what's going on and I can say, "Well, the COVID is not circulating right now so I don't have to worry about that." So NREVSS is a great tool for a lot of families, and they like to know what is going on in their community.

Dr. Steven Gordon:

Thank you. Turning to RSV, you had mentioned obviously we have vaccines for flu that we can give to people over 6 months of age. You have got SARS-CoV-2 vaccines as well that can go down to very young children. But can you tell us why you are excited about the premise now of an additional armamentarium of vaccine for our youngest kids? And I wonder if you can walk us through that, Frank. And if you can also start putting your virology hat on, why is it called RSV?

Dr. Frank Esper:

Yes. RSV stands for respiratory syncytial virus which is basically is Latin for a virus that makes your cells wavy and spindly looking. It is a description of what happens when a virologist would take RSV and we put it on a plate of cells and try to make it grow. And this is what the cells look like. The cells get a very characteristic called syncytia formation where these cells kind of fuse and become spindly. And so, it was called this is a virus that causes the cells to syncytialize and that therefore the respiratory syncytial virus because it came from the respiratory tract. It was actually identified in chimpanzees first. So, they were seeing sick chimpanzees. They said, "Well, we got to figure out what's going on here obviously." And they found the virus and then they realized that this is actually a virus in children and adults as well. It was recognized in the 1950s.

I will say that the reason I am very upbeat is because as a pediatrician, we have been fighting RSV for as long as there has been pediatricians. This is a gauntlet that every pediatrician runs through, every pediatric hospital runs through each and every year. Again, very characteristically during the respiratory virus season, but specifically it was for the most part a January, February virus. And it would fill up our hospitals. We would have bed crunches because there were just too many babies coming in. The numbers for children getting hospitalized, it is the number one cause of hospitalization for infants under one year of age. Upwards around the medians around 2% of all infants. You are talking about all children, 2%. That may seem like a small percentage, but you multiply it by every child that's a lot. That 2% of children would end up being admitted to the hospital because they need oxygen, because they were struggling to breathe. Now, thankfully we would be able to support them and thankfully the majority of them will do just fine. And death from RSV in the infants was fairly rare. But they would all get it. They would all be sick, and we would have just a hospital full of children who are wheezing, who are struggling to breathe that we have to give oxygen to and trying to find staffing for it was always tough.

It is also ubiquitous so just because you are not that 2% that gets hospitalized. Nearly every child by the time that they're age two has been infected at least once with RSV. So, it is just something you can't avoid. The best thing that people were able to is delay it because two-year-olds do a heck of a lot better with RSV than two-month-olds. And the younger you are when you get the RSV, the worst the RSV disease. And we will talk a little bit about more about that, I'm sure.

It is really exciting that this is something that has been kind of one of those things where we dread it each and every year but learned helplessness almost. Like we know we are it's going to come and there is nothing we can do other than just batting down the hatches and help all these kids, but we can't prevent it. And now there is a light at the end of the tunnel that we very well might be able to prevent a lot of these children from getting hospitalized. And so, in what has happened in 2023, the year of RSV, is very exciting to me that we're going to be able to do a lot better going forward with some of the vaccinations and some of the other medications that we have.

Dr. Steven Gordon:

Well, thank you for that backdrop, because I think anyone that has had a child or a grandchild in the hospital, even under support, it is still a lot of angst, a lot of emotional stress.

Dr. Frank Esper:

It is hard to look at a baby struggling to breathe. They are flaring. They are breathing so fast. There you can see their ribs because they are using every muscle, they can to try to breathe through very small airways that are all clogged up. And that is what RSV does. RSV causes significant destruction of the airway cells, but specifically within the bronchioles which are the little breathing tubes, the windpipes of a small infant. And the smaller you are, the smaller your windpipes are. And so, the smaller those windpipes are, it's a lot easier for them to be clogged up by a virus like RSV, which then basically leads to a lot of mucus that plugs them up, leads to air trapping, leads to what's called broncoconstriction where those small air pipes get even smaller because they constrict. And it is like breathing through a straw. But even a baby at a baby's size and they do not have a lot of muscles either, that's one of the reasons why they need so much help.

And so, it's tough watching them go through this, again, knowing that I can't give you any medicine to prevent the infection, I just have to support you to get through that and that's giving a lot of oxygen, that's making sure that they don't get dehydrated because babies get dehydrated really quick. And that is one of the biggest problems that we see with a lot of these babies is that they certainly can't eat, they certainly can't drink, they are just working trying to breathe. And then in very rare circumstances, they have to go to the ICU and the ventilator has to help them until, this virus goes away.

Dr. Steven Gordon:

Well that thought obviously, I think we have a good understanding about the why. Now I am wondering about, two strategies available currently. You have got active immunization of the expected mother, or you have got a passive immunization strategy for the newborn. I wonder if you can walk us through each pathway.

Dr. Frank Esper:

Yes. So, we now have effective vaccines and it is not that we haven't tried. All right. So, here is the thing. I mean, we have known this virus since 1956 and it was so ubiquitous. It was just as ubiquitous back then as it is today, that every child was getting sick. Every pediatrician was just slammed every winter. Every hospital was slammed every winter. They said, "We need a vaccine." It was one of the first, just like measles and diphtheria and pertussis, we needed a vaccine against RSV. It was recognized early. It was one of the first vaccines. Well, an early vaccine that was developed and the first vaccine for RSV was developed no more than 10 years after it was recognized. So, in around mid '60s, 1960s.

They used a formalin-inactivated vaccine. So, they would just basically take the vaccine and kill it with formalin and then they would use that as the primer for your immune system or the baby's immune system in this case, to develop an antibody response. Because if they are vaccinated then the next time, they see the actual virus in the real world, they will already have some pre-existing immunity, and the baby won't get nearly as sick. And that is how it was drawn up on paper. And that is how it worked with other vaccines.

So why would RSV be any different? Well, because it is. And what happened was as bad a response as a vaccine could. The formalin-inactivated vaccine of the 1960s did not protect against RSV, it actually made RSV worse. And this response was called enhanced RSV disease. So, the formalin-inactivated vaccine, we looked at in the beginning studies. There were four studies that were all going into phase two, phase three of the vaccine trials. And what we found is that the infants who received the vaccine were much more likely to get hospitalized from severe disease. 80% of vaccine recipients were hospitalized after getting this vaccine and then becoming RSV infected. Then the controls which was only like 5%. And they were very sick. And actually, two infants died because of the vaccines that they received from RSV. They shut down those studies really quick when they recognize this, and they basically stymied RSV vaccine development for the next multiple decades.

We had to figure out what enhanced RSV disease is. Why, did it happen? And so much of the subsequent research was really working on what happened, how did it happen, and how to make sure it does not happen again. And so, we realized that this formal and inactivated RSV vaccine, it made some neutralizing antibodies and that is what it showed in a Petri Dish. But in a patient, those neutralizing antibodies were not very strong. They were only weakly neutralizing. In fact, did not really kill the virus very well in the patient. They did not bind very well. They fell off too easily. And in even those, that bound, in some cases potentiated the infection, allow the virus to use the antibody receptor to get inside cells and perpetuate the infection. In addition to that because of this bad antibody response from the vaccine, it led to an aberrant immune response that was TH2 dependent which means it was much more inflammatory. And this TH2 inflammatory response just made the mucus plugging and the secretions even worse within those small airways. And there was, in addition to that immune complex deposition, there was eosinophils that were invading into those airways. And eosinophils are also a very inflammatory cell. It just made the inflammation worse, made the plugging worse, the air trapping worse, the respiratory distress worse. And so, we have been extremely cautious about doing any RSV vaccines since that point in time. And it was, for that reason that we just have not had a lot of other vaccines. They've tried, but one of the things that would slow things up is that you had to also make sure that whatever vaccine that you're going to try to come up with, not only does it have any other adverse effects, but you got to make sure that it doesn't have this specific adverse effect. And that has delayed the ability for us to have a vaccine.

So fast forward to 2013 when they recognized that there is a pre-fusion form of one of the very important proteins of RSV called the fusion glycoprotein, it's actually the fusion glycoprotein that actually gives RSV its name. It is the fusion glycoprotein that actually causes the syncytia. And for the longest time we knew that, but we were working on what is called the bound form or the post-fusion form, and there is a pre-fusion form, and it turns out the pre-fusion form is head and tails better at preventing infection and disease than the post-fusion form. And once that was found we said, "Hey, we've been going down the wrong path. We've been looking at the wrong protein, or at least wrong protein confirmation and now we have a much better one." But because of that, now we have a good vaccine. There was also a good recognition about adults that all adults are not just big children, and that they are very sick from RSV too. And it is a lot easier to enroll adults in clinical trials than it is children. Children have a much more protections associated with them on clinical trials. It is harder to convince parents to enroll their child and you have this problem of enhanced RSV act disease that doesn't occur in adults.

So, it made sense from a business sense really to say let's make a vaccine against adults and that is what happened over the last 10 years. They said, "Let's make a good vaccine first and then we can see whether or not this vaccine will help children. And we have a better protein to work on it against. And we don't have to worry about enhanced respiratory disease." Good. And that is where we stand right now with vaccines. We have a really good vaccine in adults, but we haven't forgotten about the kids. And so, we were saying, "Hey, we have a very good, very safe vaccine in adults. We can actually vaccinate pregnant mothers." And in those pregnant mothers you don't have to worry about the enhanced RSV disease, but the moms can pass all those now really good antibodies to the babies. The babies, the youngest babies, the ones who are at most risk of getting severe RSV disease. And so vaccinating moms has been something that the RSVpreF vaccine was FDA approved and shown to be safe and effective. The vaccine was 80% effective in preventing hospitalization in the newborns for the first three months of age. So, for the first three months where these kids were always coming in because they were so young, they would get so sick from RSV. 81% now reduction in how many kids got so sick that they had to get vaccinated. And by six months of age, it was up 69%. So nearly 70% even at six months of age. And so, this has been a really good vaccine, an adult vaccine, that actually prevents disease in the child. And that has been really, really good.

The second prong of this two-prong attack, all right? We now have a vaccine that we can give to moms to protect the youngest babies, but now we also know because of that pre-fusion protein. We have actually been able to say, "You know what we could do? We can make an antibody and give antibodies to babies when they are young to prevent. You know, it's basically just like giving them an immune system until they're able to make their own immune system because it's all about timing." We just have to get them through till they're big enough that they won't get so sick. All right? Again, they can make till two years of age it is a heck of a lot better than if they got sick at two months of age. So, we just need to get through that two-month to one year timing. And we have actually been doing this for several decades with an antibody that we used for very at-risk babies, and it did work, but it was against the wrong protein again. It was the post-fusion protein. Again, we could do so much better with the pre-fusion protein and boy, did we. And so, this pre-fusion protein has shown that it would actually prevent hospitalization in three-fourths of all kids and 90% of all, prevent 90% of all the ICU admissions. So, it prevents hospitalizations, it prevents ICU admissions, even prevents a lot of just showing up for disease too, if we just give them these antibodies. And this was really embraced by the National Institutes of Health. It was really embraced by the Centers for Disease Control, and they brought it on the pediatric vaccine schedule. So that the insurance companies would cover it and they would be able to be covered by Medicaid. And so, they did things really well so that we can get all children this antibody to prevent RSV disease and it is available for all children who are born during or right before the RSV season, that it can prevent that disease. You give it any time before eight months of age but usually you can give it before one week of age and a lot of times we try to do it right before one week. So, your first visit to the pediatrician after the baby is born is one where you can actually get this antibody to protect that baby for the next season plus. And it has been a very, very good. We just had a report from MMWR, real world experience with this immunization and those antibodies protected 90% of hospitalizations in the real world. It was fantastic. We as pediatricians no longer have to run this gauntlet every winter. With this type of response, it is going to be a lot less. And as a pediatrician a lot less work means everyone is doing better.

Dr. Steven Gordon:

As you said I think if we put this in a patient centered outcome, decreased medically attended colds or prevention, it is huge in the hospitalizations and then some of the deaths that still occur from RSV. If we play this back a little bit, the question is who won't get the vaccine or is there not an indication? You mentioned the caveat about respiratory viral season and then you also entered this whole thing saying, "Well, um ... you know, that's kind of a moving target as well."

Dr. Frank Esper:

It is. It is.

Dr. Steven Gordon:

So, I guess to put it the other way, is there a child that you would look at that wouldn't be a candidate either if the mom got vaccinated in the third trimester or a newborn?

Dr. Frank Esper:

At some point in time the answer should be every child. Every child should get some. All right? We don't want any child left out. The problem right now is there's a couple of things, but right now it is supply. Supply is one of the biggest things. The RSV antibody that we give to babies has only just been approved and they are still trying to ramp up production. But the response from families and response from mothers has been extremely positive, and to this point the most recent data from February up to 40% of eligible infants have received this antibody. That's really good for something that only started four or five months ago and has only been going up. It's not just who received it, but a lot of families have said when it becomes available, I am definitely going to do it. It's only a very small percentage that said no, I don't trust this, and this is a bad thing. Very small percentage of US families feel that way. The vast majority of people are like, "Yes, protect my baby." Because a lot of families know what a really sick kid looks like. And if you can avoid it, it's not much of a thought.

The vaccine in moms is also going up. And a vaccine in moms is somewhere in the 20 to 25% range. So that is a little bit slower, but absolutely we are seeing a lot of movement with that. And because of the supply, the Centers for Disease Control said, "Well, we want one or the other, so to speak." If the mom got the vaccine before two weeks before delivery, then you probably don't need the antibodies. But remember, that protection is only until six months, right? And the monoclonal antibody you can treat up to eight months. So, there is a little two-month wiggle room that if you really feel that this patient will benefit from it, you might get both. But supply being what it is right now, if mom was vaccinated over two weeks before, you don't need the immunization. But if mom didn't get the vaccine and or you were born early, you can get these antibodies within one week of coming home and that will help.

We try to gauge when the RSV season is. The problem is that while I told you that everything was a well-defined machine for these viruses that was before COVID and COVID kind of knocked these viruses off their routine. And the poster child to that was RSV. RSV, which was normally a January, February virus got pushed all the way to August one year after COVID. And it is slowly moving back to its traditional set point. So, it's a little harder for us to gauge, if it's between September to March we say you are in the RSV season and we would be giving you those antibodies.

Dr. Steven Gordon:

You know, some of our listeners, Frank, I think if we can talk about the safety signal, this appears to be a very safe vaccine especially when we're talking about the monoclonal antibody, maybe some injection sight tenderness here or there.

Dr. Frank Esper:

Yes. I mean, there is a very small amount that would have an adverse event from the monoclonal antibodies, OK?. And that is just basically redness, a little swelling that you would get because you got injected. Most people would say, "Well, duh? That's what you would expect after you get stuck with a needle." So, the babies will have a little bit of extra crying and things, but those are very routine. True serious adverse events in the baby are very rare.

We were extremely cautious in the mom vaccinations, who would also basically have a little bit of swelling and redness and things like that. And sometimes they would have a little bit of a fever too. We did also note that if a mom got this vaccine early in the pregnancy, wasn't statistically significant, we saw higher numbers of premature delivery and maternal high blood pressure. And while it wasn't significant, we said, "You know what, we're just going to be extra cautious here." And we found a very safe zone between 32 weeks and 36, 37 weeks of your pregnancy. So right at the end, right at the tail end of the pregnancy when the baby is almost ready to come out on term. We would give the vaccine at that point in time and very small problems with deliveries and things like that afterwards. So, as it stands right now, we are vaccinating the moms at the very end of their pregnancy and really not seeing a lot of significant side effects.

I would say the biggest problem, at least in my mind, is the confusion that comes from having a baby who gets an immunization and a mom who gets a vaccination. And to most of the people out there, immunization and vaccination are basically interchangeable words, but that is not true. The babies are getting an antibody. The moms are getting a protein vaccine that develops an antibody. And as you can imagine and the CDCs have said, "You know, we've mistakenly given a vaccine to a baby who should have gotten antibodies and we've mistakenly given antibodies to a mom who should have gotten vaccine." And you have to be extra cautious about that. And there is two vaccines for adults and only one of them should be given to mom, but sometimes the second one was mistakenly given to mom. So, we have to do a lot of clerical double-checking to make sure everyone is getting the right medication. This is what happens when you have three new RSV interventions that happen in the same year. I mean, we need them. We so need them, but we also have to make sure that we're doing the right thing.

Dr. Steven Gordon:

That's been a great overview. With our last topic, which is related, I think most infectious disease people would rate vaccines as probably the greatest public health benefit back to generating vaccines and more coming out. But one of the things I think we all were educated within the pandemic was the concept of vaccine hesitancy, and I'm wondering what lessons you learned or how you talk to parents or families about vaccines in general, not just about the RSV vaccine. In trying to use persuasion and motivational interviewing as opposed to maybe in the past where it was more, "Dr. Frank says this and there it goes."

Dr. Frank Esper:

Dr. Frank said this, and it goes. It certainly doesn't happen in my house. That's for sure. But the vaccines were such a boon back in the '50s and '60s, all right? And you have to understand that we saw so many children die from measles, and we saw so many children die from diphtheria, and we saw so many people, so many children paralyzed from polio, and we saw so many pertussis and all these diseases that we just don't see today. I think that now that we are two to three generations away from a true direct knowledge of how bad it was, has kind of said, "Well, this is just something that's in the history books." But it's still shows how important it is. And honestly there is still plenty of areas in the world where you will see bad pertussis, bad measles, bad diphtheria, even polio. You know, areas of the world like New York that will have cases of polio showing you that a vaccine is not just one and done. But it is something that we need to always be vigorous about. We have attained a level of protection that we need to be active to keep that level of protection. And when we see more and more measles cases each year, we're seeing a lot of measles outbreaks because if we let up a little bit, if we let our foot off the gas pedal, it's going to come back. These viruses are not just going to go happily into extinction, all right? They are going to keep fighting their way back and the only one that we've ever truly vanquished was smallpox. But there is a lot of other viruses out there that are just going to keep sticking around.

So, vaccine hesitancy has been a growing problem. In fact, the World Health Organization ranks it as one of the top ten problems that faces the world from an infectious disease standpoint. And it is also a problem of misinformation and disinformation. It is a problem of lack of understanding because immunity is so hard. Most doctors can't understand the immune system. And it's basically if you think about it to a lot of people, it's almost magical. You get infected with something, or you get vaccination, something magic happens and then there is a bad outcome. And you think, well, obviously, that's what's going on. Stop that process. But it's like, that's not how it works. They don't see the proportion, the disproportionate benefit of all these vaccines to a very small amount of adverse events. And the only way to really help with the vaccine hesitancy is to have a relationship with the family. And it's not just the mom and dad. Sometimes it is the vaccine hesitancy of grandma that they are talking to mom and dad or it is the vaccine hesitancy of a friend that is talking to mom and dad and they don't have a concern except people that they know, and trust are telling them of a concern. And when we start hearing, “Oh, there's a bunch of chatter here and someone told me this and my friends, friends, friend had a problem and I'm a trusted individual to this family." They are like the best thing to do is stop and say, "If there is smoke, there might be fire”, stop. And vaccine hesitancy has grown not because people are averse to vaccines, not because they are against vaccines.

There's an extremely small percentage of people who are truly against vaccines, but they are loud and they know how to get their message out and they know that their message may not convince others to be against vaccines, but are going to be hesitant and hold back and say, "What's going on?" And that's their job. That's what getting that misinformation out is basically telling everybody to pause. But pausing means you are giving these viruses and you are giving these diseases the opportunity to come back, that's what we're seeing. And so, the best thing to do is to have that trust. The best thing to do is to talk to a pediatrician, your pediatrician, the one who knows your baby as long as your baby has been here. All right? Or your nurse practitioner. And to get out there and to talk with them and to actually give them that time because a lot of we're recognizing in pediatrics five minutes isn’t enough to see a kid. We knew that already, but we also have to really dedicate time about these vaccines. This is not just a checkbox thing. We have to make sure that we address the family's concerns because those concerns are real and they're going to be hesitant unless we are really forthright in telling you this is what's going on.

And we've also, I think, as a medical profession have been too lax in combating the disinformation. We have basically been saying, "Oh, this is just a bunch of people that we don't..." You know, there is a small number of people on the internet. Oh, it's nothing. No, it's something. And now there is also active campaigns to say, "Listen, if these people can lead to disinformation out on the internet and on the message boards. We can lead to information on that.” We have worked on getting the word out about what these vaccines are helping.” And stories about how they are helping, not the scary stories that say, "Don't do this," but the good stories that says, "Hey, this is what saved these children." And so, we are being a lot more active and not just playing catch-up anymore. And I think that's a good thing.

Dr. Steven Gordon:

Well, Frank, thanks for sharing that. I think that is so true. There are tools now for clinicians. And I like your approach, many of us adopt, by first recognizing that there is some hesitancy and stopping and with empathy and compassion being curious as to why are you potentially hesitant? Because we get that. Before anyone sticks someone in my arm or my kid's arm, I want someone to be engaged and curious about that. And then as you said, meeting patients or their families where they are, and it may not be a one and done. It may be a dialogue but keeping that opportunity open to consider as opposed to as you said, coming to a conflict that may not lead to another success in the arm but leading that bridge to decision. So, I think that is something that I have also learned in practice.

I wonder now, you have got such a great overview here and you are clearly passionate and excited. I'm wondering for the audience if there's any other book recommendation you might give to them. Not necessarily about RSV or vaccine that you have read that you might pass along to our listening audience.

Dr. Frank Esper:

You know, it is funny. There are a lot of good books out there. One by Peter Hotez is a great one! Vaccines Did Not Cause Rachel's Autism is a great discussion about coming to grips with a child who has special needs and special challenges. We always worry that when we get a bad diagnosis in our children, we as parents, "What did we do? We missed something. We did something." We feel, you know, the burden of somehow, we caused this, and the answer is no. You didn't, you didn't and it's coming to recognition with that. That's a really good book that that I enjoy. 

But with vaccinations and understanding the vaccines, I think that there is a lot of good information that's more up to date if you just stick with going to the Centers for Disease Control. If you have a question about that, you just have to type in CDC, measles vaccine. And they will give you a lot of information that is actually well written too that you can understand that it's not half Latin. It's not all science speak. It's for people to truly understand when they have no medical background to say, " What's going on? How it works? Where do we do it? Why do we do it?" I think the Centers for Disease Control has been doing a really good job in getting that out. I think again that's another lesson, I think from the pandemic that has also been, that they took out very well. Because a lot of vaccine hesitancy not just against COVID vaccine, but it kind of trickled down to other vaccines when there was a lot of hesitancy about one vaccine it's almost guilt by association. "What about these other ones that we've been using for, I don't know, six decades, you know?" And, and having great response. But there is a problem and I guess it requires consistent effort to make sure that everybody understands the importance and consistent effort that we are going to keep ourselves protected against tetanus and pertussis and all these other types of diseases that are out there.

Dr. Steven Gordon:

Well, I want to thank you, Dr. Esper who's been our guest today for his views and insight on vaccines with a particular focus on RSV vaccines in children. Again, my name is Dr. Steven Gordon, Chairman of Department of Infectious Diseases and appreciate everyone listening and wish everyone a very good day. Thank you.

Raed Dweik:

Thank you for listening to this episode of the Respiratory Exchange Podcast. For more stories and information from the Cleveland Clinic Respiratory Institute, you can follow me on Twitter @RaedDweikMD.