This Podcast Will Kill You - Ep 111 RSV: What’s syncytial anyway?

Episode Date: January 24, 2023

We’re kicking off our sixth season in the same way we ended our fifth: with another headline-making respiratory virus. But as our listeners know, not all respiratory viruses are the same, and it’s often those differences among them that play the biggest role in their spread or the symptoms they cause. This episode, we’re exploring the virus that everyone has been talking about lately. No, not that one. Or that one. The other one. Yes, we’re talking about respiratory syncytial virus, or RSV. For many people, the recent surge in RSV infections that dominated headlines this winter may have been the first time they had heard of this viral infection or realized how deadly it could be. But for others, RSV has long inspired fear and dread. In this episode, we Erins explain why this virus deserves such notoriety, how long we’ve recognized the dangers of infection, and what hope the future may hold for novel RSV treatments or vaccines. If at any point you’ve wondered what all the fuss is about this virus or how to pronounce syncytial, then this is the episode for you! See omnystudio.com/listener for privacy information.

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HGTV is taking over the iconic Bachelor Mansion. If they thought picking a soulmate was hard, just wait until they have to pick the right shade of egg shop. Bachelor Mansion Takeover, special series Monday at 8 on HGTV. In October 2019, our family doubled in. number from three to six when our triplets were born at 35 weeks gestation. We already had our two and a half-year-old daughter Annie and then we had Isabel, Lenny and Teddy. Their weights ranged from £4.2 to £4.7 at birth. They were small but everyone agreed they were good sizes for triplets. Because they were born early, they needed some help with breathing and maintaining

their own temperatures, but all were discharged from NICU two weeks later. We had a lot of visits from community nurses to check on their health. They checked their weight and for any signs of infection. I was told a number of times to watch out for a virus called RSV, as it was a risk this time of year, especially for very young babies, and especially for those with a sibling who was attending nursery or school. I understood that we ticked a few of these risk boxes,

but I wasn't concerned. I thought we'd be okay. When Lenny was five weeks old and not yet the weight of most newborn babies, he seemed more sniffly than usual. He was drinking his milk more slowly and he had been sick a couple of times. I thought he had a cold. I thought he would get better in a few days. One morning, we woke up and I went through the usual morning routine. Lenny seemed like he was okay, but he still had a cold. So I left him to last so I could feed the others and spend a bit more time with him. But as I picked him up to feed him, I thought he looked pale.

He seemed maybe a bit colder than usual. I felt panic. I was worried. I still couldn't drive, having only had a C-section weeks ago. So I phoned my husband and he came home and took us to the hospital. By the time we got there and after only a 10-minute drive, Lenny had gotten much worse. In fact, he was rushed straight through to resource And what felt like tens of staff rushed into the room to help him

He had become so sick, so quickly That they thought he could have sepsis He was tested for a number of illnesses And the swabs later came back positive for RSB By this time, Lenny had been admitted to the high dependency unit He had been put on a CPAP machine to help with his breathing It was later switched to bi-pap and he narrowly avoided being intubated after he stabilised.

He needed support with nutrition and hydration and was given a cocktail of drugs. The other two triplets were admitted to a ward overnight for observations, but were discharged the next day. We were advised to keep Isabelle and Teddy away from the hospital so they wouldn't pick up any infections. It was a heartbreaking logistical nightmare caring for our three apparently well children on our critically ill baby all at once. Lenny spent five nights in hospital,

which was amazing considering how ill he was when he got there. He recovered as quickly as he had got sick, and I felt so positive and thankful to take him home. Little did I know that we were only midnight, at this point. Less than a week later, Isabel seemed to not be drinking her milk very well. After what had happened with Lenny,

we had learned to watch out for signs that baby, were struggling to breathe, and Isabel was exhibiting a number of red flags. She was sucking in a little around her rib so that we could see the slight outline of her rib cage, and there was a little recession in the front of her neck, too. It suggested she was struggling to breathe. I took her to hospital. I was concerned, but not really worried, as she seemed nowhere near as sick as Lenny had been. But while she was being examined, she had napnea, and it was clear that she was starting to struggle. significantly with her breathing. She was admitted to the high dependency unit

where Lenny had been given oxygen support. All night long, the machines beeped endlessly and the nurse would rush over to do what she could. The following day is about deteriorated. Her tiny body struggled to breathe so much that now her entire rib cage would be visible at points. Despite all the support, her oxygen levels were too low and she went from CPAP to bi-PAP and then was moved to PICU and intubated.

The procedure was a struggle because she was so small and she was left with a bloody nose and a collapsed lung. She was so sick that I asked the doctors as much as I could bear to if I was going to lose her, and no one could give me the reassurance I wanted. Slowly she became stable on the ventilator, but she didn't improve. As the days passed, we sat beside her bedside, and the nurses took so many samples of blood from her feet to check her blood gases

that her feet looked like pincushions. Canula after cannula came out and it became harder for the doctors to find places to fit new ones. Her body convulsed as it couldn't expel the mucus from her lungs and the nurses would rush to suction it through the endotracheal tube. It hadn't made sense to me why Isabel was so much sicker than Lenny, but it transpired that Isabel had had had. ADRSV, and she'd developed bronchulitis like her brother, but she'd developed a complication, pneumonia.

Thanks to the amazing care she received at the Royal Manchester Children's Hospital, Isabel recovered and she came home in time for Christmas with her brothers and her big sister. On our last day in PICU, I remember a doctor telling me to be careful for the rest of the winter and for next winter too, and she was right. Isabel was admitted to hospital with broncholitis the following winter. but as a much stronger one-year-old. And it was not so scary this time around. She needed some help with breathing and nutrition,

but she was okay. As she started to feel better, she even began to enjoy all the attention from the lovely staff as they came into her room. Each one who came in looked right at her and said, Hello. And after she was discharged, I was putting her to bed one night. And she stood up and she looked at me and she said her first word,

Hello. I will be forever thankful to the incredible medical and nursing staff who saved my babies. Oh my gosh. What a horrifying, terrifying experience. I know. Thank you so much, Lucy, for sharing your experience with us and our listeners. It's, it's terrifying. It is. I'm so glad that everyone is now doing well. Me too. Oh, hi, I'm Aaron Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you. Welcome to season six. Season six.

Whoever would have thought that we could make it this far. You and I certainly did not think that. But it's funny, like, when we first started out, we thought, oh, we've got like two seasons maximum. We like laid out all of the topics. And then over the years, especially. thanks to listeners who have reached out and suggested things, that list just keeps getting longer and longer and longer. And now it's like, we don't see an end in sight, which is scary because

there are a lot of things that can kill you. But it's also really great because we get to talk about them all. Yeah. And we love getting to make this podcast. So thank you all again for listening. Yeah. And sticking with us for our sixth season. It's going to be a good one. It is. We've got a lot of very interesting topics planned for this next season. So you'll just have to stay tuned to see what we're going to be talking about. Right. And who knows what global pandemics will be thrown at us next that will change our order of topics, etc. Erin, please. I'm sorry. Too soon? Yes. Yes. We'll always be too soon. But we're kicking things off with a very hot topic, a very timely topic. And that is RSV.

RSV. It's huge. It is. And Erin, I hope you're going to tell me how to pronounce synstitial. Syncissial. Yep, you got it. Respiratory syncytial virus. But yeah, it's going to be a good episode.

I'm excited. Yeah. There's definitely a lot that I want to know about this virus. So I'm excited to dig in. Yeah. But first. But first. It's quarantini time.

It's quarantini time. It's quarantini time. How exciting. What are we drinking this week? We're drinking, hold your breath. Because, you know, it's a respiratory virus. We'll get into it all. Yeah, yeah.

We'll get there. And what's in Hold Your Breath, Erin? Spiced cranberry syrup, orange juice, and bourbon. Yum. It's really tasty. Yeah. We'll post the full recipe for that quarantini as well as our non-alcoholic placebo Rita on our website.

This podcast will kill you. And of course, all of our social media channels. We certainly will. On our website, I guess I do have to do the spiel because this is the beginning of the season. I don't know, I feel like I need to. We might have new people listening. Welcome. We have spiels that we do.

Yeah. Welcome to your first website spiel. If you go to this podcast will kill you.com, you can find all sorts of great resources, including the resources that we mention in every one of our episodes, including transcripts, including our bookshop.org affiliate account, our Goodreads list, links to merch, our Patreon, just so much stuff that you can find. So check it out. Also, shout out, our merch got recently revamped in the last couple of months. Shout out to our incredible artist Abigail Irvin Penner, who did all of this incredible artwork. And the merch is clutch. If you haven't got your hands on it

yet, you can. Okay, do we have any other business? I don't think. So let's get into it. Let's do it right after this break. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip. There, assemble and bake meals take about five minutes of hands-on prep.

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slash this podcast to get free shipping on your order and 365 day returns, now available in Canada too. That's QINCE.com slash this podcast to get free shipping and 365 day returns. Quince.com slash this podcast. I'm excited that we're starting out this season with RSB, especially because we ended last season with influenza. Yeah. It feels very, you know, full circle in a weird way. Yeah. So RSV, or as it's properly called, respiratory syncycial virus, it's one of the other really big name respiratory viruses that hospitals and hospital systems and many parents especially know all too well. We're recording this, and this one. We're recording this. will be released smack dab in the middle of what is typical RSV season here in the northern hemisphere, which usually goes from about November-ish until the end of February. Spoiler alerts, this year we saw a really early start to the RSV season, and I will not be surprised if it

ends up having a pretty long tail as well, so we might end up seeing cases well into the spring, but we'll get into all of that later first. what the heck is RSV. Yeah. Obviously, it's a virus. It's in the name. But specifically, it's a virus in the family pneumoviridae, which includes viruses in the genus Metanumavirus, which is another common cause of human respiratory infections, like common cold type infections.

And then RSV, which is in the genus OrthoNumovirus. So these are RNA viruses. They have an envelope, much like influenza. They have a non-segmented genome, unlike our friend influenza, which remember has multiple little chunks of RNA. Uh-huh. And just really off the bat, I want to emphasize how incredibly important of a virus RSV is. It is one of, if not the single leading cause of acute lower respiratory tract infections and hospitalizations, especially in kids underage 5 gloating. I have a question about this.

Already. I love it. Well, and maybe it's more of like a rhetorical question or just like an open discussion point. But I feel like even though I went to get an undergrad in biology and had to take classes on diseases, did grad school and stuff like that, really the first time I started hearing about RSV was when we were doing the podcast and talking about all these different viruses and stuff. And I really feel like suddenly now it's all over the news and you can't avoid it. And I know that part of that is because we're just seeing a really unusual number of cases. But is there anything else to that? Like, why do I feel like people have only started hearing about RSV now? Yeah, it's a good question.

I don't have a perfect answer for you. I can tell you, based on the epidemiological data that I've seen out of the past 10 years or so, we used to greatly underestimate RSV burden. Okay. And a lot of that was probably because we just weren't testing for it. So we weren't distinguishing RSV from any other particular respiratory infection. So when a kid or a grown adult or an older person got infected with a respiratory virus, it was like influenza or something else. And that was kind of the only distinction that was made.

So part of it might just be that we're doing better diagnostics so we can understand. just how important this individual virus is, I think that might be a big part of it. Okay. Okay. That makes sense. Yeah. But so being respiratory in nature, it's probably unsurprising to know that this is a virus transmitted mostly by respiratory droplets. So coughs, sneezes, that sort of thing. It can also survive for a really decent amount of time on surfaces, especially in colder weather. And so it can be transmitted very easily by fomites, things like door handles, crib railings that kids love to suck on, even your hands, all of those kinds of things. Toys at daycare centers, for example.

You know, I have a question about durability. Like, how long? I literally wrote, how long, Erin? Such a good question. So I don't know, largely because it depends so much on environmental factors. Okay, that makes sense. Yeah, but from the data that I have been able to gather, it's a good number of hours, like even several hours under not that great of conditions, and potentially several days under good conditions for viral survival. And what those conditions are depend on if the virus stays wet versus if it dries out.

And so it's really complicated. Yikes, though, several days is kind of terrifying. Yeah, maybe a couple of days. I shouldn't maybe say several makes it sound like a week, but like probably at least 48 hours. depending on certain conditions. Right, right. And some of this, like, complication and environmental durability helps explain, at least in part, some of the differences in seasonality that we see in different latitudes,

where in temperate regions, cold, low humidity winter months, where we're also all gathered inside and potentially spreading germs that way, tend to have much higher RSV transmission. Whereas in tropical latitudes, it tends to be the rainy season. which is obviously a lot more humid that tends to see higher transmission. So the seasonality aspect is really interesting. In general, the incubation period for RSV that I've seen most commonly reported is between four and six days. Could be a little less, could be a little more.

And then let's talk about the symptoms. Yeah. And for this, I'm kind of almost going to tell another little firsthand account here. Because I remember very vividly when my kid got his first RSV infection. And I remember what the doctor explained to us. And I just think it was such a good explanation of the course of RSV that I'm going to tell it to you now. So when my kid got RSV, he was probably three months old. He was definitely under four months because he only had one dose of pertussis vaccine.

And I was convinced that it was pertussis. Oh, God. It wasn't protestants. I made him test for it. But anyways, I remember that he definitely had a fever, but it came down with a little bit of Tylenol. He didn't seem all that miserable at first. But then he was just coughing so much, just coughing, coughing, coughing his brains out. And he was so snotty, like an epic amount of snot. And intermittently, I started hearing him wheeze. And of course, I was. was in med school at the time, so I would listen to him with my stethoscope. And I was like, he's wheezing. That seems bad. Like we should, at this point, we should go to the doctor. What do I do? I need a real doctor. So I brought him to see his doctor, and his doctor said, this is almost certainly RSV. It was like November peak. Here we go, RSV season. At the time, the doctor said he's not weasy at this moment, but I believe you that he was wheezing at home because he will probably continue to wheeze intermittently.

He's been sick now for two or three days. So here's what's going to happen. Over the next two or three days, so like days four to six of illness, he's either going to start to get better or he's going to get worse. And if he gets worse, here's what you'll see. He'll start breathing fast, a lot faster than usual. It'll look like he's working hard to breathe. What you'll see are retractions. which mean that if you take off his clothes, you'll be able to see his ribs where his belly pulls in underneath his ribs when he tries to breathe. Oh, my God. Or in the little V of his neck right above his chest, you can see it kind of sucking in as he takes in a breath. Those are called retractions.

If that starts to happen, you'll take him to the emergency room. And they will do care for him. And those are the two ways that this disease is going to go. And that's what the doctor told me. And it sounds terrifying. Yeah. And it is terrifying. But I will say that it was one of the most reassuring things to know, here's what to look out for, here's the things that are going to happen, and here's the kind of two ways that it's going to go and what to do in both scenarios. Yeah. Yeah. And it turns out that it's a really accurate description of the course of RSV. Kids especially are susceptible to RSV. Kids especially are susceptible to RAS. RSV infections and kids, especially in their first round with RSV, because this is a virus that tends to infect us over and over through the course of our lifetimes. But especially in that first year of RSV infection for a kid, they tend to get a fever. RSV is a very snotty virus. So you have a lot of mucus production. You're going to have a lot of coughing because of that mucus production.

And in kids, especially babies, they're not good at coughing yet. They just don't have the muscles and they don't have the reflex to get up gunk when they cough. So they don't produce a lot when they're coughing. And then they either get better over time or they get worse. And it's often that days four to six or so is when they might start to get worse. So this is a long disease that we're talking about. That's a long time to be watching a kid. like a hawk and wondering kind of which way it's going to go. Yeah, absolutely. Okay, question real quick.

Uh-huh. What are some of the factors that decide whether a kid is going to get better or going to get worse? Oh, we will absolutely get into it. Okay, okay. Yeah, in as much detail as I can give you. Okay. So I guess not a quick question then. But it's the, it is the important question. Yeah. So, but to talk a little bit more, about what the symptoms can look like in other age groups because what I just described is how the course of RSV tends to go in kids say age, especially zero to six months or a year, or kids who are being exposed to RSV for the first time. In older kids, it can look similar or it can look more like what RSV looks like in adults, which is just the common cold, right? So cough, runny nose, sinus congestion, sore throat.

Usually, RSV, even in adults, is a pretty snotty type of cold. So you might have quite a lot of congestion. In very, very little babies, like under six weeks old or very tiny babies that are very premature, they can actually have such little reserve when it comes to their respiratory system that they can present a little bit differently. Sometimes they might just look kind of lethargic, like they just don't really look like themselves. They have no energy. Sometimes they might just have apnea, which is when they just stop breathing entirely for a spell, which is terrifying.

Now, in elderly adults over age 65 or in adults or children with underlying lung conditions, like COPD or asthma, cystic fibrosis, things like that, you can also have a lot of, a more severe infection that can lead to something like a pneumonia, a viral pneumonia, which we've talked a lot about on this podcast. So then the question, you ask the question of who does this happen to? And before I get to that, what I want to talk about is what is actually happening in our airways. And I think once we understand that, we can understand who is at highest risk for severe infection. Okay. So what actually happens when we get infected with this virus?

As a respiratory virus, RSV is initially and primarily infecting the epithelial cells of our respiratory tract. I feel like we talk about these cells all the time. We do. We do. But let's do it again. I love it. Yeah, let's. These are the cells that are lining our nose, they're lining our throat, they're lining our airways. Part of what determines how severe of an infection you're going to have with RSV is going to be whether or not it establishes an infection in the lower respiratory tract, meaning down in our lungs. RSV seems to have an easier time doing this in either an initial infection, so you've never been exposed before you have no immunity whatsoever. that means infections in the very young, as well as in the very old or the immunocompromised. So those are the three biggest groups that we're going to see more likelihood that you'll have a severe RSV infection because it's making its way down into your lungs.

But the other part of it is that with RSV, I keep saying there's a lot of snot, right? There's a lot of mucus. that's largely because we see a huge amount of immune response, especially in the form of neutrophils, which are one of our white blood cells that often are the first to kind of rise up to try and fight off a virus, that tend to infiltrate into spaces with an RSV infection. So if this virus is infecting the small airways of our lungs, are bronchials, which are the kind of smallest of the branches of our lungs. Then you're going to have a lot of white blood cells, these neutrophils, as well as fluid and gunk

that's getting in to your lungs itself. And fluid and gunk is never good in our lungs for anyone. But for tiny babies, especially premature tiny babies, they also have tiny little. airways. So these tiny airways are even more susceptible to obstruction. And that obstruction is what causes the primary disorder that we see in severe RSV, which is called bronchialitis. So bronchialitis is this obstruction. It's the plugging up of the tiny ends of our airways, the small bronchye and what are called the terminal bronchials. This happens because of swelling, because of mucus, because our own cells are getting sluffed off and all these immune cells are coming in.

These then get plugged up and eventually collapse. And that is what also causes that wheezing sound that I mentioned, that you can hear if you listen to a kid with bronchialitis's lungs. All this gunk makes it so that it's really hard to breathe out the air that makes it into our lungs. So it's obstructing the flow. I know. It's awful. And I just want to contrast this to the other most common lower respiratory disease that we usually talk about on this podcast, and that is pneumonia, right? Pneumonia is when we have similar kind of inflammation and fluid, but instead of being in the airway like tubules, the bronchials, it's down in the alveoli, which are those grape cluster sacks where gas exchange actually happens. So it's like a different place within your lungs where the inflammation is happening.

So it leads to a different pattern of disease. In adults that end up with severe RSV, it tends to be a pneumonia. In tiny kids, those airways are so small that they get plugged up before it even makes it down to the alveoli. That's very interesting. I know. Yeah. So the end result is almost the same in a way. you're simply getting not enough oxygen in.

In a way, yeah. Yeah. But then there are other aspects, and I imagine damage to the lungs in different ways. Exactly, yeah. So now, RSV is an incredibly common infection. Nearly everyone on the planet, by adulthood, has been infected with RSV, and probably we've been infected multiple times in our life. I had no idea.

I know. Mm-hmm. I know. I think for so long it just gets brushed off as the common cold. I will admit, too, I knew how big of a deal RSV was in kids. I did not know how big of a deal it was in older adults. Yeah, same. But there are certain groups, like we alluded to, that are at much higher risk for severe illness, this bronchialitis especially than others. And I mentioned that young babies are one of these primary groups. But I want to dig down a little bit deeper. because on top of just young babies, like being infected for the first time, there's a few other risk factors that can make kids even more susceptible to severe infection. Prematurity is one of them. So being born at before 37 weeks, those kids are almost twice as likely to be hospitalized than kids who are born at term.

Kids who are born premature who also have what's called chronic lung disease of prematurity, or it used to be called broncholmonary dysplasia. It's a whole other episode. But those kids are about 14 times more likely to need hospitalization with RSV infection. And for those kids with chronic lung disease, the risk is also higher throughout infancy until about age two instead of just the first six months. And kids born with congenital heart disease also have a much higher risk of being hospitalized about three times as high as kids with no other risk factors.

And then, like I mentioned, kids who have various immunodeficiencies or underlying lung conditions. Gotcha. But because this is such a prevalent virus, when you look at absolute numbers, the majority of kids that get hospitalized are often otherwise healthy and don't have any underlying risk factors, which just goes to show you how incredibly prevalent this virus is. Like, every kid is getting infected. Erin, what is syncycia? I don't know. Yeah, I feel like I should know. I feel like we should know.

I mean, I don't know. Okay, Aaron, I googled it. Okay, good. Syncytum, which is the singular, the plural is syncycia, a single cell or cytokosmic mass containing several nuclei formed by fusion of cells or by division of nuclei. Okay, I did know that somewhere in my brain because the reason that it's called respiratory syncytial virus is because the gunk that you see in the lungs of kids postmortem who have died from RSV bronchialitis looks like that. It looks like a syncytum. Okay. So, I mean, I have in here why they called it respiratory syncytial virus, but because it produced syncytial changes.

And then I was like, Aaron will talk about syncyt so I don't have to worry about that. Nope. Okay, well, now we know. Yeah. That's actually hilarious. So what do we do to deal with this infection if kids get really sick from it? And what do we do to prevent it? I guess those are kind of two big questions. To treat it, we don't have anything specific. So the treatment for RSV, if it's a mild infection, it's supportive care at home, right? If it's hospitalization, like a severe infection, then it's using very powerful suction to suck snot out of tiny kids' faces and breathing assistance, which usually means high flow oxygen.

and if a kid is really, really sick or just really small and doesn't have the reserves to be able to keep fighting to breathe, then it's mechanical ventilation, which means intubation and a breathing machine, which has its whole own host of possible complications. Yeah. But that's really all that we have. There was an antiviral that was tried but hasn't been shown to be effective. Lots of people want to think that bronchodilators like we use for asthma, so like albuterol, think albuterol inhalers. They have no real benefit in RSV bronchialitis. Same thing with steroids. So it's really all just this supportive care, which is scary when you think about places that don't have access to high levels of oxygen at high flow or mechanical ventilation.

or hospitalization in general. Yeah. There's a lot of places like that. Yeah. And so when would you test for RSV? This is such an interesting question, Erin. It's an interesting question because there's not an easy answer on an individual level. On a public health level, it's good to know what viruses people have.

Like what viruses are circulating, what viruses are running around. and in what ratios? So from a public health perspective, it makes a lot of sense to test as many people as you can that are coming into hospital systems if you have the capacity to do that. On an individual level, whether a kid has RSV bronchialitis or bronchialitis caused by any other respiratory virus, which is possible. RSV is not the only thing that causes this same phenomenon of the plugging up of the small airways, the same way that influence is not the only thing that causes viral pneumonia, right? So on an individual level, it really doesn't change management all that much to test or to not test. And tests can be expensive. They can be hard to get. So it might

not be worth it to test an individual person for RSV. Okay. So there's not an easy answer there, But it is, it's an interesting kind of, you know, public health versus individual health versus like, does it change a doctor's or someone's management of a person who comes in with these symptoms? Right, right. Yeah. And when we don't have any specific treatments, the way that we do for, say, influenza, then, yeah, it doesn't. It doesn't really change things that much. So a lot of times people aren't getting tested, which means we are underestimating our RSV burden compared to other viruses. Yeah.

Yeah. We do have, not a vaccine, spoilers, and I'll talk more about that later, but we do have an interesting preventative treatment that is a monocotal antibody called palivizumab that we can use as prophylaxis, kind of like a vaccine in a way, for kids with certain risk factors, like the ones that I mentioned, kids who are born premature. who are under a certain age, like six months, or who maybe have congenital heart disease or chronic lung disease of prematurity. This is amazing, right? Yeah. This is something that has good evidence can reduce severe disease and reduce hospitalization in these really high-risk kids and babies. But, because there's always buts, it is incredibly expensive.

One estimate that I saw from, I believe it was the UK, was like 5,000 pounds per dose. Oh, my gosh. I know. And I didn't see numbers on how expensive it is in the U.S. More. It's cumbersome. Yeah, more. It's cumbersome because it is an injection like a vaccine, and it has to be given once a month, usually, for five months during that RSV season.

And it's imperfect. It doesn't prevent infection necessarily, but it does. reduce the risk of hospitalization. So because of all these limitations, I actually have no idea what the actual availability and access of this is, not just across the globe. I imagine the access across the globe is non-existent in a lot of places, especially if you think about not just low and middle-income countries that might not have access to an expensive drug, but also tropical latitudes where there isn't as well-defined of a season of RSV. But even in, say, rural parts of the U.S., I just don't know what access is actually like.

It's hard to know. But that does exist, which I think is really promising. And I'll talk a little bit more at the end about other things that we're trying to do in terms of prevention for this incredibly prevalent disease. Yeah. And the last thing that I just want to kind of mention, because I know someone is going to want to know about it, and it's really cool and interesting, even though I'm going to be like, I don't know the answer, is the association between RSV and asthma. Okay, so I was going to ask about this, but I was also going to ask a more open-ended question that wasn't really a question, which I know is annoying, but like it would be very interesting to look at in places with a clearly defined RSV season, birth month, and then like relationship

to asthma and other later in-life lung function or chronic lung diseases. Yeah, like if you were born where you got RSV in your first six months of life versus your later six months of life. Exactly. And your tendency to develop asthma. Oh, that's super interesting. I wonder if that study has been done. It probably has.

Yeah, I'll have to look for it because that's super interesting. But there are definitely associations between RSV infection, especially severe RSV infection in childhood, being associated with the later development of asthma or what's often called reactive airway disease in younger kids because you can't diagnose asthma until four or five years old. Oh, okay. But as of right now, we do not have a clear sense of whether kids who are genetically predisposed to the development of asthma, something about them makes them more susceptible to RSV or severe RSV infection. Mm-hmm. Or is there something about RSV infection, severe RSV infection, that either precipitates or maybe even expedites the development in asthma in kids who. who are predisposed. Ooh, that's hard to disentangle.

It's very hard, and it's super interesting, and at this point, it could kind of go either way. We know that there's an association, but we don't know in which direction it might go. I think from what I could tell, we have a little bit more data to suggest the former. So it's maybe kids who are genetically predisposed to asthma. Like, they'll probably develop asthma later in life are more likely to get a severe RSV infection versus the other way around, but it's still a really muddy picture, so we still don't know for sure. I have a question about the strains or subtypes or whatever they're called of RSV and the difference among them, and yeah, what we know about sort of how severity may change from year to year.

Yeah, the short answer is I don't have a ton of information for you on that. from what I found there's at least two major strains, RSV-A, RSVB, and then there are other subtypes within that and other clinical strains that have been identified. But in general, both of these major strains circulate A and B at the same time. A tends to be overall a little bit more prevalent and perhaps a little bit more transmissible. But from what I found, we don't have great data on strain differences when it comes to disease severity or things like that. And I think it's probably because of how much we've just underestimated RSV in general. I don't know how often even if we're testing for RSV, we're testing for strains of RSV.

Speaking of transmissibility, do we have an R not estimate for this virus? Good question. It can vary, of course. But most estimates that I saw were around three. So for a reminder for anyone, that means that for every one person who's infected with RSV, they'll go on to infect three people on average. Right. Yeah. That's RSV biology, Erin. It's a lot. It's a lot. It's scary. I can't believe how much I didn't know about it despite how prevalent it is. I know. And to use, I guess, like outdated lingo, I would say it seems like a very slept-on virus. Yeah. And I feel like I'll talk even more about that

later. But first, Aaron, tell me what we know about where the virus came from, et cetera. Okay, I'll do the best I can right after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions.

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Texting enrolls you for occurring automated text marketing messages. Message and data rates may apply or play stop, opt out. Visit ISSA online for details. Excuse me. What do you do for a living? Wait tables. You like it? Not really.

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today because RSV did what respiratory viruses do best. They spread. That's, you know, I don't know. That's the best answer I have. But that's not going to be all of the history section because that would be a pretty lousy podcast episode if I ended it there. So let's get into it a little bit, starting with how we first learned about this virus. In October of 195 at the Walter Reed Army Institute of Research in Silver Spring, Maryland, a group of 20 quote-unquote normal chimpanzees around 15 to 20 months old began showing signs of a respiratory disease, runny nose, sneezing, coughing the usual. And at first, it was just a handful of the chimpanzees, but within a few days, nearly all of them had gotten sick. As listeners of this podcast are well aware, an outbreak of an

apparently contagious disease in a population of lab animals sets off some pretty loud warning bells. And so the researchers at the Institute were very eager to find what pathogen might be responsible. They took some throat swabs from the animals and ran a bunch of tests on it. I'm not going to bore you with the details. But ultimately what they found was not a familiar old measles or polio or coxacki virus, but a new thing entirely. A virus, they named the chimpanzee cariza agent. Hmm. Not RSV.

I was really expecting that to go a different way. Yeah. The link between this virus and the observant. illness in the chimpanzees was confirmed when a few other chimpanzees got sick after being intentionally infected with the virus, and also when a lab worker got sick after unintentionally being infected. They all produced antibodies against the pathogen. Researchers Morris, Blount, and Savage published the account of this first observed epizovatic of the chimpanzee cariza agent in 1956, And in it, they didn't really hint at answering or even acknowledging the question of, like, how scared we need to be about this new pathogen.

It seems to be able to infect both chimpanzees and humans. It's a clearly contagious respiratory, you know, a scary thing, but they didn't really talk about it. But in their very last sentence, they did suggest that this agent may be a lot more widespread than just in chimpanzees at the Walter Reed instance. Oh, oh. Quote. However, a number of human beings, particularly adolescents and young adults, have antibodies in their serra directed against the Kariza agent, suggesting that these individuals have experienced infection with the new agent or one closely related to it. Very shortly after this paper was published, two more came out that showed that this virus may be a significant cause of respiratory infections, especially in certain age groups. And the authors of these studies, basically what they did was they was set out to test what pathogens they could potentially find or isolate from infants with severe lower respiratory illness. And they wanted to see, okay, what's this illness being caused by? Are there any new viruses or bacterial species that we need to worry about? And so on. And it just so happens that one of the viruses they isolated from these sick infants was indistinguishable. from the chimpanzee cariza agent.

Interesting. And the more people looked, the more they found that this virus, which was assumed to be new, may not be new at all and may actually be responsible for an incredible number of lower respiratory tract infections, particularly among infants and young children, although already adults were also seen to have antibodies against the virus and to get sick themselves,

suggesting that reinfection was not just possible but potentially common. And these authors also suggested in these papers that given the fact that chimpanzees are not the sole host, nor were likely to be the reservoir species of this virus, and they actually got it from humans, perhaps chimpanzee cariza agent was not the most fitting name, with its ability to produce sensational changes in tissue cultures, which we now know what that means, And its manifestation as a respiratory infection, maybe it should be called something along the lines of respiratory syncytrial virus. Definitely not like our most, I don't know, captivating story of how something got its name, but I like it.

It's not, but I like it. And you know what I like about it is it's like not controversial. Yeah. Like it's like, let's name this virus after what it does. What concept. Wow. Yeah. And yeah, it happened pretty soon in the late 1950s, basically.

Wow. Okay. And what followed was what we often see with the identification of a new virus. People start looking for it. They start seeing more and more of it. And then the gaps in knowledge about the virus's epidemiology, pathophysiology, symptomology, all, you know, and so on, all started to be slowly filled in. For instance, as early as 1958, 1959 or so, physicians notice that the virus could cause illness with a huge range of severity, from inapparent infection to fatal bronchialitis. They noticed that the age group with the highest infection rates and severest symptoms was infants, who also may have the highest rates of viral

shedding. They noticed that even though some infections may be milder, they all still seem to involve the lower respiratory tract, and that infections, at least in America followed this seasonal trend, which is the one that you described, Aaron, infections rising in November, December, peaking in January, February, and falling to low levels by April. Over the next decades into the 1970s and the 1980s, RSV became a very familiar name during the winter months, one of the usual suspects when somebody brought their infant or child into the doctor's office for acute respiratory symptoms, and also a huge cause of hospitalizations for young children. For instance, studies from the 1980s reported that during that decade, an estimated

100,000 children were hospitalized for RSV each year in the U.S., costing $300 million annually. Whoa. So how did this virus become so prevalent in such a short amount of time? Maybe it didn't. Yeah. Probably didn't. I think more likely it was there all along. I've tried to look into the evolutionary origins of RSV and earlier suspected outbreaks in human history,

but I didn't really have much luck. And to me, honestly, that makes sense, right? Yeah. Like, in terms of its relationship with humans throughout history, RSV doesn't cause a super distinct infection. Many other viruses can cause illness that looks a lot like RSV, and so it's kind of hard to look back retrospectively as we know. know and go, was that RSV? Was that influenza? Like, what could that have been? Right. It could have been any or all of the above. Yeah, exactly. Rhinovirus, antirovirus, adenovirus, coronavirus. Absolutely. Like, the list goes on. The list goes on. And I think the timing of its

identification in those chimpanzees probably coincided with improvements in microbiological techniques that allowed researchers to distinguish among viruses, which in previous decades had been fairly difficult. Whether or not there was an actual increase in the prevalence of the virus over the 1970s, 1980s, 1980s, or it just looked that way because people finally had the tool to determine what was making you sick, it's unclear. I did wonder, I tried to look into this, but I didn't really see anything. I wondered whether there was a connection between the rise in daycare, if there was a rise in daycare during that time, that also led to a rise in

infections. But I didn't really find any papers that had investigated that. So it's just going to remain my little personal questions for now. Yeah, our own little mystery. Yeah. Yeah. Or if how that changed, like, the timing of infection. Right. The first six months versus the first year, you know, like when, yeah, I don't know. In any case, it seems pretty likely that RSV has been around for a very long time, contributing to the rise in respiratory infections that humans have seen in colder months or in rainy months for thousands of years. On the evolutionary side of things, like I said, there's not really much info that I could find about where specifically RSV came from and when it was estimated to have first infected humans. So I decided to broaden my search a bit to

see if there had been any research on the evolutionary origins of the subfamily that RSV is part of, pneumoviride, or the family paramyxiviride. The subfamily, pneumovirone, contains viruses that are very similar to human RSV, including murine pneumovirus, canine, pneumovirus, bovine RSV, Ovine, RSV, and caprine RSV. And the parimixivirde has some very familiar names, measles, mumps, distemper, Newcastle disease. I found a paper from 2012 that I actually read for our mumps episode as well. I was like, this sounds familiar. And then I searched in my folders. And in that paper, the authors tested bat and rodent species for paramexiviruses, and they found a bunch of novel viruses in bats that seem to be relatives of RSV and humans. This doesn't mean

that RSV came from bats. Just that this bat RSV-like virus and human RSV and bovine RSV all share a common ancestor. It does, to me, present the possibility that human RSV and other human pneumoviruses or paramyxiviruses originally spilled over from a mammal species, whether that was bat or cow or rat or something entirely different. Interestingly, just a little asterisk, human RSV is more closely related to bovine RSV than to these bat or mouse RSV-like viruses. Oh.

Yeah. I wish I had more details for you and also for myself because I'm really curious to know more about the evolutionary origins of this virus. But sadly, I don't have that information. If any of you out there listening has a paper or just has some info with some details, please send it our way. I'd love to read it. And I think even more recently, they've even split RSVs, the RSVs, into a new family, a little separate from the parameda severity. So I feel like the whole phylogeny of... It's separate from paramyxivirida?

Yeah, but it's new since like 2016. Oh, this paper was 2012, yeah. Yeah, we'll probably see the phylogeny of RSV continue to change as we, you know, dig more down into the different strains and et cetera. Yeah, I mean, especially after this RSV season, I would imagine there to be a lot more research on the, so maybe in a couple of years we'll revisit. Just like with influenza. Well, that explains why I had a hard time finding.

evolutionary origins. I was like, what is this thing? Okay. Okay, but regardless of how RSV got into humans or when we first started getting sick from it, very soon after it was discovered, it became apparent what a huge problem this disease could be. And so naturally researchers and physicians began trying different methods to either treat or prevent RSV infections. Vaccination, like you mentioned, Aaron, was one route that was explored. early on and continues to be explored. But like you said, we don't have a vaccine for RSV. And I know you're going to talk a lot more about why that is and also where we stand with some of the vaccines in development today. There's also ribavirin, a synthetic nucleoside, immunoglobulin therapy,

other experimental therapies like RNA interference therapy, and so on, which I'm sure you'll talk more about some of these like potential horizons for RSV treatment. In terms of the history of RSV specifically, that's really all that I have to offer. It was first recognized relatively recently as an important respiratory infection in young children. Its role in infecting older people and people who are immunocompromise has been observed more recently. We've learned a lot about the year-to-year dynamics of the virus and circulating strains. But don't worry, I'm not just going to stop here and leave you with this super-duper record. short history section, especially for the season premiere. Like, I can't do that. Instead,

I'm going to do a mini deep dive on a topic related to not just RSV, but many other respiratory viruses and respiratory diseases. It's a life-saving therapy that you hope to never need, but are grateful for when it's there, a device whose history goes back further than I ever imagined, and one that frequently dominated headlines, especially during the first couple months of the COVID pandemic. I'm talking about the mechanical ventilator. I can't tell you how excited I am about this. Well, it's going to be a very, like, cursory history. There's more details out there that I will post papers and everything.

But it is going to be an exciting history. So I hope you like it. I can't wait. So like you said, Erin, supportive. care is really all we have at this time to treat RSV. And when cases are severe, sometimes that includes a mechanical ventilator. So I started thinking about where this amazing technology came from and how our understanding of the risks of lung injury and how breathing works has led to improvements in artificial ventilation. Our story starts in the mid-16th century with the anatomist

Andreas Veselius, whose name we may or may not have mentioned on the podcast before, I can't remember, but whose anatomical illustrations, I'm pretty certain we've posted on our social media. Got it. At this point in history, we didn't really know a whole lot about the inner workings of respiration. Basically, the writings of Galen from the second century CE describing breathing as necessary to maintain circulation and keep your heart beating, that's more or less as far as humanity had gotten in describing the purpose and mechanics of ventilation. So Vesalius had a pretty open playing field then when it came to making advances in understanding form and function, especially respiration. In his 1543 anatomy treatise dehumanic corpus, Vesalius described what we would today recognize as positive pressure ventilation.

Quote, but that life may be restored to the animal, an opening must be attempted in the trunk of the trachea, into which a tube of reed or cane should be put. You will then blow into this so that the lung may rise again and take air. How interesting. Isn't that, like, fascinated to think of that? Yeah. Of course, this wasn't Vesalius just hypothesizing about how you could perform artificial respiration. He actually experimented on animals to show this.

Yeah. Yeah. Doing a bunch of tracheotomy, it sounds like. Of course. As did Robert Hook, whose name you've definitely. heard on the podcast. He coined the term cell, made incredible advances in microscopes, was also an astronomer, architect, physiologist, basically a big deal in the sciences in the 1600s, even though he reportedly had an abrasive personality that prevented his work from being known

for a while, just a bit of, you know, seasoning on that. Yeah. In one of his many scientific ventures, Hook set his sights on testing Galen's hypothesis that the active breathing was necessary for circulation. He took a dog, made a bunch of cuts in this poor dog's chest wall and plura, and then used bellows, like the things you use to blow air into a fireplace, to create a constant flow of air into the lungs, and observed what happened when he stopped. Wow. Quote. This, as in pumping air into the airway using bellows, being continued for a pretty while, the dog lay still, as before, his eyes beating very regularly. But upon ceasing this blast, then suffering the lungs to fall and lie still,

the dog would immediately fall into dying convulsive fits. But be as soon revived again by renewing the fullness of his lungs with a constant blast of fresh air. end quote. With this gruesome experiment, Hook showed that it was indeed airflow into the lungs that was necessary for circulation and thus life. Another hundred plus years would pass

before scientists learned what oxygen was and recognized its importance in respiration, which is a whole separate and cool story that I would love to tell someday. But one unfortunate consequence of this discovery of oxygen was that mouth-to-mouth resuscitation, which had been developed by that time, it fell out of use because people believed that the air you would be exhaling into someone else's lungs

during mouth-to-mouth would not contain oxygen, yeah, would be depleted. How interesting. Yeah. Huh. The next big advancement in artificial ventilation happened about 100 years after then, when scientists began playing around with negative pressure ventilation. I'm going to pause here to explain briefly how negative pressure and positive pressure ventilation works and the difference between them. When you breathe, your diaphragm contracts, which expands your chest cavity and allows you to fill your lungs with air, specifically your alveoli, which is where oxygen is exchanged for carbon dioxide in your blood.

When you exhale, your diaphragm relaxes and you exhale out that carbon dioxide. along with a mixture of other gases, including oxygen. This normal lung function can be disrupted by a number of things, including respiratory infections such as RSV, as you described, Aaron, and in severe cases, someone may need the assistance of a ventilator to make their lungs work and take in the oxygen they need. So how do these ventilators work? There are two general strategies, at least like how they're grouped historically, for artificial ventilation. There's negative pressure ventilation, which was the first to be developed and

widely applied starting in the early 1900s but isn't really in use anymore. And there's positive pressure ventilation, which is what the ventilators we see today use. Negative pressure ventilation works like this. Basically, you seal someone's body from the neck down, or at the very least, leaving just their mouth and nose open, into an enclosed, airtight, room or box. Then you suck out all the air from that space, creating negative pressure. This causes the chest cavity to expand with air, allows your lungs to draw in that air, and then you would pump air back into the room or box, so bringing the pressure back up, and that would lead to exhalation. This is how an iron lung works. I was just going to say that sounds like an iron lung.

Exactly. Yeah. Positive pressure ventilation, on the other hand, involves using pressurized air to fill the lungs, such as with like an oxygen mask over your face, for instance, or in more extreme circumstances, doing like you said, air and intubation, so tubing applied directly to the lungs that essentially takes over the whole breathing process from inhalation to exhalation. And this is what we see in hospitals today, these big specialized machines that were the topic of much concern and discussion during COVID peaks when hospitals began to run out of them, for instance. And many places didn't have them, for instance.

And importantly, much smaller devices than a negative pressure. Yes, that is, yeah, definitely. All right, but now let me get back into the history of the development of these types of mechanical ventilation and why we switched from mostly negative pressure to positive pressure devices. One of the first negative pressure ventilation boxes was developed by a scientist named Alfred Jones in the 1860s, and this is where air pressure within the box was altered using a plunger annually. Yeah. Jones advertised his ventilator as the cure for an impressive number of conditions, such as paralysis, neuralgia, asthma, bronchitis, dyspepsia, and deafness.

Deafness. Yeah. I don't understand. But it was the 1860s, like anything goes. Yeah. An early version of what would later be known as an iron lung was developed in the 1870s with the intention of placing these along the scent to resuscitate people who had drowned. Oh.

Yeah. Kind of an interesting little thought there. But the real iron lung, the one that was so integral during the first half of the 20th century during polio outbreaks, it's the iron lung that you're picturing right now in your head, that was developed by Philip Drinker and Lewis Shaw at the Harvard School of Public Health in the late 1920s. Drinker got the idea after treating people with paralytic forms of respiratory failure, especially from polio. So he thought if only I could develop some sort of machine that would maintain ventilation support, you know, just for a little bit of time without having to tend to it, you know, have it be automatically administered, just until their lungs heal enough so that they can breathe on their own, just until they get better.

And he first tested his iron lung on cats and then found success, and then he tested it on himself and then other volunteers. But the first patient to use drinker's iron lung was an eight-year-old girl who was having trouble breathing due to a polio infection. Her breathing was getting weaker and weaker, her lips were turning blue, and just at the point when her doctor doctor thought she wouldn't be able to recover, they decided to try the iron lung. Almost immediately after being placed in the device, she recovered consciousness and asked for ice cream. Which I love. I thought that was so sweet. That's so eight-year-old. I love it. So cute. She was able to be taken out of the iron lung after just three and a half hours.

Wow. Ultimately, she did end up dying from pneumonia, but this instance showed that the device held great potential for breathing assistance. The iron lung and other negative pressure ventilation devices were certainly a huge step forward in terms of respiratory support, but they did leave a lot to be desired. If you picture one of these things, your body has to be sealed off from it. And that makes it impossible for healthcare workers to tend to any other part of your body that's inside this iron lung, for instance, not to mention the discomfort that you would feel not being able to move or like just be trapped in this, you know, machine. And so to deal with this lack of access to the body, they thought, let's just build a whole

negative pressure room where you can hold multiple patients in like bunk beds and you have their heads just like sticking out of the wall. And then like a nurse or a doctor could go into that room and then tend to the patient's bodies. Interesting. Yeah. That obviously not the most logistically sound solution. Difficult. Yeah. The need for an alternative solution to iron lungs became very apparent during the polio epidemic of the 1950s, where cases were so high that hospitals ran out of iron lungs.

And you can look up these photos of hospital wards with rows upon rows of the machines. When there was an iron lung shortage, some hospitals resorted to performing tracheostomies and then manually ventilating patients, which was previously, only something done like in an emergency or while operating. I want to read you a description of the situation from a hospital in Copenhagen in 1950. Quote, during several weeks, we had 40 to 70 patients in our hospital requiring continuous or intermittent bag ventilation. To do this, we have employed about 200 medical students daily. Oh my gosh.

Yeah, daily. I read one paper that put the total number of students providing manual ventilation at 1500 and the total number of hours at 165,000. Wow. Doing continuous handbagging ventilation. Yeah. Yeah. That's not easy to do. No. And it was actually because it was easier to put all of these patients needing ventilation in one area of the hospital that marked the beginnings of ICU's. Huh. Oh, that's a fun fact. Isn't that? Another silver lining to this was that, It became obvious that positive pressure ventilation, as in the handbagging that had to be done, resulted in about half the mortality rate of the negative pressure ventilation. I am so interested in the order that things have gone here because the very first accounts that you talked about with the dog and the bellows. Like, that's positive pressure.

So to go from that to like, hey, let's do this. We're going to do it in a really weird round. about cumbersome way of negative pressure and then come back to being like, oh, no, actually, positive pressure is a lot easier and makes a lot more sense. It's just, oh, that's so, so fascinating. So there definitely were positive pressure ventilation devices that were either being designed or in like limited use alongside these negative pressure ventilation machines, like the iron lung. And I wonder whether it was the prevalence of polio and like paralytic or partial paralysis in your respiratory system or whatever that may have been the more pressing need at times. But I don't really know.

Like why does one idea catch on and one doesn't? Marketing. I'm just saying. Yeah. Kind of. But even the person who developed the iron lung also was working on a positive pressure ventilation device. Interesting. So it's, yeah.

Yeah, this polio epidemic during the 1950s really showed that like, hey, we should maybe not do that anymore and turn towards positive pressure ventilation. Get to work on making this one more efficient as well. Exactly. Huh. Yeah. And so I think that's really was this turning point, this realization at how much better outcomes were with positive pressure ventilation in polio alone. That led to attention and like all. of the funding basically being put into positive pressure ventilation machines.

Cool. And so after this turning point of the 1950s, positive pressure ventilation machines, that's where most of the attention began to be focused. And so it really became about improving the functionality, just like making little tweaks here and there on those machines. Because they came onto the scene during a time when their main purpose was to essentially replaced respiratory muscles or respiratory function. But over the next decades, especially with declining rates of polio thanks to the vaccine, they began to be used to correct the levels of

oxygen that someone was getting, which was possible due to a greater understanding of the different gases in our blood and how to measure them and monitor continuously and then make tiny adjustments here and there. And so all of this was done in sort of like a, you know, gradual fashion. We've come a very long way since those early ventilators, not just the iron lung, but the first positive pressure ventilators that came on the scene. And we've come a long way both in terms of technological improvements in these ventilators, as well as strategies of use, like full support to partial support, because there are, like I mentioned, there are risks and negative health consequences to using these ventilators. And so that's been really crucial over the past few years.

but we're still learning very, very much as the COVID pandemic has made painfully clear. The ventilators that we currently use are expensive. They require highly trained individuals. They are not as bulky as iron lungs, but are still bulky and not very mobile. And we really need cheaper, more transportable and easier to use ventilators to increase access to these life-saving devices. And this seems to be a pretty exciting and active area of research. I didn't do very much digging into, like, where are we staying today? Because that's more of your thing.

But I did come across one paper that described a soft implantable robotic ventilator, which helps diaphragm function. So that could be kind of cool. Hopefully we'll see some improvements or cool new approaches to ventilation in the future. But the future is outside of my jurisdiction for this podcast. as is the present, really. So I'll hand it over to you, Erin, to tell me where we stand with this virus today. And just how unusual 2022 to 2023 was in terms of case numbers.

Ooh, I can't wait to tell you right after this break. As always on this podcast, Erin, we're going to be working with estimates here and not exact numbers. Love it. Especially when we look globally. But I have some pretty grim things to talk about right now. Not surprised. RSV, according to one of the papers that I read, is estimated to be the second leading cause of infant mortality after the neonatal period. Wow.

And 99% of these deaths, the overwhelming majority of these deaths, are happening in low and middle income countries. Is number one, diarrheal diseases? believe so, although the paper didn't actually specify, but I'm pretty sure it's diarrhea. Yeah. So when we, what does that mean in terms of actual numbers? Unfortunately, a lot of this data is a little bit old. It's from about 2010, the best estimates that we have. I don't think there's been huge declines by any means in RSV infection. So we'll kind of just use these estimates as like general numbers. But the estimated total annual global burden of RSV in children under age five, because this is the group that we look at the most significantly, is almost 34 million episodes of acute lower respiratory illness. So that's not even close to everyone who's affected, but these are the kids who are getting quite sick, lower respiratory tract infections. That's so many.

This likely results in about three and a half million hospitalizations. And again, remember that when we talk about hospitalizations in a lot of places, there's not access to hospitals. So keep that in mind. And an estimated 253,000 deaths globally in kids under five in 2010. Oh, my gosh. 250,000 children. And again, these are probably underestimates, though these estimates and the reason that 2010 numbers are often cited is because they're thought to be a lot more accurate than previous

estimates, which were way lower. Okay. Like way lower. If we look at the U.S. specifically, because I have some data from the U.S., it's estimated that there are over 2 million outpatient visits for RSV in kids under age five, two million kids going to the doctor with RSV. Wow. Anywhere from about 58 or 60 to 80,000 hospitalizations every year.

And an additional 60 to 120,000 hospitalizations for adults over age 65. Yeah. Which is so much higher than I realized. Yeah. It's estimated that between 6 and 10,000 adults over age 65 die from RSV every year. Oh my gosh. 6 and 10,000, according to the CDC, and between 100 and 300 deaths in kids under age 5. Wow.

I know. It's a lot. And like we kind of alluded to a little bit earlier, while this is generally, while this is generally a seasonal virus in temperate regions. So in North America, our winter goes from November-ish to February-ish, and that tends to be when we see RSV starting to build up in November peaking around February and then declining thereafter. It circulates year-round, but that tends to be when the peaks are and when hospitalization tends to be the highest. The COVID-19 pandemic has changed a lot of things.

We talked about that in our influenza episode at the end of last season, and I'm sure we'll talk about it in future respiratory episodes as well. And the truth of it is, I don't think we fully understand how much it's going to change and how lasting this change is going to be. But for the year and a half, two years where we were really quite locked down, so like 2020, 2021, we saw significant, less RSV, especially in young kids, than we had seen previously, like a lot less. Right.

A lot less hospitalizations and just a lot less doctor's visits in general for RSV and other respiratory infections. 2022, what we saw was really early RSV, starting at the end of summer and reaching peaks even into October and November, like what are normally peak numbers. We're recording this right now, full disclosure, in December of 2022, and this will be released at the end of January. I don't know what's going to happen. I don't have a crystal ball. But I won't be surprised if this infection has either another peak or has a very, very long tail, right? where we see a lot more infections just persisting for longer, more hospitalizations for longer. Because there's a large cohort of kids who might be being exposed to RSV for the first time later in their life,

because this is the first time they've been around other kids. Yeah. Right. So it's really interesting, kind of how it's all going to play out and what it's going to mean in the long term. Like, what's our RSV season going to look like next year or the year after? I don't think that we know. Yeah. And it's interesting, but also very stressful. Seems like not a big enough word for it. Yeah. Yeah, definitely. Especially because, as I mentioned, we still don't have a vaccine.

Yeah. I mean, when reinfections are common, how do you make a vaccine? So it's an interesting story, the vaccines. There have been, I don't even know how many different candidate vaccines that have made it through various stages of preclinical and clinical trials, even as far as, you know, phase three clinical trials. But so far, it's just been very difficult to develop a vaccine that has a good balance of immunogenicity, so actually stimulating enough. of an immune response to be protective, especially in the kids who are the most vulnerable, right, the youngest of kids age zero to six months or up to a year, who are going to be infected for the first time who we know are at highest risk of severe infection, stimulating enough of an immune response to provide protection while also being safe and not causing any

adverse effects. There was a vaccine candidate back in the 19th. 60s that was an inactivated version of an RSV virus that was inactivated with formalin that ended up causing significantly worse disease in that vulnerable population in young infants. Yeah. It caused what was called an enhanced respiratory disease after a first vaccination in kids who had never been exposed to RSV before. And that is terrible and horrific. And because of that, it really set things back a ways because it's going to, of course, make people a lot more cautious when it comes to future vaccines and clinical trials, especially for that population who is so vulnerable to begin with.

And longtime listeners of this podcast will know and remember from many of our episodes just how rigorous safety standards are when it comes to vaccines and their testing and implementation. which over the years, especially since the 1960s, has only become more rigorous, right? Yeah. Which is a good thing, but it also means that it takes a lot longer to develop these vaccines. That's kind of the long and short answer of why we still don't have one. There are dozens of vaccine candidates. And what I think is really interesting is that not only are there candidates of various vaccine platforms that are understudy, like everything from live attenuated vaccines to whole inactivated or killed vaccines,

to component vaccines or protein vaccines to RNA RNA, like, yeah, nucleic acid-based vaccines, like the COVID ones. So there's people doing research on like every different vaccine type that you can imagine. But there's also different populations. that people are trying to target for protection, which is really interesting in the context of RSV. So first, we know that older adults are also at really high risk. So there's people working on vaccines that are going to target older adults to just boost their immunity or something like that. There's also an effort to target just older kids in general because older kids, especially after six to 12 months, that's when we tend to,

to start to use, usually at 12 months, live attenuated vaccines. But then there's these really vulnerable, tiny infants. And we don't have vaccines for them right now. And we had really bad experience with the vaccines we tried to develop in 1960. So another potential way to protect those youngest babies who are most vulnerable is maternal vaccination. So vaccination during pregnancy, the way that's, we do for pertussis. Yep. And so there's also groups that are working on developing maternal

vaccines that produce enough immunity that can be passed through the placenta and potentially through breast milk as well to provide protection to these youngest of infants. So cool. Plus, as I mentioned, there is already a monoclonal antibody that is in use and there is work on additional monoclonal antibodies or other ways to give monoclonal antibodies that might be more cost-effective, et cetera. And even though, like you mentioned, Aaron, we get reinfected with this virus all the time, right? Which makes you think, like, how can you develop a vaccine for something that we just get reinfected with all the time? Flu. Right, flu? Yeah. But what we know about RSV is that it's that first exposure that is often one of the most highest risk times. And we know that

things like maternal antibodies or these monoclonal antibodies or previous infection where you've developed at least some antibodies provides protection against severe disease and hospitalization, which means it provides protection against death. Right. And so because of that, there is this theoretical we should be able to develop a vaccine that's at least protective against severe disease and hospitalization. Right. Doesn't need to be like perfect for everyone at all, like at all times.

There are priorities that you can put into vaccine development. Yeah. Right. And so that's, yeah, there's a lot of hope and there's so many different groups that are working on all of these different aspects. Oh my gosh, so many. But as of now, we still don't have one. We also, this is a human-specific virus and we don't have good animal models for RSV, which makes it that much harder to develop vaccines. Yeah.

But there's, I think, a lot of. hope on the horizon. And I think like you mentioned, Aaron, this is something that we're hearing about more and more and more. And the more that diseases get pressed, the more that they get funding and the more that they get funding, the faster that we get new technologies. Yeah. So. Hopefully we'll see that in the future then. Yeah, exactly. But that is RSV. Wow. What a way to start season six. Yeah. I'm pretty excited. about it. I have a bunch of papers. I want to shout out just a couple of them. So in terms of the history of RSV, that first paper by Morris at all from 1956 is actually kind of an interesting

read. And then for the history of mechanical ventilation, there are several papers. One I really liked by Petty from 1990. And I also want to shout out a TED-Ed video that I watched to teach me how ventilators work because I had no idea. And I will link to that video on our website as well. I also had quite a number of papers. One of my favorites, just very like broad overview, was an older paper by Welliver from 2003 in the Journal of Pediatrics. If you want more on RSV and asthma and those, you know, details, there was a paper by Hahn at all from 2011. I have a number of different papers on vaccines and where we stand with vaccine candidates and vaccine research. And we'll post all of our sources from this episode and every one of our five other

seasons worth of episodes on our website, this podcast will kill you.com under the episodes tab. We certainly will. Thank you again so much, Lucy, for sharing your story with us. Yeah. Yeah. Yeah. Thank you. Thank you also to Leanna Squillichie for our all. Audio mixing, we are thrilled to have you on board for the first time this season. We are. And speaking of audio, thank you to Bloodmobile, who provides the music for this episode and all of our episodes. Thank you to the Exactly Right Network. And thank you to you, listeners. Thanks for joining us again this season. Welcome back.

As always, send your suggestions. There is now a submit-your-first-hand account link on our website. And yeah, we always love hearing from you. You're the best. You make this possible. And an extra shout out to our patrons. Thank you so much for your support. Always. We love you.

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