Speaker 1: In October twenty nineteen, our family doubled in number from
Speaker 1: three to six when our triplets were born at thirty
Speaker 1: five weeks gestation. We already had our two and a
Speaker 1: half year old daughter, Annie, and then we had Isabelle,
Speaker 1: Lennie and Teddy. Their weights ranged from four pound two
Speaker 1: to four pounds seven at birth. They were small, but
Speaker 1: everyone agreed they were good sizes for triplets. Because they
Speaker 1: were born early. They needed some help with breathing and
Speaker 1: maintaining their own temperatures, but all were discharged from NICKYU
Speaker 1: two weeks later. We had a lot of visits from
Speaker 1: community nurses to check on their health. They checked their
Speaker 1: weight and for any signs of infection. I was told
Speaker 1: a number of times to watch out for a virus
Speaker 1: called RSB, as it was a risk this time of year,
Speaker 1: especially for very young babies, and especially for those with
Speaker 1: a sibling who was attending nursery or school. I understood
Speaker 1: that we tipped a few of these risk boxes, but
Speaker 1: I wasn't concerned. I thought would be okay. When Lenny
Speaker 1: was five weeks old and not yet the weight of
Speaker 1: most newborn babies, he seemed more sniffly than usual. He
Speaker 1: was drinking his milk more slowly, and he had been
Speaker 1: sick a couple of times. I thought he had a cold.
Speaker 1: I thought he would get better in a few days.
Speaker 1: One morning, we woke up and I went through the
Speaker 1: usual morning routine. Lenny seemed like he was okay, but
Speaker 1: he still had a cold. So I left him till
Speaker 1: last so I could feed the others and spend a
Speaker 1: bit more time with him. But as I picked him
Speaker 1: up to feed him, I thought he looked pale. He
Speaker 1: seemed maybe a bit colder than usual. I felt panic.
Speaker 1: I was worried. I still couldn't drive, having only had
Speaker 1: a sea section weeks ago, so I phoned my husband
Speaker 1: and he came home and took us to the hospital.
Speaker 1: By the time we got there, and after only a
Speaker 1: ten minute drive, Lenny had gotten much worse. In fact,
Speaker 1: he was rushed straight through to reesos and what felt
Speaker 1: like tens of staff rushed into the room to help him.
Speaker 1: He had become so sick so quickly that they thought
Speaker 1: he could have sepsis. He was tested for a number
Speaker 1: of illnesses, and the swabs later came back positive for RSB.
Speaker 1: By this time, Lenny had been admitted to the High
Speaker 1: dependency unit. He had been put on a seapap machine
Speaker 1: to help with his breathing. It was later switched to
Speaker 1: BiPAP and he narrowly avoided being intubated. After he stabilized,
Speaker 1: he needed support with nutrition and hydration and was given
Speaker 1: a cocktail of drugs. The other two triplets were admitted
Speaker 1: to Award over night for observations, but were discharged the
Speaker 1: next day. We were advised to keep Isabelle and Teddy
Speaker 1: away from the hospital so they wouldn't pick up any infections.
Speaker 1: It was a heartbreaking logistical nightmare caring for our three
Speaker 1: apparently well children on our critically ill baby all at once.
Speaker 1: Lennie spent five nights in hospital, which was amazing considering
Speaker 1: how ill he was when he'd got there. He recovered
Speaker 1: as quickly as he had got sick, and I felt
Speaker 1: so positive and thankful to take him home. Little did
Speaker 1: I know that we were only midnightmare at this point.
Speaker 1: Less than a week later, isabel seemed to not be
Speaker 1: drinking her milk very well. After what had happened with Lennie,
Speaker 1: we had learned to watch out for signs that babies
Speaker 1: were struggling to breathe and Isabel was exhibiting a number
Speaker 1: of red flags. She was sucking in a little around
Speaker 1: her rib so that we could see the slight outline
Speaker 1: of her rib cage, and there was a little recession
Speaker 1: in the front of her neck too. It suggested she
Speaker 1: was struggling to breathe. I took her to hospital. I
Speaker 1: was concerned, but not really worried, as she seemed nowhere
Speaker 1: near as sick as Lennie had been. But while she
Speaker 1: was being examined she had napnia and it was clear
Speaker 1: that she was starting to struggle significantly with her breathing.
Speaker 1: She was admitted to the high dependency unit where Lenny
Speaker 1: had been and given oxygen support. All night long, the
Speaker 1: machines beaped endlessly and the nurse would rush over to
Speaker 1: do what she could. The following day, Isabel deteriorated. Her
Speaker 1: tiny body struggled to breathe so much that now her
Speaker 1: entire rib cage would be visible at points. Despite all
Speaker 1: the support, her oxygen levels were too low and she
Speaker 1: went from seepap to BiPAP and then was moved to
Speaker 1: PICU and intubated. The procedure was a struggle because she
Speaker 1: was so small, and she was left with a bloody
Speaker 1: nose and a collapse lung. She was so sick that
Speaker 1: I asked the doctors as much as I could bear
Speaker 1: to if I was going to lose her, and no
Speaker 1: one could give me the reassurance they wanted. Slowly she
Speaker 1: became stable on the ventilator, which she didn't improve as
Speaker 1: the days passed. We sat beside her bedside and the
Speaker 1: nurses took so many samples of blood from her feet
Speaker 1: to check her blood gases that her feet looked like
Speaker 1: pin cushions. Anula after canula came out and it became
Speaker 1: harder for the doctors to find places to fit new ones.
Speaker 1: Her body convulsed as it couldn't expel the mucus from
Speaker 1: her lungs, and the nurses would rush to suction it
Speaker 1: through the endotracheal tube. It hadn't made sense to me
Speaker 1: why Isabel was so much sicker than Lennie, but it
Speaker 1: transpired that Isabel had had RSV and she'd developed bronchiolitis
Speaker 1: like a brother, but she developed a complication pneumonia. Thanks
Speaker 1: to the amazing care she received at the Royal Manchester
Speaker 1: Children's Hospital, Isabel recovered and she came home in time
Speaker 1: for Christmas with her brothers and her big sister. On
Speaker 1: our last day in Picu, I remember a doctor telling
Speaker 1: me to be careful for the rest of the winter
Speaker 1: and for next winter two and she was right. Isabel
Speaker 1: was admitted to hospital with bronchiolitis the following winter, but
Speaker 1: as a much stronger one year old, and it was
Speaker 1: not so scary this time around. She needed some help
Speaker 1: with breathing and new Trician, but she was okay. As
Speaker 1: she started to feel better, she even began to enjoy
Speaker 1: all the attention from the lovely staff as they came
Speaker 1: into her room. Each one who came in looked right
Speaker 1: at her and said hello. And after she was discharged,
Speaker 1: I was putting her to bed one night and she
Speaker 1: stood up and she looked at me and she said
Speaker 1: her first word hello. I will be forever thankful to
Speaker 1: the incredible medical and nursing staff. You saved my babies.
Speaker 2: Oh my gosh, I what a horrifying, terrifying experience.
Speaker 1: I know.
Speaker 3: Thank you so much, Lucy for sharing your experience with
Speaker 3: us and our listeners. It's ah, it's terrifying.
Speaker 2: It is. I'm so glad that everyone is now doing well.
Speaker 2: Me too.
Speaker 3: Hi, I'm Aaron Welsh and I'm Aaron Allman Updike, and.
Speaker 2: This is this podcast Will Kill You.
Speaker 3: Welcome to season six.
Speaker 2: Season six.
Speaker 3: Whoever would have thought that we could make it this far?
Speaker 2: You and I certainly did not think that. But it's
Speaker 2: funny like when we first started out, we thought, oh,
Speaker 2: we've got like two seasons maximum, We like laid out
Speaker 2: all of the topics, and then over the years, especially
Speaker 2: thanks to listeners who have reached out and suggested things,
Speaker 2: that list just keeps getting longer and longer and longer,
Speaker 2: and now it's like we don't see an end in sight,
Speaker 2: which is which is scary because it's like there are
Speaker 2: a lot of things that can kill you, but it's
Speaker 2: also really great because we get to talk about them all.
Speaker 3: Yeah, and we love getting to make this podcast. So
Speaker 3: thank you all again for listening, yeah and sticking with.
Speaker 2: Us for our sixth season.
Speaker 3: It's going to be a good one.
Speaker 2: It is. We've got a lot of very interesting topics
Speaker 2: planned for this next season, so you'll just have to
Speaker 2: stay tuned to see what we're going to be talking about.
Speaker 3: Right and who knows what global pandemics will be thrown
Speaker 3: at us next that will change our order of topics, etc.
Speaker 2: Aaron, I'm sorry, no too soon. Yes, yes, we'll always
Speaker 2: be too soon. But we're kicking things off with a
Speaker 2: very hot topic, very timely topic, and that is rs
Speaker 2: v R s V. It's huge, it is and erin.
Speaker 2: I hope you're going to tell me how to pronounce sensicial.
Speaker 3: Sensicial respiratory sensicial virus. But yeah, it's gonna be. It's
Speaker 3: gonna be a good episode. I'm excited.
Speaker 2: Yeah, there's definitely a lot that I want to know
Speaker 2: about this virus, so I'm excited to dig in. Yeah,
Speaker 2: but first first, it's quarantiny time.
Speaker 3: It's quarantin any time.
Speaker 2: Exciting. What are we drinking this week?
Speaker 3: We're drinking Hold your Breath because you know it's a
Speaker 3: respiratory virus. We'll get into it all.
Speaker 2: Yeah, yeah, we'll get there.
Speaker 3: And what's in Hold your Breath?
Speaker 2: Erin spiced cranberry syrup, orange juice, and bourbon.
Speaker 3: Yum, it's sunsty Yeah. We'll post the full recipe for
Speaker 3: that quarantine as well as our non alcoholic plusy Brita
Speaker 3: on our w website. This podcast will kill You dot
Speaker 3: com and of course all of our social media channels.
Speaker 2: We certainly will on our website. I guess I do
Speaker 2: have to do the spiel because this is the beginning
Speaker 2: of the season. I don't know, I feel like I need.
Speaker 3: We might have new people listening. Welcome. We have spiels
Speaker 3: that we do.
Speaker 2: Yeah, here, Welcome to your first website spiel. If you
Speaker 2: go to this podcast will Kill You dot com, you
Speaker 2: can find all sorts of great resources, including the resources
Speaker 2: that we mentioned in every one of our episodes, including transcripts,
Speaker 2: including our bookshop, dot org affiliate account, our Goodreads list,
Speaker 2: links to merch our, Patreon, just so much stuff that
Speaker 2: you can find, so check it out.
Speaker 3: Also shout out our merch got recently revamped in the
Speaker 3: last couple of months. Shout out to our incredible artist
Speaker 3: Abigail Irvin Penner who did all of this incredible artwork.
Speaker 3: And the merch is clutch. If you haven't got your
Speaker 3: hands on it yet, you can.
Speaker 2: Okay, do we have any other business think so let's
Speaker 2: get into it. Let's do it right after this break.
Speaker 3: I'm excited that we're starting out this season with RSV,
Speaker 3: especially because we ended last season with Influenza. Yeah, it
Speaker 3: feels very you know full circle in a weird way.
Speaker 2: Yeah.
Speaker 3: So, RSV, or as it's properly called, respiratory sensicial virus.
Speaker 3: It's one of the other really big name respiratory viruses
Speaker 3: that hospitals and hospitals and many parents especially know all
Speaker 3: too well. We are recording this and this will be
Speaker 3: released smack dab in the middle of what is typical
Speaker 3: RSV season here in the Northern Hemisphere, which usually goes
Speaker 3: from about November ish until the end of February. Spoiler alerts.
Speaker 3: This year we saw a really early start to the
Speaker 3: RSV season, and I will not be surprised if it
Speaker 3: ends up having a pretty long tail as well, so
Speaker 3: we might end up seeing cases well into the spring.
Speaker 3: But we'll get into all of that later. First, what
Speaker 3: the heck is RSV. Yeah, obviously it's a virus, it's
Speaker 3: in the name, but specifically it's a virus in the
Speaker 3: family Numoviridae, which includes viruses in the genus metaanumavirus, which
Speaker 3: is another common cause of human respiratory infections like common
Speaker 3: cold type infections, and then RSV, which is in the
Speaker 3: genus orthoneumovirus. So these are RNA viruses. They have an
Speaker 3: envelope much like influenza. They have a non segmented genome,
Speaker 3: unlike our friend influenza, which remember has multiple little chunks
Speaker 3: of RNA uh huh, And just really off the bat,
Speaker 3: I want to emphasize how incredibly important of a virus
Speaker 3: RSV is. It is one of, if not the single,
Speaker 3: leading cause of acute lower respiratory tract infections and hospitalizations,
Speaker 3: especially in kids underage five globally.
Speaker 2: I have a question about this already. I love it. Yeah, well,
Speaker 2: and maybe it's more of like a rhetorical question or
Speaker 2: just like an open discussion point. But I feel like,
Speaker 2: even though I went to get an undergrad in biology
Speaker 2: and had to take classes on diseases, did grad school
Speaker 2: and stuff like that, really the first time I started
Speaker 2: hearing about RSV was when we were doing the podcast
Speaker 2: and talking about all these different viruses and stuff. And
Speaker 2: I really feel like, suddenly, now it's all over the
Speaker 2: news and you can't avoid it. And I know that
Speaker 2: part of that is because we're just seeing a really
Speaker 2: unusual number of cases, But is there anything else to that? Like,
Speaker 2: why do I feel like people have only started hearing
Speaker 2: about RSV now?
Speaker 3: Yeah, it's a good question. I don't have a perfect
Speaker 3: answer for you. I can tell you, based on the
Speaker 3: epidemiological data that I've seen out of the past ten
Speaker 3: years or so, we used to greatly underestimate RSV burden, Okay,
Speaker 3: And a lot of that was probably because we just
Speaker 3: weren't testing for it, so we weren't distinguishing RSV from
Speaker 3: any other particular respiratory infection. So when a kid or
Speaker 3: a grown adult or an older person got infected with
Speaker 3: a respiratory virus, it was like influenza or something else,
Speaker 3: and that was kind of the only distinction that was made.
Speaker 3: So part of it might just be that we're doing
Speaker 3: better diagnostics so we can understand just how important this
Speaker 3: individual virus is. I think that might be a big
Speaker 3: part of it.
Speaker 2: Okay, Okay, that makes sense.
Speaker 3: Yeah, But so being respiratory in nature, it's probably unsurprising
Speaker 3: to know that this is a virus transmitted mostly by
Speaker 3: respiratory droplets, so coughs, sneezes, that sort of thing. It
Speaker 3: can also survive for a really decent amount of time
Speaker 3: on surfaces, especially in colder weather, and so it can
Speaker 3: be transmitted very easily by fomites, things like door handles,
Speaker 3: crib railings that kids love to suck on, even your hands,
Speaker 3: all of those kinds of things, toys at daycare centers
Speaker 3: for example.
Speaker 2: You know, I have a question about durability, Like I know.
Speaker 3: Yeah, I literally wrote how long Aaron? Such a good question.
Speaker 3: So I don't know, largely because it depends so much
Speaker 3: on environmental factors.
Speaker 2: Okay, that makes sense.
Speaker 3: Yeah, but from the data that I have been able
Speaker 3: to gather, it's a good number of hours, like even
Speaker 3: several hours under not that great of conditions, and potentially
Speaker 3: several days under good conditions for viral survival. And what
Speaker 3: those conditions are depend on if the virus stays wet
Speaker 3: versus if it dries out, and so it's really complicated.
Speaker 2: Yikes, though several days is I kind of terrifying.
Speaker 3: Yeah, maybe maybe a couple of days. I shouldn't maybe
Speaker 3: say several makes it sound like a week, but like
Speaker 3: probably at least forty eight hours depending on certain conditions, right, right,
Speaker 3: And some of this complication and environmental durability helps explain,
Speaker 3: at least in part, some of the differences in seasonality
Speaker 3: that we see in different latitudes, where in temperate regions, cold,
Speaker 3: low humidity winter months where we're also all gathered inside
Speaker 3: and potentially spreading germs that way tend to have much
Speaker 3: higher RSV transmission, whereas in tropical latitudes it tends to
Speaker 3: be the rainy season, which is obviously a lot more humid,
Speaker 3: that tends to see higher transmission. So it's the seasonality
Speaker 3: aspect is really interesting. In general, the incubation period for
Speaker 3: RSV that I've seen most commonly reported is between four
Speaker 3: and six days, could be a little less, could be
Speaker 3: a little more. And then let's talk about the symptoms. Yeah,
Speaker 3: and for this, I'm kind of almost going to tell
Speaker 3: another little first hand account here because I remember very
Speaker 3: vividly when my kid got his first RSV infection, and
Speaker 3: I remember what the doctor explained to us, and I
Speaker 3: just think it was such a good explanation of the
Speaker 3: course of RSV that I'm going to tell it to
Speaker 3: you now. So when my kid got RSV, he was
Speaker 3: probably three months old. He was definitely under four months
Speaker 3: because he only had one dose of Protestis vaccine and
Speaker 3: I was convinced that it was Protestant. Oh god, it
Speaker 3: wasn't protests. I made him test for it. But anyways,
Speaker 3: I remember that he definitely had a fever, but it
Speaker 3: came down with a little bit of til and all.
Speaker 3: He didn't seem all that miserable at first, but then
Speaker 3: he was just coughing so much, just coughing, coughing, coughing
Speaker 3: his brains out, and he was so snotty, like an
Speaker 3: epic amount of snot And intermittently I started hearing him wheeze,
Speaker 3: And of course I was in med school at the time,
Speaker 3: so I would listen to him with my stethoscope, and
Speaker 3: I was like, he's wheezing. That seems bad, Like we
Speaker 3: should at this point, we should go to the doctor.
Speaker 3: What do I do? I need a real doctor. So
Speaker 3: I brought him to see his doctor, and his doctor said,
Speaker 3: this is almost certainly RSV. It was like November peak.
Speaker 3: Here we go RSV season. At the time. The doctor said,
Speaker 3: he's not wheezy at this moment, but I believe you
Speaker 3: that he was wheezing at home, because he will probably
Speaker 3: continue to wheeze intermittently. He's been sick now for two
Speaker 3: or three days, So here's what's going to happen over
Speaker 3: the next two or three days. So like days four
Speaker 3: to six of illness, he's either going to start to
Speaker 3: get better or he's going to get worse. And if
Speaker 3: he gets worse, here's what you'll see. He'll start breathing fast,
Speaker 3: a lot faster than usual. It'll look like he's working
Speaker 3: hard to breathe. What you'll see are retractions, which mean
Speaker 3: that if you take off his clothes, you'll be able
Speaker 3: to see his ribs where his belly pulls in underneath
Speaker 3: his ribs when he tries to breathe, Oh my god,
Speaker 3: or in the little v of his neck right above
Speaker 3: his chest, you can see it kind of sucking in
Speaker 3: as he takes in a breath. Those are called retractions.
Speaker 3: If that starts to happen, you'll take him to the
Speaker 3: emergency room and they will do care for him. And
Speaker 3: those are the two ways that this disease is going
Speaker 3: to go. And that's what the doctor told me. And
Speaker 3: it sounds terrifying, yeah, and it is terrifying, but I
Speaker 3: will say that it was one of the most reassuring
Speaker 3: things to know. Here's what to look out for, here's
Speaker 3: the things that are going to happen, and here's the
Speaker 3: kind of two ways that it's going to go, and
Speaker 3: what to do in both scenarios.
Speaker 2: Yeah, yeah, and it turns.
Speaker 3: Out that it's a really accurate description of the course
Speaker 3: of RSV. Kids especially are susceptible to RSV infections, and
Speaker 3: kids especially in their first round with RSV, because this
Speaker 3: is a virus that tends to infect us over and
Speaker 3: over through the course of our lifetimes, but especially in
Speaker 3: that first year of RSV infection. For a kid, they
Speaker 3: tend to get a fever. RSV is a very snotty virus,
Speaker 3: So you have a lot of mucus production. You're going
Speaker 3: to have a lot of coughing because of that mucus production.
Speaker 3: And in kids, especially babies, they're not good at coughing yet.
Speaker 3: They just don't have the muscles and they don't have
Speaker 3: the reflex to get up gunk when they cough, so
Speaker 3: they don't produce a lot when they're coughing. And then
Speaker 3: they either get better over time or they get worse.
Speaker 3: And it's often that days four to six or so
Speaker 3: is when they might start to get worse. So this
Speaker 3: is a long disease that we're talking about. That's a
Speaker 3: long time to be watching a kid like a hawk
Speaker 3: and wondering kind of which way it's going to go.
Speaker 2: Yeah, absolutely, Okay, question real quick uh huh. What are
Speaker 2: some of the factors that decide whether a kid is
Speaker 2: going to get better or going to get worse?
Speaker 3: Oh, we will absolutely get into it, Okay, Okay, yeah,
Speaker 3: in as much detail as I can give you.
Speaker 2: Okay, So, I guess not a quick question then.
Speaker 3: But it's the it is the important question.
Speaker 2: Yeah.
Speaker 3: So, But to talk a little bit more about what
Speaker 3: the symptoms can look like in other age groups, because
Speaker 3: what I just described is how the course of RSV
Speaker 3: tends to go in kids, say age especially zero to
Speaker 3: six months or a year, or kids who are being
Speaker 3: exposed to RSV for the first time. In older kids,
Speaker 3: it can look similar or it can look more like
Speaker 3: what RSV looks like in adults, which is just the
Speaker 3: common cold, right, So, cough, runny nose, sinus, congestion, sore throat.
Speaker 3: Usually RSV, even in adults, is a pretty snotty type
Speaker 3: of cold. So you might have quite a lot of
Speaker 3: congestion in very very little babies, like under six weeks old,
Speaker 3: or very tiny babies that are very premature, they can
Speaker 3: actually have such little reserve when it comes to their
Speaker 3: respiratory system that they can present a little bit differently.
Speaker 3: Sometimes they might just look kind of lethargic, like they
Speaker 3: just don't really look like themselves. They have no energy.
Speaker 3: Sometimes they might just have apnea, which is when they
Speaker 3: just stop breathing entirely for a spell, which is terrifying.
Speaker 3: Now in elderly adults over age sixty five, or in
Speaker 3: adults or children with underlying lung conditions like COPD or asthma,
Speaker 3: cystic fibrosis, things like that, you can also have a
Speaker 3: more severe infection that can lead to something like a pneumonia,
Speaker 3: a viral pneumonia, which we've talked a lot about on
Speaker 3: this podcast. So then the question you ask, the question
Speaker 3: of who does this happen to? And before I get
Speaker 3: to that, what I want to talk about is what
Speaker 3: is actually happening in our airways? And I think once
Speaker 3: we understand that, we can understand who is at highest
Speaker 3: risk for severe infection. Okay, so what actually happens when
Speaker 3: we get infected with this virus as a respiratory virus
Speaker 3: RSV is initially and primarily infecting the epithelial cells of
Speaker 3: our respiratory tract. I feel like we talk about these
Speaker 3: cells all the time.
Speaker 1: We do.
Speaker 2: Let's do it again. I love it.
Speaker 3: Yeah, let's these are the cells that are lining our nose,
Speaker 3: they're lining our throat, they're lining our airways. Part of
Speaker 3: what determines how severe of an infection you're going to
Speaker 3: have with RSV is going to be whether or not
Speaker 3: it establishes an infection in the lower respiratory tract, meaning
Speaker 3: down in our lungs. RSV seems to have an easier
Speaker 3: time doing this in either an initial infection so you've
Speaker 3: never been exposed before, you have no immunity whatsoever. That
Speaker 3: means infections in the very young, as well as in
Speaker 3: the very old, or the immunal compromised. So those are
Speaker 3: the three biggest groups that we're going to see more
Speaker 3: likelihood that you'll have a severe RSV infection because it's
Speaker 3: making its way down into your lungs. But the other
Speaker 3: part of it is that with RSV, I keep saying
Speaker 3: there's a lot of snot right, there's a lot of mucus.
Speaker 3: That's largely because we see a huge amount of immune response,
Speaker 3: especially in the form of neutrophills, which are one of
Speaker 3: our white blood cells that often are the first to
Speaker 3: kind of rise up to try and fight off a
Speaker 3: virus that tend to infiltrate into spaces with an RSV infection.
Speaker 3: So if this virus is infecting the small airways of
Speaker 3: our lungs are bronchioles, which are the kind of smallest
Speaker 3: of the branches of our lungs, then you're going to
Speaker 3: have a lot of white blood cells, these neutrophills, as
Speaker 3: well as fluid and gunk that's getting in to your
Speaker 3: lungs itself, and fluid in gunk is never good in
Speaker 3: our lungs for anyone, but for tiny babies, especially premature
Speaker 3: tiny babies. They also have tiny airways. So these tiny
Speaker 3: airways are even more susceptible to obstruction, and that obstruction
Speaker 3: is what causes the primary disorder that we see in
Speaker 3: severe RSV, which is called bronchiolitis. So bronchiolitis is this obstruction.
Speaker 3: It's the plugging up of the tiny ends of our airways,
Speaker 3: the small bronchi and what are called the terminal bronchioles.
Speaker 3: This happens because of swelling, because of mucus, because our
Speaker 3: own cells are getting left off and all these immune
Speaker 3: cells are coming in. These then get plugged up and
Speaker 3: eventually collapse, and that is what also causes that wheezing
Speaker 3: sound that I mentioned that you can hear if you
Speaker 3: listen to a kid with bronchiolitis's lungs. All this gunk
Speaker 3: makes it so that it's really hard to breathe out
Speaker 3: the air that makes it into our lungs, so it's
Speaker 3: obstructing the flow. I know, it's awful, and I just
Speaker 3: want to contrast this to the other most common lower
Speaker 3: respiratory disease that we usually talk about on this podcast,
Speaker 3: and that is pneumonia.
Speaker 2: Right.
Speaker 3: Pneumonia is when we have similar kind of inflammation and fluid,
Speaker 3: but instead of being in the airway like tubules the bronchials,
Speaker 3: it's down in the alveoli, which are those grape cluster
Speaker 3: sacks where gas exchange actually happens. So it's like a
Speaker 3: different place within your lungs where the inflammation is happening.
Speaker 3: So it leads to a different pattern of disease. In
Speaker 3: adults that end up with severe RSV, it tends to
Speaker 3: be a pneumonia. In tiny kids, those airways are so
Speaker 3: small that they get plugged up before it even makes
Speaker 3: it down to the alveoli.
Speaker 2: That's very interesting, I know. Yeah, So the end result
Speaker 2: is almost the same in a way, you're simply getting
Speaker 2: not enough oxygen in in a way. Yeah, yeah, but
Speaker 2: then there are other aspects, and I imagine damage to
Speaker 2: the lungs in different ways exactly. Yeah.
Speaker 3: So now RSV is an incredibly common infection. Nearly everyone
Speaker 3: on the planet by adulthood has been infected with RSV,
Speaker 3: and probably we've been infected multiple times in our life.
Speaker 2: I had no idea.
Speaker 3: I know, I know, I think for so long it
Speaker 3: just gets brushed off as the common cold. I will
Speaker 3: admit to I knew how big of a deal RSV
Speaker 3: was in kids, I did not know how big of
Speaker 3: a deal it was in older adults.
Speaker 2: Yeah. Same, But there are certain.
Speaker 3: Groups, like we alluded to, that are at much higher
Speaker 3: risk for severe illness this bronchiolitis, especially than others. And
Speaker 3: I mentioned that young babies are one of these primary groups.
Speaker 3: But I want to dig down a little bit deeper
Speaker 3: because on top of just young babies like being infected
Speaker 3: for the first time, there's a few other risk factors
Speaker 3: that can make kids even more susceptible to severe infection.
Speaker 3: Prematurity is one of them. So being born at before
Speaker 3: thirty seven weeks, those kids are almost twice as likely
Speaker 3: to be hospitalized than kids who are born at term,
Speaker 3: kids who are born premature who also have what's called
Speaker 3: chronic lung disease of prematurity, or it used to be
Speaker 3: called broncho pulmonary dysplasia. It's a whole other episode. But
Speaker 3: those kids are about fourteen times more likely to need
Speaker 3: hospitalization with RSV infection. And for those kids with chronic
Speaker 3: lung disease, the risk is also higher throughout infancy till
Speaker 3: about age two instead of just the first six months.
Speaker 3: And kids born with congenital heart disease also have a
Speaker 3: much higher risk of being hospitalized, about three times as
Speaker 3: high as kids with no other risk factors. And then,
Speaker 3: like I mentioned, kids who have various immune deficiencies or
Speaker 3: underlying lung conditions. Gotcha, But because this is such a
Speaker 3: prevalent virus, when you look at absolute numbers, the majority
Speaker 3: of kids that get hospitalized are often otherwise healthy and
Speaker 3: don't have any underlying risk factors, which just goes to
Speaker 3: show you how incredibly prevalent this virus is. Like every
Speaker 3: kid is getting infected. Erin what is sensitia? I don't know, Yeah,
Speaker 3: I feel like I should know.
Speaker 2: I feel like we should know. I mean I don't know, okay, Erin,
Speaker 2: I googled it, Okay, good, sensitium, which is the singular
Speaker 2: the plural is sensitia, a single cell or cytocosmic mass
Speaker 2: containing several nuclei formed by fusion of cells or by
Speaker 2: division of nuclei.
Speaker 3: Okay, I did know that somewhere in my brain because
Speaker 3: the reason that it's called respiratory sensicial virus is because
Speaker 3: the gunk that you see in the lungs of kids
Speaker 3: post mortem who have died from RSV bronchiolitis looks like that.
Speaker 3: It looks like a sensicium.
Speaker 2: Okay, So I mean I have in here why they
Speaker 2: called its respiratory sensicial virus, but because it produced sensicial changes.
Speaker 2: And then I was like, Erin, I'll talk about sensitius
Speaker 2: so I don't have to worry.
Speaker 3: No, Okay, Well, now yeah, that's actually hilarious. So what
Speaker 3: do we do to deal with this infection if kids
Speaker 3: get really sick from it? And what do we do
Speaker 3: to prevent it? I guess those are kind of two
Speaker 3: big questions to treat it. We don't have anything specific.
Speaker 3: So the treatment for RSV if it's a mild infection,
Speaker 3: it's supportive care at home, right. If it's hospitalization, like
Speaker 3: a severe infection, then it's using very powerful suction to
Speaker 3: suck snot out of tiny kids' faces, and breathing assistance,
Speaker 3: which usually means high flow oxygen. And if a kid
Speaker 3: is really really sick or just really small and doesn't
Speaker 3: have the reserves to be able to keep fighting to breathe,
Speaker 3: then it's mechanical ventilation, which means intubation and a breathing machine,
Speaker 3: which has its whole own host of possible complications. Yeah,
Speaker 3: but that's really all that we have. There was an
Speaker 3: anti viral that was tried but hasn't been shown to
Speaker 3: be effective. Lots of people want to think that broncho
Speaker 3: dilators like we use for asthma, so like albuterol, think
Speaker 3: albuterol inhalers. They have no real benefit in RSV baranchiolitis.
Speaker 3: Same thing with steroids. So it's really all just this
Speaker 3: supportive care, which is scary when you think about places
Speaker 3: that don't have access to high levels of oxygen at
Speaker 3: high flow or mechanical ventilation or hospitalization in general.
Speaker 2: Yeah, there's a lot of places like that. Yeah, and
Speaker 2: so when would you test for RSV?
Speaker 3: Oh, this is such an interesting question. Arin It's an
Speaker 3: interesting question because there's not an easy answer on an
Speaker 3: individual level. On a public health level, it's good to
Speaker 3: know what viruses people have, like, what viruses are circulating,
Speaker 3: what viruses are running around, and in what ratios. So
Speaker 3: from a public health perspective, it makes a lot of
Speaker 3: sense to test as many people as you can that
Speaker 3: are coming into hospital systems if you have the capacity
Speaker 3: to do that. On an individual level, whether a kid
Speaker 3: has RSV bronchiolitis or bronchiolitis caused by any other respiratory virus,
Speaker 3: which is possible. RSV is not the only thing that
Speaker 3: causes this same phenomenon of the plugging up of the
Speaker 3: small airways, the same way that influence is not the
Speaker 3: only thing that causes viral pneumonia. Right, So on an
Speaker 3: individual level, it really doesn't change management all that much
Speaker 3: to test or to not test, and tests can be expensive,
Speaker 3: they can be hard to get, so it might not
Speaker 3: be worth it to test an individual person for RSV. Okay,
Speaker 3: So there's not an easy answer there, but it is
Speaker 3: it's an interesting kind of you know, public health versus
Speaker 3: individual health versus like does it change a a doctor's
Speaker 3: or someone's management of a person who comes in with
Speaker 3: these symptoms?
Speaker 1: Right?
Speaker 2: Right?
Speaker 3: Yeah, And when we don't have any specific treatments the
Speaker 3: way that we do for say influenza, then yeah, it
Speaker 3: does it. It doesn't really change things that much. So a
Speaker 3: lot of times people aren't getting tested, which means we
Speaker 3: are underestimating our RSV burden compared to other viruses.
Speaker 2: Yeah.
Speaker 3: Yeah, we do have not a vaccine spoilers, and I'll
Speaker 3: talk more about that later, but we do have an
Speaker 3: interesting preventative treatment that is a monoclodal antibody called pallavismab
Speaker 3: that we can use as prophylaxis kind of like a
Speaker 3: vaccine in a way for kids with certain risk factors
Speaker 3: like the ones that I mentioned, kids who are born premature,
Speaker 3: who are under a certain age like six months, or
Speaker 3: who maybe have congenital heart disease or chronic lung disease
Speaker 3: of prematurity. This is amazing, right, Yeah, this is something
Speaker 3: that has good evidence can reduce severe disease and reduce
Speaker 3: hospitalization in these really high risk kids and babies. But
Speaker 3: because there's always butts, it is incredibly expensive. One estimate
Speaker 3: that I saw from I believe it was the UK,
Speaker 3: was like five thousand pounds per dose. Oh my gosh,
Speaker 3: I know, And I didn't see numbers on how expensive
Speaker 3: it is in the US. It's cumbersome. Yeah, More it's
Speaker 3: cumbersome because it is an injection like a vaccine, and
Speaker 3: it has to be given once a month, oh usually
Speaker 3: for five months during that RSV season, and it's imperfect.
Speaker 3: It doesn't prevent against infection necessarily, but it does reduce
Speaker 3: the risk of hospitalization. So because of all these limitations,
Speaker 3: I actually have no idea what the actual availability and
Speaker 3: access of this is, not just across the globe. I
Speaker 3: imagine the access across the globe is non existent in
Speaker 3: a lot of places, especially if you think about not
Speaker 3: just low and middle income countries that might not have
Speaker 3: access to an expensive drug, but also tropical latitudes where
Speaker 3: there isn't as well defined of a season of RSV.
Speaker 2: Yeah, but even in.
Speaker 3: Say rural parts of the US, I just don't know
Speaker 3: what access is actually like, it's hard to know, but
Speaker 3: that does exist, which I think is really promising. And
Speaker 3: I'll talk a little bit more at the end about
Speaker 3: other things that we're trying to do in terms of
Speaker 3: prevention for this incredibly prevalent disease.
Speaker 2: Yeah.
Speaker 3: And the last thing that I just want to kind
Speaker 3: of mention because I know someone is going to want
Speaker 3: to know about it, and it's really cool and interesting,
Speaker 3: even though I'm going to be like, I don't know
Speaker 3: the answer, is the association between RSV and asthma.
Speaker 2: Okay, So I was going to ask about this, but
Speaker 2: I was also going to ask a more open ended
Speaker 2: question that wasn't really a question, which I know is annoying,
Speaker 2: but like it is would be very interesting to look
Speaker 2: at in places with a clearly defined RSV season birth
Speaker 2: month and then like relationship to asthma and other later
Speaker 2: in life lung function or chronic lung diseases.
Speaker 3: Yeah, like if you were born where you got RSV
Speaker 3: in your first six months of life versus your later
Speaker 3: six months of life exactly and your tendency to develop asthma. Oh,
Speaker 3: that's super interesting. I wonder if that study has been done.
Speaker 2: It probably has, Yeah, I'll have to look.
Speaker 3: For it because that's super interesting. But there are definitely
Speaker 3: associations between RSV infection, especially severe RSV infection in childhood
Speaker 3: being associated with the later development of asthma or what's
Speaker 3: often called reactive airway disease in younger kids because you
Speaker 3: can't diagnose asthma until four or five years old. Okay,
Speaker 3: but as of right now, we do not have a
Speaker 3: clear sense of whether kids who are genetically predisposed to
Speaker 3: the development of asthma something about them makes them more
Speaker 3: susceptible to RSV or severe RSV infection, or is there
Speaker 3: something about RSV infection severe RSV infection that either precipitates
Speaker 3: or maybe even expedites the development in asthma in kids
Speaker 3: who are predisposed.
Speaker 2: Oh, that's hard to disentangle.
Speaker 3: It's very hard, and it's super interesting, and at this
Speaker 3: point it could kind of go either way. We know
Speaker 3: that there is an association, but we don't know in
Speaker 3: which direction it might go. I think from what I
Speaker 3: could tell, we have a little bit more data to
Speaker 3: suggest the former. So it's maybe kids who are genetically
Speaker 3: predisposed to asthma, like they'll probably develop asthma later in life,
Speaker 3: are more likely to get a severe RSV infection versus
Speaker 3: the other way. But it's still a really muddy picture,
Speaker 3: so we still don't know for sure.
Speaker 2: I have a question about the strains or subtypes or
Speaker 2: whatever they're called of RSV and the difference among them,
Speaker 2: and yeah, what we know about sort of how severity
Speaker 2: may change from year to year.
Speaker 3: Yeah, the short answer is, I don't have a ton
Speaker 3: of information for you on that. From what I've found,
Speaker 3: there's at least two major strains RSVA RSVB, and then
Speaker 3: there are other subtypes within that and other clinical strains
Speaker 3: that have been identified. But in general, both of these
Speaker 3: major strains circulate A and B at the same time.
Speaker 3: A tends to be overall a little bit more prevalent
Speaker 3: and perhaps a little bit more transmissible. But from what
Speaker 3: I found, we don't have great data on strain differences
Speaker 3: when it comes to disease severity or things like that.
Speaker 3: And I think it's probably because of how much we've
Speaker 3: just underestimated RSV in general. I don't know how often
Speaker 3: even if we're test for RSV, we're testing for strains
Speaker 3: of RSV.
Speaker 2: Speaking of transmissibility, do we have an r not estimate
Speaker 2: for this virus? Good question.
Speaker 3: It can vary, of course, but most estimates that I
Speaker 3: saw were around three. So for a reminder for anyone,
Speaker 3: that means that for every one person who's infected with RSV,
Speaker 3: they'll go on to infect three people on average. Right, Yeah,
Speaker 3: that's RSB biology.
Speaker 2: Erin, it's a lot, it's a lot. It's scary. I
Speaker 2: can't believe how much I didn't know about it, despite
Speaker 2: how prevalent it is. And to use I guess like
Speaker 2: outdated lingo, I would say, it seems like a very
Speaker 2: slept on virus.
Speaker 3: Yeah, and I feel like I'll talk even more about
Speaker 3: that later, but first, Erin, tell me what we know
Speaker 3: about where the virus came from, et cetera.
Speaker 2: Okay, I'll be the best I can right after this
Speaker 2: break to answer your question very briefly. We don't know
Speaker 2: exactly where RSV came from. Of course we don't, And
Speaker 2: you didn't ask like you usually do, how we got
Speaker 2: to where we are today. Oh yeah, but I can
Speaker 2: say that we probably got to where we are today
Speaker 2: because RSV did what respiratory viruses do best, they spread. That's,
Speaker 2: you know, I don't know. That's the best answer I have.
Speaker 2: But that's not going to be all of the history
Speaker 2: section because that would be a pretty lousy podcast episode
Speaker 2: if I ended it there. So let's get into it
Speaker 2: a little bit, starting with how we first learned about
Speaker 2: the virus. In October of nineteen fifty five, at the
Speaker 2: Walter Reed Army Institute of Research in Silver Spring, Maryland,
Speaker 2: a group of twenty quote unquote normal chimpanzees around fifteen
Speaker 2: to twenty months old began showing signs of a respiratory disease.
Speaker 2: Runny nose, sneezing, coughing, the usual, And at first it
Speaker 2: was just a handful of the chimpanzees, but within a
Speaker 2: few days nearly all of them had gotten sick. As
Speaker 2: listeners of this podcast are well aware, an outbreak of
Speaker 2: an apparently contagious disease in a population of lab animals
Speaker 2: sets off some pretty loud warning bells, and so the
Speaker 2: researchers at the institute were very eager to find what
Speaker 2: pathogen might be responsible. They took some throat swabs from
Speaker 2: the animals and ran a bunch of tests on it.
Speaker 2: I'm not going to bore you with the details, but
Speaker 2: ultimately what they found was not a familiar old measles
Speaker 2: or polio or or cocksacky virus, but a new thing entirely,
Speaker 2: a virus they named the chimpanzee Caariza agent not RSTY
Speaker 2: the link.
Speaker 3: You're expecting that to go a different way.
Speaker 2: Yeah. The link between this virus and the observed illness
Speaker 2: in the chimpanzees was confirmed when a few other chimpanzees
Speaker 2: got sick after being intentionally infected with the virus, and
Speaker 2: also when a lab worker got sick after unintentionally being infected.
Speaker 2: They all produced antibodies against the pathogen. Researchers Morris, Blount,
Speaker 2: and Savage published the account of this first observed epizootic
Speaker 2: of the chimpanzee Caariza agent in nineteen fifty six, and
Speaker 2: in it they didn't really hint at answering or even
Speaker 2: acknowledging the question of, like, how scared we need to
Speaker 2: be about this new pathogen. It seems to be able
Speaker 2: to infect both chimpanzees and humans. It's a really contagious respiratory,
Speaker 2: you know, a scary thing. But they didn't really talk
Speaker 2: about it. But in their very last sentence they did
Speaker 2: suggest that this agent may be a lot more widespread
Speaker 2: than just in chimpanzees. At the Walter Reed Institute quote. However,
Speaker 2: a number of human beings, particularly adolescents and young adults,
Speaker 2: have antibodies in their SIRA directed against the Kariza agent,
Speaker 2: suggesting that these individuals have experienced infection with the new
Speaker 2: agent or one closely related to it. Very shortly after
Speaker 2: this paper was published, two more came out that showed
Speaker 2: that this virus may be a significant cause of respiratory infections,
Speaker 2: especially in certain age groups. And the authors of these
Speaker 2: studies basically what they did was they set out to
Speaker 2: test what pathogens they could potentially find or isolate from
Speaker 2: infants with severe lower respiratory illness. Okay, and they wanted
Speaker 2: to see, Okay, what's this illness being caused by. Are
Speaker 2: there any new viruses or bacterial species that we need
Speaker 2: to worry about? And so on? And it just so
Speaker 2: happens that one of the viruses they isolated from these
Speaker 2: sick infants was indistinguishable from the chimpanzee cariza agent. Interesting,
Speaker 2: and the more people looked, the more they found that
Speaker 2: this virus, which was assumed to be new, may not
Speaker 2: be new at all and may actually be responsible for
Speaker 2: an incredible number of lower respiratory tract infections, particularly among
Speaker 2: infants and young children. Although already adults were also seen
Speaker 2: to have antibodies against the virus and to get sick themselves.
Speaker 2: Suggesting that reinfection was not just possible, but potentially common.
Speaker 2: And these authors also suggested in these papers that given
Speaker 2: the fact that chimpanzees are not the sole host nor
Speaker 2: were likely to be the reservoir species of this virus,
Speaker 2: and they are actually got it from humans, perhaps chimpanzee
Speaker 2: caariza agent was not the most fitting name. With its
Speaker 2: ability to produce sensicial changes in tissue cultures, which we
Speaker 2: now know what that means, and its manifestation as a
Speaker 2: respiratory infection, maybe it should be called something along the
Speaker 2: lines of respiratory sensicial virus. Definitely not like our most
Speaker 2: I don't know, captivating story of how something got its name,
Speaker 2: but I like it. Not but I like it.
Speaker 3: And you know what I like about it is it's
Speaker 3: like not controversial. Yeah, Like it's like, let's name this
Speaker 3: virus after what it does? What comes?
Speaker 2: Wow? Yeah, and yeah it happened pretty soon and then
Speaker 2: late nineteen fifties basically wow, okay, And what followed was
Speaker 2: what we often see with the identification of a new virus.
Speaker 2: People start looking for it, they start seeing more and
Speaker 2: more of it, and then the gaps in knowledge about
Speaker 2: the virus's epidemiology, the path of physiology, symptomology, all you know,
Speaker 2: and so on all started to be slowly filled in.
Speaker 2: For instance, as early as nineteen fifty eight nineteen fifty
Speaker 2: nine or so, physicians noticed that the virus could cause
Speaker 2: illness with a huge range of severity, from in apparent
Speaker 2: infection to fatal bronchiolitis. They noticed that the age group
Speaker 2: with the highest infection rates and severest symptoms was infants,
Speaker 2: who also may have the highest rates of viral shedding.
Speaker 2: They noticed that even though some infections may be mild
Speaker 2: or they all still seemed to involve the lower respiratory tract,
Speaker 2: and that infections, at least in North America followed this
Speaker 2: seasonal trend, which is the one that you described aaron
Speaker 2: infections rising in November December, peaking in January February, and
Speaker 2: falling to low levels by April. Over the next decades,
Speaker 2: into the nineteen seventies and the nineteen eighties, RSV became
Speaker 2: a very familiar name during the winter months, one of
Speaker 2: the usual suspects when somebody brought their infant or child
Speaker 2: into the doctor's office for acute respiratory symptoms and also
Speaker 2: a huge cause of hospitalizations for young children. For instance,
Speaker 2: studies from the nineteen eighties reported that during that decade
Speaker 2: and estimated one hundred thousand children were hospitalized for RSV
Speaker 2: each year in the US, costing three hundred million dollars annually.
Speaker 2: Who So, how did this virus become so prevalent in
Speaker 2: such a short amount of time. Maybe it didn't, Yeah,
Speaker 2: probably didn't. I think more likely it was there all along.
Speaker 2: I've tried to look into the evolutionary origins of RSV
Speaker 2: and earlier suspected outbreaks in human history, but I didn't
Speaker 2: really have much luck. And to me, honestly that that
Speaker 2: makes sense, right, Like, in terms of its relationship with
Speaker 2: humans throughout history, RSV does cause a super distinct infection.
Speaker 2: Many other viruses can cause illness that looks a lot
Speaker 2: like RSV, And so it's kind of hard to look
Speaker 2: back retrospectively as we know and go was that RSV
Speaker 2: was that influenza? Like? What could that have been?
Speaker 1: Right?
Speaker 3: It could have been any or all of the above, Yeah, exactly,
Speaker 3: rhinovirus and enterovirus, adinovirus, coronavirus, like the list goes on.
Speaker 2: The list goes on, And I think the timing of
Speaker 2: its identification in those chimpanzees probably coincided with improvements in
Speaker 2: microbiological techniques that allowed researchers to distinguish among viruses, which
Speaker 2: in previous decades had been fairly difficult. Whether or not
Speaker 2: there was an actual increase in the prevalence of the
Speaker 2: virus over the nineteen seventies, nineteen eighties, nineteen nineties, or
Speaker 2: it just looked that way because people finally had the
Speaker 2: tool to determine what was making you sick. It's unclear.
Speaker 2: I did wonder. I tried to look into this, but
Speaker 2: I didn't really see anything. I wondered whether there was
Speaker 2: a connection between the rise in daycare, if there was
Speaker 2: a rise in daycare during that time that also led
Speaker 2: to a rise in infections. But I didn't really find
Speaker 2: any papers that had investigated that. So it's just going
Speaker 2: to remain my little personal question.
Speaker 3: Yeah, our own little mystery.
Speaker 2: Yeah yeah, Or if how that changed, like the timing
Speaker 2: of infection right the first six months versus the first year,
Speaker 2: you know, like when? Yeah, I don't know. In any case,
Speaker 2: it seems pretty likely that RSV has been around for
Speaker 2: a very long time, contributing to the rise in respiratory
Speaker 2: infections that humans have seen in colder months or in
Speaker 2: rainy months for thousands of years. On the evolutionary side
Speaker 2: of things, like I said, there's not really much info
Speaker 2: that I could find about where specifically RSV came from
Speaker 2: and when it was estimated to have first infected humans.
Speaker 2: So I decided to broaden my search a bit to
Speaker 2: see if there had been any research on the evolutionary
Speaker 2: origins of the subfamily that RSV is part of, Numoviina,
Speaker 2: or the family paramixa Virida. The subfamily Numovina contains viruses
Speaker 2: that are very similar to human RSV, including murnumovirus, canine pneumovirus,
Speaker 2: bovine RSV, ovine RSV, and caprine RSV, and the paramix
Speaker 2: of Virida has some very familiar names measles, mumps, distemper,
Speaker 2: Newcastle disease. I found a paper from twenty twelve that
Speaker 2: I actually read for our mumps episode as well. I
Speaker 2: was like, this sounds familiar, and then I searched in
Speaker 2: my folders, and in that paper, the authors tested bat
Speaker 2: and rodent species for paramix viruses, and they found a
Speaker 2: bunch of novel viruses in bats that seemed to be
Speaker 2: relatives of RSV in humans. This doesn't mean that RSV
Speaker 2: came from bats, just that this bat RSV like virus
Speaker 2: and human RSV and bovine RSV all share a common ancestor.
Speaker 2: It does to me present the possibility that human RSV
Speaker 2: and other human pneumaviruses or paramixaviruses originally spilled over from
Speaker 2: a mammal species, whether that was bat or cow or
Speaker 2: rat or something entirely different. Interestingly, just a little asterisk
Speaker 2: human RSV is more closely related to bovine RSV than
Speaker 2: to these bat or mouse RSV like viruses. Ooh yeah,
Speaker 2: I wish I had more details for you, and also
Speaker 2: for myself, because I'm really curious to know more about
Speaker 2: the evolutionary origins of this virus, but sadly I don't
Speaker 2: have that information. If any of you out there listening
Speaker 2: has a paper or just has some info with some details,
Speaker 2: please send it our way. I'd love to read it.
Speaker 3: And I think even more recently they've even split rsvs
Speaker 3: the rsvs into a new new family a little separate
Speaker 3: from the paramixevere day.
Speaker 2: So I feel like the whole philogical it's of it's
Speaker 2: separate from paramixevere Day.
Speaker 3: Yeah, it's but it's new since like twenty sixteen.
Speaker 2: Ah, so I think April was twenty twelve.
Speaker 1: Yeah.
Speaker 3: Yeah, we'll probably see the like phylogeny of RSV continue
Speaker 3: to change as we you know, dig more down into
Speaker 3: the different streams and et cetera.
Speaker 2: Yeah, I mean, especially after this RSV season, I would
Speaker 2: imagine there to be a lot more research on the
Speaker 2: so maybe in a couple of years we'll revisit.
Speaker 3: Just like with influenza.
Speaker 2: Well that explains why I had a hard time finding
Speaker 2: evolutionary origins. I was like, what is this thing? Okay, okay,
Speaker 2: But regardless of so how RSV got into humans or
Speaker 2: when we first started getting sick from it, very soon
Speaker 2: after it was discovered, it became apparent what a huge
Speaker 2: problem this disease could be, and so naturally researchers and
Speaker 2: physicians began trying different methods to either treat or prevent
Speaker 2: RSV infections. Vaccination, like you mentioned aaron, was one route
Speaker 2: that was explored early on and continues to be explored.
Speaker 2: But like you said, we don't have a vaccine for RSV,
Speaker 2: and I know you're going to talk a lot more
Speaker 2: about why that is, and also where we stand with
Speaker 2: some of the vaccines in development today. There's also ribevierin
Speaker 2: a synthetic nucleoside imglobulent therapy, other experimental therapies like RNA
Speaker 2: interference therapy and so on, which I'm sure you'll talk
Speaker 2: more about some of these potential horizons for RSV treatment.
Speaker 2: In terms of the history of RSV specifically, that's really
Speaker 2: all that I have to offer. It was first recognized
Speaker 2: relatively recently as an important respiratory infection in young children.
Speaker 2: Its role in infecting older people and people who are
Speaker 2: immunocompromise has been observed. More recently, We've learned a lot
Speaker 2: about the year to year dynamics of the virus and
Speaker 2: its circulating strains. But don't worry. I'm not just going
Speaker 2: to stop here and leave you with this like super
Speaker 2: duper record short history section, especially for the season premiere,
Speaker 2: like I can't do that. Instead, I'm going to do
Speaker 2: a mini deep dive on a topic related to not
Speaker 2: just RSV, but many other respiratory viruses and respiratory diseases.
Speaker 2: It's a life saving therapy that you hope to never need,
Speaker 2: but are grateful for when it's there a device whose
Speaker 2: history goes back further than I ever imagined, and one
Speaker 2: that frequently dominated headlines, especially during the first couple months
Speaker 2: of the COVID pandemic. I'm talking about the mechanical ventilator.
Speaker 3: I can't tell you how excited I am about this.
Speaker 2: Well, it's going to be a very like cursory history.
Speaker 2: There's more details out there that I will post papers
Speaker 2: and everything, but it is going to be an exciting history.
Speaker 2: So I hope you like it. I can't wait. But
Speaker 2: like you said, Aaron, supportive care is really all we
Speaker 2: have at this time to treat RSV, and when cases
Speaker 2: are severe, sometimes that includes a mechanical ventilator. So I
Speaker 2: started thinking about where this amazing technology came from and
Speaker 2: how our understanding of the risks of lung injury and
Speaker 2: how breathing works has led to improvements in artificial ventilation.
Speaker 2: Our story starts in the mid sixteenth century with the
Speaker 2: anatomist Andreas Vesalius, whose name we may or may not
Speaker 2: have mentioned on the podcast before I can't remember, but
Speaker 2: whose anatomical illustrations I'm pretty certain we've posted on our
Speaker 2: social media.
Speaker 3: Got it.
Speaker 2: At this point in history, we didn't really know a
Speaker 2: whole lot about the inner workings of respiration. Basically, the
Speaker 2: writings of Galen from the second century CE describing breathing
Speaker 2: as necessary to maintain circulation and keep your heart beating.
Speaker 2: That's more or less as far as humanity had gotten
Speaker 2: in describing the purpose and mechanics of ventilation. So Visilius
Speaker 2: had a pretty open playing field then when it came
Speaker 2: to making advances in understanding form and function, especially respiration.
Speaker 2: In his fifteen forty three anatomy treatise De Humanicorporus, Visilius
Speaker 2: described what we would today recognize as positive pressure ventilation. Quote,
Speaker 2: but that life may be restored to the animal, and
Speaker 2: opening must be attempted in the trunk of the trachea,
Speaker 2: into which a tube of reed or cane should be put.
Speaker 2: You will then blow into this so that the lung
Speaker 2: may rise again and take air. How interesting isn't that? Like?
Speaker 2: Fascinated that? Yeah? Of course this wasn't Visalias just hypothesizing
Speaker 2: about how you could perform artificial respiration. He actually experimented
Speaker 2: on animals to show this. Yeah.
Speaker 3: Yeah, doing a bunch of tracheatomies sound like.
Speaker 2: Of course, as did Robert Hook, whose name you've definitely
Speaker 2: heard on the podcast. He coined the term cell made
Speaker 2: incredible advances in microscopes. Was also an astronomer, architect, physiologist,
Speaker 2: basically a big deal in the sciences in the sixteen hundreds,
Speaker 2: even though he reportedly had an abrasive personality that prevented
Speaker 2: his work from being known for a while. Just a
Speaker 2: bit of you know, see something on that yeah. In
Speaker 2: one of his many scientific ventures, Hook set his sights
Speaker 2: on testing Galen's hypothesis that the act of breathing was
Speaker 2: necessary for circulation. He took a dog, made a bunch
Speaker 2: of cuts in this poor dog's chest wall and pleura,
Speaker 2: and then used bellows like the things you used to
Speaker 2: blow air into a fireplace, to create a constant flow
Speaker 2: of air into the lungs, and observed what happened when
Speaker 2: he stopped wow quote this as in pumping air into
Speaker 2: the airway using bellows being continued for a pretty while,
Speaker 2: the dog lay still as before, his eyes beating very regularly.
Speaker 2: But upon ceasing this blast then suffering the lungs to
Speaker 2: fall and lie still, the dog would immediately fall into
Speaker 2: dying convulsive fits, but be as soon revived again by
Speaker 2: renewing the fullness of his lungs with a constant blast
Speaker 2: of fresh air. End quote. With this gruesome experiment, Hook
Speaker 2: showed that it was indeed airflow into the lungs that
Speaker 2: was necessary for circulation and thus life. Another one hundred
Speaker 2: plus years would pass before scientists learned what oxygen was
Speaker 2: and recognized its importance and respiration, which is a whole
Speaker 2: separate and cool story that I would love to tell someday.
Speaker 2: But an unfortunate consequence of this discovery of oxygen was
Speaker 2: that mouth to mouth resuscitation, which had been developed by
Speaker 2: that time, it fell out of use because people believed
Speaker 2: that the air you would be exhaling into someone else's
Speaker 2: lungs during mouth to mouth would not contain oxygen. Yeah,
Speaker 2: it would be depleted. How interesting? Yeah, huh. The next
Speaker 2: big advancement in artificial ventilation happened about one hundred years
Speaker 2: after then, when scientists began playing around with negative pressure ventilation.
Speaker 2: I'm going to pause here to explain briefly how negative
Speaker 2: pressure and positive pressure ventilation works, and the difference between them.
Speaker 2: When you breathe, your diaphragm contracts, which expands your chest
Speaker 2: cavity and allows you to fill your lungs with air,
Speaker 2: specifically your alveoli, which is where oxygen is exchanged for
Speaker 2: carbon dioxide in your blood. When you exhale, your diaphragm
Speaker 2: relaxes and you exhale that carbon dioxide along with a
Speaker 2: mixture of other gases, including oxygen. This normal lung function
Speaker 2: can be disrupted by a number of things, including respiratory
Speaker 2: infections such as RSV as you described aarin, and in
Speaker 2: severe cases, someone may need the assistance of a ventilator
Speaker 2: to make their lungs work and take in the oxygen
Speaker 2: they need. So how do these ventilators work. There are
Speaker 2: two general strategies, at least like how they're grouped historically.
Speaker 2: For artificial ventilation. There's negative pressure ventilation, which was the
Speaker 2: first to be developed and widely applied starting in the
Speaker 2: early nineteen hundreds, but isn't really in use anymore. And
Speaker 2: there's positive pressure ventilation, which is what the ventilators we
Speaker 2: see today use. Negative pressure ventilation works like this. Basically,
Speaker 2: you seal someone's body from the neck down or at
Speaker 2: the very least leaving just their mouth and nose open,
Speaker 2: into an enclosed air tight room or box. Then you
Speaker 2: suck out all the air from that space, creating negative pressure.
Speaker 2: This causes the chest cavity to expand with air, allows
Speaker 2: your lungs to draw in that air, and then you
Speaker 2: would pump air back into the room or box, so
Speaker 2: bringing the pressure back up, and that would lead to exhalation.
Speaker 2: This is how an iron lung works.
Speaker 3: I was just gonna say that sounds like an iron
Speaker 3: lung exactly.
Speaker 2: Yeah. Positive pressure ventilation, on the other hand, involves using
Speaker 2: pressurized air to fill the lungs, such as with like
Speaker 2: an oxygen mask over your face for instance, or in
Speaker 2: more extreme circumstances, doing like you said, airin intubation, so
Speaker 2: tubing applied directly to the lungs. That essentially takes over
Speaker 2: the whole breathing process from inhalation to exhalation. And this
Speaker 2: is what we see in hospitals today, these big specialized
Speaker 2: machines that were the topic of much concern and discussion
Speaker 2: during COVID peaks, when hospitals began to run out of them,
Speaker 2: for instance, and many places didn't have them for instance.
Speaker 3: And importantly, much smaller devices than a negative pressure But.
Speaker 2: Yes, that is yeah, definitely all right. But now let
Speaker 2: me get back into the history of the development of
Speaker 2: these types of mechanical ventilation and why we switched from
Speaker 2: mostly negative pressure to positive pressure devices. One of the
Speaker 2: first negative pressure ventilation boxes was developed by a scientist
Speaker 2: named Alfred Jones in the eighteen sixties, and this is
Speaker 2: where air pressure within the box was altered using a
Speaker 2: plunger annually. Yeah. Jones advertised his ventilator as the cure
Speaker 2: for an impressive number of conditions such as paralysis, neuralgia, asthma, bronchitis, dyspepsia,
Speaker 2: and deafness. Deafness, Yeah, I don't, I don't understand, but
Speaker 2: it was the eighteen sixties, like anything goo. An early
Speaker 2: version of what would later be known as an iron
Speaker 2: lung was developed in the eighteen seventies with the intention
Speaker 2: of placing these along the scent to resuscitate people who
Speaker 2: had drowned. Oh yeah, kind of an interesting little thought there.
Speaker 2: But the real iron lung, the one that was so
Speaker 2: integral during the first half of the twentieth century during
Speaker 2: polio outbreaks, it's the iron lung that you're picturing right
Speaker 2: now in your head. That was developed by Philip Drinker
Speaker 2: and Lewis Shaw at the Harvard School of Public Health
Speaker 2: in the late nineteen twenties. Drinker got the idea after
Speaker 2: treating people with paralytic forms of respiratory failure, especially from polio.
Speaker 2: So he thought, if only I could develop some sort
Speaker 2: of machine that would maintain ventilation support, you know, just
Speaker 2: for a little bit of time without having to tend
Speaker 2: to it, you know, have it be automatically administered, just
Speaker 2: until their lungs heal enough so that they can breathe
Speaker 2: on their own, just until they get better. And he
Speaker 2: first tested his iron lung on cats and then found success,
Speaker 2: and then he tested it on himself and then other volunteers.
Speaker 2: But the first patient to use Drinker's iron lung was
Speaker 2: an eight year old girl who was having trouble breathing
Speaker 2: due to a polio infection. Her breathing was getting weaker
Speaker 2: and weaker, her lips were turning blue, and just at
Speaker 2: the point when her doctor thought she wouldn't be able
Speaker 2: to recover, they decided to try the iron lung. Almost
Speaker 2: immediately after being placed in the device, she recovered consciousness
Speaker 2: and asked for ice cream, which I love. I thought
Speaker 2: that was so sweet.
Speaker 3: That's so eight year old, I know, so cute.
Speaker 2: She was able to be taken out of the iron
Speaker 2: lung after just three and a half hours. Wow. Ultimately,
Speaker 2: she did end up dying from pneumonia, but this instance
Speaker 2: showed that the device held great potential for breathing assistance.
Speaker 2: The iron lung and other negative pressure ventilation devices were
Speaker 2: certainly a huge step forward in terms of respiratory support,
Speaker 2: but they did leave a lot to be desired. If
Speaker 2: you picture one of these things, your body has to
Speaker 2: be sealed off from it, and that makes it impossible
Speaker 2: for healthcare workers to tend to any other part of
Speaker 2: your body that's inside this iron lung, for instance, not
Speaker 2: to mention the discomfort that you would feel not being
Speaker 2: able to move or like just be trapped in this
Speaker 2: you know machine. And so to deal with this lack
Speaker 2: of access to the body, they thought, let's just build
Speaker 2: a whole negative pressure room where you can hold multiple
Speaker 2: patients in like bunk beds, and you have their heads
Speaker 2: just like sticking out of the wall, and then like
Speaker 2: a nurse or a doctor could go into that room
Speaker 2: and then tend to the patient's bodies. Interesting. Yeah, that
Speaker 2: obviously not the most logistically sound solution. Difficult, Yeah, the
Speaker 2: need for an alternative solution. Two iron lungs became very
Speaker 2: apparent during the polio epidemic of the nineteen fifties, where
Speaker 2: cases were so high that hospitals ran out of iron lungs.
Speaker 2: And you can look up these photos of hospital wards
Speaker 2: with rows upon rows of the machines. When there was
Speaker 2: an iron lung shortage, some hospitals resorted to performing tracheostomies
Speaker 2: and then manually ventilating patients, which was previously only something
Speaker 2: done in an emergency or while operating. I want to
Speaker 2: read you a description of the situation from a hospital
Speaker 2: in Copenhagen in nineteen fifty quote. During several weeks, we
Speaker 2: had forty to seventy patients in our hospital requiring continuous
Speaker 2: or intermittent bag ventilation. To do this, we have employed
Speaker 2: about two hundred medical students daily. Oh my gosh, yeah daily.
Speaker 2: I read one paper that put the total number of
Speaker 2: students providing manual ventilation at fifteen hundred and the total
Speaker 2: number of hours at one hundred and sixty five thousand.
Speaker 3: Wow.
Speaker 2: Doing continuous handbagging ventilation.
Speaker 3: Yeah yeah, it's not easy to do.
Speaker 2: No, And it was actually because it was easier to
Speaker 2: put all of these patients needing ventilation in one area
Speaker 2: of the hospital that marked the beginnings of ic use.
Speaker 3: Huh. Oh that's a fun fact.
Speaker 2: Isn't that. Another silver lining to this was that it
Speaker 2: became obvious that positive pressure ventilation, as in the handbagging
Speaker 2: that had to be done, resulted in about half the
Speaker 2: mortality rate of the negative pressure ventilation.
Speaker 3: I am so interested in the order that things have
Speaker 3: gone here because the very first accounts that you talked
Speaker 3: about with the dog and the bellows, like, that's positive pressure.
Speaker 3: So to go from that to like, hey, let's do this,
Speaker 3: but we're going to do it in a really weird, roundabout,
Speaker 3: cumbersome way of negative pressure, and then come back to
Speaker 3: being like, oh no, actually, positive pressure. It's a lot easier,
Speaker 3: it makes a lot more sense. It's just oh, that's
Speaker 3: so so fascinating.
Speaker 2: So there definitely were positive pressure ventilation devices that were
Speaker 2: either being designed or in like limited use alongside these
Speaker 2: negative pressure ventilation machines like the iron lung. And I
Speaker 2: wonder whether it was the prevalence of polio and like
Speaker 2: paralytic or partial paralysis in your respiratory system or whatever
Speaker 2: that may have been the more pressing need at times.
Speaker 2: But I don't really know, like why does one idea
Speaker 2: catch on and one doesn't marketing. Yeah, but even the
Speaker 2: person who developed the iron lung also was working on
Speaker 2: a positive pressure ventilation device. Interesting, so it's yeah, yeah, this,
Speaker 2: this polio epidemic during the nineteen fifties really showed that like, hey,
Speaker 2: we should maybe not do that anymore and turn towards
Speaker 2: positive pressure ventilation.
Speaker 3: Work on making this one more efficient as.
Speaker 2: Well, exactly. Yeah, And so I think that's really was
Speaker 2: this turning point, this realization at how much better outcomes
Speaker 2: were with positive pressure ventilation in polio alone. That led
Speaker 2: to attention and like all of the funding basically being
Speaker 2: put into positive pressure ventilation machines.
Speaker 3: Cool.
Speaker 2: And so after this turning point of the nineteen fifties
Speaker 2: positive pressure ventilation machines, that's where most of the attention
Speaker 2: began to be focused. And so it really became about
Speaker 2: improving the functionality, just like making little tweaks here and
Speaker 2: there on those machines, because they came onto the scene
Speaker 2: during a time when their main purpose was to essentially
Speaker 2: replace respiratory muscles or respiratory function. But over the next decades,
Speaker 2: especially with declining rates of polio, thanks to the vaccine.
Speaker 2: They began to be used to correct the levels of
Speaker 2: oxygen that someone was getting, which was possible due to
Speaker 2: a greater under standing of the different gases in our
Speaker 2: blood and how to measure them and monitor continuously and
Speaker 2: then make tiny adjustments here and there, and so all
Speaker 2: of this was done in sort of like you know,
Speaker 2: gradual fashion. We've come a very long way since those
Speaker 2: early ventilators, not just the iron lung but the first
Speaker 2: positive pressure ventilators that came on the scene, and we've
Speaker 2: come a long way both in terms of technological improvements
Speaker 2: in these ventilators as well as strategies of use like
Speaker 2: full support to partial support, because there are, like I mentioned,
Speaker 2: there are risks and negative health consequences to using these ventilators,
Speaker 2: and so that's been really crucial over the past few years.
Speaker 2: But we're still we're still learning very very much. As
Speaker 2: the COVID pandemic has made painfully clear. The ventilators that
Speaker 2: we currently use are expensive, they require highly trained individuals,
Speaker 2: They are not as bulky as iron lungs, but are
Speaker 2: still bulky and not very mobile, and we really need cheaper,
Speaker 2: more transportable, and easier to use ventilators to increase access
Speaker 2: to these life saving devices, and this seems to be
Speaker 2: a pretty exciting and active area of research. I didn't
Speaker 2: do very much digging into like where we stand today,
Speaker 2: because that's more of your thing. But I did come
Speaker 2: across one paper that described a soft implantable robotic ventilator
Speaker 2: which helps diaphragm function, so that could be kind of cool.
Speaker 2: Hopefully we'll see some improvements or cool new approaches to
Speaker 2: ventilation in the future. But the future is outside of
Speaker 2: my jurisdiction for this podcast, as is the present, really,
Speaker 2: so I'll hand it over to you, Aaron, to tell
Speaker 2: me where we stand with this virus today and just
Speaker 2: how unusual twenty twenty two to twenty twenty three was
Speaker 2: in terms of case numbers.
Speaker 3: I can't wait to tell you right after this break.
Speaker 3: As always on this podcast, Aaron, we're going to be
Speaker 3: working with estimates here and not exact numbers. Love it,
Speaker 3: especially when we look globally. But I have some pretty
Speaker 3: grim things to talk about right now.
Speaker 2: Not surprised.
Speaker 3: RSV, according to one of the papers that I read,
Speaker 3: is estimated to be the second leading cause of infant
Speaker 3: mortality after the neonatal period. Wow, and ninety nine percent
Speaker 3: of these deaths, the overwhelming majority of these deaths are
Speaker 3: happening in low and middle income countries.
Speaker 2: It is number one diarrheal.
Speaker 3: Diseases, I believe so, although the paper didn't actually specify,
Speaker 3: but I'm pretty sure it's diarrhea. Yeah, So when we
Speaker 3: what does that mean in terms of actual numbers. Unfortunately,
Speaker 3: a lot of this data is a little bit old.
Speaker 3: It's from about twenty ten. These the best estimates that
Speaker 3: we have. I don't think there's been huge declines by
Speaker 3: any means in RSV infection, so we'll kind of just
Speaker 3: use these estimates as like general numbers. But the estimated
Speaker 3: total annual global burden of RSV in children under age five,
Speaker 3: because this is the group that we look at the
Speaker 3: most significantly, is almost thirty four million episodes of a
Speaker 3: Q lower respiratory illness. So that's not even close to
Speaker 3: everyone who's affected, but these are the kids who are
Speaker 3: getting quite sick lower respiratory tract infections.
Speaker 2: That's so many.
Speaker 3: This likely results in about three and a half million hospitalizations.
Speaker 3: And again remember that when we talk about hospitalizations, in
Speaker 3: a lot of places, there's not access to hospitals so
Speaker 3: keep that in mind. And an estimated two hundred and
Speaker 3: fifty three thousand deaths globally in kids under five in twenty.
Speaker 2: Ten, Oh my gosh, two hundred.
Speaker 3: And fifty thousand children. And again these are probably underestimates though.
Speaker 3: These estimates, and the reason that twenty ten numbers are
Speaker 3: often cited is because they're thought to be a lot
Speaker 3: more accurate than previous estimates, which were way lower, Okay,
Speaker 3: way lower. If we look at the US specifically, because
Speaker 3: I have some data from the US, it's estimated that
Speaker 3: there are over two million outpatient visits for RSV in
Speaker 3: kids under age five, two million kids going to the
Speaker 3: doctor with RSV. Wow, anywhere from about fifty eight or
Speaker 3: sixty to eighty thousand hospitalizations every year, and an additional
Speaker 3: sixty to one hundred and twenty thousand hospitalizations for adults
Speaker 3: over age sixty five Yhi is so much higher than
Speaker 3: I realized.
Speaker 2: Yeah, it's estimated.
Speaker 3: That between six and ten thousand adults over age sixty
Speaker 3: five die from RSV every year, six and ten thousand,
Speaker 3: according to the CDC, and between one hundred and three
Speaker 3: hundred deaths in kids under age five.
Speaker 2: Wow, I know it's a lot.
Speaker 3: And like we kind of alluded to a little bit earlier.
Speaker 3: While this is generally a seasonal virus in temperate regions,
Speaker 3: so in North America, our winter goes from November ish
Speaker 3: to February ish, and that tends to be when we
Speaker 3: see RSV starting to build up in November, peaking around February,
Speaker 3: and then declining thereafter. It circulates year round, but that
Speaker 3: tends to be when the peaks are and when hospitalization
Speaker 3: tends to be the highest. The COVID nineteen pandemic has
Speaker 3: changed a lot of things. We talked about that in
Speaker 3: our influenza episode at the end of last season, and
Speaker 3: I'm sure we'll talk about it in future respiratory episodes
Speaker 3: as well. And the truth of it is, I don't
Speaker 3: think we fully understand how much it's going to change
Speaker 3: and how lasting this change is going to be. But
Speaker 3: for the year and a half, two years where we
Speaker 3: were really quite locked down, so like twenty twenty twenty
Speaker 3: twenty one, we saw significantly less RSV, especially in young kids,
Speaker 3: than we had seen previously, like a lot less, a
Speaker 3: lot less hospitalizations, and just a lot less doctor's visits
Speaker 3: in general for RSV and other respiratory Infections twenty twenty two.
Speaker 3: What we saw was really early RSV starting at the
Speaker 3: end of summer and reaching peaks even into October and November,
Speaker 3: like what are normally peak numbers. We're recording this right now,
Speaker 3: full disclosure in December of twenty twenty two, and this
Speaker 3: will be released at the end of January. I don't
Speaker 3: know what's going to happen. I don't have a crystal ball,
Speaker 3: but I won't be surprised if this infection has either
Speaker 3: another peak or has a very very long tail right
Speaker 3: where we see a lot more infections just persisting for longer,
Speaker 3: more hospitalizations for longer because there's a large cohort of
Speaker 3: kids who might be being exposed to RSV for the
Speaker 3: first time later in their life because this is the
Speaker 3: first time they've been around other kids.
Speaker 2: Yeah.
Speaker 3: Right, So it's really interesting kind of how it's all
Speaker 3: going to play out and what it's going to mean
Speaker 3: in the long term, Like what's our RSV season going
Speaker 3: to look like next year or the year after. I
Speaker 3: don't think that we know.
Speaker 2: Yeah, and it's it's interesting but also very stressful. Seems
Speaker 2: like not a big enough word for it.
Speaker 3: Yeah, Yeah, definitely especially because, as I mentioned, we still
Speaker 3: don't have a vaccine.
Speaker 2: Yeah, yeah, I mean when reinfections are common. Yeah, how
Speaker 2: do you.
Speaker 3: How do you make a vaccine? So it's an interesting
Speaker 3: story the vaccines. There have been I don't even know
Speaker 3: how many different candidate vaccines that have made it through
Speaker 3: various stages of pre clinical and clinical trials, even as
Speaker 3: far as you know, phase three clinical trials. But so
Speaker 3: far it's just been very difficult to develop a vaccine
Speaker 3: that has a good balance of immunogenicity, so actually stimulating
Speaker 3: enough of an immune response to be protective, especially in
Speaker 3: the kids who are the most vulnerable, right the youngest
Speaker 3: of kids age zero to six months or up to
Speaker 3: a year, who are going to be infected for the
Speaker 3: first time, who we know are at highest risk of
Speaker 3: severe infection, stimulating enough of an immune response to provide
Speaker 3: protection while also being safe and not causing any adverse effects.
Speaker 3: There was a vaccine candidate back in the nineteen sixties
Speaker 3: that was an inactivated version of an RSV virus that
Speaker 3: was inactivated with formuline that ended up causing significantly worse
Speaker 3: disease in that vulnerable population in young infants. It caused
Speaker 3: what was called an enhanced respiratory disease after a first
Speaker 3: vaccination in kids who had never been exposed to RSV before,
Speaker 3: and that is terrible and horrific, and because of that,
Speaker 3: it really set things back a ways because it's going
Speaker 3: to of course, make people a lot more cautious when
Speaker 3: it comes to future vaccines and clinical trials, especially for
Speaker 3: that population who is so vulnerable to begin with. And
Speaker 3: longtime listeners of this podcast will know and remember from
Speaker 3: many of our episodes just how rigorous safety standards are
Speaker 3: when it comes to vaccines and their testing and implementation,
Speaker 3: which over the years, especially since the nineteen sixties, has
Speaker 3: only become more rigorous, right, which is a good thing,
Speaker 3: but it also means that it takes a lot longer
Speaker 3: to develop these vaccines. That's kind of the long and
Speaker 3: short answer of why we still don't have one. There
Speaker 3: are dozens of vaccine candidates, and what I think is
Speaker 3: really interesting is that not only are there candidates of
Speaker 3: various vaccine platforms that are understudy, like everything from live
Speaker 3: attenuated vaccines to whole inactivated or killed vaccines, to component
Speaker 3: vaccines or protein vaccines to bah bah bah blah mRNA
Speaker 3: and RNA like yeah, nucleic acid based vaccines like the
Speaker 3: covid ones. So there's people doing research on like every
Speaker 3: different vaccine type that you can imagine. But there's also
Speaker 3: different populations that people are trying to target for protection,
Speaker 3: which is really interesting in the context of RSV. So first,
Speaker 3: we know that older adults are also at really high risk,
Speaker 3: So there's people working on vaccines that are going to
Speaker 3: target older adults to just boost their immunity or something
Speaker 3: like that. There's also an effort to target just older
Speaker 3: kids in general, because older kids, especially after six to
Speaker 3: twelve months, that's when we tend to start to use,
Speaker 3: usually at twelve months live attenuated vaccines. But then there's
Speaker 3: these really vulnerable tiny infants, and we don't have vaccines
Speaker 3: for them right now, and we had really bad experience
Speaker 3: with the vaccines we tried to develop in nineteen sixty
Speaker 3: So another potential way to protect those youngest babies who
Speaker 3: are most vulnerable is maternal vaccination. So vaccination during pregnancy
Speaker 3: the way that we do for protessis YEP, and so
Speaker 3: there's also groups that are working on developing maternal vaccines
Speaker 3: that produce enough immunity that can be passed through the
Speaker 3: placenta and potentially through breast milk as well to provide
Speaker 3: protection to these youngest of infants. So cool. Plus, as
Speaker 3: I mentioned, there is already a monoclonal antibody that is
Speaker 3: in use, and there is work on additional monoclonal antibodies
Speaker 3: or other ways to give monoclonal antibodies that might be
Speaker 3: more cost effective, et cetera. And even though, like you
Speaker 3: mentioned Aaron, we get reinfected with this virus all the time, right,
Speaker 3: which makes you think, like, how can you develop a
Speaker 3: vaccine for something that we just get reinfected with all
Speaker 3: the time? Flu?
Speaker 2: Right? Flu?
Speaker 3: Yeah, But what we know about RSV is that it's
Speaker 3: that first exposure that is often one of the most
Speaker 3: highest risk times. And we know that things like maternal
Speaker 3: antibodies or these monoclonal antibodies or previous infection where you've
Speaker 3: developed at least some antibodies provides protection against severe disease
Speaker 3: and hospitalization, which means it provides protection against death, right.
Speaker 3: And so because of that, there is this theoretical we
Speaker 3: should be able to develop a vaccine that's at least
Speaker 3: protective against severe disease and hospitalization.
Speaker 2: Right, doesn't need to be like perfect for everyone at
Speaker 2: all times, priorities exactly that you can put into vaccine development.
Speaker 3: Yeah, right, and so that's yeah, it's there's a lot
Speaker 3: of hope and there's so many different groups that are
Speaker 3: working on all of these different aspects.
Speaker 2: Oh my gosh, so many, but as of now, we.
Speaker 3: Still don't have one. We also, this is a human
Speaker 3: specific virus, and we don't have good animal models for RSV,
Speaker 3: which makes it that much harder to develop vaccines. Yeah,
Speaker 3: but there's I think a lot of hope on the horizon,
Speaker 3: and I think, like you mentioned, Aaron, this is something
Speaker 3: that we're hearing about more and more and more. And
Speaker 3: the more that diseases get press the more that they
Speaker 3: get funding, and the more that they get funding, the
Speaker 3: faster that we get new technologies.
Speaker 2: Yeah. So hopefully we'll see that in the future then, yeah, exactly.
Speaker 2: But that is RSV. Wow, what a way to start
Speaker 2: season six.
Speaker 3: Yeah, I'm pretty excited about it.
Speaker 2: I have a bunch of papers I want to shout
Speaker 2: out just a couple of them. So in terms of
Speaker 2: the history of RSV, that first paper by Morris at
Speaker 2: All from nineteen fifty six is actually kind of an
Speaker 2: interesting read. And then for the history of mechanical ventilation,
Speaker 2: there are several papers. One I really liked by Petty
Speaker 2: from nineteen ninety and I also want to shout out
Speaker 2: a ted Ed video that I watched to teach me
Speaker 2: how ventilators work because I had no idea, and I
Speaker 2: will link to that video on our website as well.
Speaker 3: I also had quite a number of papers. One of
Speaker 3: my favorites, just very like broad Overview, was an older
Speaker 3: paper by Wellever from two thousand and three in the
Speaker 3: Journal of Pediatrics. If you want more on RSV and
Speaker 3: asthma and those you know details, there was a paper
Speaker 3: by han at All from twenty eleven. I have a
Speaker 3: number of different papers on vaccines and where we stand
Speaker 3: with vaccine candidates and vaccine research. And we'll post all
Speaker 3: of our sources from this episode and every one of
Speaker 3: our five other seasons worth of episode on our website
Speaker 3: this podcast will Kill You dot Com under the episodes tab.
Speaker 2: We certainly will thank you again so much, Lucy for
Speaker 2: sharing your story with us. Yeah, yeah, thank you.
Speaker 3: Thank you also to Leanes Guilichi for our audio mixing.
Speaker 3: We are thrilled to have you on board for the
Speaker 3: first time.
Speaker 2: This season, we are and speaking of addit than you.
Speaker 2: Thank you to Bloodmobile, who provides the music for this
Speaker 2: episode and all of our episodes.
Speaker 3: Thank you to the Exactly Right Network.
Speaker 2: And thank you to you listeners. Thanks for joining us
Speaker 2: again this season. Uh AS always send your suggestions. There
Speaker 2: is now a submit your first hand account link on
Speaker 2: our website. And yeah, we always love hearing from you.
Speaker 2: You're the best. You make this possible.
Speaker 3: An extra shout out to our patrons, Thank you so
Speaker 3: much for your support. Always we love you. We do well.
Speaker 2: Until next time, wash your hands.
Speaker 3: You filthy animals.
Speaker 2: Um