Speaker 1: My name is Titiano. I'm from the northeast of Italy.
Speaker 1: I live in a small town in the northeast. I'm
Speaker 1: a school teacher. I teach English in a secondary school here.
Speaker 1: In February there was all the attention was on a
Speaker 1: couple of tourists going around and so on. Then on
Speaker 1: the twenty first, we got our first cases here in Italy.
Speaker 1: They were limited to a small number of towns in
Speaker 1: the north. What happened was that following week it was
Speaker 1: a short Tuesday, so schools were already closed for a
Speaker 1: couple of days. So over the course of that weekend,
Speaker 1: the first ten or so towns were quarantined and all
Speaker 1: the schools in the north were closed. What happened next
Speaker 1: is that the regions asked for and got an extension
Speaker 1: of the closure of the schools. So it's been three
Speaker 1: full weeks now since schools have closed, and there's another
Speaker 1: three weeks planned ahead of us. At least I'm at
Speaker 1: school teacher, so it's been not easy to cope with
Speaker 1: all of this. So the thing is, the schools stopped,
Speaker 1: but the rest of the country went on. But things
Speaker 1: started moving fast. So we are now under this lockdown
Speaker 1: which means that we cannot leave our homes unless it's
Speaker 1: for either work reasons or basic needs. Kind of a
Speaker 1: soft lockdown, because we can actually move, but we have
Speaker 1: to provide some sort of declaration of written statement for
Speaker 1: the reason why we are out of our homes. Until
Speaker 1: the government came out with the lockdown, I think people
Speaker 1: didn't really appreciate what that meant. And so it was
Speaker 1: just a few days before that that there were still
Speaker 1: parties going on and restaurants and so on for the
Speaker 1: let's say, for the lockdown we are under now. So
Speaker 1: if I was to you know, go out small without
Speaker 1: a good reason, So if police is going to stop
Speaker 1: you and check your statement, so if it's for worksons,
Speaker 1: they are going to call your workplace and that so
Speaker 1: there is a fine or you could face charges. You
Speaker 1: could go to jail, but that's only for extreme cases
Speaker 1: after the last regulations. So this past week, I think
Speaker 1: that people are taking the thing more seriously and from
Speaker 1: what I see from my immediate vicinity and people I know,
Speaker 1: we are starting to embrace the social distancing and so
Speaker 1: we are moving to skype calls with friends and we're
Speaker 1: you know, the indoors life as much as you can,
Speaker 1: and as a school teacher I maybe have a slightly
Speaker 1: different perspective than most other people because we started from
Speaker 1: the very beginning to find ways to still keep doing
Speaker 1: school in some form, but there wasn't really a plan
Speaker 1: for that, so a lot of it was left to
Speaker 1: our own you know, creativity and good will to do things.
Speaker 1: There are there are still issues with that. The first
Speaker 1: one is that it's very hard to keep in touch
Speaker 1: with all our students because of course not everybody is available,
Speaker 1: not everybody has the same resources, and it's hard and
Speaker 1: it's impact families, especially families where the parents are still
Speaker 1: working and so they need to take care of the children.
Speaker 1: Traditionally here families are very close knit and this was
Speaker 1: something that often grandparents did. But parents are of course
Speaker 1: one of the most impacted categories for the yeah for
Speaker 1: the virus, so that that has raised some issues. We
Speaker 1: have one of those flash mobs on the balconies every
Speaker 1: day basically, you know, I mean a small town, so
Speaker 1: there's not a lot of houses around here. Every day
Speaker 1: there's someone either playing songs or the other day they
Speaker 1: were tapping for the people in the medical professions, which
Speaker 1: are doing a great job and taking Dublin gifts to
Speaker 1: cover every everything. So that's that's good. There's this other
Speaker 1: thing that's going on now, which is the kids are
Speaker 1: making these rainbow paintings and with an action that is basic,
Speaker 1: everything will be fine in Italian and they are, you know,
Speaker 1: sharing those pictures on the social media. This is bringing
Speaker 1: out a lot of you know, good things. I see
Speaker 1: that really people care, people care about their neighborhoods, people
Speaker 1: care about what's going on. That's a big thing. H
Speaker 1: h yah m m m hm hm h.
Speaker 2: You just heard from Tiziano, who was kind enough to
Speaker 2: spare us a few minutes to chat about his experiences
Speaker 2: while under lockdown in Italy. Thanks so much for chatting
Speaker 2: with us.
Speaker 3: Yeah, we really appreciate it.
Speaker 4: Hi.
Speaker 3: I'm Aaron Welsh and I'm Erin alman Updyke and.
Speaker 2: You're listening to this podcast will kill you?
Speaker 5: Oh?
Speaker 3: Yes you are?
Speaker 1: You are?
Speaker 2: Yes, Welcome to our first ever minisode series, which we're
Speaker 2: calling Anatomy of a Pandemic, and which is shaping up
Speaker 2: to be less of minisodes and more like full length ones.
Speaker 3: So yeah, it's Maxiodes.
Speaker 2: Sorry, not sorry, I don't know.
Speaker 3: It's long strap in.
Speaker 2: There's a lot of information out there, and there's a
Speaker 2: lot of ground to be covered, so you know, we're
Speaker 2: gonna do the best we can. And this is this
Speaker 2: is the first ep episode of six that we're dropping
Speaker 2: all at once, but throughout this pandemic, as it progresses,
Speaker 2: we're going to keep revisiting different topics or visiting new
Speaker 2: topics to get you all the information that you could
Speaker 2: ever want about COVID nineteen yep. So we asked everyone
Speaker 2: out there for questions, and hundreds of you submitted your questions.
Speaker 2: So first of all, thank you so very much because
Speaker 2: that really helped us to figure out what you wanted
Speaker 2: to know and how to organize these episodes, and so
Speaker 2: we are so excited to bring you not one, but
Speaker 2: six of these episodes where we ask the experts to
Speaker 2: answer your questions.
Speaker 3: So today we're starting with chapter one, the virus itself,
Speaker 3: and that's what we're going to cover in this episode.
Speaker 3: But before we get started, we have to report, of
Speaker 3: course that if ever it was quarantin any time, right
Speaker 3: now is most definitely quarantine time.
Speaker 2: Most definitely.
Speaker 3: Quarantinies have been making the rounds in social media, and
Speaker 3: first of all, we appreciate everyone shouting us out in that,
Speaker 3: yeah we do. So what are we drinking today?
Speaker 2: Erin, we are drinking what we're just calling Quarantini one,
Speaker 2: because you know, let's keep it simple.
Speaker 3: We'll keep it simple. Disclaimer, if you're going to listen
Speaker 3: to all six of these episodes in one sitting, you
Speaker 3: don't need to make all six Quarantinies.
Speaker 2: That's probably a bad idea, I personally, So I'm recording this.
Speaker 2: It's eight my time, and I'm drinking coffee.
Speaker 3: It's ten am my time. I'm drinking water. But I
Speaker 3: did drink at Quarantini last night while researching.
Speaker 2: I drank a couple while taking the pictures of them all.
Speaker 2: It's important you gotta taste us.
Speaker 3: So what is Quarantini number one?
Speaker 1: Erin?
Speaker 2: Quarantine number one has rum, it has coconut cream, it
Speaker 2: has lime juice, and and you know, we wanted to
Speaker 2: make these so that hopefully they are things that you
Speaker 2: might have lying around the house, more simple ingredients and
Speaker 2: so on. But I will suggest if you happen to
Speaker 2: have Apricot licour pop, some of that in there as well.
Speaker 3: If your bar card is as well stocked as Aaron Welshit.
Speaker 2: Apricot licour is really good in tiki drinks. Yeah, that's
Speaker 2: all I would say.
Speaker 3: I believe you.
Speaker 2: We will post the recipe for that quarantini Quarantini one,
Speaker 2: as well as the non alcoholic Placy burrita on all
Speaker 2: of our social media pages and our website. Excellent.
Speaker 3: All right.
Speaker 2: So, so, way back in February, which feels honestly like
Speaker 2: an entire lifetime ago, we did a whole episode about
Speaker 2: coronaviruses in general, and so we wanted to give you
Speaker 2: a really quick recap on that. All right, So, coronaviruses
Speaker 2: are not brand new alien viruses. There are large family
Speaker 2: viruses that infect a number of different animals. SARS COVID two,
Speaker 2: which stands for Severe Acute Respiratory syndrome coronavirus number two,
Speaker 2: which is a little bit of a mouthful. This is
Speaker 2: the official name for the virus that causes the disease,
Speaker 2: COVID nineteen. You can break that down to see where
Speaker 2: that comes from. It's coronavirus disease nineteen COVID nineteen. And
Speaker 2: so this is a virus that is new to humans
Speaker 2: and it emerged, as it turns out, or as it
Speaker 2: likely turns out, in November twenty nineteen. Obviously, this is
Speaker 2: now a pandemic, and so we are going to talk
Speaker 2: in this episode about the biology of this new virus
Speaker 2: and some of the characteristics that have allowed it or
Speaker 2: facilitated it to reach pandemic proportions exactly.
Speaker 3: So let's do a quick primer about viruses in general,
Speaker 3: especially for any new listeners who haven't heard all of
Speaker 3: my many virus spiels many times over. So, viruses are
Speaker 3: essentially just packets of genetic material. They're made of either
Speaker 3: DNA or RNA along with protein. Viruses can't replicate on
Speaker 3: their own, so unlike most bacteria, for example, which can
Speaker 3: multiply just by replicating their DNA and then dividing into two,
Speaker 3: viruses have to infect a cell of some kind, a
Speaker 3: host cell, and use that host cellular machinery to actually
Speaker 3: replicate their genetic material. So, in the case of SARS
Speaker 3: covy two, this is an RNA virus. It's a positive
Speaker 3: strand RNA virus. So that means that once it gets
Speaker 3: into your cells, that viral RNA is released into our
Speaker 3: human cells, and then our cells do two things with
Speaker 3: this RNA number One, they start copying it directly as
Speaker 3: if it was our own RNA. And number two, what
Speaker 3: RNA does in normal cell is it codes for protein.
Speaker 3: So our cells start to use this viral RNA to
Speaker 3: make the proteins that that viral RNA codes for, and
Speaker 3: then the replicated RNA plus those proteins get assembled into
Speaker 3: new little virus packets, okay, and those new viruses can
Speaker 3: then burst forth from the cell and go on to
Speaker 3: infect another cell, either in your body or in another host.
Speaker 3: So that's how RNA viruses work. DNA viruses do essentially
Speaker 3: the same thing, except that in order to make protein
Speaker 3: from DNA, your cells have to first translate it into
Speaker 3: that RNA. So RNA viruses sort of skip that step,
Speaker 3: and as you'll hear our expert talk more about, they
Speaker 3: also tend to make more mistakes in that process of replication.
Speaker 3: But either way, viruses are using your host machinery to
Speaker 3: do this. They can't replicate outside of host cells.
Speaker 2: Cool.
Speaker 5: Cool.
Speaker 2: So in this episode, we talk to a virologist, doctor
Speaker 2: Angela Rasmussen from Columbia University, to answer your questions about
Speaker 2: the biology of this virus, how it works, how it
Speaker 2: infects your cells, and what markers it uses to get
Speaker 2: into our cells, and then we also chat about its
Speaker 2: mutation rate and what that means for disease severity, to
Speaker 2: its longevity on surfaces, and whether the existence of multiple
Speaker 2: strains is a concern.
Speaker 3: So she'll introduce herself to you right after this break.
Speaker 4: I'm doctor Angela Rasmussen. I'm on the faculty at the
Speaker 4: Center for Infection and Immunity at the Columbia Mailman School
Speaker 4: of Public Health. I'm a virologist who studies I specialize
Speaker 4: in studying the host response to infection. So when you
Speaker 4: get infected with a virus, your body responds to that
Speaker 4: there's an immune response, an inflammatory response. Sometimes there can
Speaker 4: be metabolic responses and I study those and sometimes those responses,
Speaker 4: depending on what they are, can mean the difference between
Speaker 4: getting rid of an infection and having a mild short
Speaker 4: illness versus having a chronic illness or a more severe disease.
Speaker 4: So the viruses that I've been studying lately are ebolavirus,
Speaker 4: MERSED coronavirus, influenza virus, other hemorrhagic fever viruses, and of course,
Speaker 4: now like many of my colleagues, I'm also studying SARS
Speaker 4: coronavirus two our COVID nineteen.
Speaker 2: That is the reason that we've brought you on today.
Speaker 2: So thank you so much, first of all for agreeing
Speaker 2: to be on the podcast. And yeah, so jumping right
Speaker 2: into the sarskov two, what are the origins of this virus?
Speaker 2: Where did it come from?
Speaker 4: So we don't know for sure, and I suspect that
Speaker 4: that's going to be my answer to almost every single
Speaker 4: one of your questions today. But we do know that
Speaker 4: there was a very very similar virus found in a
Speaker 4: bat in a cave in China in twenty seventeen. And
Speaker 4: this virus is a member of the same genus as
Speaker 4: Stars coronavirus or SARS classic and SARS coronavirus to this
Speaker 4: novel coronavirus that we're all dealing with now. There are
Speaker 4: a number of these viruses that have been discovered. They're
Speaker 4: called bat sars like coronaviruses, very clever original name because
Speaker 4: they are very much genetically like SARS coronavirus and now
Speaker 4: SARS coronavirus too. We do know that this virus, probably
Speaker 4: based on our analysis of the genome, evolved from a
Speaker 4: rus one of these batsars like coronaviruses. We don't know
Speaker 4: if there was another animal involved in the spread of
Speaker 4: this virus from its wildlife reservoir the animal that had
Speaker 4: it in the wild to humans. What we do know
Speaker 4: is that this spillover, which is the transmission of a
Speaker 4: virus from its wildlife reservoir into humans, was probably a
Speaker 4: single event, meaning that there weren't multiple instances of animals
Speaker 4: infecting people. After the first patient or patients weren't infected
Speaker 4: with this from whatever animal it came from, it's been
Speaker 4: transmitted human to human ever since. The reason why it's
Speaker 4: important to understand eventually if this came directly from a
Speaker 4: bat or if it came from a different animal is
Speaker 4: that both STARS classic and MERS coronaviruses were amplified in
Speaker 4: an intermediate species, so both stars and mers are thought
Speaker 4: to have also originated in bats. However, SARS classic was
Speaker 4: transmitted into humans most likely from an animal called a civet,
Speaker 4: and murrs. Coronavirus is known to be transmitted primarily from
Speaker 4: dromedary camels to humans, so we don't know if there
Speaker 4: was another animal in between the bat and the human
Speaker 4: that also was involved in the spillover from its wildlife reservoir.
Speaker 2: To follow up on that, So you mentioned that this
Speaker 2: likely came from one spillover event, So from one infected animal,
Speaker 2: whether it was a bat or a different intermediate host
Speaker 2: into a human. How can we tell whether it's one
Speaker 2: spillover event or multiple.
Speaker 4: Yeah, so you can tell that by looking at the genome.
Speaker 4: And one thing that's been really incredible and also really
Speaker 4: hard to keep up with about this particular epidemic is
Speaker 4: that this is really the first time that we've had
Speaker 4: sequence data from the virus genome really really soon after
Speaker 4: the first patients were reported, So the first viral sequences
Speaker 4: were uploaded and shared with the international scientific community in
Speaker 4: early January. So we've been able to analyze the genome
Speaker 4: of this virus since before we actually were able to
Speaker 4: even isolate the virus. So we can look at the
Speaker 4: genome of this virus, and we can look at the
Speaker 4: specific individual changes in one isolate of the virus versus another,
Speaker 4: and by looking at those changes, we can deduce how
Speaker 4: many different viruses came out of the bats versus went
Speaker 4: from person to person. There are specific genetic signatures that
Speaker 4: are associated in many cases with bat coronaviruses and coronaviruses
Speaker 4: that are transmitted with in bats, including some sequences that
Speaker 4: are part of the envelope glycoprotein which is called spike,
Speaker 4: and that molecule is on the surface of the virus
Speaker 4: and it allows the virus to enter a cell that
Speaker 4: it's going to infect. That protein spike has changes sometimes
Speaker 4: that are specific to bats versus specific to humans, and
Speaker 4: we can look at that as well to determine how
Speaker 4: recently the virus emerged from a bat versus emerged from
Speaker 4: a human.
Speaker 2: Awesome, thank you?
Speaker 4: Did that make sense? Okay? Yes, absolutely, okay, good.
Speaker 3: So kind of along those lines of the proteins on
Speaker 3: the surface, are those related to how the virus gets
Speaker 3: in and actually causes disease. What do we know about
Speaker 3: the mechanism of how this virus causes disease in humans?
Speaker 4: So that's a very excellent question because it gets into
Speaker 4: what I study the host response. So there are two
Speaker 4: things to any virus infection. To keep in mind, the
Speaker 4: virus can infect cells, and that determines whether it can
Speaker 4: establish an infection get inside, versus the viruses what we
Speaker 4: call pathogenicity, or ability to cause disease. Not all viruses
Speaker 4: cause severe disease. Some viruses, most viruses that can cause disease,
Speaker 4: which we call pathogens. Those pathogens in some people will
Speaker 4: cause very mild disease and in some will cause very
Speaker 4: severe disease, and we're seeing that in terms of the
Speaker 4: fairly broad range of disease presentations of COVID nineteen. So
Speaker 4: the ability to get into the cell is just one part.
Speaker 4: And of course, in order to cause disease, a virus
Speaker 4: has to be able to infect the cell. So those
Speaker 4: proteins on the surface of the cell or on the
Speaker 4: surface of the virus particle called spike. Spike binds the
Speaker 4: host cellular receptor, which is in humans. The molecule we
Speaker 4: know about anyways is called ACE two, and ACE two
Speaker 4: is on a variety of different tissues, but there's a
Speaker 4: lot of it in your lungs, which is why this
Speaker 4: causes a pulmonary disease. So certainly in that sense, the
Speaker 4: virus spike protein is involved in determining that this is
Speaker 4: going to be a pulmonary disease. Similarly, we know that
Speaker 4: ACE two is expressed in the gastrointestinal tract, and there
Speaker 4: have been reports that infectious virus has been found in
Speaker 4: the stool of some patients. Also, people have reported diarrhea,
Speaker 4: which may again suggest that the ability to infect the
Speaker 4: intestine because of that receptor binding the spike protein on
Speaker 4: the surface of the virus particle allows this virus to
Speaker 4: cause a gastrointestinal disease. But when you're talking about what
Speaker 4: is the difference between a virus in two different people,
Speaker 4: causing a mild cold like illness in one person versus
Speaker 4: causing severe pneumonia in another, that difference is often related
Speaker 4: to to the host response, and that can be determined
Speaker 4: by a lot of different things. It can be determined
Speaker 4: by genetics, It can be determined by the health state
Speaker 4: of that individual, which we again already know as a
Speaker 4: risk factor because people with pre existing medical conditions are
Speaker 4: more susceptible to severe disease. So really a lot of
Speaker 4: the disease is likely caused by a sort of out
Speaker 4: of control inflammatory response in infected tissues, and that largely
Speaker 4: depends on the person who's infected, as well as their
Speaker 4: overall health condition and sometimes the circumstances in which they're infected.
Speaker 1: That was so.
Speaker 2: Beautiful, such a great answer.
Speaker 4: Yeah, thank you. I get passionate about the host response.
Speaker 2: So recently, there was a paper that was published that
Speaker 2: found that there were two strains of the virus, and
Speaker 2: they named these strains L and S. And these strains,
Speaker 2: according to this paper, seem to differ in their very life,
Speaker 2: one being more aggressive than the other. And this finding
Speaker 2: has seemed to be a little bit controversial. So can
Speaker 2: you talk about why it is controversial and whether the
Speaker 2: possibility of multiple strains is a real concern and maybe
Speaker 2: whether this finding is actually valid. Are there multiple strains
Speaker 2: of stars kov two?
Speaker 4: Right? So this definitely gets down into the an inherent
Speaker 4: property of RNA viruses like coronaviruses, and that is that
Speaker 4: every time the virus copies its own genome in order
Speaker 4: to replicate or make more viruses, the virus makes mistakes.
Speaker 4: The enzyme that copies the genome does not have proofreading
Speaker 4: capability the way that the analogous enzymes that we have
Speaker 4: that copy our DNA genomes do, so that means that
Speaker 4: the virus makes mistakes. We call these mutations. Many of
Speaker 4: these mutations are silent, they don't have any effect on
Speaker 4: the way the virus works. Many more of them will
Speaker 4: have a negative effect on the way the virus works
Speaker 4: and make it so that the virus can't work essentially,
Speaker 4: and some of them will confer an advantage. These mutations
Speaker 4: occur randomly, so there has to be a selection pressure
Speaker 4: to maintain mutations from generation to generation. And some of
Speaker 4: these advantages can be an enhancedability to replicate in various
Speaker 4: host cells. It can be the ability to evade the
Speaker 4: host immune response. It can be something that would make
Speaker 4: the virus more capable of infecting cells or capable of
Speaker 4: inducing a response that would lead to more severe disease.
Speaker 4: So right now we don't know what a lot of
Speaker 4: those theoretical mutations would be that could make the virus
Speaker 4: more virulent, capable of infecting more cells, or more pathogenic,
Speaker 4: capable of causing more intense disease. The paper that you
Speaker 4: mentioned is controversial because essentially it's grouping these two viruses
Speaker 4: into what they're calling strains. But what are normal groupings
Speaker 4: of RNA viruses that have replicated in multiple hosts. What
Speaker 4: makes a virus a strain a different strain often depends
Speaker 4: a lot on which virus you're talking about. In this case,
Speaker 4: if we're talking about two different genotypes or virus genomes
Speaker 4: that encode virus genes that result in differential disease or
Speaker 4: more severe disease in one person versus less in another.
Speaker 4: Whether that's a strain or not is sort of up
Speaker 4: for debate. What I think is controversial about this paper
Speaker 4: is that essentially they were just grouping a variety of
Speaker 4: different clinical isolates of the virus and then going back
Speaker 4: to the clinical data that have been recorded about those
Speaker 4: patients and making assumptions that these genetic changes is that
Speaker 4: distinguished these two groups were responsible for any differences they
Speaker 4: found in the patient's conditions. That is, it's really hard
Speaker 4: to say, first of all, the group the viruses and
Speaker 4: the L group versus I think, what is it the
Speaker 4: S group. Yeah, the differences between those viruses, they're not
Speaker 4: all it's not just two viruses. They're groups of viruses
Speaker 4: that cluster together when you look at their genomes and
Speaker 4: compare them. So it's really difficult to say that any
Speaker 4: one of the specific genomic changes that are characteristic of
Speaker 4: either group are directly responsible for causing increased or decreased disease.
Speaker 4: Severity gotcha.
Speaker 2: So it's possible or likely that there might be multiple
Speaker 2: quote unquote strains of this virus, but whether or not
Speaker 2: that translates into any manifestations in terms of disease. Disease
Speaker 2: severity is not yet clear and we probably won't know
Speaker 2: it for a while.
Speaker 4: Yeah, that's fair to say. And this is really also
Speaker 4: a question that needs to be addressed in terms of
Speaker 4: doing experiments to understand what are our features of the
Speaker 4: virus that make it more pathogenic or able to cause disease.
Speaker 4: So the only way to really look at that is
Speaker 4: either through human volunteers or patients who at least could
Speaker 4: be identified very early after infection and then followed over
Speaker 4: time we call longitudinal observations, or by looking in animal
Speaker 4: models to try to understand the various mechanisms of pathogenesis.
Speaker 4: My personal suspicion and again this plays to my bias
Speaker 4: for the host response. But when you're looking at humans
Speaker 4: who are genetically diverse, you will see the same virus,
Speaker 4: the same idea dental strain of a virus cause two
Speaker 4: different types of disease and two different individual people. So
Speaker 4: even when you're looking at a fairly large patient population
Speaker 4: and you're just making correlations between certain clinical features that
Speaker 4: were recorded by their doctors during clinical care, as well
Speaker 4: as the genomic sequence of their disease, you're not really
Speaker 4: able to look at any of those mechanisms that might
Speaker 4: distinguish a host from one from another. So you can
Speaker 4: look at the differences in the virus, but you're never
Speaker 4: going to know what's different from one person to the next.
Speaker 4: So it's really difficult to conclude, even on a data
Speaker 4: set of hundreds or thousands of patients, that a genetically
Speaker 4: different strain of a virus is the only thing that
Speaker 4: is causing one person's disease to be more severe than another's, Right, Right,
Speaker 4: that makes sense.
Speaker 2: Yeah, Stars as being a much deadlier corona virus. I
Speaker 2: think a lot of people that wrote to us express
Speaker 2: their concern about whether this virus SARS covy two might
Speaker 2: mutate into something more deadly, such as SARS classic. You
Speaker 2: mentioned or you talked a bit about the mutation rate
Speaker 2: of this virus and mRNA viruses. Can you say anything
Speaker 2: to our listeners about whether there's a risk of this
Speaker 2: virus mutating into something more deadly, and especially maybe also
Speaker 2: in the context of control measures or how behavior might
Speaker 2: influence viral evolution.
Speaker 4: Right, So this is a concern, and I think one
Speaker 4: of the reasons is that mutation is a very scary
Speaker 4: sounding word, and it's not been helpful I think that
Speaker 4: a lot of movies are always like, oh my god,
Speaker 4: it's mutated and it's now airborne or something, and the
Speaker 4: thing is coronaviruses are RNA viruses. RNA viruses. Mutation is
Speaker 4: an inherent property that they all have because the enzyme
Speaker 4: that replicates the genome is prone to making these mistakes.
Speaker 4: Every RNA virus will have. The normal mutation rate for
Speaker 4: an rnavirus is about one in every thousand units of
Speaker 4: the genome that gets copied is a mistake or mutation.
Speaker 4: Coronaviruses actually have an enzyme that does some limited proofreading,
Speaker 4: so their mutation rate is lower than many other RNA viruses,
Speaker 4: but it's still higher than for enzymes that replicate DNA,
Speaker 4: so it still has a relatively high mutation rate, and
Speaker 4: there will be mutations every single time the genome is copied.
Speaker 4: In terms of mutating to become more virulent or more lethal,
Speaker 4: it's really really difficult to predict that because mutations don't
Speaker 4: stick around unless there's some sort of selection pressure. It's
Speaker 4: hard to imagine what the selection pressure would be to
Speaker 4: make the virus more lethal. If anything, viruses are selected
Speaker 4: to become less lethal only because viruses can't replicate without
Speaker 4: a host, and if you kill your host before they
Speaker 4: can transmit the virus to another host, that pretty much
Speaker 4: cuts off that virus's evolutionary chain. So I think that
Speaker 4: it's likely certainly that the virus could mutate or has mutated,
Speaker 4: and there will be mutations every time the virus copies
Speaker 4: itself within a single person. Much less is transmitted to
Speaker 4: another person. But it's very difficult to say that the
Speaker 4: virus would be evolving on its own the capacity to
Speaker 4: be more lethal. Now, however, if there is an antiviral
Speaker 4: drug developed, for example, and that targets a specific part
Speaker 4: of a viral protein, then it's possible that that would
Speaker 4: be a selection pressure for the virus to evolve resistance.
Speaker 4: That's one example of how viruses can become more lethal
Speaker 4: by evading countermeasures. If there's a vaccine, it's possible that
Speaker 4: the parts of the virus the vaccine recognizes could be
Speaker 4: a pressure for those parts to mutate. The way that
Speaker 4: your immune system works for most vaccines is by making antibodies,
Speaker 4: and those antibodies recognize a shape on the surface of
Speaker 4: the virus. So if you think of a virus as
Speaker 4: a three dimensional sort of ball that's covered with spikes.
Speaker 4: Antibodies would recognize the shape of those particular spikes. It's
Speaker 4: possible that a virus could evolve a slightly different shaped
Speaker 4: spike that those antibodies from a prior infection or from
Speaker 4: a vaccine would then not be able to recognize. So
Speaker 4: that is another way in which a virus could potentially
Speaker 4: evolve to become more lethal in the sense that it
Speaker 4: would be able to again evade a countermeasure that we
Speaker 4: had developed for it. Will that happen? I don't know.
Speaker 4: A lot of that depends on the types of antivirals
Speaker 4: that we find are able to work against this virus,
Speaker 4: as well as the vaccine strategies that are being tested
Speaker 4: right now, how well they work and how well they
Speaker 4: are able to induce immunity. We do know from some
Speaker 4: other viruses though, that certainly antiviral drug resistance is something
Speaker 4: that happens. We know that from influenza evolving to be
Speaker 4: resistant to osul tamavir or tama flu. We know that influenza,
Speaker 4: normally it's a surface antigens or the proteins that are
Speaker 4: recognized by vaccines change all the time, so that's why
Speaker 4: we have to get a flu shot every year. So
Speaker 4: there are certainly examples in the wild world of virology
Speaker 4: that viruses can do this, But on its own, I
Speaker 4: don't think that there's any particular pressure that I've seen
Speaker 4: anyways that would cause SARS coronavirus to spontaneously evolve greater
Speaker 4: lethality or virulence.
Speaker 2: Gotcha.
Speaker 3: So, speaking of antivirals, remdesevir is going around the news.
Speaker 3: There's potentially trials happening. It seems to be maybe promising
Speaker 3: for looking at treatment for SARS covid or for COVID
Speaker 3: nineteen the disease. Could you tell us a little bit
Speaker 3: about what this drug is and how it works.
Speaker 4: Certainly so. Remdesevir is a nucleoside analog that means that
Speaker 4: it is shaped a lot like the ATC's and g's
Speaker 4: that make up a given virus genome or human genome
Speaker 4: for that matter. When viruses are replicating, the enzymes that
Speaker 4: copy the genetic material is reading the existing genome, so
Speaker 4: it knows where to put which ATC or G. Remdesevir
Speaker 4: works by fooling that enzyme into thinking that it is
Speaker 4: an ATC or G and gets inserted into the genome
Speaker 4: and then with when enough of that happens, the genome
Speaker 4: doesn't work. It's also thought that some of these so
Speaker 4: called nucleoside analog drugs can also activate components of your
Speaker 4: innate anti viral immune system, making yourselves more capable of
Speaker 4: responding to and resisting viral infection. So that's thought to
Speaker 4: be the mechanism of ac action for remdesevir as far
Speaker 4: as I know. So, these these nucleoside analogs don't always
Speaker 4: work for some RNA viruses, but there is data in
Speaker 4: non human primates suggesting that rendesevir is effective at treating
Speaker 4: MRS coronavirus, and now so people have showed I think
Speaker 4: in vitro at least that it's capable of reducing virus
Speaker 4: tiders of STARS coronavirus too. So we do know that
Speaker 4: these nuclear side analogs can be effective against certain RNA
Speaker 4: virus infections. We just won't know if it's effective in
Speaker 4: people until the clinical trials have been completed.
Speaker 2: Gotcha. Our sign off for this podcast is wash your hands,
Speaker 2: you filthy animals. We've been saying it for years.
Speaker 3: Yeah, we started it just kidding.
Speaker 2: Yeah, So can you tell us why hand washing is
Speaker 2: a great way to reduce the risk of getting a
Speaker 2: respiratory infection.
Speaker 4: Yeah, that's that's a great one. And this is so
Speaker 4: both for enveloped viruses, which coronaviruses are. The envelope that
Speaker 4: I'm talking about is a membrane that is derived from
Speaker 4: your cells. On the surface of the virus particle. The
Speaker 4: spike protein that I've talked about that's needed to bind
Speaker 4: the receptor and for the virus to enter the cell
Speaker 4: is embedded in this envelope, in the membrane. That's why
Speaker 4: spike is called an envelope glycoprotein because it's part of
Speaker 4: the envelope. So either alcohol based hand sanitizers or soap
Speaker 4: will disrupt that membrane. If you disrupt that membrane, wash
Speaker 4: it away, there's no more spike, the virus can't get
Speaker 4: into your cells. The virus is intactivated. Soapy water is
Speaker 4: more effective than hand sanitizer because that also has the
Speaker 4: added effect of physically washing things off of your hands. So,
Speaker 4: in addition to disrupting the membrane and making any viruses
Speaker 4: or some bacteria or other microorganisms that have a membrane
Speaker 4: that can be disrupted by soaper, hand sanitizer. That's great,
Speaker 4: but in general, there may be other things. There may
Speaker 4: be non envelope viruses on your hands. Soap and water
Speaker 4: washes them away physically so that they're no longer on
Speaker 4: your hands at all, whether it disrupts the envelope or not.
Speaker 4: For that reason, washing your hands is by far the
Speaker 4: best thing you can do to reduce your own risk,
Speaker 4: besides practicing, of course, social distancing. Hand washing is better
Speaker 4: than hand sanitizer, although it is important to note that
Speaker 4: for this particular virus, hand sanitizer as long as it's
Speaker 4: sixty percent alcohol or more, will work in between hand washes.
Speaker 2: So one of the other questions that we've gotten a lot,
Speaker 2: and I'm also curious to know and have been sort
Speaker 2: of keeping a good amount of skepticism with whatever I read,
Speaker 2: is just how long this virus can survive on different
Speaker 2: kinds of surfaces, so hard surfaces, soft surfaces, And maybe
Speaker 2: how does this compare with some of the other common
Speaker 2: respiratory viruses.
Speaker 4: Yeah, so a great preprint just came out, Like to
Speaker 4: pitch my collaborators at Rocky Mountain Labs. This is Niltchevan
Speaker 4: Direml who is with Vincent Munster at NIAID. Rocky Mountain
Speaker 4: Labs have just released a preprint with some of their colleagues,
Speaker 4: I believe at Princeton, showing that SARS coronavirus two and
Speaker 4: SARS classic have some different properties as well as some
Speaker 4: similar properties for remaining infectious on various surfaces. So they
Speaker 4: looked at experimentally generated aerosols, which for STARS coronaviruses is
Speaker 4: only an issue for the most part in hospital settings
Speaker 4: where there are aerosol generating procedures. But they showed that
Speaker 4: for both of these the aerosol half life is only
Speaker 4: about three hours. So that's good news in that you know,
Speaker 4: if somebody that you love or care about is working
Speaker 4: in a hospital or an ICU or is getting treated there,
Speaker 4: these aerosols are not going to persist for days at
Speaker 4: a time in the environment. They also looked at survival
Speaker 4: of the virusrus on copper, stainless steel, plastic, and cardboard,
Speaker 4: and the virus lasts the longest on stainless steel and plastic,
Speaker 4: so it lasts forty eight to seventy two hours, and
Speaker 4: it can potentially be there for longer than that. But
Speaker 4: what's important to note is that there was a three
Speaker 4: log reduction, so a thousand times less virus that was
Speaker 4: infectious after seventy two hours. So even though you can
Speaker 4: detect infectious virus on surfaces plastic or stainless steel surfaces,
Speaker 4: after three days, it's a greatly reduced amount of virus
Speaker 4: compared to stars. Classic SARS coronavirus two lasted longer on cardboard. However,
Speaker 4: it didn't last longer than twenty four hours, so before
Speaker 4: everybody gets worried about getting packages in the mail or
Speaker 4: opening letters or calling ordering stuff from Amazon. It also
Speaker 4: was essentially undetectable after twenty four hours, so cardboard is
Speaker 4: probably not a surface that's going to retain the virus
Speaker 4: for days and days at a time. What we don't
Speaker 4: know is that the effect that temperature and humidity and
Speaker 4: other environmental conditions would have on this, because they didn't
Speaker 4: look at that in this paper. However, the same group
Speaker 4: had previously done work with MRS coronavirus and that showed
Speaker 4: that temperature and humidity were also really, really important factors
Speaker 4: in terms of the virus being able to persist and
Speaker 4: remain infectious on various surfaces. So my take home from
Speaker 4: this is that I assume that the virus under ideal
Speaker 4: conditions can last for a couple days on surfaces, So
Speaker 4: I just try to again wash my hands and where
Speaker 4: I can disinfect shared communal surfaces like tables. Take precautions
Speaker 4: to avoid being exposed to virus that may be on
Speaker 4: shared surfaces, but it's probably not going to persist in
Speaker 4: the environment for more than a couple days.
Speaker 3: Awesome, And you mentioned that this is a virus that's
Speaker 3: spread by respiratory droplets. What do we know so far
Speaker 3: about the minimum infective dose of this virus.
Speaker 4: Well, that's a great question, and I that is definitely
Speaker 4: a question for which I will say I don't know, okay,
Speaker 4: And this has been discussed a lot in the context
Speaker 4: of that reduction I was talking about on surfaces after
Speaker 4: sevent you know, forty eight to seventy two hours, depending
Speaker 4: on the material. If you have a thousand times less
Speaker 4: virus after a couple days, is that enough virus to
Speaker 4: establish an infection. It's really hard to say, and probably
Speaker 4: a lot of that also depends on the root of
Speaker 4: infection too. So if you are touching your hands to
Speaker 4: your nose, the inside of your nose, your nostrils is
Speaker 4: a mucous membrane. It's a mucosal surface. Mucus itself acts
Speaker 4: as a barrier that prevents virus particles from coming into
Speaker 4: contact with the cells that are in your nose to
Speaker 4: infect them. That's going to be different than in your
Speaker 4: mouth and in your eyes, and all of these different
Speaker 4: mucosal surfaces that could potentially be infected. There are inherent mechanisms,
Speaker 4: barrier mechanisms that protect those surfaces from being infected. So
Speaker 4: it's not enough to necessarily have one infectious virus particle.
Speaker 4: You may have to have a certain number of those
Speaker 4: infectious virus particles to overcome these other obstacles to infection
Speaker 4: that your body has. We don't really know what that is.
Speaker 4: I don't think that anybody has looked at that, And
Speaker 4: because the animal model work is still in development, we
Speaker 4: can't really look at that in the context of a
Speaker 4: controlled experiment where we would be able to look at
Speaker 4: different amounts of virus on different surfaces and see which
Speaker 4: animals got infected and then how sick they got.
Speaker 2: Gotcha, gotcha? So in our first episode on coronavirus, we
Speaker 2: ended our interviews by asking our interviewees what about this
Speaker 2: disease concerns you, and what about the response or how
Speaker 2: the epidemic has been progressing reassures you?
Speaker 4: Oh boy, the second part of the question nothing.
Speaker 5: Yeah, oh gosh, no, I've been What scares me the
Speaker 5: most by far about this is the federal response here
Speaker 5: in the US.
Speaker 4: It has been unacceptable for a variety of reasons, and
Speaker 4: I suspect that largely because the response has been heavily
Speaker 4: politicized and influenced by considerations that should not be a
Speaker 4: factor in public health responses. Worrying about case numbers from
Speaker 4: you know, an electability point of view is a really,
Speaker 4: really terrible way to approach an effective public health response.
Speaker 4: That concerns me greatly because initially I felt, you know,
Speaker 4: I was concerned about this, but I felt that if
Speaker 4: we were on top of it in terms of surveillance
Speaker 4: and testing, then we could really limit and contain spread.
Speaker 4: In January, when there were a few patients coming into
Speaker 4: the United States with travel history who were identified and
Speaker 4: rapidly sequestered, and there didn't seem to be a ton
Speaker 4: of secondary transmission, I felt pretty calm that we were
Speaker 4: responding to this correctly, identifying and isolating patients, which is
Speaker 4: what you should do. Doing contact tracing back when it
Speaker 4: was manageable to do that. Then it turns out through
Speaker 4: genomic analysis that it looks like here in Seattle anyways,
Speaker 4: we've had community transmission since that first patient arrived, and
Speaker 4: potentially transmission from other patients who may not have even
Speaker 4: been identified. And some of this has been the absolutely
Speaker 4: unacceptable slow rollout of effective testing and the continued failure
Speaker 4: to adequately increase testing capacity and throughput. I think that
Speaker 4: that has really really harmed our ability to contain this outbreak.
Speaker 4: And while where we can, we should still make efforts
Speaker 4: to contain it by doing contact tracing and isolation and
Speaker 4: quarantine on these tried and true public health methods, part
Speaker 4: of our focus now has to be mitigation, and that
Speaker 4: has to be the so called flattening the curve, trying
Speaker 4: to limit and reduce spread or the speed of spread
Speaker 4: to avoid overwhelming hospitals, Trying to make sure that there
Speaker 4: is a safety net in place for people who can't
Speaker 4: afford to work from home, who don't have sick leave,
Speaker 4: who may not have adequate insurance. We need to make
Speaker 4: sure that all of those things are addressed so that
Speaker 4: we can at least mitigate the effects that this is
Speaker 4: going to have on our healthcare systems and on our
Speaker 4: public health as a country and really as a as
Speaker 4: a species on this planet. We really need to have
Speaker 4: all hands on deck, including full engagement from the public.
Speaker 4: And I'm concerned that with the amount of misinformation that
Speaker 4: our federal leadership has provided, the constant still downplane of
Speaker 4: the seriousness of this situation, I'm very concerned that some
Speaker 4: of these measures won't even work. And I'm not so
Speaker 4: much concerned for myself. I'm not in a high risk category.
Speaker 4: I do have asthma, but I still, you know, I
Speaker 4: don't think that I would be personally likely to die
Speaker 4: from this. But of course I'm concerned about all those
Speaker 4: other people who do have pre existing health conditions, who
Speaker 4: are immunosuppressed, who are older, who have underlying medical conditions
Speaker 4: that would cause them to have a bad outcome, or
Speaker 4: other people who may not even have coronavirus, but are
Speaker 4: unable to access medical treatment that they need for other
Speaker 4: things because our hospital systems are overwhelmed. So my concerns, really,
Speaker 4: my concerns about the virus are the least of my
Speaker 4: concerns for this with regard to this public health crisis, awesome.
Speaker 2: Thank you again so much, doctor Rasmussen for joining us.
Speaker 2: We really appreciate you taking the time out of your
Speaker 2: busy schedule.
Speaker 3: And it was really lovely chatting with you. Thanks.
Speaker 2: All right, So we wanted to wrap up each of
Speaker 2: these episodes with a what did we learn section, and
Speaker 2: we wanted to take the top five things, or the
Speaker 2: five key things that we learned from our conversation with
Speaker 2: these experts. So we'll go through each of these five things.
Speaker 2: We've already talked about. This this is this is different
Speaker 2: than our normal episodes, where none of what we're saying
Speaker 2: to each other is a surprise. Yeah, I don't know,
Speaker 2: it's how we had to do it.
Speaker 3: It's how it's I think it's important because, like you know,
Speaker 3: we go over We went over a lot in this episode.
Speaker 3: We're going to go over a lot in every episode,
Speaker 3: and I think that kind of trying to wrap it
Speaker 3: up and see what are the most important points is
Speaker 3: going to be It was helpful for me even to
Speaker 3: go through.
Speaker 2: So absolutely, it's it's very easy to get lost in
Speaker 2: the details of this and so let's big picture this situation,
Speaker 2: all right.
Speaker 3: So one of the biggest things that we learned is
Speaker 3: that this particular virus stars covey you because of the
Speaker 3: specific receptors that it uses to get into ourselves, that
Speaker 3: ACE two. This virus can and does infect the lower
Speaker 3: respiratory tract. So that's why we are seeing as severe
Speaker 3: of disease in some cases as we're seeing. And that
Speaker 3: is something that sets this virus apart from a lot
Speaker 3: of other coronaviruses, the more common ones that circulate and
Speaker 3: cause the common cold. But this is a similarity that
Speaker 3: SARS CoV two shares with its closest relative, if viruses
Speaker 3: have relatives, and that is SARS classic SARS.
Speaker 2: One number two. We also learned that this novel virus
Speaker 2: can definitely survive on surfaces for at least some time,
Speaker 2: and we're going to provide a link to that paper
Speaker 2: that doctor Rasmussen mentioned on our website and in the
Speaker 2: show notes. But what we still don't have a great
Speaker 2: handle on is what exactly that means for transmission, because
Speaker 2: we don't know how many viral particles it takes to
Speaker 2: actually make you sick, or how different environmental conditions like
Speaker 2: temperature and humidity, how these might affect the longevity of
Speaker 2: the virus. But what we'll touch on in another episode
Speaker 2: in more detail, is that we don't even know how
Speaker 2: much virus people are shedding, So really, the best thing
Speaker 2: you can do is just kind of assume that your
Speaker 2: saliva and the saliva of everyone around you is infectious.
Speaker 2: So wipe down surfaces, wash your hands before you touch
Speaker 2: your face. These are the basic steps that will protect
Speaker 2: you not only from getting this virus but also from
Speaker 2: spreading it to others. And it'll also do those things
Speaker 2: for so many other viruses too.
Speaker 3: Yeah. Absolutely, Number three we also learned I like this one.
Speaker 3: The viruses are not evil creatures intentionally setting out to
Speaker 3: kill you.
Speaker 2: There's no malice.
Speaker 3: There's no malice there.
Speaker 2: They're just as far as we're aware.
Speaker 3: I guess we haven't asked the viruses. But and the
Speaker 3: thing about this is, mutation doesn't have to be a
Speaker 3: scary word. So yes, because this SARS CoV two is
Speaker 3: an RNA virus, it does have a higher mutation rate
Speaker 3: than a DNA virus might, or than a bacterial disease might,
Speaker 3: And certainly it has a higher mutation rate than our
Speaker 3: cells have, but that doesn't necessarily mean it's going to
Speaker 3: mutate to become more virulent or make you more sick,
Speaker 3: and it's probably uncommon that it would mutate in really
Speaker 3: drastic ways. There's been a lot of talk about this
Speaker 3: is going to mutate to be airborne, and we'll talk
Speaker 3: in more detail in a future episode about what respiratory
Speaker 3: droplet versus airborne transmission really means, but in general, it's
Speaker 3: very uncommon for viruses to mutate in that drastic of
Speaker 3: a fashion to change their mode of transmission.
Speaker 2: Okay, okay, number four. So the other thing that doctor
Speaker 2: Raspins and helped clarify is that we don't know for
Speaker 2: sure yet if there are different strains of this virus.
Speaker 2: But even if there are different strains, we don't know
Speaker 2: if that will actually result in different virulence or infectivity
Speaker 2: between those strains, because so much of what goes into
Speaker 2: disease severity is related directly to our individual host response,
Speaker 2: and so it's really hard to tease apart the individual
Speaker 2: effects of certain virus strains and how much a particular
Speaker 2: viral strain is going to affect us or cause disease
Speaker 2: or be more infectious than another. And so that's something
Speaker 2: I think is really important to remember as this talk
Speaker 2: of strains comes into the news is that this is
Speaker 2: also something that's going to probably take a bit to
Speaker 2: figure out whether there are any differences in the infectivity
Speaker 2: or virulence among any of the strains that we might detect.
Speaker 4: Yeah.
Speaker 3: Absolutely. And finally, the fifth and I don't know, maybe
Speaker 3: most important thing we've learned from this episode is something
Speaker 3: that all of our listeners already knew, and that is
Speaker 3: wash your hands. Because washing your hands is really effective
Speaker 3: at reducing the spread and the chance that you're going
Speaker 3: to get infected or spread an infection to somebody else.
Speaker 3: Washing your hands really works.
Speaker 2: And alcohol based hand sanitizers also work as well if
Speaker 2: you don't have the availability to wash your hands in
Speaker 2: a certain time. But we do want to note that
Speaker 2: hand washing is better because it actually washes those little
Speaker 2: viruses and bacteria off of your hands, whereas a hand
Speaker 2: sanitizer just kind of leaves a sea of dead bodies
Speaker 2: on your hands, a sea of dead body that sells
Speaker 2: and viral particles.
Speaker 3: Exactly, Aaron, Do we have any references that we'd like
Speaker 3: to shout out for this episode?
Speaker 2: We do so, so we've got a couple of papers.
Speaker 2: One is by Van Dormalin at All from obviously twenty
Speaker 2: twenty because we're talking about SARS CoV two, and we
Speaker 2: also have and that's titled Aerosol and Surface Stability of
Speaker 2: SARS CoV two as compared with sars kov one. And
Speaker 2: so this is the one that doctor Rasfusen mentioned that
Speaker 2: looked at how well the virus survives on different surfaces.
Speaker 2: And then the other paper that we mentioned in our
Speaker 2: interview that referred to the L and S strains of
Speaker 2: SARS CoV two is by tang at All and that's
Speaker 2: also from twenty twenty and it is titled on the
Speaker 2: Origin and Continuing Evolution of SARS CoV two.
Speaker 3: And as always, we'll post the links to all of
Speaker 3: our sources for this episode and every single episode on
Speaker 3: our website. We're also working on a specific COVID nineteen
Speaker 3: section of our website where you can get answers to
Speaker 3: frequently asked questions to share with friends and family.
Speaker 2: And thanks again to doctor Rasmussen for dropping some knowledge
Speaker 2: on us and on all of you out there listening.
Speaker 3: Absolutely I will say too if you want like lots
Speaker 3: and lots of detail on the virology of this virus.
Speaker 3: There's a whole podcast series called This Week in Virology
Speaker 3: that has been doing a lot of updates about COVID
Speaker 3: nineteen and stars CoV two and they have a lot
Speaker 3: of details. It's hosted by a bunch of virologists. Ologies
Speaker 3: also had a great virology episode that interviewed another expert
Speaker 3: about this virus. And there's a whole bunch of other
Speaker 3: podcasts out there too if you just can't get enough.
Speaker 2: Thanks to Bloodmobile for providing the music for this episode
Speaker 2: in all of our episodes.
Speaker 3: And thank you for listening. We'll see you soon for
Speaker 3: chapter two.
Speaker 2: Until next time, wash your hands, you filthy animals.
Speaker 1: O o oh