This Podcast Will Kill You - Ep 43 M-m-m-my Coronaviruses

Episode Date: February 4, 2020

What better time to explore the world of coronaviruses than amidst an outbreak of the 2019 novel coronavirus that brings to mind memories of SARS and MERS? On this very special episode of This Podcast Will Kill You, we’ll take you through what we know about this diverse group of viruses, from the mild strains constantly circulating to the epidemic ones that make headlines with their lethality. Want to know how exactly these royal viruses make you sick? Or what went on during the 2002-2003 SARS epidemic? Don’t worry - we’ve got you covered. And to help us get a grasp on the current 2019-nCoV outbreak that’s got the world’s attention, we’ve brought on four experts from Emory University to give us the lowdown: Dr. Colleen Kraft, Dr. G. Marshall Lyon, Dr. Aneesh Mehta, and Dr. Carlos del Rio.*Please keep in mind, we recorded this episode on Sunday, Feb 2 and conducted the interviews between Jan 29 and 30, 2020. Since recording, the statistics on 2019-nCoV that we and our guests reported have changed as the epidemic continues to evolve. The figures are changing fast, but the basic info is still relevant.To follow the 2019-nCoV outbreak, our experts recommend the following as reliable sources of information: WHO 2019-nCoV website, especially the Situation Reports Map Dashboard of 2019-nCoV Cases by Johns Hopkins Center for Systems Science and Engineering CDC 2019-nCoV website And to learn more about the amazing work that our special guests do on the regular, follow them on Twitter!Colleen S. Kraft, MD, MSc (@colleenkraftmd)G. Marshall Lyon, MD, MMSc (@GMLyon3)Aneesh K. Mehta, M.D., FIDSA, FAST (@AneeshMehtaMD)Carlos del Rio, MD (@CarlosdelRio7) See omnystudio.com/listener for privacy information.

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Fang Lin began to feel feverish just as the weather was starting to turn dry. Fang made it through that day and night, having to pause during his work in the chop room to catch his breath and he took frequent cigarette breaks on the back stairs. The next evening, when he went out for a cigarette break and sat down on the back steps, he couldn't get up. His fever had climbed, probably to over 103 degrees, and he found that no matter how deeply he breathed, he felt perpetually winded. His body aches had reached a point where whatever position he stowed or sat in, he felt as if his muscles were

being pulled from his bones. The antifebrile medication did nothing to assuage his fever, which may have spiked north of 104.5. Twice he was unable to rouse himself from his sleeping palate in time to reach the toilet in the hall, each time soiling his trousers. He found that if he moved even slightly to roll over or sit up, he would be completely out of breath. The muscle aches were so severe, he recalls, that he found staying still unbearable, yet any movement would leave him gasping for breath. What was happening to him? Fang knew he was ill, but he still assumed he was suffering from another of those respiratory infections that regularly burned to the click. Everyone seemed to have a hack and cough of some sort, whether it was due to cigarettes, persistent asthma, or air pollution

was impossible to say. But he had been on his back for several days now and wasn't feeling any better. Most terrifying for him, when he was conscious, was the sense that no matter how deeply he breathed, he felt that what he was inhaling was not oxygen, but some other odorless, tasteless gas with similar properties but without the life-sustaining force of simple oxygen. He was running out of air, yet he felt he was breathing freely. He now had to stay perfectly still. To move was to suffocate. Stay still and breathe. Breathe as deeply as possible. On about the sixth day of his illness, he lost all track of his environment. From then on, there were only dark dreams and the sensation that his life was literally being squeezed from him. His muscle aches would come in steady rolling waves and would peak as gripping cramps around his spine and in his neck and upper legs, a dreadful tightening that would coincide with a gasping inability to draw in enough oxygen. He lay still and struggled to stay awake so that he could focus on maintaining his steady, ineffectual breathing. He feared that if he fell asleep, he might forget to breathe, and that would be it.

Perhaps that is what dying is, he wondered, your body forgetting how to breathe. But he did begin to drift off, always remembering, even in his unconscious state that he must stay still. Any movement at all, even a wiggling of toes, even blinking, used precious oxygen. That was air he didn't have. So he lay perfectly still, and in those moments between severe cramps and muscle aches when his bowels were settled, he would drift into dark snatches of unconsciousness. But it was a cruel sleep, one that never let him forget, for even a moment, his suffering. During those naps, he would always feel very far from home and very alone.

A terrifying idea began to glow in the darkness. He would die, far from home, away from his family. He understood, finally, the importance of that Chinese tradition of rushing home. home when you were ill, even if only to pass away. And then he thought of another matter. Who would pay for the cost of his funeral arrangements? Oof, indeed, Aaron. That was adapted from Chapter 7 of China Syndrome by Carl Terro Greenfeld. And that description was of SARS. SARS.

Yes. And on this episode of This Podcast Will Kill You, we'll Kill You, we are talking all things coronavirus. Because you guys asked for it and we oblige. I'm Erin Welsh. And I'm Aaron Alman Updike. Welcome. Welcome. So this episode we're talking all things coronavirus, which means the endemic ones that cause basically like a mild cold in humans, SARS, MERS, and then the 2019 novel coronavirus, which doesn't yet have a catchy acronym. Right. And the reason that we're talking about all of these is because, for one thing, they are all related to one another. And what we can tell about this 2019 novel coronavirus, a lot of that comes from the information that we have from these other coronaviruses. So we wanted to give you the full picture of all of these things.

We were not planning on covering coronavirus this season. No. But yeah, it's making big headlines and for good reason. So we want to help everyone to understand what coronaviruses are and as much as we can let you know about what's going on with the current coronavirus outbreak. A few things to keep in mind. We are not experts. Once more for the people in the back, we are not experts. So we are not the ones on the ground doing this research.

working on this outbreak, we are going to tell you what we know, and because we're not experts, we're going to bring in some people who have much more expertise than we do to talk about what's going on with the current novel coronavirus outbreak. But we will do what we do best, which is tell you about the biology and the history of coronaviruses in general. Yeah. Should we also note that we are recording this on at 9.30 a.m. on February 2nd. This is something that's happening so rapidly that by the time you listen to it, things will be drastically different. The earliest you would be hearing this is on February

4th. So it's likely that some of the numbers that we are reporting about the 2019 novel coronavirus will have changed. But hopefully the broad strokes will still be enough to get you the information that you want. And we'll also point you in the direction of where you can find reputable sources to stay abreast on what's going on with the current outbreak. Yes. I guess, though, we should start with quarantinis. We should because we must. This week's quarantini is called the breathtaking. And it's called that because that was the colloquial name for SARS in China when it first started making the rounds.

I love it. And Aaron, what's in the breathtaking? Well, it has to start, of course, with a corona. And we should also point out that Corona beer has nothing to do with coronavirus at all. And this is not sponsored. Not sponsored. It also has anchorese chili lique, and some lime juice and some tomatoo salsa. A little spicy something or other to get you through this episode.

Yeah, it's basically like a Michelada. And we will post the full recipe for this quarantini as well as. is our non-alcoholic placebo rita on our website. This podcast will kill you.com and all of our social media channels. Okay. I mean, I think we should probably just jump right in. People are already chomping at the bit. Yeah, they want to. We should just, we should stop messing around here. Let's take a quick break and then we'll talk biology. Sounds great. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no

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Quince.com slash this podcast. Straight off the bat, I want to let you all know that coronaviruses are nothing new. Nope. Nothing new. This novel coronavirus that's making headlines is a new, individual-specific virus. Yes.

However, coronaviruses, like, say, influenza viruses are a large group of RNA viruses that we not only have known about for a long time, but have been circulating among humans and many, many other species of animals for a very, very long time. Okay. Fun fact. This is my only fun fact. Oh, great. Corona means crown.

Mm-hmm. And the reason that coronaviruses are called crown viruses is because when you look at them on a scanning electron microscope, they have a little halo crown of proteins around the outside. Oh, isn't that cute? Viral royalty. Yes, royal virus. That's the end of my fun fact. Here's how kind of this episode biology is going to be structured. All right.

First we're going to talk about the most common human coronavirus. in general. These are the ones that circulate all the time. Almost definitely, if you are listening to this podcast, you've been infected with a coronavirus at some point in your life. And then we'll talk about the three big headline-grabbing coronaviruses. That is SARS, MERS, and the newest 2019 N. CoVee. Cool.

Gotcha. Sounds great. All right. So coronaviruses in general, there are several different large groups of coronaviruses, and a lot of them actually infect animals, all different kinds of animals, pigs, chickens, cats, and in animals, they often cause GI illness, so like diarrhea and stuff like that, but they can also cause respiratory illness. There are four human coronaviruses that are really common, and they cause the common cold.

Yeah. So these are upper respiratory tract infections in general. So the question first that we like to answer is what exactly do they do in your body and how do they make you sick? What is their pathophysiology? Turns out that for the four human coronaviruses, we don't entirely know their pathophysiology because like for many viruses, we don't have really great animal models to study them. But from some really interesting, and probably ethically questionable studies that they've done in humans where they intentionally infect, quote-unquote, volunteers. When were these studies from? The 80s and early 2000s. Okay. That's, yeah.

That's, yeah. Anyways, what we do know from these studies is that these four human coronaviruses colonize the upper respiratory tract, so your nose and throat in general. Okay. And we know that they invade and replicate in your respiratory. epithelium, so the sort of first cells lining your respiratory tract. So in the case of these four common coronaviruses, that's pretty much where they seem to stop. They're not super infectious in these human studies up to like a third of people that they inoculated didn't actually even get

infected with the virus. And most of those that did had very mild or maybe moderate colds. So we all know what the common cold looks like, right, Erin? What kinds of symptoms do you have? Runny nose, sneezing, coughing. There you go. Exactly. Yeah, so these are very mild upper respiratory symptoms. Cough, runny nose, stuffy nose, maybe you get a headache, maybe rarely you'd spike a fever, but in general, you're not all that sick. The way that common cold viruses like coronavirus are generally transmitted is by respiratory droplets. So since they make you cough and sneeze, when you cough and sneeze out, liquid droplets, full of virus, and that's how the next person gets infected. So it's not like something like measles that we talked about that can hang out airborne in the room

for many, many hours in the air. Right. These are viruses that are contained in water droplets that you cough and sneeze out. It is also possible that these droplets can land on surfaces and the virus can then live on these surfaces and be transmitted from, say, a doorknob to your mouth if you touch a doornaub and then touch your mouth. That makes sense? Yes. Okay. So that's the four common coronaviruses. They don't cause a lot of morbidity or illness. They don't cause a lot of mortality except in very, very, very rare cases. And it's estimated that anywhere from 10 to 30% of all common colds around the world are caused by one of these four coronaviruses.

Huh. Yeah. So they're really common. Yeah. And I think that's important to keep in mind because even when SARS first came on the scene, while we'll see that it was very novel in the type of disease and the severity of disease it caused, it wasn't a completely unknown, alien invasion virus. Right. And neither is this new novel coronavirus that's circulating today.

Okay, so let's get into the more serious things. And that starts with SARS. SARS stands for severe acute respiratory syndrome. What was novel about SARS when it first came on the scene in 2002 is that it caused a very serious illness in people. It caused an illness that was so severe, compared to what coronaviruses normally cause, which is like a cough and runny nose, that we didn't recognize it as a coronavirus for a long time. And there's a number of reasons for that, many of which I'm sure, Aaron, you'll get into. Right. Okay. But at least in part, it's because we didn't expect before SARS that coronaviruses could cause the kind of disease we saw with SARS, right? So why did we see more severe infection? And the

answer is that while SARS still mostly affects the respiratory tract, unlike the other coronaviruses, SARS is able to extend its infection to the lower respiratory tract. So not just your nose and throat, but actually colonize your lungs and cause disease in your lungs itself. What allows the SARS-CoV to do that? Like, what is stopping the other four endemic, milder coronaviruses from invading your lungs? Good question. And this was one of my, I put a little asterisk next to this because I thought you might ask it. So let's talk about it. So remember that viruses can't replicate on their own, right?

They have to enter our cells in order to replicate and then use our cellular machinery in order to replicate and make new viruses. So in order to do that, they have to get into our cells. And the first step in doing that is to bind to some receptors on our cells and use those receptors to get into our cells. Different viruses use different proteins and bind to different proteins in our cells. And what proteins they bind to and where in our body those proteins are found, like what cell types have those proteins, determines what's called the tropism of the virus. What organs in our body, the virus tends to invade.

Oh, like where it goes. Okay. Yeah. Exactly. And so, in the case of SARS, we found out later, we know now, that SARS binds to a protein called ACE2, angiotensin-converting enzyme. This protein is expressed in very high concentrations in our lungs and also in our small intestine and some other organs too, kidneys, etc. Because this is the protein that SARS uses to bind,

it was able to then invade our lungs because our lung tissue has a lot of ACE on its surface. I didn't look up exactly. what proteins the other four coronaviruses use to invade because there's four of them and that would be too long of an episode, but it's not generally ACE, right? So the other coronaviruses use different receptors that they recognize that are located more in the upper respiratory tract. It seems like knowing the proteins that these viruses bind to would be great targets for treatment. Absolutely, yeah. So there's been some ideas because we have, ooh, this is probably getting too much, Erin. But we have drugs that actually target ACE because it's an

important component of how your body manages blood pressure. Whoa. Oh my gosh. Yeah. So we have things called ACE inhibitors. So there's this thought that like, oh, could maybe you use these to treat SARS? We don't, as far as I know there isn't actually good evidence that that works. But it's like, yeah, cool idea. Let's do some research on it. But yeah, knowing knowing how. viruses get into our body is often a good place to try, at least try, to target for treatments. I'll just say we don't have any, though, at this point for SARS or MERS or the novel coronavirus. Just throwing that out there. Okay. There we go. So yeah, so SARS gets into your lungs and is able to cause a lung infection. Lung infection means pneumonia. So this is a virus causing viral pneumonia.

So the symptoms of SARS, because it's a more extensive disease, tend to start more systemically. So fever is the number one symptom of SARS, actually. Okay. Fever, chills, myalgas, like you described in the firsthand account, these muscle aches can get really, really severe. And then you do still get some upper respiratory symptoms, but a lot of the symptoms are more lower respiratory. So you'll get a cough, but less of the like runny nose type symptoms that we see with other coronaviruses. And then as this disease progresses and more damage is caused to the lungs themselves, you'll get other more serious symptoms like shortness of breath, tachypnea, which means a really fast breathing rate,

pleuracy, which is like pain in your chest and lungs when you breathe. And then depending on how late in the course, of disease people present to the hospital because this is a very serious illness most people will present to the hospital, almost everyone, when you take an x-ray of their chest, it will look like what we call ground glass opacifications. Oh my gosh, that sounds terrible. It is terrible. So if you've ever seen an x-ray of a normal chest, like a not ill chest x-ray, you know that the lungs are filled with air, so they're mostly black because air is black on x-ray. So you can see the outlines of ribs, and then you can see sort of black in between the ribs with maybe little bits where you can see

like blood vessels and things like that. That's a normal, not sick chest x-ray. With SARS, it looks like you're looking through like a bathroom, you know, the glass they put on bathroom windows? Yeah, I have some of that on my bathroom window. Exactly. So it looks like that. So it's not so opaque that you can't still see like the shadow of your heart and your ribs. You can still see that. It's not completely whited out like it might be with a bacterial pneumonia. Oh, because the bacteria has colonized, whereas this is just inflammation? Well, bacteria still produce a lot of inflammation, but it'll be localized to one spot and it'll be so much in like one corner of the lung that it's totally whited out. Okay. Whereas this is bilateral often.

throughout your whole lung fields, top and bottom, often. It's all just kind of murky looking. That sounds terrible. Yeah, it's bad. It's not good. And then this can sort of just progress. So about one third of people with SARS will get better on their own, but 20 to 30 percent end up needing mechanical ventilation because their lungs are just so inflamed that they're not able to get enough oxygen

in on their own. And I want to point out that this kind of supportive treatment is the only treatment that we have since we don't have any antivirals for SARS. And overall, what we saw from the SARS outbreak was a case fatality rate of just under 10%. So about 10% of people who were infected with SARS ended up dying from SARS or SARS complications. That's a very high mortality rate. It is. And it varied a lot based on demographic factors. So in people older than 65, the mortality rate was over 50%. Wow. I didn't realize it was that high. Yeah, it was really high. So that's kind of what the disease looked like for SARS. We learned a lot about it after the outbreak because as you can probably see with what's going on with the new outbreak right now, it's really hard to get good information while the outbreak is going on, right? Because you're just kind of dealing with like trying to keep people alive.

Well, and also there's steps to publishing reliable information that has to go through peer review process. And some of those things are lifted right now and people are getting early drafts out. But it's then, you know, what information is reliable? Sample sizes tend to be small, et cetera, et cetera. Yeah. But so things that we know now, looking back at SAR, since the outbreak has passed is we know that with SARS, subclinical infection, so like asymptomatic infection, was really rare. So in looking at seroprevalent studies of people in areas where there were high rates of SARS, there's very little evidence of infection in people who didn't have symptoms of SARS. Interesting. Okay. Yeah. So we know that in the case of SARS, infection almost

always led to symptoms, and in general, those symptoms were very severe. And the other thing that we learned about SARS was that the viral load, so how much virus you had in your body, was a really driving factor of infectivity. Okay. And so in the case of SARS, the incubation period, so the time from when you first got infected to showed symptoms, was usually about four to seven days. And viral load actually increased slowly over that time. So people were most infectious about 10 days after first getting infected. And so that means that people for SARS were really only infectious if and when they showed symptoms, which made SARS relatively easy to screen for and to help contain.

So that's pretty much SARS. Okay. So let's move on. The next most famous coronavirus was MERS, Middle East Respiratory Syndrome. So was MERS just the same thing as SARS but in a different part of the world? No, not really. It was another novel coronavirus that was discovered in 2012 after an outbreak in, I believe, Saudi Arabia was the first identified cases. Is that right, Aaron?

So it was first isolated from an outbreak in Saudi Arabia, but retrospective testing showed that it actually, the first, the first, first cases seem to be in Jordan earlier that year. That's right. That's right. Okay. So, symptomatically, MERS presented very similarly to SARS in a lot of ways. It started off with fever. Myalja's muscle pain was really common. Oh, I forgot to mention this, but a really common symptom for SARS was actually diarrhea and in some cases nausea and vomiting. So you often, in addition to this viral pneumonia, had pretty extensive GI symptoms. You also saw this in MERS. And then like with SARS, you would get a really rapidly progressive viral pneumonia.

You'd have similar findings on chest x-ray, those ground glass opacities, and it could lead to respiratory failure and potentially death. We know that MERS also had a similar incubation period, a similar time to symptoms, as SARS. Does it also bind to the ACE2 protein? Oh, I'm so glad that you asked, Erin. No. Really? As it turns out, MERS binds to a different protein called DPP4, dipeptidyl peptidase. This is another protein.

It's similar to ACE, but it's expressed in high levels in the lungs and the kidney. So can you guess another very common symptom of MERS that's different? from SARS. Renal failure. Renal failure. Absolutely. So ACE is also expressed in the kidney. So you can still get renal failure with SARS, but it's more common in MERS because I think DPP4 is expressed at very high levels in the kidney. Right. Oh, how fun. Okay, unless you have MERS. So let's talk about some of the differences between MERS and SARS. First off, MERS, way more deadly. Yes. Okay. So in looking at the outbreaks of MERS, The case fatality rate is close to 40%. About 36%.

That's very, very, very high. It's very high. For SARS, it was just under 10%. So a case fatality rate of 40% sounds very terrifying. So let's calm ourselves down for a minute and not freak out too much about MERS. Here's a few reasons why. Number one, it turns out that MERS is not nearly as, infectious as SARS. So person-to-person transmission is not very efficient for MERS.

Why is that? You know, that's a really good question that we don't fully understand the answer to. What we do know is that when we compare the R-NOTs, so the average number of cases from a primary case to a secondary case, for SARS, it was probably around two to three, I think. Is that right? Yeah. For MERS, it's like 0.7. Okay. Do you think it has something to do with the tropism of the virus? Is it in the lungs as much?

Is the infectious dose different between SARS and MERS? It could be the infectious dose, absolutely. I think that probably has a lot to do with it. It could be the tropism, although DPP4, like it causes just as bad of a viral pneumonia, if not worse. But here's another important part about MERS. and this I think helps, at least I think this makes more sense as to why it maybe doesn't transmit as well. The vast majority of cases of MERS, not even just the deaths, but the people who were infected with MERS, 75% of them had some kind of underlying disease, some kind of comorbidity.

So it seems like maybe MERS requires that a person is already a little sick, so they have diabetes or some kind of underlying lung disease or heart disease, something that makes their immune system not work as effectively that allows for MERS to colonize, infect them, and then make them very, very sick. Gotcha. Whereas with SARS, you know, healthy people got infected, sick people got infected. SARS just infected pretty much anyone. Does that make sense? Yes.

So overall, that's the good news about MERS. It's a lot less transmissible. almost every outbreak or group of cases had at least some documented spillover events. And it thought that there were many, many individual spillovers that happened with MERS, whereas SARS, you'll probably talk more about, was one big outbreak. Right. And MERS, the vast majority of people who have been shown to be infected had at least some underlying comorbidities. Okay. So that's MERS and SARS.

You saved a special one for last. The special one for last. So those two novel coronaviruses, as a recap, are different than the other four coronaviruses that circulate because they cause more serious illness by infecting the lower respiratory tract. So that brings us to today, 2019 NCOV. the newest coronavirus on the block. I don't have all the answers for you about what is this virus and what's the fatality rate and etc, et cetera, not only because we're not the experts on this topic, but because this is such a new virus and an ongoing outbreak that we can't answer all of these questions.

We can make estimates based on the fact that we've seen SARS and MERS in the past, we can guess that in a lot of ways this novel coronavirus likely operates very similarly to SARS and MERS and honestly the other coronaviruses. So how do we think it's transmitted? Most likely respiratory droplets, right? That's how all coronaviruses tend to be transmitted. it's certainly possible that fomites or surfaces can be an important part of transmission, so we don't know how long this particular coronavirus can survive on, say, a doorknob or your cell phone, but we know it can probably live for at least a period of time since other coronaviruses can survive for many hours. And what it appears, based on the number of people who have had severe symptoms,

is that this novel coronavirus is also able to infect our lungs and cause serious viral pneumonia. So this is a more severe coronavirus than the four typical coronaviruses. We don't know anything about the protein that it binds to? So there has been at least one study that has shown that it likely actually uses ACE2 as well, at least potentially. But that study was, it's very preliminary and it wasn't. using a live virus. They like conjugated it to a herpes virus and it was just in cell culture. So no, we don't know for sure what protein this novel coronavirus is using. It might be the same one as SARS. It might not be. Okay. We also don't quite know what the R not is. So the basic

reproductive value. There've been a lot of people trying to make estimates. It seems at this point on February 2nd, like it's likely between two and two and a half maybe. That's the estimates that I've seen. So probably similar to SARS, maybe not quite as infectious, although we've seen numbers go up a lot more rapidly than with SARS. And one thing that I think is really, really important is that we cannot estimate a case fatality rate until this outbreak is over. Yeah.

Period. And I think that there's a lot of people on the internet right now saying, well, the mortality rate is this and the case fatality rate is that. We can't estimate either of those numbers right now at all. We can calculate a proportion of, you know, total deaths from this disease so far. But because, so, okay, February 2nd at 10 a.m., there are currently, 14,600 total cases that we know about. 348 of those have recovered, and 305 of them have died thus far. Okay.

So if you use those numbers, then it would look like a proportionate mortality of around 2%. But this is not a fixed number. 14,200 of those 14,600 are still sick. and we don't know how severe their illness is going to be and whether they're going to end up in the recovered group or the death group. And there are thousands more tests that haven't been run. So we really don't know at all what the case fatality rate is going to be at this point. Makes sense. Yeah. But otherwise, this likely operates, it seems similarly to SARS. So it's estimated that the incubation period is likely no more than 14 days.

That's like the max that we've seen in both SARS and MERS. So if you're two weeks out from being, say, next to someone with this novel coronavirus and you haven't gotten sick, you're probably not going to get sick. And then there's a lot of other questions about like when exactly are you infectious, how many asymptomatic or subclinical infections might there be? And at this point, it's looking like it's more likely than with SARS that there might be. kind of low level illness rather than only serious severe cases. Right, which might be part of the reason why the number of infected has surpassed SARS already. Exactly. Right. Yeah. But we don't have a ton of answers. And so later in this episode, we'll talk more about what we know about this outbreak overall and what's being done about this outbreak with some experts on the topic,

people who know a lot more than we do. Yes. But first, Erin, can you help us to understand where these coronaviruses came from and how we got through the SARS and MERS outbreaks and kind of the lay of the land? I think I can help out with that a little bit. Let's take a quick break first. Anyone who works long hours knows the routine. Wash, sanitize, repeat.

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and get no traction. Seriously, sponsored jobs posted directly on Indeed are 95% more likely to report a higher than non-sponsored jobs. It really is a no-brainer. Spend less time searching and more time actually interviewing candidates who check all your boxes. Less stress, less time, more results. When you need the right person to cut through the chaos, this is a job for Indeed's sponsored jobs. And listeners of this show will get a $75 sponsored job credit to help your job get the premium status it deserves at Indeed.com slash podcast. Just go to Indeed.com slash podcast right now. Terms and conditions apply. Need to hire? This is a job for Indeed's sponsored jobs. All right. Are you ready for this? Oh, I'm so ready. It's a big one. Okay. And there's a ton of info here. So I tried to organize it into discrete units, just like you did. Okay. So I'm going to start with talking about the ecology and origins of coronaviruses in general. And then I'm going to focus on the 2002-2003 SARS epidemic. Then I'll talk a little bit about MERS.

And finally, we'll go into what's been on everyone's mind, which is the 2019 novel coronavirus. Awesome. All right. Let's go. As you mentioned, Aaron, SARS and MERS and this 2019 novel coronavirus are all types of coronaviruses. And as a subfamily, they're pretty diverse. So like you said, they can be found all over the world in different animal species, in wildlife,

in domestic animals, in humans. And they can cause different degrees of illness in all these. animals. It's difficult to know exactly how long coronaviruses have been infecting humans, but it's likely that it goes way back, particularly for those mild endemic strains. And it's also possible, of course, that there have been historical epidemics of more deadly coronaviruses like SARS and MERS and so on. But the first one that we are, that we were aware of is the one from the SARS outbreak 2002 to 2003. And then MERS popped up in 2012. And then finally, this one in 2019.

The common thread among these more virulent or deadly coronaviruses is that they all seem to have their origins in bats. So with SARS-CoV, it was likely a spillover event from bats to civets to humans. And with MERS Co-V, the in-between animals were camels. We're not exactly sure yet how the 2019 novel coronavirus spilled over into humans. but according to two papers, one of which I want to point out is not peer-reviewed. It's just a draft of an early paper. Bats have been implicated as the source as well.

Makes sense. SARS-MERS 2019, novel coronavirus. These viruses are novel to humans, but the way that the outbreaks occurred is not. And before I get into the nitty-gritty on each of these coronavirus outbreaks, I wanted to talk more generally about emerging infectious. diseases. Yes. Because, yeah, because these coronavirus outbreaks won't be the last. And if we want to be able to control or predict these spillover events, we have to understand the factors driving them. The incidence of emerging infectious disease events has risen significantly over time. And the majority of these have their origins in wildlife. And the term emerging infectious disease can

also be used to describe something that has evolved, like an antibiotic-resistant strain of bacteria. or something that's been with humans for a long time but has recently increased in incidents like Lyme disease. But it also can mean pathogens that are branded to humans. And with this last category, the so-called emerging disease hotspots, so the places around the globe where spillover events are most likely to occur based on what we've already seen, these tend to be concentrated in the tropics, so like in low latitude areas and subtropics. That's also happens to be where animal and pathogens.

diversity is high, and also in resource limited countries, particularly those with high population densities. As our human population grows, as we continue to build and spread into natural areas, as urbanization increases, as the climate changes, humans and domestic animals become more likely to interact with wildlife and with pathogens from wildlife. And we've seen this time after time with Ebola, with Marburg, with Hendra, with NEPA, with bird flu, and with many more. Detection or surveillance of novel pathogens in these areas is challenging, mostly because the funds just aren't there, both nationally and internationally. And if we want to reduce the likelihood of another outbreak like this

or be better at controlling it from the start, we need to channel more resources into early detection and surveillance, both in humans and wildlife, conservation of natural areas, and especially interdisciplinary collaboration like we see in a one-health approach, with ecologists, epidemiologists, physicians, etc., all working together. Get it, Erin. There should also be a push towards the free and open exchange of information, which is actually something great that I've noticed with this 2019 novel coronavirus, so there are several

scientific journals that are saying we're putting all of these articles, we're taking these from behind the paywall, we're making them free to the public, open access, publish early with like, you know, note that it was a draft or whatever. But there are still so many journals and journal articles that are behind a paywall. And this current outbreak of 2019 novel coronavirus, it's probably not going to be the thing to wipe out the human race. No. But the next one could be, unless we make certain changes and we work really hard on the prevention and surveillance aspect of this. Okay. Now are you all scared?

Just kidding. SARS. The earliest signs of the SARS epidemic began in November 2002 in Guangdong Province in China. In Guangdong Province, as well as many other places throughout the country, open-air markets and restaurants featured animals of all different species, often held in tiny, enclosures with their poop and breath and blood all mingling constantly. Poop and breath. Yeah.

There were many restaurants that offered any part of any species you could possibly want. And to ensure that the meat was fresh, the animals on the menu were often held in cages in alleys behind the restaurant. It was at these restaurants and markets that the first cases of SARS would emerge. On November 16, 2002, an official on the village committee was admitted to a hospital in Foshan Guangdong province complaining of respiratory symptoms. His family also came down with the illness. Over the course of the next month, case numbers of this mysterious atypical pneumonia steadily rose. By December 25, 2002, 35 people were infected and 8 had died.

And this is important to note it was a retrospective count, for the most part. Okay. But deaths were apparent. And so with these number of deaths from a mysterious respiratory ailment, some public health officials were growing suspicious and a little bit concerned. Rumors started to circulate of an influenza epidemic, possibly avian influenza. And since the outbreak of avian influenza in Hong Kong in 1997, there was constant vigilance

for the virus because it is extremely deadly. And if person-to-person transmission was established, that could be a real problem. But other people doubted that it was avian influenza. This was, after all, the winter season, when it seemed like everyone had a respiratory complaint of one kind or another, and rumors circulated every year about a mysterious hemorrhagic fever or a wild skin disease. These rumors were different, though.

For one, these rumors all focused on the respiratory ailment and were pretty consistent, at least as far as rumors go. cloudy chest x-rays, burning fevers, and high prevalence among medical personnel. The first official public statement about the SARS epidemic was released on January 3, 2003, a little over a month since the beginning of the outbreak. At this point, there were 48 people infected and nine dead. Another retrospective count. This statement was published on the front page of the Haywan Daily.

It read, quote, there is no epidemic in Haywan. there is no need for people to panic. Regarding the rumor of ongoing epidemic in the city, health department officials announced at 1.30 a.m. this morning, there is no epidemic in Haywan. The official pointed out that people don't need to panic and there is no need to buy preventative drugs, end quote. Despite this incredibly reassuring statement, people panicked.

They rushed to the pharmacy, buying all the acetaminopin and antibiotics that they could get their hands on, because antibiotics are available over the counter without a preemptive. prescription there. And they're very useful against viruses. Not. They're not. They're not useful at all. They are not. They're not. Public health officials were dispatched to the HAYWAN number one hospital to conduct an investigation into the mysterious pneumonia. Some suspected a species of chlamydia, which can cause pneumonia, but the infection didn't respond to broad spectrum antibiotics. Others thought maybe it was caused by a virus, possibly influenza or possibly a virus not yet described.

They also interviewed patients and medical staff about their experiences. Disturbingly, they found that several patients had been to multiple hospitals, moving either by their own choice or being transferred. Uh-oh. Yeah. By the end of January, rumors were soon swirling yet again, this time in Zhang Shan, about the atypical pneumonia, which was now circulating in more.

multiple hospitals in a city, as well as popping up outside of hospitals. By this time, it had earned the nickname Breath Taker or Breathstalker, which is where we got our quarantining name. And whereas in Haywan, the disease was largely confined to one hospital, what was going on in Zhangshan appeared to be the first community outbreak of the mysterious disease. And it would later be determined that the first known super spreader of SARS, nicknamed the Poison King was transferred from Zhang Shan where he had infected six medical personnel to Guangzhou, where he would continue to infect people.

And these super spreaders, it's no fault of their own. People didn't know how to control the infection at this point or how infectious it was. But these super spreaders would be a hallmark of the SARS outbreak, where a lot of the infections originated from one source like that. Okay. So by late January, medical officials were pretty. certain that it was caused by an extremely infectious virus transmitted through respiratory droplets. But getting that information out there was a different story. Because it was standard practice among

the Chinese government to keep this information top secret and classified, to not share it among anyone less than the topmost ranking public health officials, not the public, and certainly not to the outside world. So the rest of the world finally caught wind of a mysterious and deadly outbreak in China on February 10th, 2003, at which point an estimated 393 people were infected and 40 had died, retrospective count. Somebody posted a report on pro med. ProMed. All right.

You read it? Quote. There's like, also, this is like a quote within a quote. So just keep that in mind as I'm trying to say it. Okay. This morning, I received this email and then searched your archives and found nothing that pertained to it. Does anyone know about this problem?

And then here's the email. Another quote. Have you heard of an epidemic in Guangzhou? An acquaintance of mine from a teacher's chat room lives there and reports that the hospitals have been closed and people are dying. And double quotes. So around this time, the WHO got an email describing panic in Guangdong as the death toll from a mysterious pneumonia was climbing. The official word from the Chinese government was still lacking. But once other countries started reporting on this disease,

speculating with what little information they had, panic and anxiety set in any way. And the Chinese government was forced to hold a press conference on the disease in Guangdong. And this press conference held on February 11th, which was one day after the pro-med announcement, was full of assurances that this disease wasn't anything to be concerned about. They said there were only 305 people infected, and it was already under control. Meanwhile, in Hong Kong, a doctor, from Guangzhou arrived at a hotel where he was staying for a wedding. This would be the next super spreader. He started to feel worse and worse and eventually sought medical care, but it was too late to stop the spread of the virus. Also at this hotel was a woman from Toronto, a Chinese-American

businessman, and a Hong Kong local who went to the hotel to visit a friend. All of these left the hotel to continue on their travels to return home, unknowingly bringing with them this hitchhiking virus. And this marked the real start of the global spread of the virus. Hong Kong, Toronto, Hanoi, Singapore, Beijing, these would be the next hotspots of infection. On February 28, 2003, parasitologist Carlo Urbani, based in Vietnam, alerted the WHO about a highly contagious atypical pneumonia

after treating the Chinese American businessman who had stayed in that hot zone hotel in Hong Kong. and several health care workers who had also come down with this pneumonia after treating this person. Back in Toronto, a similar scene was unfolding. So the woman who was infected in Hong Kong died in a hospital back in Toronto, and five of her family members were found to be infected as well. On March 15, the WHO was notified of a possible SARS-infected doctor traveling from New York back home to Singapore with a stopover in Frankfurt. mid-flight, the doctor, his wife, and his mother-in-law were all cordoned off.

And then as soon as the plane landed in Frankfurt, they were placed in isolation. That's one of the few moments that I really do remember from the SARS outbreak. When it was like, there's a person traveling in the plane. Yeah, and like on the plane and then they like quarantined them when they landed in Germany. Like I don't know why that's one of the moments. I wasn't that into disease at the time. I was in high school, but I remember that. You should read his account.

It's really interesting because he talks about the depression of isolation and how much insight it gave him as a physician to know what his patients had been going through. So this doctor, his wife and his mother-in-law, all three of them developed SARS. I don't know if they infected anyone else, actually. I don't remember. But regardless, these signs of a global spread or potential. global spread prompted the WHO to declare a travel advisory and to come up with a name. And as we said, locations were out, but acronyms can be catchy. So someone suggested SARS, and it stuck. But what no one realized at the time was that SARS was very similar to what China

called Hong Kong, special administrative region, SAR. Oh. In a way, it was, it placed a lot of stigma on Hong Kong as like, because who had already experienced stigma about the avian influenza? outbreak in 1997 and subsequent outbreaks. And then it was sort of further stigmatized Hong Kong. Okay. At the hospitals where the people with atypical pneumonia were being treated, the pattern that emerged was that healthcare workers were becoming infected by the dozens. There weren't enough beds to put all of the sick people.

And there were too few people left to help care for them. So hospitals were beginning to crash. some were some emergency hospitals were being built and one practice that developed was to form dirty teams which were composed of medical staff that had volunteered to treat the infected people and they would live at the hospital in isolation and those who were not on the dirty team would not be permitted to go near the patients and so this would reduce the number of medical staff that was potentially exposed and filling out the dirty team was never a problem more people volunteered than there were places.

Wow. Always. Yeah. And the SARS epidemic, like this coronavirus epidemic and other epidemics, is filled with these stories of selfless people, especially health care workers, many of whom lost their lives to the illness. And one of these was the parasitologists that I mentioned earlier, Carlo Urbani, who, just before he died, asked to have his lung tissue sent to the CDC so they could use it for research. That's who in the movie Contagion, that's who Kate Wins its character is based off of.

I didn't realize that. That's cool. Yep. Wow. On March 21st, researchers at Hong Kong University announced they had found that the pathogen causing this atypical pneumonia was a coronavirus, beating the CDC by a couple of days. And up to this point, a coronavirus, as we have said, had never been known to cause such severe disease. And it was kind of low on the list of potential agents because of that. Right. And also there was a couple cases of H5N1 avian influenza that had shown up in Hong Kong.

And so it was kind of thought, maybe this is just a mutated strain. And for some reason, we're not detecting it in these samples and so on. Anyway, on March 21st, there it was coronavirus. And that allowed people to test whether people were infected or not, which was a great help in terms of understanding the extent of the epidemic. At this time, though, the Chinese government was still refusing to give up any information on the disease, holding firm with its February 11th totals of 305 people sick. The real numbers, as of March 18, 2003, another retrospective count,

were around 1,400 infected and 137 dead. Wow. And those are global totals. And those numbers would continue to climb as the nature of transmission changed a bit. Earlier in the epidemic, transmission mostly seemed to be happening within hospitals, which is why there was such a high proportion of those infected being health care workers. But then there was a bit of a shift to community outbreaks, notably in Hong Kong, at the end of March. Several people showed up to the Prince of Wales Hospital in Hong Kong with symptoms of SARS,

but they had no obvious connection to or contact with other infected people. So what was making them sick? Turns out they all happened to be residents of a housing complex called Amoy Gardens. Pretty soon after this discovery, the housing complex was put under strict isolation. No one in, no one out. And this went on for weeks. Whoa. But what if that wasn't enough?

They had to find out how this had spread in the housing complex before they had to. started doing the same in other parts of the city. Elevators? Eh, maybe, but air and water were both tested and found to be clean. Rats may have contributed, but they alone couldn't account for the infection pattern that had been observed. And around this time, researchers realized that the virus could be spread in fecal matter from infected people. And so their new hypothesis became that fecal matter containing viruses was being aerosolized every time a toilet was flushed. The contaminated droplets were spread to other apartments via a dried up U-trap, which is that thing under the sink. And so when there's standing water, that water acts as a barrier,

but a lot of the U-traps had dried up. And so it was effectively spraying poopy virus particles. Dude. Yeah. And it is like it's important to note that that is still a little bit debated, whether it was that or the rats or some combination of multiple things. But regardless, it was, it was like a sequence of really unfortunate events. The isolation seemed to work, though, of Amoy Gardens. Those cases there seem to mark the peak of the epidemic in Hong Kong, and by April it was largely over there. Part of this was because increased precautions at hospitals

in terms of personal protective equipment, the formation of these dirty teams. Part of it was because contact tracing and an e-SARs database were proving effective at identifying potentially exposed people and isolating them. And part was that community outbreaks died out as people changed their daily routine. Hong Kong became a virtual ghost town during the epidemic as people who could leave did so and others stockpiled food and dared not go outside. Okay.

April, moving on to April. Okay. April 1st, 2003, an estimated 2,300 people in terms of people in terms of. infected, 255 dead. Globally. Globally. Okay. Even though the epidemic in Hong Kong seemed to be waning, it spread in other places

was a concern to the WHO, who was still getting the same numbers from government officials in China, unchanged for about two months. So the WHO resorted to making surprise visits to hospitals in Beijing, where the official numbers were 12 infected and three dead. at at least one of these hospitals, minutes before the WHO were due to arrive, a fleet of ambulances pulled up and the hospital director ordered all 31 SARS-infected health care workers to get into the ambulances where they were driven around until the WHO left. The WHO showed up to the hospital to the promising site of an outbreak nearly over.

Regardless, they still amended their estimates of those infected in Beijing to like one to 200 people. In reality, it was much higher than that. And I want to note that among health care workers and among people in the community, there was ample communication. People were trying to get the word from one hospital to another, from one city to another, to get some sort of idea of the scope of the outbreak, how to protect yourself, what was being done, et cetera. But communicating that info to press outside of China could have serious repercussions because it would be the sharing of state secrets. What was needed was a whistleblower, and what we got was a whistleblower. And so this whistleblower was named Dr. Jiang Yan Yun, and Jiang, who had treated many of the

students injured in the Tiananmen Square massacre, became aware of the extent of the SARS crisis in Beijing when he called a hospital to check on a friend of his who had lung cancer. and the doctors that he had talked to, who were respiratory specialists, sounded panicked, as they described how at least 60 people were infected with SARS, many of them health care workers, and that this was happening in hospitals all over the city. Remember, the official numbers were still 12 total infected in Beijing at this point. Oh. Yeah.

Jiang did a bit more calling around and made tallies of the number of estimated SARS cases. in different hospitals across Beijing. And he sent those numbers and a note to a couple of Chinese TV stations, but unfortunately his note was ignored. But it was eventually picked up by Time magazine, which made it into international news. That there was an epidemic could no longer be denied. And on April 16th, an official announcement was made by the Chinese government

saying that the SARS situation is, quote, extremely grave. The numbers were revised from 12 to 339 infected in Beijing, with hundreds more suspected. And it wasn't just 305 people infected in all of China, which is the number that the government had been sticking to since early February. It was over 2,200. Wow. With, again, many more suspected. And then the government did a remarkable thing. they canceled the week-long spring holiday and admitted that they were wrong.

After the announcement, the number of cases went up tremendously and continued to grow, but was that because people now felt they could report accurate numbers? Was the epidemic actually growing? But with this sudden shift to finally acknowledging that SARS was a big freaking deal, the propaganda around it changed. There was now 24-hour coverage of the epidemic, whereas previously there had been almost none in China specifically. And then whereas before sharing information about SARS meant betraying state secrets,

the government now threatened the death penalty to anyone spreading misinformation or hiding aspects of infection. Yes. Swing one pendulum to the other. Yes. The Chinese Ministry of Health finally put into place some preventative measures, foremost among them being thermal scans. for fevers. So these scanners were put into place at train stations, banks, office buildings everywhere. And if you were found to have a fever, you would be rushed off in an ambulance and placed under quarantine for up to 21 days. And even though this method was perhaps crude, it was

probably pretty effective because a person was found to be most infectious, as you mentioned, between 10 and 21 days after infection. And during that period, they would almost certainly have a fever. this quality of SARS made it easier to control, as we've talked about, and the authoritarian aspect of China was a double-edged sword, because on one hand, it restricted the flow of information that would end up fueling the outbreak. But on the other hand, once the epidemic had been acknowledged, it could mobilize people and put into effect practices, some that are questionable in terms of civil liberties, that might have been more delayed in a more democratic society. This is where public health becomes difficult, man.

This is where public health becomes difficult. Because these are civil liberties that are being trampled on. But that's why I say, you know, it's been called this double-edged sword. All right, we're almost done with the SARS outbreak. Okay. Throughout May and into June, the epidemic began to wind down. as Vietnam, Singapore, Hong Kong, and Beijing are all declared free of SARS. Okay.

First case was in November. Now it's May. Okay. So like half a year. Okay. Yeah. In July, Toronto and Taiwan see no new cases, and it's been announced by the WHO that SARS has been contained worldwide. Awesome. The final tally of infected and dead is 8,098,98 people infected.

774 people dead. The economic costs of an outbreak like SARS are extreme. People lost jobs, personal bankruptcies, went through the roof. Tourism and travel revenue fell tremendously. The economies crashed in many of the affected areas. But I think what is often not as highly considered is the personal impact. Many people lost their lives, and those lucky enough to survive the infection often experience long-term health consequences, and many also experienced PTSD or depression, and were highly

stigmatized for a period after. So the cost of an epidemic like this are far-ranging, and some costs are more easily quantified than others, and I think that's important to keep in mind as we talk about the 2019 novel coronavirus outbreak, and as we'll get into also a little bit of the issue of stigma and xenophobia that are surrounding things like this. Yeah. And how travel bans, restricting people from entering certain countries, does not seem to be effective and is actually a way of disguising xenophobia and racism.

Yeah. We can look back at times when we've instituted travel bans in past outbreaks and see that they, in general, cause a lot more harm than good. So I think that's really important to keep in mind considering that they've already been put in place supposedly during this outbreak. Yep. So. Okay. Let's move on to MERS.

Let's. All right. This is going to be really fast, I promise. Cool, cool, cool, cool, cool, cool, cool. All right, so MERS. Most cases have an association with dromedary camels. An analysis of past samples show that the virus may have been circulating in camels at least since the early 1980. which is 30 years before the first known human case.

And this also suggests a long history of association between camels and the virus. And I also want to note, though, that MERS-related viruses have been found in bat species on five continents. So it suggests that, yeah. There are like clusters of, you know, MERS-related coronaviruses, SARS-related coronaviruses that are found in bat populations or animal populations that don't have the ability to infect humans or it don't appear to. But it does show that this is a very diverse and wide-ranging group of viruses. Yeah.

Yeah, yeah, yeah. Okay. So MERS COV was first isolated in June 2012 from a 60-year-old man from Saudi Arabia who died of pneumonia and renal failure. And as I mentioned earlier, this wasn't the first case of MERS. So retrospective testing showed that there was a cluster of cases in a family in Jordan a few months earlier to this. with likely human-to-human transmission occurring. Yes. Since then, there have been a handful of MERS outbreaks,

though none as large as SARS, or as the 2019 coronavirus is turning out to be. Most of these outbreaks or clusters seem to be regional with limited spread outside of the hospital setting and with most infected people being close context of the index case. Yeah. Since its first appearance in 2012, it has caused outbreaks in Saudi Arabia,

the United Arab Emirates, South Korea, and many, many other countries have had isolated cases or very small outbreaks, clusters. Some outbreaks have been larger than others. And as of December 29th, 2019, there have been 2,49 lab diagnosed cases and 861 deaths. And 84% of these cases were reported from Saudi Arabia. Yep. Okay. novel coronavirus. 2019 novel coronavirus.

This is what everyone had to wait an hour and a half to get to this point. We're sorry, not sorry. Not sorry. These are important things to understand the context of this outbreak. Absolutely. I agree. I mean, I think that there's a really important lessons to be learned from SARS in particular, but just from the way that these outbreaks occur and how they progress.

And, you know, we learn something new every single time. So as I, as I, you know, hammered our. over and over again in the SARS history, the Chinese government seemed very reticent in keeping the rest of the world updated on how the outbreak was progressing. And that does not seem to be the case so far with the 2019 novel coronavirus. And I think that's a really important thing to consider. There's been a huge push towards the free and open exchange of information, as we mentioned, with these early articles being published in certain journals. The sequence of the virus has already been published. Like, this is pretty incredible and very encouraging, I think. We are getting information

so incredibly rapidly in this outbreak, more than we ever could have seen in the past, which is incredible. But I think also, in some ways, people are now freaking out about it, because there's a lot of triple exclamation mark all caps going on that maybe isn't always valid. And so I I think trying to understand this outbreak, what's really going on in context, is really important. Yes, absolutely. So what is going on? Yeah. Well, in December 2019, a bunch of people became sick with atypical pneumonia after visiting the Wuhan-Huanan seafood wholesale market, which also sells non-aquatic animals such as birds and rabbits.

This cluster of 27 pneumonia cases, seven of them severe, was reported by the Wuhan Municipal Health Commission on December 31st, 2019. On January 9th, it was announced that a novel beta coronavirus, which is just a subtype of coronavirus. That's the same subtype as SARS and MERS. Yes. The next day, January 10th, the genome sequence of the virus was announced, was published. That is incredible. We're talking in less than two weeks from first cases. It's incredible. Yeah.

So genomic analysis suggests that the virus likely originated from a bat, as I mentioned before, and then maybe jumped into an animal that was at that market. This is yet to be determined. I'm sure that in the upcoming months, more will be discovered about the origins and the exact nature of that initial spillover event. The numbers of infected and dead have continued to grow since that first cluster was announced. So, Erin, how about we check in on how the current epidemic is progressing? Let's. Do you want to take a break first? Let's take a break.

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So as of right now, this will change by the time you listen, there have been 14,628 confirmed cases of novel coronavirus. The vast majority of these 14,451, have been in mainland China. The rest have been in a number of countries across the globe. There have been 305 total deaths confirmed from this novel coronavirus, only one of which has taken place outside of China. And that was in the Philippines. There have been 348 people that are confirmed to have recovered from this infection thus far. Cool?

Cool. Cool. So that's the details that we have. That's about it, Erin. There's a lot of questions that remain. Right. And like we've hopefully informed you all, we are not experts on this topic. So to give you guys a better sense of what is being done, what can be done, and kind of what the differences are that we've seen so far between so far,

SARS and MERS and this novel coronavirus, we had the fortune of interviewing four people who are much better experienced in outbreaks and infectious disease and coronaviruses than we are. So let's talk to them about what's going on, shall we? Let's do that. Hello, my name is Anish Mata. I am an infectious disease physician at Emory University. I specialize in infectious disease care of oncology, so cancer patients, and solid organ transplant patients. And I am also a member of the Emory Sears Community Diseases Unit, which is our biocontainment unit at Emory University Hospital.

My name is Colleen Craft. I'm an infectious disease physician at Emory University Hospital. I'm also trained in medical microbiology. And so I sort of enjoy my... role of bridging those two worlds between diagnostics and also seeing patients. I love being on both sides of that, of the computer screen, if you will. I've been at Emory Hospital since 2010. So my name is Carlos Del Rio.

I am a professor of medicine and global health at Emmer University. I have been involved in infectious disease for many, many years. I almost finished my fellowship in 1988, 89. So I've been doing this for 30 plus years. Most of my work is around HIV, but I've been involved also in infectious disease in generally, and particularly in global aspects of infectious disease. I was very involved with Mexico during the 2009 swine flu pandemic, and I've worked closely with CDC and with Mexico in working on that outbreak and in controlling that outbreak.

I also, I am a co-PI of the recently funded Emory vaccine treatment and evaluation unit, so I work a lot also in vaccinology and in the use of vaccines to prevent infectious diseases. My name is Marshall Lyon. I am an MD, and I am an infectious disease physician at Emory University Hospital in Atlanta, Georgia. My day job, if there is such a thing, is the director of transplant infectious diseases, and that is the bulk of my clinical care is taking care of patients who have had a transplant or are being considered for transplant and get an infection. So we deal a lot with viruses, both latent viruses and community-acquired viruses. One of my other roles is as a physician in Emory's serious community-acquired. communicable diseases unit as one of the high-level biocontainment units in the United States

when broke in Wuhan and started to become more of an issue, you know, we started to pay attention and started thinking that potentially a case might come our way. And so we've certainly been paying attention to the outbreak as it's unfolded in China and what and the measures that the public health U.S. is putting in place to try to keep the public safe. So we'd love for you to talk about this new coronavirus that's been making headlines. This isn't the first time that we've seen a coronavirus causing a disease outbreak, but this virus is new. So can you tell us a little bit about this 2019 NCOV?

So the first sort of novel coronavirus we saw was SARS. And then more recently, we saw the Middle Eastern Respiratory Syndrome coronavirus or otherwise called MERS KV. And we've learned a lot from those novel viruses that have developed, which I think have us a little bit better prepared now for what we're seeing. And that's this novel 2019 coronavirus. So this is actually an interesting outbreak because when it first started, the majority of patients seem to have had contact with this wet market or the seafood market in Wuhan. And so it looked like it was more a point source outbreak or a zoonotic outbreak. And so when we think of those, we think that people who get sick all had a common exposure

and that if you weren't exposed to whatever that agent is or that location, in this case the market, then you probably didn't have risk of getting infected or getting disease. It was only later when it appeared, so when the second wave of patients began to come in, but it became evident that there was now person-to-person transmission of what we now know is novel coronavirus 2019. And so now it starts to take the epidemic or the outbreak takes on a different characteristic, where you have to think about how do we limit contact with sick individuals. Right. Quick question about viral or about pneumonia caused by viruses.

What is the mechanism by which that occurs? Like why is that look different than one caused by bacteria? One of the things we should think about is when viruses cause pneumonia, that is when we become fearful sort of as clinicians. And so that's a lot of what happened we think in 1918. is that we believe that some of those deaths that were so dramatic probably came from influenza virus pneumonia, which I think is a lot different than how we think about pneumonia's today, which are typically bacterial. And so I think for me, when this started,

when it was kind of announced on December 31st, you know, our first question is, how frequently does this cause a viral pneumonia versus, you know, kind of a bronchitis or even the upper respiratory tract, which is what we usually think about coronaviruses? The things that really worry me about a viral pneumonia as opposed to a typical bacterial pneumonia is that when we have a bacterial pneumonia, we generally, though not universally, see that pneumonia in one region of the lung. One of the things that often concerns me about patients with a viral pneumonia, it's usually affecting multiple regions of the lung, potentially all of the regions of the lung. And in that situation, there's so much inflammation produced that the ability for the lungs

to extract oxygen out of the air gets minimized very rapidly. And you see patients develop something we call acute respiratory distress syndrome, where they cannot exchange oxygen and require a lot of ventilary and oxygen support to keep all the systems of the body running. And also in that inflammatory condition that you can develop a bacterial pneumonia on top of the viral pneumonia's inflammation. And that can compound the issue and further cause not only damage to the lung, but further develop problems in oxygenating the body. And finally, the other concerning issue that goes on with viral pneumonia is the fact that we have very limited therapies, unlike bacterial pneumonia and antibiotics to address these.

There are some antivirals that are out there, but most of them do not have any ability to treat the viral pneumonia that we are seeing nowadays. I know that it's sort of early stages in this outbreak, and there's still a lot that we don't know about this virus and how it behaves, particularly I was trying to get a handle on the infectious period and how that overlaps with the, a period during which symptoms are apparent. And so I know that that's sort of now more in the gray

zone, but correct me if I'm wrong about that. But based on how we've seen this virus spread so far and what also we have seen in past coronavirus outbreaks, what do you think we might be able to expect in the next few weeks or months as this outbreak progresses? Yeah, so you're right. We are in a gray zone about our understanding of this. But I think there are a few things that we do know. So the incubation period seems to be somewhere around five days as sort of the median or the mode of the incubation period. And there is variation probably anywhere from two to the longest being 14 days.

We're pretty comfortable that 14 days is kind of the outside limit. And what we are starting to learn from what's happening in China is there may be an infectious progrom before someone gets sick. And so a prodrome is a period of time where someone can actually transmit the virus to somebody else, but they don't have any symptoms of illness. And they don't know that they're about to get sick. They feel normal. And so unfortunately what that means is identifying people once they're sick,

won't absolutely terminate this epidemic. And this is slightly different than SARS because SARS was really transmitted by sick individuals and that most of the outbreaks could all be traced back to someone who had developed illness but was not in medical isolation. So in terms of looking at this outbreak, so far, how does it seem that this virus might differ from say the SARS coronavirus or the MERS coronavirus, both in terms of the disease that it seems to cause and also how the outbreak is actually progressing. So I'm currently at a ASM biothreats meeting where I got to hear Tony Fauci this morning from NIAID talk about this virus. And I think one of the things that he really

talked about that we're noticing is the total number of cases from SARS, you know, we've almost succeeded and we're only like, you know, a couple weeks in. So I think the main question that remains to be answered is really how severe is this? Yeah, I believe what we're seeing with this current novel corona outbreak is quite concerning as far as the tenor of infection and spread goes. Initially, I thought it was similar to SARS, which is quite concerning in itself, but the number of cases that we've just had in the past week alone and now exceeding the total number of cases of SARS that we had previously is concerning not only for China and the population there, but given the amount of travel that occurs from China to China, the ability for this virus to spread.

The other concerning thing that I think is out there is lessons that we learned from SARS was that hospitals and health care systems, clinics, can sort of be incubators for the spread of these type of coronaviruses. And that's something that really was hearkened by SARS. And we've learned a lot of lessons from that. But I think still there's a lot of vulnerability in our health care systems or the virus to spread within health care systems and therefore create broader outbreaks that can spread throughout the community. So as with SARS, it seems that there's a decent proportion of cases with this novel coronavirus that are health care workers who are likely exposed while treating someone who is infected.

Does there seem to be any other pattern in the people who develop maybe severe disease or more negative outcomes? So certainly, like with many respiratory viruses, you know, it seems that people, we're older or have other chronic illnesses are more likely to have severe disease and have the first 70-some-odd cases that were reported out of China of the patients that died, I think the average age was 75 years old. And so that is, it's a similar pattern to what we see with the viruses that we're familiar with. Could you elaborate a bit on the first steps that are normally taken when an outbreak like this occurs and you think, okay, we might need to be prepared?

if somebody happens to be infected and comes to the U.S.? What U.S. public health has done is first for over a week now, they've been screening passengers who are coming in from China, looking for anyone who might be ill or might have fever so that if they are sick, they're going to be identified quickly. And then contact tracing could be done of everyone who was on the airplane with them. So early identification is one of the keys in terms of limiting then subsequent contact to that sick individual. So the other sort of measure that is then put in place is social distancing.

So if you have something that's passed from person to person, especially a coronavirus, which uses the droplet method of transmission, if you can distance the infected individual more than two meters from anyone else, then in theory they would not be passing that virus on to someone else. And so if you, you know, cover your mouth, wear a mask, et cetera, all those things can sort of decrease the amount of drop-up production that a sick individual will make and therefore reduce the amount of droplets that are in the environment which someone else could be exposed to. So those are sort of the early measures that the public health is using right now

to try to prevent an outbreak in the United States. The interconnectedness of everything and sort of this decreasing barrier between humans and wildlife has really seemed to be the pattern that's emerged behind all of these recent outbreaks of novel diseases. So what do you think in terms of prevention that can be done to prevent the spillover from these animal hosts to humans? The first thing is we need to invest more in global health. security and we haven't done enough in investing in global health security at the level we should. And I quote Dolly Parton when she said, you know, you have no idea how expensive it is to look

this cheap. You know, if you think the cost of investing in global security is high, wait until you get the bill for what is this outbreak is going to cost us. So not investing in global health security is going to make you spend more money at the end of the day with climate change, with connectivity like flights that we talked about, with growing population. all those things together are essentially a recipe for more and more outbreaks. They're not going to end. They're just going to be the question I always have is what's next, not will we have something? In speaking more broadly, not just about the 2019 coronavirus, but in any sort of novel outbreak

or emerging infectious disease, what are some of the logistical issues in infection control, both maybe at a hospital level and then also with multiple countries working together? Well, you know, I mean, that's where WHO fits in, right? That's when you need to have international collaboration. You need to have international cooperation. And African China should be a concern to the U.S., to England, to, you know, every other country in the world. So we all need to work together. We need to also get away from saying, oh, this is a problem of China, let China deal with it.

This is not our problem. Because at the end of the day, that's not true. So the nationalism has to disappear. Microbes are to not recognize borders. they travel without passports, and therefore we should get away from thinking about countries and think more about the globe. So one of the, I guess, challenging things about an outbreak like this today is the role of media and social media and the rapid spread of information, which is sort of this double-edged

sort. What role do you see social media in particular playing in the spread of information during an outbreak such as this? Well, I think it's important that all media, whether it's traditional media or social media, presents the facts that surrounds any sort of an outbreak. And I think that because social media and our global information age does allow us to get information so quickly, it almost feels as if China is next door when it's actually halfway around the world. By the same token, it also enables people like yourself who are putting together podcasts to reach the masses to put the truth out there and to help people see things in perspective. As of today, which is January 30th, China is reporting that they have around 7 to 8,000 confirmed cases.

This is in a country of 1.5 billion people. That's a lot of people. and it still is a very tiny minority of their population, which has so far been affected. In the United States, we've had five confirmed imported cases, and that's, you know, again, in a country of 330 million. This is, it's a very small number compared to the larger population. And so I think that social media should be trying to put forth the truth and to try to keep the perspective of things that are going on. But by the same token, I think that social media should continue to examine this and look at it.

And I think I'm not sure how big of a part social media played in this or the fact that social media exists now where it didn't really exist to this extent in 2003. I think that the Chinese government has actually been fairly transparent with this outbreak and with what they're doing as compared to the, the SARS outbreak in 2003. I think social media has been good because it to some extent has kept government honest. Some of the media has been great. Some of the media, not so much. I mean, I think that newspapers sell headlines, right? So talking about the end of the world and this is going to kill us all against people's attention. But the reality is we tend to forget about the common things. I mean, for example, right now, CDC estimates that over 6,000 people in the U.S. have died of influenza. this epidemic, and yet we're more concerned about the coronavirus, and we should be telling people,

you know, get your flu shot and wash your hands and you a respiratory etiquette, because that's going to be more important. That's going to save you from influenza, but it's also probably going to help you with preventing some other restatory viruses. So I think that the media needs to inform, needs to communicate, and more importantly, I think the media needs to rely on reliable sources. I cringe a little bit when, you know, the media starts quoting an expert in nutrition as an expert in these diseases. We need to talk to people that. know what they're talking about. And there are plenty of experts out there. While I was doing the research for this episode, I came across a bunch of articles

that compared this current outbreak of the 2019 coronavirus to things like the 1918 influenza pandemic and, of course, SARS. And in many ways, SARS kind of feels like a bit of a bullet dodged because the control measures that we used, contact tracing and quarantine, these things worked really well. What do you think? that says about the current outbreak? I really like what you said about the bullet being dodged because I think if you think about us having the most population on earth that has ever been a human population, some of that is really because we have learned how to do things to prevent ourselves from dying from infectious diseases. So in 1918, I can only imagine it was so

scary to think about you didn't have really anything. I mean, supportive care really was like nothing. And so when you think about having mechanical ventilation and whole specialties of, you know, sub-specialties of, you know, pulmonary critical care that are dedicated to super sick people with bad lungs, I just think we have made a lot of advancements. And what Anish and I have seen since even Ebola virus five years ago and, and sorry, and MERS is this rapid development of bringing in therapeutics into clinical use a lot sooner than we've ever seen before. And that's because we're getting used to saying, you know, the longer we wait, the less information we have, the less knowledge we have. Even the fact that we've

had the sequence of this virus so quickly is pretty amazing, even from five years ago. And so I really like you're dodging the bullet, but I think it's pretty cool to think about all the kind of advancements that we have, even in the last decade, not even since, you know, 100 years ago. Less of dodging the bullet and more building the shield, I guess. Yeah, I agree. I like that analogy of building the shield. And, you know, one of the great lessons we learned from SARS. And Colleen and I really witnessed this during the Ebola outbreak was how important it was to communicate information about what's going on with patients, what's going on in the public health setting, what's going on immunologically and with a virus very rapidly to

health care environments and scientists and public health officials around the world. And with this outbreak, we're seeing exactly the same thing. As soon as there were reports coming up, the sort of the infectious disease community, the public health community, the emergency medicine community throughout the United States was coming together. We're having conference calls. We're having rapid communication. And importantly, our colleagues in China were putting out all this information about what they were seeing.

They put out immediately the sequence of the virus so people could work on diagnostic testing and learn more very rapidly. And I think those are the lessons that we've learned as a global public health community on how to really address these new challenges. is. One of the questions that many of our listeners are very concerned with is basically how scared should we be of this, which is a pretty big and loaded question. So could you maybe talk

about something about this virus or this outbreak in particular that is quite concerning to you? And then maybe something that also is reassuring that maybe, you know, this isn't the end of the world, we hope. Yes. So I'm pretty sure it's not the end of the world. But one never knows. I would say that there's always this initial panic about something new. And without being glib, I want to say that this isn't like an alien invasion of something we've never seen. We have dealt with things that are similar. And so it falls within our paradigm to be able to figure out, you know, yes, it may be more severe, but we understand how these things are transmitted. We also understand how to protect ourselves.

In terms of what makes me nervous, I think, is the surface aspect of virus transmission. And so what does that mean? It's kind of what I've already been saying. But if somebody coughs on like a seat that I now sit in or a surface that I now touch because I'm getting, you know, like a fast food takeout or something, how long does it stay on that surface? and how much of that has to be transmitted to me to make me really sick. And maybe I'll add something. But before I do, I just have to say, Dr. Kraft has really taught me to fear my cell phone and make sure I clean it all the time.

It really, like it literally has poop bugs on it. I don't let my children touch my phone and I lens wipe clean it every day. I know. I looked down at my cell phone and I was like, oh, dear. I just like kicked it out of the way. I was like, no. I, you know, every time I talk to Dr. Kraft, I make sure I don't have myself run in my hand.

I think every reporter I've talked to in the past 72 hours, the first question is, should we panic? And my answer is, there's no reason to panic. There are things that are worrisome. The thing that I think is worrisome to me is how quickly it's read and how quickly we found cases in other countries. which means that we really need to institute good controls and screenings to make sure that we don't have continuous spread. I think just like any novel infection, early on, one of the greatest fears is what we don't know about it.

I think we will learn more about the virus in the coming weeks that will be reassuring to us. But there's still some that's unknown and how it's transmitted, how severe the disease can get, and who's most susceptible for. But as my colleague Dr. Kraft mentioned, there are a lot of things that are reassuring about this. I think going back to their experience with SARS, what we learned from both the experience in China and our experience with our colleagues in Canada and here in the United States is that once we're able to identify the infection and the signs of the infection, we're actually able to do really good epidemiologic contact tracing and appropriately isolate people. put people who were at risk in appropriate monitoring, and suddenly the cases started to get to go down very rapidly.

And the morbidity and the mortality from SARS start to go down rapidly. And so I think we have the tools in place to understand how to control infections like this. And it has worked with SARS. It has worked with MERS KV in preventing the spread around the world of MERS KV. And I think it will continue to work,

those lessons will work here. with the novel coronavirus? What scares me? I mean, I'm more scared about driving home this evening and getting killed in an accident than I'm about this virus, quite honestly. So, you know, I think we all need to put into perspective risk and realize what the risks are.

I think what concerns me is that, is that, yes, this virus can continue to spread and can reach at places like, for example, Africa and other places that are not going to be able to control it as quickly as China has been able to. And again, it makes me worry about the lack of support for international and global health security and the need that we need to have to talk to Congress and talk to others and say, hey, we have to invest in global health security. We have support WHO and other agencies. And we really need to think about how to make global health security

a priority for all of us, because the reality is right now that we're all worried about this. It's the right time to do that. What do you think our listeners can do on an individual level to try to push that cause forward a bit more, having more investment in global or national health security. I think you send an email or call to run your problem and say, hey, you know, with this outbreak, I have worried that we're not investing enough in global health security and we need to do that. I think we need to grab the attention of the people that have the, that are the funders, right? That was so fantastic. Thank you again so much to Dr. Anish Menta, Dr. Colleen Craft, Dr. Carlos Delria, and Dr. Marshall Lyon. Those interviews were so wonderful,

and we really appreciate you taking the time to come and talk to us. And a huge thank you to Sonia Bell from Emory University who hooked us up for these interviews. We never would have gotten to talk to such experts without you. Thank you so much. Thank you, Sonia. Before we dive into sources and stuff like that, I feel like there's a couple things that we wanted to say. Yeah, hugely important things. One is influenza. Yeah, okay, listen, like Dr. Kraft especially mentioned in her interview, the ways that we can protect ourselves against this novel coronavirus will also protect us against things that really you should be more concerned about than this novel coronavirus at this point because you're far more likely to be infected with influenza

than you are with this novel coronavirus even in China. Across the entire world, let's talk about what a toll influenza has taken thus far, shall me? Yeah, you're not just more likely to be infected, you're also more likely to be hospitalized or die from influenza than you are from the 2019 novel coronavirus. Have you gotten your flu shot this year? Have you? Because thus far, in the United States.

States alone, it's estimated that there have been in this flu season between 180,000 and 300,000 hospitalizations from influenza and upwards of 10,000 deaths due to influenza in the U.S. alone. Just in these few weeks where we have seen 14,000 confirmed cases of novel coronavirus, there have been over 40,000 confirmed cases worldwide of influenza. And that's just the confirmed cases, the vast majority of influenza cases are not reported. Get your flu shot, if you haven't. Protect yourself, protect others. Please. I think that one of the lessons that we can take away from this outbreak, as with past coronavirus outbreaks and other types of spillover events, is that these epidemics reveal these international wealth disparity.

Oh my gosh, yeah. It can decide who will get the vaccines, who will get the treatments, who has the financial support for control or importantly prevention and emergency preparedness. Yeah. As several of our interviewees said, microbes don't know country boundaries. They don't acknowledge them, recognize them. These are not national concerns. This is a call for international concern.

An epidemic in one place is an epidemic globally with the end up. interconnectedness that we have. And I think that, you know, some of the ugly sides of these epidemics are this, you know, pointing fingers and saying, oh, it's, it's this country's problem, not mine. And that's not effective, right? When we have something that's of international concern, what we need is international collaboration and working together. And I think what's great is that we have seen a lot of that in this novel coronavirus outbreak. We see people, exchanging information and talking with each other in order to do our best to prevent this outbreak from getting worse.

Exactly. Okay. Sources? Sources. I have oodles of sources, but I want to shout out a few of them. A couple books that I read that focused on SARS. One is called 21st Century Plague by Thomas Abraham. Another is called China Syndrome, the true story of the story of the.

the 21st century's first great epidemic by Carl Terro Greenfeld. That's where our first-hand account was drawn from. And then I have a few other articles. A couple I want to shout out are by Kui et al, in 2019, origin and evolution of pathogenic coronaviruses. And by Jones at all in 2008, global trends of emerging infectious diseases. And then also by Lee at all 2005, bats are natural reservoirs of SARS-like coronaviruses. Excellent. I read a great chapter in the book Viral Infections of Humans all about coronaviruses in general,

if you're interested in that. Two articles I loved. One was the severe acute respiratory syndrome in the New England Journal of Medicine about SARS and one called Middle East Respiratory Syndrome in The Lancet. And then if you'd like the most up-to-date information about the novel coronavirus, which I know that's what you all are here for, our experts recommended a third. few sources that we also have been relying upon. That is the World Health Organization Situation Report. They are updating this daily. Every single day, there's a new situation report that's released so you can get the most up-to-date information on the number of cases. Oh, look, they just updated it. Let's see what it says. Yep, it's a little less up-to-date than the other

up-to-date source, which is the Johns Hopkins website of a map that's continuously updating. And finally, the CDC has a great site on the novel coronavirus if you're interested in specific things that you can do to help prevent yourself from getting infected, wash your hands and cover your mouth. And we'll post the links to all of these in the show notes and on our website. Awesome. Thank you again so much to our wonderful, wonderful guests. We really appreciate it. And thank you to Bloodmobile for providing the music for this episode and all of our episodes. And thank you to you, listeners, for allowing us to keep making this podcast. It is our absolute favorite thing to do. And with that, wash, wash, wash your hands.

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