In this episode, Dr. Amish Adalja joins me to talk about the coronavirus outbreak at the Johns Hopkins University, and why he s less concerned about it than I am. We talk about why he thinks it s unlikely to be much worse than it has been so far, and what it means for our understanding of the disease and the potential impact on public health. And we talk about how the media is exaggerating the seriousness of the problem, and how we can try to make sense of it. We also talk about some of the reasons why Amish is less worried about the spread of this virus than I have been, and some reasons why I think he s more worried than he has been. This episode is the second part of a two-part conversation I did with Amish, and the first part will be released next Wednesday. I hope you enjoy it and find it useful, and I will be back with a new episode on this topic in 48 hours or so. Thanks to Amish for joining me, and for being willing to share his thoughts on the topic with the rest of the podcasting community. Sam Harris Make sense? The Making Sense Podcast is a podcast by Dr. Sam Harris, a professor at Johns Hopkins, on infectious disease and public health professor at the University of Maryland, Baltimore, Maryland, and a regular contributor to The New York Times bestselling author of The Pandemic: A Handbook of Biological Risks, a new book on global catastrophic biological risks. and The Handbook of Bioterrorism and Disaster Medicine, a volume on global catastrophes, a book on pandemic risk, written by a leading experts in the field of infectious disease epidemiology and disaster risk, by the Handbook of catastrophism and disaster medicine, and edited by a Nobel Prize-winning author. , we discuss the dangers of the emerging pandemic, and their impact on our world, and other things we can do to prepare for the coming pandemic. We hope you'll join us in the making sense, and find some common ground between the facts and the facts, and let us know what you think about the problem and what we can learn from them. . Thank you for listening, and remember to stay tuned for the next week's Making Sense! , and keep sharing your thoughts on this episode of Making Sense, by Sam's next episode on the next one. (Make sense, folks!
00:07:13.580And we try to really keep on top of these issues and kind of be the leading voice on them.
00:07:17.460And you do seem to be the leading voice because the Johns Hopkins dashboard seems to be the dashboard that everyone is using to track the spread of this disease.
00:07:28.040Yeah, that was something that people put together rapidly.
00:07:32.600That's actually, I think, from one of the engineering schools that's put that together.
00:07:35.380But it's been really useful, and it's been refreshing to see the world using Johns Hopkins' talent to help understand what's going on.
00:07:42.140Okay, so it's March 10th, the day we're recording this.
00:07:45.560I think we'll probably release this on the 11th.
00:07:48.800And at the moment, there are around 118,000 confirmed cases and a little over 4,000 deaths.
00:07:56.600And I know we have a denominator problem still, so we don't actually know how many people have been infected.
00:08:02.180So it still requires some guesswork to estimate the case fatality rate.
00:08:07.460But what is your best estimate at this point?
00:08:10.180So the best estimate, I think, is derived mostly from the South Korean data where there's been extensive testing, the most per capita testing that's been done in any country where they actually have drive-through testing centers.
00:08:20.840There, you're seeing the case fatality rate at 0.6.
00:08:39.820And I think the lower bound is going to be somewhere, I would say, a little bit above seasonal flu, which is 0.1%.
00:08:45.460So it's somewhere in there, but it's still a lot of fluctuation and still a lot of uncertainty.
00:08:50.340Okay, so that is actually quite a bit more sanguine than anything I had heard up until now.
00:08:57.180I mean, you know, I recorded my previous podcast 48 hours ago, and there you have, I think it was the Lancet reporting 1.2% to 1.6% or somewhere in there.
00:09:08.760I mean, something like, you know, half the rate of the most dire predictions of around 3%.
00:09:14.060So you're reasonably confident that 0.6% is the upper bound, which now we're talking about six times more lethal than the seasonal flu.
00:09:23.1200.6 seems to be the best way to look at this.
00:09:25.780When you think about the fact that we've had major testing constraints in many countries, and South Korea has been very aggressive at testing, and that's where they're seeing their number.
00:09:33.260So I think that that's the easiest parameter to try to put into this big world of unknown about this.
00:09:39.580And I definitely think the 1%, 3% numbers are way off because of the severity bias.
00:09:44.360It's important to remember that seasonal flu is 0.1%, so it's still a magnitude higher, and it will be more difficult than dealing with the seasonal flu to deal with this virus.
00:09:54.640I want to talk about the comparison with flu with respect to both severity and contagiousness in a minute.
00:10:02.440But I'm wondering, so have any of these ships that essentially have been rather unfortunate and accidental science experiments where you have people cooped up in a giant floating Petri dish with this virus, and then you just have them quarantined, and so we can see what happens.
00:10:20.640Have any of these ships provided a clear picture of the case fatality rate here?
00:10:26.700I mean, I am sure there's an age bias with respect to the cohorts who are on the ships, but why don't we have a clear picture based on what's happened in each of these cases?
00:10:35.740I think you just answered your own question, that there is a severe age bias when you're on a cruise ship, because remember, those are going to be older people.
00:10:42.980Those are going to be people with medical conditions that like to go on these trips.
00:10:46.280It's not going to necessarily be the representative sample of the population that you need to actually calculate a proper case fatality ratio.
00:10:53.720What the ships do offer us is some idea of the attack rate, even though that's also limited, because sometimes those ships were doing things in order to try and prevent spread, even though it wasn't very successful.
00:11:02.780But we saw about 20% attacked in the Japanese cruise ship.
00:11:07.180So I do think that they provide some information, but it wasn't quite the perfect experiment, and I think it ended up almost being torture for some of those humans that were left on board that ship.
00:11:17.040And I wouldn't draw too much from it other than the fact that we know that this is contagious in those types of settings and that elderly people are disproportionately going to be impacted with severe illness if they are infected.
00:11:28.960Okay, so let's deal with this, the comparison with flu, because many people have been drawing comfort from the idea that if you're a healthy non-smoker under 70, you basically have nothing to worry about.
00:11:44.500It's more or less just like the flu, and most of us are going to get this, right?
00:11:49.260In fact, I think I even saw you say more or less this in a talk you gave.
00:11:56.120I watched a YouTube video of a lecture you were giving a couple weeks back.
00:11:59.700So most people are going to get this, and if you're healthy and not too old, it's not likely to be a problem for you.
00:12:08.300Another statistic that I've heard a lot is that 80% of cases are mild.
00:12:12.880So what is a mild case, and what is actually rational to believe here?
00:12:18.300And I say this, you know, knowing, personally knowing someone who is 50 and a, you know, an extreme skier, i.e. quite healthy, or was quite healthy until he caught coronavirus, a non-smoker, and he's now on a ventilator.
00:12:34.580Obviously, this is an anecdote, this is not science, but I don't have similar stories to tell about flu.
00:12:41.840So what's the picture in terms of comparing the severity of this generally to flu?
00:12:47.920While it is true that most cases are going to be mild and indistinguishable from the cold and the flu, this does seem to have a higher case fatality ratio.
00:12:56.140So you are more likely to see people die from this than from influenza.
00:13:00.560It is true that the deaths cluster in those that are elderly, that have other medical conditions.
00:13:06.460But it's important to know that just because something clusters there doesn't mean that other diseases, other deaths can't occur in other age groups.
00:13:12.360So we are going to see healthy people that die from this.
00:13:16.940It's not going to be as common, but it is going to happen, and it's important to prepare for that.
00:13:21.620So even we see that with influenza right now.
00:13:23.500This year's flu season, to draw the comparison back to flu, has seen the most children die from influenza in recorded history, except for during the 2009 H1N1 pandemic.
00:13:32.160So we don't often hear so much about the younger people that die from flu as well, but it is true that those deaths occur.
00:13:38.780And because this has a higher case fatality ratio likely than seasonal flu, we will see deaths in other age groups, although they will be clustered in the highest age groups.
00:13:48.560And in terms of the mildest cases, it's true to say that it would be possible for this to present as benignly as an ordinary cold.
00:13:57.940There are people walking around with the sniffles who may in fact have coronavirus.
00:14:04.180Because remember, coronaviruses are a family of viruses.
00:14:06.800There are four of them that cause seasonal colds every year, and this is now basically becoming the fifth seasonal coronavirus.
00:14:14.760And we are going to see this spectrum of illness where many people will just have the sniffles or just have a cough or a sore throat, and nothing really becomes of it.
00:14:23.420But then there are that group that have risk factors or, by luck of the draw, have a more severe case.
00:14:29.160So that's kind of one of the things that this virus has used to transmit itself so well is the fact that you've got these mild cases walking around in the community that just look like a cold, but they can then yet transmit it to other people.
00:14:40.220So that's really advantageous from an evolutionary standpoint for a virus to have this spectrum of illness with these mild cases out there that are really serving as vectors for the virus.
00:14:48.440And what do you make of the fact that it seems to be systematically more benign in children?
00:14:56.180So that's a really important question that we're all trying to answer and try to come up with hypotheses for.
00:15:02.120One is that children tend to have less robust immune responses, and maybe most of the symptoms that we're seeing, especially the severe ones, are triggered by an overabundant immune response that's more characteristic of adults than in children.
00:15:14.400And we know that that's the case for many infectious diseases.
00:15:17.260For example, chickenpox is much milder in a child than in an adult.
00:15:21.420The other is, going back to those four circulating coronaviruses that are around every year, children get a lot more colds than adults, and there might be some cross-immunity because they have many more exposures to coronavirus in their daily life than an adult might.
00:15:33.780So that cross-immunity might be somewhat protective.
00:15:35.900But this is one of the leading research questions we need to understand, especially as we're trying to figure out what the role of children are in transmission as you hear about school closures occurring around the country.
00:15:45.260Would that cross-immunity suggest that parents who have young children who also seem to get exposed to more of these viruses than people who don't have kids, would we likely be able to detect a lesser severity in their case?
00:17:12.260So that's something like measles or whooping cough.
00:17:14.240That's going to be very hard to deal with because you're going to have lots of people infected and lots of exposures.
00:17:19.680And then I think of that middle ground of like the R0s between like 2 to 4.
00:17:23.020And I put flu and I put this virus in there.
00:17:24.900And I think that's a better way to think about it than trying to look at it as some intrinsic feature that you're trying to compare between viruses.
00:17:31.100I think that gets a little bit too, trying to put too much of a statistical flavor to something that really is not completely exact that way.
00:17:52.140So the main way that it spreads from person to person is through the coughs and sneezes that people experience and the particles that emanate from their body.
00:17:59.820These are large droplets that fall to the ground in about 6 feet because of the action of gravity.
00:18:04.520And it can also be transmitted from the surfaces that people touch that may have those droplets on them.
00:18:09.360But the main mechanism is this respiratory droplets, the coughs and sneezes.
00:18:12.800Because you've got a lot of questions I get all the time about, if someone hands me a pen, can I get it from a pen?
00:18:17.440Of course, the answer is theoretically yes, but really, that's not how this virus is transmitting.
00:18:21.620It's mostly through coughs and sneezes from person to person.
00:18:24.400We don't know that there's quote-unquote airborne spread.
00:18:26.700Airborne spread is a, some people mix that up with respiratory spread.
00:18:29.640Airborne spread refers to a virus or a pathogen that can stay in the air for a long period of time.
00:18:35.660So if I got on an elevator and had measles, for example, and then you got on the elevator an hour later, that air would still be infectious.
00:18:43.180There may be some component of airborne spread in hospitals when they're doing procedures on people and they're aerosolizing the virus.
00:18:49.120Suppose they're putting a breathing tube in someone or looking down in their lungs with a telescope or giving them a treatment that requires a drug aerosol.
00:18:56.520That can sometimes cause airborne transmission.
00:18:58.640But the primary means is really these respiratory droplets.
00:19:01.940So with respect to surfaces, how long do we think it can live on a surface?
00:19:05.960If you go look in medical journals, you will find stories of coronaviruses living nine days, being viable for nine days on a surface.
00:19:15.140That's hard to extrapolate to everyday life because there's certain environmental characteristics that are conducive to the virus and certain ones that are not.
00:19:21.700So, for example, temperature, humidity, UV radiation, all of that affects the viability of a virus.
00:19:30.360It actually has this lipid envelope or this kind of fatty layer around it, which actually can dry out.
00:19:35.260So when you talk about viruses and how well they survive in the environment, if it's an enveloped virus like the coronaviruses are, it doesn't usually last that long in the environment compared to something like the norovirus, which you might have heard of from cruise ship outbreaks.
00:19:47.480That can be very difficult to get out of a off of a surface or in a in a structure that it might have been contaminated with it.
00:19:53.840So what I would say to most people is this is probably hours to day, a day or so.
00:19:57.640And it's not something that you have to worry too much about because this is a virus that's easily deactivated by your standard household cleaners that you use during cold and flu season anyway.
00:20:07.020OK, so unfortunately, I just watched a press conference given by the mayor of New York City, Bill de Blasio, where he said that this virus degrades in only a matter of minutes if it's on a surface.
00:20:20.280This is a direct quote. It's only a matter of minutes before the virus is rendered inactive in the open air.
00:20:27.520And he was referencing subway poles and plastic chairs and tabletops.
00:20:37.040Would you be confident touching a tabletop that someone had just sneezed on a few minutes later and not washing your hands?
00:20:43.120No, I think that minutes is that's not scientifically accurate.
00:20:47.120I if it was hours, I would agree with.
00:20:49.380But I don't think minutes unless this surface is a special surface that's got special characteristics on it, like it's made of copper or something that's that that's bad for the virus.
00:20:57.720But no, I don't think that minutes is correct.
00:21:00.120OK, so if you're among the nearly one million people who have watched that press conference on Facebook, please be advised.
00:21:07.420What about objects that you might have shipped to you in the mail?
00:21:12.520So someone has ordered a computer from Apple that was just freshly minted in Shanghai and made the trip.
00:21:21.800Let's say it took 10 days to get to their house.
00:21:24.500Now they're opening it like it's a very large piece of medical waste.
00:21:39.920But no, I don't think that these types of ordinary products are going to be a risk for individuals to touch or open.
00:21:46.420OK, so let's talk about flattening the curve.
00:21:50.640This is a phrase that many of us have absorbed now.
00:21:54.600What does it mean and why is it what we should be thinking about at the moment?
00:21:58.800So what we're talking about is an epidemic curve and that's the number of cases that occur over time.
00:22:02.660And what flattening the curve refers to is trying to not have this big initial spike of cases.
00:22:08.420So you still have the same area under the curve, the same number of cases, but you spread them out over time.
00:22:13.300And that's somewhat easier for communities to cope with, especially when you're talking about bed space at a hospital or or any kind of limited resource that might be that might come into short supply during a pandemic.
00:22:24.320So that's why you see people talk about, for example, closing schools or limiting social gatherings or trying to do any kind of social distancing, just trying to decrease the intensity of spread, knowing that you're still going to have the same number of cases.
00:22:36.300But they're going to be spread out and they're going to be spread out and they're more easy to deal with.
00:22:39.900So after this last podcast I recorded with Nicholas Christakis and after absorbing the growing concern around the spread of this virus, the punchline I've come away with is that if you can work from home, you absolutely should.
00:22:57.960And whatever non-essential social contact you have on the calendar should be canceled.
00:23:06.360If you have tickets to the concert that you've been looking forward to for a month and that's rolling around this weekend, you shouldn't be going to that concert.
00:23:15.520You should avoid eating in restaurants if you actually can avoid eating in restaurants.
00:23:23.100Anyone who can pull back at this point should pull back.
00:23:26.840Is that too alarmist or is that simply good advice at this point?
00:23:32.800It's all going to depend on each individual's risk hierarchy and where it all fits.
00:23:36.480If you're an elderly person or have medical problems or maybe you live with one, someone like that, and you want to decrease their exposure, it might be prudent when you have high intensity transmission in your community to take those types of actions.
00:23:47.980I don't think that the whole world needs to take those actions.
00:23:52.740But I think that you have to really look at each location that the virus is spreading in and make a distinction on whether or not you think that this social distancing is going to help or it's going to not have an impact.
00:24:05.500Because if you have widespread community involvement with this virus already, social distancing is maybe going to decrease your individual risk, but then you have to put that into your own value hierarchy and decide, yes, this is really important to me, so I'm going to risk it and just be very meticulous with my hand hygiene and not touch my face.
00:24:21.420Or this is something that I didn't really want to go to anyway and I'm not going to do it.
00:24:24.420Once we get to a point where if there's high intensity transmission, then you might see more stricter recommendations coming out about that type of non-essential travel.
00:24:35.280But I do think that you're going to see variations across the country and variations with each person's risk preference.
00:24:42.500And we do know that social distancing can cause damage because it's going to cause economic disruption when that happens.
00:24:49.180So there are some things that are easier to do, like telecommuting, but some things that might be a little bit harder to do.
00:24:54.620And I think that it's going to be difficult.
00:24:56.240And we didn't do so much of that during 2009 H1N1.
00:24:59.080We had some school closures and people did some things, but not as aggressive as we're seeing now.
00:25:03.820So it will be interesting to see how this actually plays in an American setting with people trying to adjust their daily life to this virus.
00:25:10.800And I think eventually you're going to see people start to be able to cope with it a little more as this doesn't go away without a vaccine.
00:25:18.360Right. So let me just push back on two points there.
00:25:21.420So we know that we're not doing and have not been doing adequate testing.
00:25:26.260So we really can't be confident that we know how fully it has spread in our community.
00:25:33.900How can a person assess that it hasn't yet spread much in the community and they don't have to worry about going down to the local coffee shop?
00:25:41.340And two, given that the primary vector of contagion is having someone cough or sneeze too close to you, even more than anything that you can control by assiduous handwashing,
00:25:57.140going to the rock concert puts you shoulder to shoulder with people who at any moment might turn and cough and sneeze on you.
00:26:04.780So I'm not quite sure how to be confident going into those spaces, given those two facts.
00:26:11.980So you're not going to be able to completely avoid this virus in that type of a setting if you're in a concert or if you're at something where you're going to have multiple interactions with people that are not in a controlled manner.
00:26:21.720And rock concerts are going to be very different than certain other activities like going to a restaurant or going to a coffee shop where you can have some distance between people.
00:26:31.680And I do agree that we don't quite know how much this is transmitting in our communities.
00:26:35.340But one indicator that you can use is looking at what hospitals are doing.
00:26:39.780You're going to hear about, even if there is a small proportion that get critically ill and need ICUs, you're going to hear about that in your community.
00:26:47.080So I think in most communities, we haven't heard about people in the ICUs.
00:26:51.420There are definitely cases in ICUs, but we don't have large numbers of them, which may be an indicator that there's been less community transmission or maybe this is less severe than we thought because we're not seeing those ICU patients all across the United States.
00:27:03.100So it does become difficult because of the testing problem.
00:27:06.120And I do think that there is some level of community spread going on in every city in the United States.
00:27:12.360But then what lesson should we draw from the experience in Italy right now?
00:27:17.380I mean, it seems like there's no reason to think that we are different from Italy apart from the timing at which the virus first landed.
00:27:27.480What's happening in Italy now that is basically forcing the whole country into lockdown and straining the health system to the breaking point?
00:27:35.800And why wouldn't you expect that to happen here if we just carry on business as usual?
00:27:40.700I do think that the experience in Italy and hearing about these ICU bed shortages is something that kind of hits home for America because the health systems are somewhat similar, not completely similar.
00:27:51.000And it's unclear to me exactly what's driving the force of infection in Italy and how that might be different in the United States.
00:27:56.880We do know they have an older population than the United States, so that may account for more severity than here, but it's not that much older.
00:28:04.200I think that the Italian government is taking an approach where they want to try and flatten the curve in a very drastic manner, kind of following what China did.
00:28:11.820And I think that paradoxically may make things worse because you're going to panic the population and you're going to inundate the hospital with scared individuals.
00:28:18.300And other parts of the health care system are going to suffer, just like it did in China, where people with heart attacks and strokes had difficulty getting their way to a hospital.
00:28:25.200I think that we have to really drill into the Italian numbers and understand how much testing they're doing, what is their real case fatality ratio there, and try and use that information the best we can to prepare our hospitals and our ICUs for what might be a very severe season.
00:28:41.560I do think that some of those drastic social distancing measures may be necessary in certain situations, but I don't think that you can have a blanket lockdown and expect that to actually work or be effective and not have negative consequences that might outweigh any positive there.
00:28:56.820But this is all very fluid and very hard to quite—these aren't easy decisions to make, and there's a lot of uncertainty here, and that makes it hard to make any kind of specific recommendation on what to do without having full data and knowing what's exactly going on in the ground in Italy.
00:29:13.460To come back to my question, because I really do want to sharpen this up and have listeners come away with a clear plan of action, again, my heuristic here is that if you can work from home and if you can cut out social contacts—
00:29:31.460there are people who can't, obviously, there are jobs that are synonymous with being in that particular store or restaurant or office—but if you can pull yourself out of society to whatever degree and thereby deny this virus a path through you and your life to others, that seems to me to be an intrinsically wise and ethical thing to do.
00:29:58.360Apart from, again, there are economic consequences to doing that, which people who own restaurants and own retail stores are understandably worried about.
00:30:08.820But if the goal were simply to stop this thing as fully as we can, which is to say flatten the curve as fully as we can and keep the health care system running, is there any argument against taking that advice?
00:30:23.440No, I don't think there's any argument against taking that advice.
00:30:25.660I think sometimes it becomes impractical for certain people to do, but it is technically what you should be doing even during flu season if you can.
00:30:32.640And there are some things that are easier to do and some things that are harder to do.
00:30:36.340I don't think we'll see full social distancing with every American, but I do think that there will be a large proportion that do do that, especially those with high-risk conditions that are worried for their own safety or if they have relatives or they live with people that have those types of conditions.
00:30:51.940I think it's going to be hard for that to happen for everybody, and there's going to be limited social distancing in certain locales.
00:30:59.200And I think there's going to be a hesitancy to go to complete social distancing as an ideal, although theoretically, yes.
00:31:04.720I mean, if you look at the actual facts of it, yes, if everybody social distanced, you would be able to flatten the curve substantially.
00:31:12.220And in terms of actually flattening the curve and even reducing mortality, as we're seeing in China now, I mean, that is being achieved in China by the most extreme and heavy-handed quarantining of the whole society that has ever occurred.
00:31:31.240I saw at some point recently, I forget where, it probably was on social media, that South Korea seems to also be driving this contagion downward.
00:31:42.600Is that true? Is there any place else that's having success the way China is?
00:31:47.180We have seen, I guess, variations of the Chinese model in other countries with Singapore, with Hong Kong, as well as even Taiwan, where they have done some extreme social distancing.
00:31:56.580We're even seeing it now being implemented in New York State and Westchester County.
00:32:01.700China, I think, took a very authoritarian approach because they had that tool available to them and really went to an extreme level that we really haven't seen probably since medieval age to medieval time with basically locking down 60 million people, suppressing free speech in terms of what doctors were allowed to say, and making it very difficult to even leave that area using armed guards.
00:32:24.380And that was something that we were very, you know, from a public health standpoint, most people were very kind of appalled by that type of a reaction.
00:32:33.740And now you're seeing people say, maybe that flattened the curve there, maybe that bought the world some time.
00:32:38.740And I don't know if that's the truth or not, because this spread very quickly.
00:32:42.260And I wonder, you know, when I saw this virus emerge in late December, and we realized quickly that this was something that was spreading between human to human very efficiently and had been spreading at least since November, unbeknownst to anybody.
00:32:55.240We knew that this wasn't going to be just a China problem, that it likely had left China.
00:33:00.300And a lot of us really argued that this probably should have moved from containment at a very early stage to mitigation with less of that type of lockdown mentality and more with fortifying hospitals, vaccine development, antivirals, diagnostic testing, and really taking a different approach, more like the one we took during 2009 H1N1.
00:33:21.160Right. But it's true that H1N1 is not as contagious, right?
00:33:24.040I don't know if it's not as contagious. We know that H1N1 infected a billion people over six months.
00:33:29.860So that's pretty contagious. And 61 million people were infected with H1N1.
00:33:33.600So it wasn't something that was small. And I think that's the best model we have.
00:33:37.140We don't know where this one's going to end. And I would say this is around the same contagiousness level of H1N1, maybe a little bit more because we don't have, in H1N1, we had certain age groups that were less likely to be infected because of prior immunity that they had.
00:33:49.940And I think that the approach of containment probably wasn't the best one to take for this type of virus.
00:33:55.320And it might have expended public health resources that could have been better spent fortifying hospitals.
00:34:00.900And of course, the Chinese built new hospitals and did things during this outbreak.
00:34:04.620And I think that some of that Chinese stuff is not replicable in other parts of the world because there are certain values in other countries that people do not want to transcend that China did.
00:34:16.800And I think those are very good values. And I myself objected to what China did there because I do think that there's another cost that's not necessarily this disease that you have to kind of figure into what happened in China.
00:34:29.620And especially the fact that this is now being held out as an example by by certain individuals, I think, really can put us in a domino effect of this kind of draconian response that may in the end, we might lose more than we gain from it.
00:34:41.820Yeah, I mean, I think there's nothing to emulate in the Chinese model apart from drawing the conclusion that insofar as you can avoid social contact, that is the way to mitigate the spread of this thing.
00:34:56.980And if you really manage to avoid it, if you could wave a magic wand and impart a new norm of social distancing to everyone, you know, not at the point of a rifle, but at the point of a bright idea, we could change the level of contagion a lot.
00:35:15.460But it's just whether everyone can get the message all at once. And we have a kind of coordination problem and we have massive economic incentives pointing the other direction, which worries me.
00:35:27.720Right. And you have to remember that, you know, people run businesses, people that that that if people can't work and they get then they eventually aren't going to be able to eat.
00:35:34.160So there's going to have to be some tradeoff that you have there between social distancing and then being able to be productive and be able to flourish.
00:35:43.100So how much does smoking play a variable here? I don't know the rates, the relative rates of smoking in China and in Italy compared to the U.S., but is there any reason to believe that smoking is part of the epidemiological picture here in terms of the severity of the disease?
00:36:01.340We definitely have seen smokers get severe illness in China, but the number looking at some of the data, some of my colleagues are looking at that and at least the data that's been published, we haven't been able to see a major signal there.
00:36:10.640But it is true from a physiological standpoint that smoking is something that is conducive to respiratory viruses being much worse in a smoker than in a nonsmoker because it does damage all of these airway protective mechanisms that you have and makes you more at risk for diseases like emphysema and bronchitis, which make you more likely to have a severe case.
00:36:29.440So I do think smoking plays a role. How much of a role it's playing currently is hard to tell, but I do think all things being equal, a smoker is going to have a harder time with this virus than a nonsmoker.
00:36:39.220And it may be responsible for some of the severe illness that we're seeing in certain countries where there are higher smoking prevalences.
00:36:44.340So in addition to being old, the risk seems to go up with every decade here.
00:36:51.920So, you know, in addition to being over 50 and being a smoker, the points a person might have against them include heart disease, lung disease, cancer, compromised immune systems, diabetes.
00:37:04.800Is there anything to add to that list or is that comprehensive?
00:37:08.620I think that's pretty comprehensive. I mean, obviously, you're going to need to get a lot of data on the severe cases to see if there's any other disease processes, but they all kind of fit into that cluster that you're mentioning there.
00:37:20.180Obviously, I think people who are on dialysis, I might add as well, kidney disease is also a high risk for people to have a severe infection.
00:37:27.260But it's really any of these chronic medical conditions that keep people going to the hospital, keep them having to take medications, especially ones that interfere with their immune system, as well as advancing age.
00:37:36.160It also seems like being a man is a chronic medical condition here, perhaps on other fronts as well.
00:37:42.100So do we still think that it's hitting men harder than women?
00:37:45.760It does appear to be a signal that we're seeing in the data that males are disproportionately getting more sick with this than females are.
00:37:53.220And I think we've seen that with other infectious diseases, even influenza is worse in males than females.
00:37:58.080And that may have to do with some idiosyncrasies and the differences between the immune system in a male and a female in the influence of certain sex hormones like testosterone and estrogen on the way the immune system functions.
00:38:09.220And maybe men have a more, actually, I think they have a more exuberant immune response, which is responsible for how sick you feel.
00:38:14.500And that's likely what might be behind this, but it's something that needs to be investigated.
00:38:18.280What about the idea that a higher exposure creates a more severe expression of the virus?
00:38:25.760So I think this was alleged with respect to medical workers in China getting it, you know, some of them being quite young and dying.
00:38:33.540Is it a story of you're exposed or not, or it really matters just how much a dose you got of the virus initially?
00:38:40.660There definitely is a dose response because we do this in animal challenge models where when you're trying to look at a virus, you might give them a really, really high dose of something to see what the, how much, what the lethal dose is.
00:38:51.700So there definitely is an inoculation effect.
00:38:54.180So the more you're exposed to, the intensity of the exposure could give you an overwhelming infection that might be hard to recover from versus someone who gets a smaller exposure.
00:39:02.280The kinetics of that haven't all been worked out, but we've seen that with many, many different pathogens, that the, that the load that you're exposed to does have an impact on the severity of symptoms and how quickly you become ill.
00:39:16.120I've heard reports of lung damage in people who recover.
00:39:19.860There's a giant green number on the Johns Hopkins website.
00:39:23.480I think last I looked, it was, you know, 65,000 people had recovered.
00:39:27.640How cheerful a picture is it to recover from this?
00:39:30.940So I would look at that number that you've seen, the 65,000 number with a little bit of, put a little context to it.
00:39:37.380When we use the word recovered in terms of this type of data, they're talking about officially recovered by those ministries of health in those countries.
00:39:44.160And what they're using there is fever free for a certain number of days and two negative diagnostic tests.
00:39:49.800That's not really what recovery means to an individual.
00:39:52.240For me, what recovery means to an individual is that they're able to, to do their activities of daily living.
00:39:56.940And so I think that many more people than that have actually recovered because that's more of a epidemiological distinction that they're trying to decide when can they discharge someone and not have them infect other people.
00:40:08.120When are they clear of the virus, basically not clear of symptoms.
00:40:11.480Recovery is going to depend upon how severe in general your, your infection was.
00:40:14.880Obviously, if you just had a mild illness that was indistinguishable from the common cold, there really is no recovery period.
00:40:19.400You're going to have about a week of illness and you're going to bounce back just fine.
00:40:21.680So if you're in a hospital and suppose you have pneumonia or you end up on a mechanical ventilator or in respiratory failure, then that recovery is going to be months and months with lung damage, with taking you a while to get back your same exercise tolerance if you've actually had damage to your lungs from this.
00:40:36.320So it's going to really depend on how severe the initial insult was from this virus.
00:40:40.320And those that are in ICUs are going to have protracted, protracted recovery periods, just like with any other type of pneumonia.
00:40:46.340So let's talk about what might be on the horizon with respect to treatment and prevention.
00:40:55.020What do you think the plausible timeline is for developing an antiviral treatment?
00:41:00.360So fortunately for us, we have this ability to repurpose antivirals that may have been used for other causes, other, for other reasons, and then, and then try them out on this virus.
00:41:10.520So for example, there is a product called Remdesivir, which was used in the Ebola trials in the Democratic Republic of the Congo and didn't do so well in those trials.
00:41:18.120But it had activity against coronaviruses and actually animal studies against the Middle East Respiratory Syndrome coronavirus that look good.
00:41:24.620So that's currently in phase two clinical trials right now.
00:41:27.280And we are hoping to see results from that in a couple of weeks.
00:41:30.120It's already been given to patients on compassionate use basis.
00:41:32.720So there is a lot of hope that that antiviral will appear maybe in several months after we get data from the clinical trials.
00:41:39.960There are a whole host of other things.
00:41:41.440There's actually a malaria drug that they're repurposing that happens to have activity against this virus.
00:42:06.760What's actually the belief now with respect to the efficacy of chloroquine as a treatment?
00:42:12.360We haven't done human trials on it, but there is a lot of studies in vitro, even before the SARS and before all these other coronaviruses,
00:42:20.700trying to use it against the other common cold-causing coronaviruses.
00:42:23.780And it seems to exhibit an antiviral effect against the virus.
00:42:27.240And that's why what people are trying to count on is, does this have activity against this specific coronavirus?
00:42:32.720And what we're seeing is some anecdotal reports of people using it, but there has been some effort to try and study this in a randomized controlled trial
00:42:39.620and see if what they've seen in a test tube actually works in humans.
00:42:42.580Are any of these other countries who don't have the same requirements that the FDA imposes on us out ahead of us in testing remedies?
00:42:52.540Do you know what China is doing with respect to antivirals?
00:42:55.920I know China has multiple clinical trials going on, not just of these antivirals that we mentioned, but also of traditional Chinese medicine.
00:43:03.180So there is basically, I think, hundreds of clinical trials have been registered in China regarding different antiviral compounds.
00:43:09.720So that's where the most cases are, too.
00:43:11.820So you have to remember that it's difficult to recruit patients for trials,
00:43:16.160especially in an emerging infectious disease outbreak when there may not be that many patients out there to actually recruit to put into your clinical trials.
00:43:23.560So you're going to see the vast majority of trials being done in China because that's where the bulk of patients are.