#97 – Peter Hotez, M.D., Ph.D.: COVID-19: transmissibility, vaccines, risk reduction, and treatment

1. 0:00 – 0:11

   Intro

   1. PAPeter Attia0:01

      [upbeat music]

2. 0:11 – 4:51

   Episode Setup and Why This Conversation Is Happening Now

   1. PAPeter Attia0:11

      Hey everyone. Welcome to The Drive Podcast. I'm your host, Peter Attia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, full stop, and we've assembled a great team of analysts to make this happen. If you enjoy this podcast, we've created a membership program that brings you far more in-depth content if you want to take your knowledge of this space to the next level. At the end of this episode, I'll explain what those benefits are, or if you want to learn more now, head over to peterattiamd.com/subscribe. Now, without further delay, here's today's episode. [upbeat music] My guest today is Dr. Peter Hotez. Dr. Hotez is a renowned vaccine scientist, a pediatrician, and an expert on the current coronavirus outbreak. His titles are almost too numerous to get into at this point, but I'll make an attempt to do so. He's the Dean of the National School of Tropical Medicine and Professor of Pediatrics and Molecular Virology and Microbiology at the Baylor College of Medicine, where he's also the director of the Texas Children's Center for Vaccine Development and the Texas Children's Hospital Endowed Chair of Tropical Pediatrics. I learned of Peter a few months ago for unrelated reasons that pertained to microbiology, vaccination, et cetera, and had wanted to interview him at the time and kind of postponed it for a number of unrelated reasons. More recently, about three weeks ago, I saw him talking about coronavirus, which was really around the time I started to think I had miscalculated. This would have been mid-February, the second week of February, and I started to realize at that point in time that this was going to be a much bigger deal than I had naively assumed in January. I reached back out to him and said, "Peter, let's get on a podcast when the time is right," and assumed that that would mean when we had enough facts that it was worth talking about. But what I did not really anticipate was the past seven days until they were upon us, uh, basically about a week ago. So if you're listening to this on the 14th of March, that would have been about the 6th of March. A lot of things really changed in my mind, and I reached back out to Peter and said, "Hey, we should probably talk at the end of next week," which gives you enough time to manage the very important responsibilities that you have, but also, um, allows us to sort of fill in some pretty big gaps in knowledge. And we attempt to do that, and, and this podcast is actually quite short by the standards of our podcast. It's about an hour long, and I think what we'll probably do is shorter, more frequent podcasts at this point in time because the information is changing at a very rapid rate, such that anything we talk about on this podcast is likely to be background information at best a week out. So we do talk about a number of things. We talk obviously about the etiology of the virus, the difference between the, you know, the virus, which is SARS-CoV-2, and the disease state that it causes, COVID-19. We talk about how it spread. We talk about where it came from, what we know about it, what we don't know about it, what some of the treatment options may be, may not be, why a vaccine is probably not likely in the near term. We talk about something called convalescent serum, which is something that looks kind of promising, and at this point, anything promising we want to put sort of all hands on deck with interpreting. So with that said, let's just get to this interview with Peter, and we'll be following this up with a number of other interviews. Also, I should point out on pretty much every day I'm putting updates up on Instagram where you can find me at peterattiamd.com is the website, and that'll point you to Instagram, or you can just go to Instagram at Peter Attia MD, and that'll be kind of daily updates. But as I said, expect to see podcasts at a slightly irregular cadence just as a way that we can sort of communicate with you. This podcast and all podcasts pertaining to the coronavirus will have show notes available to all listeners. So these podcast show notes and the subsequent ones that pertain to this subject matter will not be behind the paywall for subscribers, so this will be available to everybody. We will attempt to provide show notes as quickly as we can, so hopefully that allows everyone to access this information without any bottleneck. Without further delay then, please enjoy my discussion today with Dr. Peter Hotez. [upbeat music] Peter, thank you so much for making time to speak with us. You're in unbelievably high demand. I saw you on the news at 5:30 this morning your time, and I don't think you've stopped since. And of course, you've been nonstop for weeks now, and you've been very generous in making time to speak with me and my team prior to today. So again, greatly appreciated on behalf of many people listening.

3. 4:51 – 7:24

   SARS-CoV-2 vs. COVID-19 and Three Coronavirus Pandemics

   1. PAPeter Attia4:51

      Let's start with a little bit of just the nomenclature. People are a little bit confused, I think, about the nomenclature between COVID-19, SARS-CoV-2. Maybe explain which one's the virus, which one's the disease, and what the history is here.

   2. PHDr. Peter Hotez5:04

      Sure. COVID-19 is the official designated name of the disease by the World Health Organization. The causative agent is the SARS-CoV-2 virus, SARS coronavirus 2. Just like there's AIDS and there's HIV, there's the name of the disease and, and the name of the virus. And, and the fact that it's called SARS 2, as I often like to call it, has some meaning because there's a lot of similarity in the type of virus it is compared to the original SARS, which I often call SARS 1, that, uh, originated out of Southern China in 2003 and caused a very serious pandemic, a deadly pandemic that affected Toronto, Canada, among other places. This is a somewhat different type of disease in terms of transmissibility and fatality. We can talk about some of the differences between SARS 1 and SARS 2.

   3. PAPeter Attia5:55

      Maybe we should do that because I think transmissibility and lethality are two things that are very important to understanding this, and maybe touching on the distinction between SARS 1 and SARS 2 will be helpful.

   4. PHDr. Peter Hotez6:07

      But yeah, so actually we've act- we've had now three major pandemics caused by coronaviruses in the 21st century. You know, up until then, when I was being trained in microbiology and infectious diseases, we knew about coronaviruses, but they were considered of relatively minor importance. They were coronaviruses that caused upper respiratory infections in kids, and rarely they would cause lower respiratory tract infections. But we had our first really serious experience with a coronavirus in 2003 when SARS 1 caused a serious pandemic that disrupted the economy of China and Canada and elsewhere. Another second coronavirus occurred in 2012 with Middle Eastern Respiratory Syndrome that emerged out of Saudi Arabia. That was around 2012. And now this is the third one, SARS 2. So the point is we've had a new coronavirus pandemic every decade of this 21st century. So hopefully we're starting to realize these are pretty serious actors here in terms of global health threats. Uh, and that has a relevant, a lot of relevance when we talk about ultimately developing vaccines and why we should prioritize coronaviruses moving forward.

4. 7:24 – 12:26

   Why Both Lethality and Transmissibility Make This Virus Dangerous

   1. PAPeter Attia7:24

      Peter, six days ago I spoke with a colleague of yours who will remain nameless just because we didn't speak on the record, and I asked him point blank, "What is your level of concern today?" And keep in mind, this was a discussion on March 7th, six days ago. I said, "What is your concern with SARS-CoV-2 relative to the coronaviruses responsible for MERS and SARS, which were very deadly viruses?" And he said something to the effect of, "I am much more concerned with what I'm seeing today." Do you share that sentiment, and do you think that that is an overreaction?

   2. PHDr. Peter Hotez7:56

      I think it is an appropriate reaction, and I would have shared that concern six days ago, but for very quirky reasons. So you might say, well, in, everyone knows or a lot of people know from the, from all the public news that SARS 2 is not as deadly as SARS 1 or as MERS, but it's a cause of serious mortality. We'll go into that a little bit more. And it's also highly transmissible. So while it isn't necessarily the most lethal virus we've ever seen, nor is it the most transmissible, it's high in both categories, and that combines in this very unique way. Let me explain that a little bit better. So SARS 1, the original one, was highly lethal, and if you had it, you were sick as hell and you were going into the hospital in the ICU, and that meant that you didn't have a lot of people walking around transmitting SARS 1, and that's one of the reasons it tended to burn out pretty quickly, although it could cause serious nosocomial outbreaks in hospitals. And MERS, too, more or less went by that same playbook. This one is fatal only for certain group-- a serious disease to certain groups, and what that means is you have a lot of other, a large segment of the population walking around shedding virus, including kids. So kids, for reasons that, and adolescents and young adults, for reasons that we don't understand, are getting the infection and transmitting the virus, but they're not getting very sick. And there's always the outlier that will, but more often than not. So the problem is you have a lot of virus circulating, and only certain groups seem to be getting serious disease, and those tend to be individuals over the age of 70, those who have underlying disability, including diabetes or hypertension or heart disease, maybe those on immunosuppressive therapy, although we don't know as much about that. Also quite interesting, healthcare workers. So a lot of healthcare workers are getting infected because this is so highly transmissible and they're coming into contact with patients. And for reasons that we don't understand, healthcare workers are getting a higher level of serious disease than you would expect given their age groups. There have been a lot of medical mysteries about this virus, why kids are not getting seriously ill, why adolescents, young adults not getting seriously ill, but why healthcare workers are getting seriously ill. So we saw this in Wuhan, in China, where this virus emerged. At least a thousand healthcare workers became infected, and about fifteen percent of those developed serious illness or in the intensive care unit. So they seem to get much sicker than you would have expected, and may-- whether that's due to a higher level of exposure or a higher inoculum of virus, and whether that is reproducible in the US, uh, we'll have to see. So those are the people that seem to be the most vulnerable, the very old, those with underlying disability, and healthcare workers. And that also is a perfect mix because you're knocking out a lot of people out of the healthcare workforce that have to self-quarantine or are getting sick. And we were seeing these tragic situations play out in China or elsewhere where colleagues, healthcare colleagues are taking care of healthcare colleagues in the ICU, and that is also highly destabilizing.

   3. PAPeter Attia11:17

      Yeah, and it's also very nonlinear because if you lose ten percent or fifteen percent in that situation of your healthcare workforce between physicians, nurses, respiratory therapists, et cetera, the knockoff effect of that is much more than a fifteen percent hit to the ability to provide care, so.

   4. PHDr. Peter Hotez11:33

      That's right, and then the other population we're seeing at high risk for getting sick are the first responders, and the first responders are coming into contact with very severely ill people. They're getting infected, and then they have to self-quarantine. So we're seeing large numbers of first responders knocked out of the workforce, and then it, it's gonna reach a point potentially where we're gonna have this perfect storm of not having enough healthcare workers and first responders to help us. And so for all of these really odd features of the virus, it starts adding up to become a very serious epidemic and highly destabilizing for any country that has large numbers of people. And of course We didn't help our case at all by the US being so behind in diagnostic testing and allowing this virus to circulate for long periods of time.

5. 12:26 – 15:59

   US Testing Failures and the Cost of Delayed Detection

   1. PAPeter Attia12:26

      As of today, Peter, do you know how many tests are available? I know that as of yesterday morning, we were at about 75,000. How long until we hit a million, which in theory was promised as of yesterday?

   2. PHDr. Peter Hotez12:37

      Who knows? The promises keep coming, and this also has a lot of serious consequences because my colleague Mark Lipsitch has done some nice studies with his doctoral student, Ruiran Li, in China showing that the cities that get hit hard in terms of depletion of healthcare workforce and run on, uh, hospital beds and ventilators are those that allow transmission to go on for long periods of time without intervening. So whether or not you're a city that is totally overrun in terms of having patients on ventilators and hospital beds and depletion of healthcare staff is very much depends on how quickly you picked up transmission. So in Wuhan, where transmission went on for six weeks without people intervening, it was a catastrophe. So it was... And we all heard the stories o- of what went on in Wuhan in creating tent cities of hospitals, as opposed to Guangdong, where they picked it up after a week, and there were 20 people in the ICU. So it's night and day. And in the US now, we probably think transmission likely began in the middle of February if our first known indigenous case occurred, I think it was around February 26th. So backdate around five or six days, the average incubation period. We're getting up there now three, four weeks where transmission has been going on undetected because we haven't had the testing available, and that's what I'm worried about is in a... two weeks from now, all of a sudden we're going to see hospitals inundated with large numbers of sick people. We don't know for sure. This is a new virus, but that is the consequence of the failure that our government has had in terms of getting testing available.

   3. PAPeter Attia14:25

      And Peter, that's a really important point that I just don't think can be overstated, which is coming back to this point of the importance of social distancing now to buy time. Because if we could do anything, at this point, there is no stopping this. The opportunity to prevent this virus from entering this country or reaching a sufficient number of the population seems pretty slim at this point. It's a question of if 100,000 people are going to be infected, and it happens over a year versus a month, that has enormous consequences. Do you think there is still an opportunity to shift that curve?

   4. PHDr. Peter Hotez15:01

      If we can get a big order of magnitude level of testing in the next week, and we can see which communities have significant levels of transmission, potentially we could intervene. So yeah, we still have to try, but boy, it would have been nice to have that three, four weeks ago when there was maybe just a handful of communities that had transmission. We could have focused all of our energy on that, and so we did lose an opportunity, I think, to prevent this from becoming a large epidemic. And I get asked about this a lot. You know, for instance, I got Alisyn Camerota on CNN ask me this morning, "Whose fault is this?" And, and I think my response to her was a bit surprising. I said, "Look, now's not the time to start assigning fault. There's gonna be time for that later, and we can have a federal investigation of where the breakdowns occurred. But I think right now we've got to focus on what the task at hand is." And

6. 15:59 – 19:44

   Convalescent Serum as a Low-Cost Intervention

   1. PHDr. Peter Hotez15:59

      I introduced this new concept this morning, both on CNN and, and on Fox News, and I did it after calling my friend and colleague, Arturo Casadevall, who's a professor at Johns Hopkins, who's been pushing this idea for a few weeks that there is a low-cost intervention that we could apply right now, and that is identifying patients who've been infected, recovered, and looking at their convalescent serous. In other words, people develop antibodies, an anti- antibody response to varying degrees, collecting that serum, isolating antibody, and then using that as a treatment, because that's all we're gonna have right now. I, I already think the window has passed when we're gonna start having significant numbers of people sick from this virus in hospitals, in intensive care units, and this is the one thing we can offer them, given the fact that we're not likely to have any effective antiviral drugs for a while. And it could be very effective based on what we learned historically from things like the 1918 flu pandemic, the Spanish flu, or even from experiences that we've heard about from SARS and MERS or even this virus in Wuhan, both as a treatment, which would require large amounts of antibody, but also as prophylaxis. So you can give a small amount and keep healthcare workers and first responders on the job because it's preventing them from, potentially from getting sick.

   2. PAPeter Attia17:32

      Peter, when it comes to convalescent serum, I want to make sure I understand something, which is from a technical standpoint, this is easy. Obviously, from a theoretical standpoint, it makes sense. This is, as you point out, not a new trick. However, when we start to think about bottlenecks in the supply chain, it does require apheresis, correct?

   3. PHDr. Peter Hotez17:49

      Yeah, it looks that way, and so we really need the help of blood banks and any aca-- I don't know if you do this only in academic health centers or whether every h- community hospital would have this capability, and we would need some guidance from the Drug Administration, from CBER, the Center for Biologics Evaluation and Research. So this is kind of a 30,000-foot aerial view of the problem. Our... Speaking to Arturo, he thinks putting together a federal task force to really look into this and to help with standardizing it and figuring out, uh, what we can do. But it has... If we have wind up having a situation similar to Italy in the United States or even part of the United States, having this at our disposal is going to be really important because otherwise we've got nothing. Otherwise, we go back to the 14th century in terms of using quarantine methods and that kind of thing, and we see what happens when we have to do that. It's not a good look for our country.

   4. PAPeter Attia18:49

      Peter, do we have a sense of how many individuals could be helped by the serum of one convalesced patient? How scalable is it?

   5. PHDr. Peter Hotez18:56

      The kinds of numbers people are throwing out are 300 mils, three to 600 mils for someone who's potentially seriously ill, so that's looks like a one-to-one donor per patient. But for the prophylaxis, if we're talking 5 mLs, a single donor could potentially prophylax dozens or maybe even 100 individuals. And who knows how off my, those numbers really are. But given the fact that it's relatively low technology, doesn't need to bring in a lot of specialized equipment, I don't think. I think it's something we need to look into, and, and Arturo gave me the permission to sound the alarm, uh, on CNN and Fox News, and we'll see how it resonates in the coming days and weeks and see if it catches fire.

7. 19:44 – 20:20

   Remdesivir and Antiviral Prospects

   1. PAPeter Attia19:44

      What about Remdesivir, which seems like one of the more promising things that could be repurposed? Do you buy that argument that this drug, which has been developed by Gilead for Ebola, is potentially... I mean, it's being used now on compassionate exemption. Do we have a sense of its efficacy, or is it too soon?

   2. PHDr. Peter Hotez20:01

      I haven't seen those numbers, and so it will require a clinical trial and whether you use combination therapy. Certainly antivirals will go a lot faster than vaccines, and we've developed a recombinant protein vaccine, but it's, you know, we'll see how quickly that can come up to speed in terms of clinical development.

8. 20:20 – 27:52

   Vaccine Timelines, Immune Enhancement, and Hotez's Stalled Vaccine

   1. PAPeter Attia20:20

      You've said in the past a vaccine is, is really not something we're going to have in the next 12 months, and it, it might even be longer than that. Can you just explain to folks two issues? One, the technical challenges of vaccinating against this coronavirus per se versus, say, an influenza, and the lessons we've learned from, say, RSV viruses. And then secondly, the logistics of getting a vaccine tested, vetted from a safety and efficacy standpoint to be used on asymptomatic people. Those seem to be two separate issues that are both stacked against us.

   2. PHDr. Peter Hotez20:53

      Well, yeah, I mean, vaccines are about the highest bar there is in terms of testing because you're essentially... Typically, you're immunizing well individuals or healthy individuals, so you have to be pristine in terms of its safety. And historically, it's been very difficult to compress those timelines to something quick. So it's not unusual for a clinical development plan for a vaccine to last a year, two years, sometimes three years to go through the series of phase I trials for safety and then graded trials for phase II to show that those are expanded safety studies, maybe getting a hint of efficacy, and then the phase III pivotal study for licensure in an area of transmission. So even under ideal circumstances, that will take time. Now, I think there are opportunities to streamline this. So my colleague, Rino Rappuoli, who's one of the real thought leaders in vaccines, he's at GlaxoSmithKline, has drawn up a lot of interesting roadmaps for doing more things in parallel rather than serially and, and accelerating those timelines. And I think that there's a lot of interest in applying that for this vaccine. But I've made the statement that I'm not sure this is the one you want to do it with, even though there's so much urgency. And the reason I say that is coronavirus vaccines have, at least in laboratory animals, shown that they could create a problem known as immune enhancement, where the vaccine could actually make things worse. This is a phenomena that was found originally with the respiratory syncytial virus vaccine, the RSV vaccine, that was a killed virus vaccine, a formal and inactivated vaccine that was tested by the National Institutes of Health at Children's Hospital in Washington in the 1960s, where vaccine recipients actually did worse than the non-vaccine recipients after they were exposed to the natural virus living in the community. And the mechanism is not still entirely clear, but those who were vaccinated had more hospitalizations, and there were even two deaths. And there was the added layer of complexity that this study, when you look at the paper, I only realized this recently, was done among almost all African American kids as well when it was done, done in Washington, D.C., and there were potentially two deaths. So this squashed enthusiasm for RSV vaccines appropriately so for a long time. And the question is, is was this unique to respiratory syncytial virus or is there others that do it? Well, after SARS in 2003, there was initial effort to, again, develop killed virus vaccines to test in animals. And unfortunately, after virus challenge, those animals also exhibited a lung pathology that bore some resemblance to what we saw in the kids with RSV in the 1960s. And we said, "Oh, no, this is, uh... Are we gonna be faced with this again?" And so the thinking was, "Well, okay, maybe that was unique to a killed virus vaccine. Let's do this with the whole spike protein." So if you look at a cartoon of what coronavirus looks like, you always see these little spikes all around it. That's the part that docks with the receptor. So a recombinant protein vaccine was made with the whole spike protein. Sure enough, we also saw immune enhancement, although it was more in the liver than in the lungs. But the thinking was, "Can we get around this? Is it gonna be impossible to develop coronavirus vaccines?" Well, then Our colleagues at the New York Blood Center, Shibo Jiang and Lanying Du, found that if they only use the receptor binding domain, the smallest part of the S protein that docks with the receptor, the acetylcholinesterase two receptor in the lungs, they seem to get protection in laboratory animals without all the immune enhancement. That was pretty exciting, and that's the concept that we partnered together to write a grant to the NIH together with the Galveston National Laboratory, where they had the virus for potentially doing preclinical studies and Walter Reed, and we wound up making a vaccine, manufacturing it, that showed pretty good levels of, high levels of efficacy and seemed to get around the problem of immune enhancement. And that's why we got so excited at the prospect of maybe we could develop this receptor binding domain as a vaccine. And we did, and we got funded by the NIH. It took us several years to do it, to show all of the safety, none of the immune enhancement, and the efficacy had it manufactured. But after then, by then, nobody was really interested in coronavirus vaccines anymore, and we couldn't attract any investment in moving into clinical trials. We kept it on stability studies, but that project more or less was done until a few weeks ago when this new coronavirus emerged, and we began look... And the Chinese were really good about putting up their data. Everyone says how non-transparent they were, but I disagree. They were very transparent. They were putting up all their data on these preprint servers like bioRxiv, medRxiv, and we were able to see that the SARS 2 coronavirus bore a lot of resemblance to SARS 1. It was about eighty percent similar in terms of its genetic code bound to the same receptor. We realized, "Oh my God, we might be... We might actually have a vaccine that we could repurpose for this epidemic." In the meantime, we also started trying to make the new one as well, the receptor binding domain for the new one, but this was already manufactured. And now we've been in this hunt to try to identify prospective donors to see if we can now move this into clinical trials. That's been a few weeks now, and I'm, you know, I'm sad to report we've still not been able to raise the money to move it into clinical trials, which is really tragic. It's already manufactured. We can move as fast as anybody. But this really goes to show you the problem of dealing with vaccines, either for neglected diseases that I've devoted my whole life to. We've made vaccines for schistosomiasis and hookworm and Chagas disease for clin- and, and moving them into the clinic through our National School of Tropical Medicine at Baylor College of Medicine and Texas Children's Hospital Center for Vaccine Development, taking on this coronavirus. But you'd think that people would be pretty eager to support us to move this forward, but so far it hasn't happened.

   3. PAPeter Attia27:26

      Should that change, I assume people can pretty easily get ahold of you if there's interest in this. What's the easiest way for people to get ahold of you at this point in time? I assume just through the university?

   4. PHDr. Peter Hotez27:36

      Yeah, just send me an email. [chuckles] My email's pretty public. It's just, uh, Hotez, last name, @bcm, stands for Baylor College of Medicine, .edu. And we can do this through either the college or Texas Children's Hospital and be fantastic.

9. 27:52 – 31:33

   ACE2 Receptor, Organ Damage, and Modes of Transmission

   1. PAPeter Attia27:52

      What do we know about the ACE2 receptor and its role here? Certainly a few weeks ago, I remember seeing a paper that discussed this in the context of the first SARS outbreak. This was a 2005 paper, and that got us very interested in looking at angiotensin receptor blockers and things like that. But is the following still our understanding, which is that the virus gains access to these cells in the lung, the type II pneumocytes that make surfactant, probably through this ACE2 receptor, though there may be a co-receptor. Once the pneumocyte is infected, it reduces its capacity to produce surfactant, which is one of the more telling pieces of the pathology. Is that still largely accurate to our understanding?

   2. PHDr. Peter Hotez28:37

      Well, I think there's a couple of things. I think, first of all, the receptor's not only in the lungs, it's also found in the intestinal tract, and you can see intestinal pathology with this, and that may even be-

   3. PAPeter Attia28:47

      And even myocardial potentially

   4. PHDr. Peter Hotez28:48

      ... And it's in an endothelial cells as well, and that may partly explain some of the diverse pathology that we're seeing. So for instance, patients who are very ill with this, if you look at the medRxiv reports coming out of China and elsewhere, a lot of them are getting acute myocardial injury. And we don't really know if that's from myocarditis or whether they're just getting myocardial infarction as a consequence of the infection. But I think that's probably a major mode of death for a lot of these patients, whether-- And it's very confusing because there's a lot of things going on at once. You have acute myocardial injury, but you're also seeing acute respiratory distress syndrome, ARDS. So therefore, is the heart injury due to the ARDS and shock, or is it occurring in parallel? And then what's the basis for the ARDS? Is it overwhelming virus invasion in the lungs, or is there an, a huge inflammatory component to this? And there's differing opinions on that, and that also has implications for treatment. Then the intestinal pathology as well, and we've seen patients, at least ten percent of the patients reported in some hospitals in Wuhan, they presented with GI symptoms and were erroneously admitted to the surgical suite. And those are the ones that wound up actually infecting large numbers of healthcare workers because nobody suspected this was SARS 2. So that's confusing as well, and you can imagine how all the confusion that would create for monitoring and figuring out who should get tested. So My colleague Paul Offit is of the opinion that he thinks the GI route is actually a major mode of transmission, has noted and, and has speculated... Well, at least he's talked to me on the phone about whether the fact that cruise ships are so widely affected, he says it reminds him a little bit of norovirus when it affects large numbers of cruise ships, so is it getting into the food? So we don't really know the modes of transmission of this. We know droplet contact is gonna be important. People are coughing microdroplets onto surfaces, and then people come into contact with them with their hands and auto-inoculate themselves in the mucous membranes of their eyes and mouth, or whether they're coughing directly onto people's faces. But the other modes of transmission are also interesting. Is there a lot of fecal-oral transmission? I don't think we know that. Is there a true airborne transmission where the virus can travel on microparticles long distances? It turns out not many respiratory viruses do that. We know measles does, chickenpox does. So we're still in this steep learning curve about this virus.

10. 31:33 – 36:44

    Surface Survival, R-Naught, and Case Fatality

    1. PAPeter Attia31:33

       Which again brings us back to this point of can you buy time, because time presumably brings clarity, reduces uncertainty. Did you see the paper today that just came out from the New England Journal of Medicine that looked at the fomite transmission?

    2. PHDr. Peter Hotez31:46

       No, I didn't see that. What did it find?

    3. PAPeter Attia31:48

       Well, here, I'm gonna pull it up. Uh, the, the telling figure in this sort of looks at d- four different surfaces, actually several, plastic, steel, cardboard, copper surfaces, and it looks at the median and half-life survival on these surfaces. And not surprisingly, I think, based on what you just said, Peter, there's pretty reasonable survival. So until you reach a level that they think is not compatible with transmission, takes about 72 hours on plastic, takes 48 hours on cardboard, takes about 24 hours on steel, and takes about 8 hours to 24 hours on copper. So couple points I'd make there from a public service announcement. There's... I've seen a lot of talk on Twitter of all you need to do is have copper on your door and nothing gets in. Well, apparently not, and we have evidence that at least a day of survivability on these fomites, and again, I think that speaks to the R nought being as high as it is. And, and maybe this is a reasonable time to explain exactly what R nought is and what we think our best estimates are of it and why it probably feeds into what you've been saying about the concern over the transmissibility.

    4. PHDr. Peter Hotez33:03

       I think all of this put together presents a picture of why this virus is, is so highly transmissible. You have the fact that this virus can live on surfaces, so the droplet contact m- mode of transmission is significant because it depends on the virus being able to survive on fomites and surfaces, and the fact that this virus will often land on people's face and they can auto-inoculate themselves, that's a mode of transmission, maybe fecal-oral, and maybe airborne transmission as well. And so what does that out- all add up to? It all add, adds up to the fact that when people have looked at it, it's a pretty high what we call reproductive number or what the Brits call R nought, what we call R subzero, which refers to the... roughly the, the working definition is the number of people that will get infected if a single individual has this virus. So the number that I carry around in my head is between 2.24 and 3.58, roughly between two and four people infected for every single individual, and some people will shift those numbers around more or less, and I think that level of transmission varies depending on location and a number of other factors, but it's pretty high. If you look at seasonal flu, for instance, uh, which is around 1.2, 1.3, so this would be two or three times more transmissible than seasonal flu. Clearly not as transmissible as measles, which is up to 12 to 18, but still quite high. So as I mentioned before, every new emerging pathogen has its own little shop of horrors. In the case of this one, it's pretty highly transmissible, and there are a lot of people in this case who are running around who are not sick that are spreading this virus around and infecting a subgroup of individuals who happen to get very ill and with very high mortality rates. So the case fatality rate of this virus is between 0.6 and 3.4%, which may not sound all that high, but that's easily between 4 and 20 times higher than influenza, and that, given the fact that there is a group walking around with this, means you're gonna have a lot of people in hospital, in intensive care units, and especially among older populations where that mortality rate is between 10 and 20%. And that's what's so devastating is the fact that when this virus goes into areas where large numbers of older people congregate, especially older people with underlying disability, can have some devastating effects. And, and the Chinese told us this was gonna happen. They told us about h- what happens when this virus goes into a nursing home or affects older people and large numbers of deaths of those individuals over the age of 70. And I don't know if it was because we didn't believe them or we just had to learn it on our own, but when we had our first community transmission in Kirkland, Washington, we saw how this virus raced through that nursing home and killed 13 people in a nursing home of about 100 individuals, so 13%, which is exactly right in that area of 10 to 20% that the Chinese told us about and- And then I became very concerned, not only from the lack of government response from the debacle with the testing, but also that there was not a lot of guidance being issued around nursing homes or assisted living facilities.

11. 36:44 – 38:58

    Hotez's Advocacy and the "Angel of Death" Testimony

    1. PHDr. Peter Hotez36:44

       And I had the opportunity to testify to Congress about our vaccine to the House Science, Space and Technology Committee. But I-- here I had the attention of Congress, and it was being filmed on C-SPAN 2 or C-SPAN, and I said, "Look, this is my chance to really sound the alarm on what's not happening to protect our old people." And as I was saying it, I knew it was being very provocative, and I was being deliberately provocative, and I knew it was gonna be on the evening news and be on the news the next day, but I felt, you know, I had to say something, and that's when I used that expression, "This is the angel of death for older people." And indeed, that had that effect, but it was a wake-up call to people, and now we're starting to see nursing homes across the country take those extra measures to carefully screen people going in and out of nursing homes, to review all of their preparedness plans, and now the Health and Human Services secretary is mobilizing inspectors around infection control. And that's an example of where I, over the years, I've always had this interesting career that balances being a working scientist, an M.D. Ph.D. vaccine scientist, developing vaccines and for neglected disease interventions, with that advocacy in places that are where I've seen gaps. So I saw a gap in getting people to care about these poverty-related neglected diseases in the early 2000s and helped raise awareness. That's now led to treatment of more than a billion people annually for neglected tropical diseases, raising awareness about diseases of the poor in places like the United States, and now we've been working with Senator Booker, Cory Booker, around this issue, getting people to counter the anti-vaccine movement. So I'm a parent of an adult daughter with autism and wrote this book called "Vaccines Did Not Cause Rachel's Autism" to kind of counter the false narrative and the misinformation from the anti-vaccine movement. And here was another example of using my voice to really help people who didn't have a voice otherwise.

12. 38:58 – 44:46

    Geographic Risk and the Coming Surge in Hospital Capacity

    1. PAPeter Attia38:58

       Peter, what geographies in the United States are you most concerned about? And then I guess I would also ask you that question at a global level, but we'll start maybe in the United States.

    2. PHDr. Peter Hotez39:07

       Well, I mean, right now it's all bets are off. I think any urban area of the US now is vulnerable, and we've seen this now take off in Seattle. We've seen this take off in, uh, New Rochelle, uh, in Westchester County. We're starting to see some uptick in New York City, and there's nothing really unique about those cities other than they're congregations of a big urban population. So on that basis, I have to believe any large urban center is vulnerable, and it could be any place is vulnerable. It's just that urban areas tend to have more physicians, and so more healthcare, better public health infrastructure, so maybe it's just being picked up there first. So I said last week, this is gonna be a difficult week for America because the testing is gonna start to gear up, and now that it's in the hands of Quest Diagnostics and LabCorp and Roche, we're gonna get a much more full picture of the extent of this virus in the United States and North America. And I think we're starting to see that the numbers are going up 1,600. Who knows what it'll look like by next week? Is it gonna be 10 times that number? I think that's quite possible, or even more. And with that, we'll undoubtedly be picking up new foci of infection.

    3. PAPeter Attia40:26

       That's a pretty frightening thought, to have a log increase in a week. But when you look at other countries that have not done well, that's exactly what we have seen, isn't it?

    4. PHDr. Peter Hotez40:35

       Well, the question is whether that's a true log increase or whether we've had that transmission all along. It's just that now we're cherry-picking communities to detect it. So or maybe both's going on simultaneously. But I suspect we're gonna see those numbers steeply rise again. And so this gets back to my, what I was talking about with Marc Lipsitch's paper, where he says the more communista- sustained community transmission goes on, the health burden's gonna be in terms of hospital beds and ICU beds and the demands on healthcare staff. I think as we pick up these new levels of transmission in places it's been going on for a while, next week... So the horror this week was we realized we're seeing a lot more cases and maybe new areas of community transmission. I would say the same for next week with the added piece, now we're gonna start to see hospital beds fill up, and that's why I'm really pushing now for blood banks to implement this new antibody therapy, uh, because I think the need's really gonna be there. And if you don't offer people any hope of anything, I think that's where panic starts to spread, where you start seeing panic not only among the population but, but among the healthcare workers, and we've got to be able to stop that. So I think just like this week was challenging because we're starting to see an increase, I think in the next two weeks may be the critical period when we may start to see this start to reach a peak.

    5. PAPeter Attia42:05

       Peter, do we have a sense of what the excess capacity is in the ICU and where the, where is the bottleneck going to be in the supply chain? Is it the number of ventilators, the number of ICU beds or beds that could be repurposed for ICU? Is it gonna be the number of anesthesiologists, respiratory therapists, nurses? There are so many things here that could-

    6. PHDr. Peter Hotez42:24

       Yeah, I think, I think only now we're really starting to look at this, and if you've ever listened to Zeke Emanuel, he's been commenting a lot about this. We don't have a great capacity. Hospitals, for cost-saving measures and everything else, have operated at slim margins, so it's not like we have a lot of excess capacity laying around. And does this mean we're going to have to build tent city hospitals? Will we have to bring in the National Guard? I think all of that... You know, it's a big unknown. I mean, the only good thing that we have going for us is we did make that sacrifice of shutting down things we love, like the National Basketball Association, the NBA, and the rodeo, and that sort of thing, and that's a good thing about America. We did this to protect our most vulnerable, our older citizens, and a lot of them veterans of foreign wars, and I think that that's important. And maybe if there is a seasonality to this virus, maybe we're just hitting it right in terms of moving into warmer weather. But we have no evidence for that.

    7. PAPeter Attia43:30

       That certainly was not the case with the first SARS, right? I mean, it didn't seem to stop when the summer came, did it?

    8. PHDr. Peter Hotez43:36

       Well, you know, if you look at the curves, the peaks that I saw looked like more around the springtime, but who knows? I mean, we certainly can't count on it. You know, and there's some people who feel that it may start to go down in the summer, but not disappear entirely and then come back in the fall. So we just don't know. As I've also been saying is confronting a new serious virus pathogen is one of the hardest things our country faces, has faced the last 20 years, and it always starts out pretty bumpy and pretty rocky, I think in part because it takes the CDC a while to figure out how the federal government and the CDC, how to work with state and local health authorities. This one has been rockier than most because of the inability to do the testing and other factors. But the problem is, unlike Ebola, which was never gonna be transmitted widely across the country because of that very low reproductive number, unless you're taking care of a dead or dying Ebola patient, you're not gonna get Ebola. This one is pretty transmissible, so our margin for error is much smaller, as the studies in China have pointed out. So we could be in for some very serious times.

13. 44:46 – 51:36

    Models, Protecting the Elderly, and What to Watch Next

    1. PAPeter Attia44:46

       Marc Lipsitch has stated that he believes we could be entering kind of a new world where two years from now, half the world's population or thereabouts has been infected by this virus. And even if you use the absolute lowest estimate of mortality that's being provided, which is 0.5% or one in 200 people dying, the impact of what I just reiterated as his estimate is staggering. Do you share that view or do you, or do you at least think that that is a plausible scenario?

    2. PHDr. Peter Hotez45:19

       Yeah, it's absolutely plausible, and Marc's an outstanding epidemiologist and, you know, a lot of these estimates are based on models. I would say the only thing about models, and I'm not a modeler, but I've collaborated with modelers to look at projections of our different vaccines and, and to give us a sense of what level of protection we would need to have a significant impact on a population and how wide a coverage we would need. And one of the things that always impresses me working with modelers is that a modest change in assumptions of what goes into the model can often have huge differences. So the only comfort I take in that is to say, well, maybe, uh, if those models are like the ones I've worked with, a few tweaks to the model can result in two or three log reductions in deaths and cases and, and that sort of thing. So it's, uh... Models are useful exercises to help you think through problems, but how predictive they are is only as good as the assumptions with the new virus agent, where we don't even know all the modes of transmission and everything else, don't fully understand reproductive number that might help us.

    3. PAPeter Attia46:32

       Yeah. As a physicist, a very famous physicist once said, "All models are wrong. Some are useful." So hopefully that model is, is woefully wrong, but I think part of that is, as you said, it's a little bit in our hands how wrong that model's going to be, isn't it? I mean, it's still... We still have some say over our response to this, both in terms at the federal level, but also at the local and state level, and then at the individual level. We can all take steps to reduce our risk and buy more time. How are you thinking about this, I don't want to say personally, because you're in a very unique position where you have to be out there talking about this. You don't have the luxury of maybe being a little bit more sequestered. But are there a certain subset of people that at this point, Peter, you would say absolutely need to be self-quarantined, either the symptomatic folks, obviously, who run the risk of infecting others if they can't be tested, but also people who are showing no signs or symptoms, but who are at high enough risk? How are you helping people create their own sort of framework around that very difficult decision?

    4. PHDr. Peter Hotez47:38

       Well, certainly older individuals where they're clustering together, we've seen the devastation, so we can't repeat the debacle that we had in that nursing home. And so it's all hands on deck with protecting those individuals. Then you could say, "Okay, Peter, well, tell us what that means. Does that mean thinking of my 90-year-old mother in the Hebrew home in Brooklyn, outside of Brookline, Massachusetts? Do we now tell her that she has to stay in her room and can't go down to the cafeteria and sit with her friends? Is that what you're telling us?" And so these are gonna be really tough decisions. We know how important socialization is for older people, or for anybody, right? But for older people in, in nursing facilities, that's really heartbreaking. And so, "Dr. Hotez, are you telling us that the grandkids can't visit, can't visit?" So these are really tough decisions for us, because at what point do you say, "We know older populations are so fragile in terms of suffering serious mental decline, and, and do you want to do that just to protect them from this virus?" And this is where I say, "Well, I'm a vaccine scientist. I'm pretty good at understanding infectious disease epidemiology because I've had to really understand how to make the best vaccine." But there's a certain point where the decisions become so tricky that I have to say, "No, I'm starting to exceed the limits of my comfort zone." Here's where we start needing some federal guidance, state and federal guidance, people to really think about this very deeply and bringing experts together that understand that, and I don't see that happening, unfortunately. What I'd like to see are key task force created around not in general as has been done, the president's created an over-- sort of an overarching task force for this, but there are so many specialized pieces to this that we have to focus on, like creating an antibody-based technology, bring those experts together, bring experts together around what nursing homes are like and how they're structured, which would include experts in the mental health of older people, those experts in diabetes and hypertension to understand what's going on, and I think that's gonna be really critical as well.

    5. PAPeter Attia50:01

       Peter, what are you personally going to be paying closest attention to in the next seven days, besides the potential for using convalescent serum, both from the sort of clinical trial standpoint and/or utilization standpoint? In, in terms of data that are gonna say, "Hey, are we heading towards the Italian path or are we heading towards sort of the Singapore path?" What data are you monitoring closely?

    6. PHDr. Peter Hotez50:29

       Well, certainly incidence and prevalence data is gonna be really important because right now there's none, right? We, we've done so little testing, so as we ramp up, and also starting to see which new communities are becoming infected, I think that's gonna be absolutely critical, and seeing if the situation that we've seen in the Pacific Northwest and New Rochelle is being replicated elsewhere or the demographics taking on a, a different characteristic. Those are some of the big things that I'll be looking for. And then also there are some vaccine trials that have started in the Washington area. Interested in following those because my understanding is the one in Seattle began with one of the vaccine trial evaluation units at the University of Washington, and it was initiated at a time where there wasn't transmission of this virus. Now there is. So you're doing something that is gonna be very interesting, but also a little bit scary because if there is immune enhancement, now we're gonna start to see it among those volunteers who are, who are getting immunized.

14. 51:36 – 56:37

    Closing Reflections on Public Communication

    1. PAPeter Attia51:36

       Peter, I want to be respectful of your time, and I promised you we would only take an hour. We've now gone a little over an hour, so I want to let you go with the ask that either we can speak again, either formally or informally, because again, I think it's probably less important to spend hours at any one point in time and maybe more important to-

    2. PHDr. Peter Hotez51:54

       And this is what I've been saying, you know, on CNN, Fox, and MSNBC, and it's not easy going from one network to the other, right?

    3. PAPeter Attia52:02

       Especially those networks.

    4. PHDr. Peter Hotez52:03

       Yeah. Well, you know, one, you have to say something nice about the president, the other one, you're not allowed to say anything nice about the president. It's all so polarized, and threading that needle is interesting. But one of the things I always say is this is where we are right now, and this virus is racing so quickly that new pathogens in general set you up to look stupid because, you know, when you're trying to learn something about a new pathogen, but this one especially because it's so fast-moving and transmissible, I would cringe if I were to look at my interviews from two or three weeks ago in terms of the things I said, I think. And probably a month from now, I would say, "Oh my God, I can't believe I said that," at what we're talking about now. So I think absolutely that's important to update this and to say and to take a step back and look to see what have we learned in the last week, you know, because we're trying to make our best guesses, best estimates on what we're seeing now. But this is, as I say, it's moving so quickly, we have to continually reevaluate that. And that's why I'd like to see The White House out there every day because this thing is moving so quickly.

    5. PAPeter Attia53:11

       Yeah. Well, look, for those listening to this, probably on a Saturday, it's now Friday night in real time, March 13th. Peter, let's let you get back to work. Let's touch base next week and, uh, continue to look at the data and in real time try to come up with the best assessments of what we can. Thank you very much, Peter.

    6. PHDr. Peter Hotez53:30

       Thanks for having me, and thanks for all your great work. One of the things that I do when I give talks about confronting anti-science, and I do that a lot standing up to the anti-vaccine movement, I say part of this is our fault because as physicians and scientists, we're too inward-looking. We've somehow decided that engaging public audiences is not important. And so the kinds of things you're doing is really critical to break that. I think the best weapon against ignorance and false information is the kinds of things that you're doing. So I just want to congratulate you on what you're doing, and there's nothing more important.

    7. PAPeter Attia54:08

       Thank you, Peter. We greatly appreciate it, and I hope you get some rest tonight, and we'll be back in touch next week.

    8. PHDr. Peter Hotez54:12

       Thanks. Me too. I hope we get some rest.

    9. PAPeter Attia54:14

       [upbeat music] Thank you for listening to this week's episode of The Drive. If you're interested in diving deeper into any topics we discuss, we've created a membership program that allows us to bring you more in-depth exclusive content without relying on paid ads. It's our goal to ensure members get back much more than the price of the subscription. Now, to that end, membership benefits include a bunch of things. One, totally kickass comprehensive podcast show notes that detail every topic, paper, person, thing we discuss on each episode. The word on the street is nobody's show notes rival these. Monthly AMA episodes or Ask Me Anything episodes, hearing these episodes completely. Access to our private podcast feed that allows you to hear everything without having to listen to spiels like this. The Qualies, which are a super short podcast, typically less than five minutes, that we release every Tuesday through Friday, highlighting the best questions, topics, and tactics discussed on previous episodes of The Drive. This is a great way to catch up on previous episodes without having to go back and necessarily listen to every one. Steep discounts on products that I believe in, but for which I'm not getting paid to endorse. And a whole bunch of other benefits that we continue to trickle in as time goes on. If you want to learn more and access these member-only benefits, you can head over to peterattiamd.com forward slash subscribe. You can find me on Twitter, Instagram, and Facebook, all with the ID Peter Attia MD. You can also leave us a review on Apple Podcasts or whatever podcast player you listen on. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit peterattiamd.com forward slash about, where I keep an up-to-date and active list of such companies.

Episode duration: 57:06