#99 – Peter Hotez, M.D., Ph.D.: Continuing the conversation on COVID-19

1. 0:00 – 0:11

   Intro

   1. PAPeter Attia0:01

      [upbeat music]

2. 0:11 – 5:25

   Intro and Reaction to the First Episode

   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] Welcome back to another, uh, COVID-19 special episode of The Drive Podcast. I'm once again joined by Dr. Peter Hotez, a renowned vaccine scientist, pediatrician, and an expert on the current coronavirus outbreak. We released an episode with Peter on March 14, which received a lot of feedback. People were very grateful for that and wanted to have him back on with other questions. It is difficult to immediately address questions that are posed in the aftermath of a podcast that's five days old, because five days in this outbreak is an eternity. So a lot of the stuff we talked about today is not actually stuff I thought I would talk about with Peter at the time that we finished our last episode, and, and again, that means it might not be germane a week from now. But nevertheless, this was recorded March 19 in the late afternoon, evening, and as such, it's probably only as relevant as that timing. Given the temporal nature of things at this moment in time, I think podcasts become pretty obsolete pretty quickly, so hopefully you're all able to listen to this today, March 20, or shortly thereafter. Moving forward, I will continue to release shorter and more irregular podcasts, probably trying to get out two or three a week. Also, I'll continue to post videos on Instagram, and eventually they'll make their way onto YouTube, usually the next day. Again, everything at this point in time is open to subscribers, non-subscribers equally, and we're also in the process of putting together a specific page on our site, that's at peterattiamd.com, that will house all of the information we're posting on this SARS-CoV-2 virus that's the, uh, responsible agent for the disease known as COVID-19. So again, podcast now with Peter. Please enjoy it. Keep in mind, hopefully within a couple of days we'll aggregate all of this stuff, all podcasts, all videos, plus all of the internal memos that we are sending to our patients. We're just gonna start putting all of that stuff out there for everyone, and that'll be on our site. So hopefully you enjoy my discussion here today with Dr. Peter Hotez. [upbeat music] Hey Peter, thank you so much for making time again to speak. I know it was less than a week ago that we sat down to do this, but a week in terms of this coronavirus seems like a year with respect to the knowledge and insight that we're gaining with respect to everything else in healthcare.

   2. PHDr. Peter Hotez3:18

      I really appreciate the opportunity to be on. This was our first podcast together, and maybe it was the topic, but the response has been extraordinary. I've been getting emails and texts from people, so many individuals, and all of them really enthusiastic and supportive and saying that we did such a good job explaining some complicated science and, and asking questions that people actually wanted to know the answer to, but maybe never articulated before, and tied so many things together and connected a lot of dots. And then in a few cases, we've even gotten people reaching out, asking if they can help to support our vaccine development efforts, and we've had some lot of really good follow-up. So thank you again for that opportunity. I was really also impressed with-- I expected to hear only from either physicians or healthcare professionals, but I've heard apparently this podcast is reaching people in all walks of life, and people who just really are kind of sick of things so dumbed down in the mainstream media. So I think we hit it at a really good level.

   3. PAPeter Attia4:27

      Well, thank you. That means a lot coming from you. And, and I agree. I've sort of always rejected the notion that people need dumbed down sound bites. I think that's probably just a, an assumption that when really vetted is probably not true for the majority of people. I think if people in medicine and science can explain things clearly and patiently, then I don't think you need to have a great background in this to understand complicated topics, and this is a case in point.

   4. PHDr. Peter Hotez4:50

      I think that's also why, you know, I've been asked to come back to CNN, Fox, and MSNBC, is because I'm willing to take a little bit of time and explain complicated concepts. And provided I can get more than 30 seconds or, or a minute or two, it seems to resonate well with people. That's what people want to hear. They don't want to hear dumbed down crap. They want to hear real things, and want to understand the nuance and know that certain things are complicated and that we don't have all the answers.

   5. PAPeter Attia5:19

      Yeah. So Peter, I want to talk about a few things that have sort of changed in the last week.

3. 5:25 – 9:40

   True Case Counts and the Threat to Healthcare Workers

   1. PAPeter Attia5:25

      Obviously, from a confirmed cases standpoint, at the time of this recording, which is Thursday afternoon, March 19, we're a little over 13,000 cases confirmed in the United States, but I think it's safe to assume that that's a small fraction of the true number of infected patients. Do you have a sense of what range you would apply to the true number of infected people?

   2. PHDr. Peter Hotez5:52

      A couple of things. First of all, you're seeing every day it's a big jump. Every day is the largest number of new COVID cases that we've ever seen. When I last looked, it was just this morning, it was just under 10,000. Now you're telling me it's 13, and before then I think it was 8,500, then 7,000. So undoubtedly a lot of that is we're finally getting some testing underway, and it's starting to catch up with the actual population who's infected. And, and where this goes, I think, is gonna be very interesting. I don't think we have a real sense of the percentage of the population infected. I think what's happening is not necessarily that this is even new transmission. These-- A lot of this are probably areas that have been undergoing transmission for a few weeks, but we're just picking it up now. So I think that's an important component. And, you know, there are models that say for every person you identify, there's 50 more, 20 more, but it-- I don't know how strong the assumptions are for those models. So I think we have a lot... But I think what's more telling is just hearing from physicians at major hospitals from all over the country, from Philadelphia, Baltimore, New York, and elsewhere, saying they are just taking care of a lot of patients, and they're already feeling overwhelmed, even this early in the epidemic. And that says to me that this thing is now revving up despite what the actual numbers of tested cases say. And it also tells me that one of my worst fears and nightmares that I talked about on the last podcast, that I've been rattling the cage about, is coming true, that this thing is rapidly approaching overwhelming health systems, and doctors and nurses, other health professionals are starting to get exposed and getting sick. And with that is a lot of worry, also a lot of heroism on the part of health professionals. But I, I'm very worried right now that we're not doing all we can, even close, to protect one of our most cherished resources in this country, which are our healthcare professionals, and I think we're really seeing this rev up now. And a few weeks ago, I testified in Congress, and I was alarmed at the fact that we weren't paying attention to our nursing facilities and assisted care living facilities, and the fact that we've had 25 deaths in that nursing home in Washington State, in Kirkland. That's when I used deliberately provocative language in Congress and said, "This is the angel of death." And I knew it was gonna get on, make a lot of headlines, and it did, but it got people's attention. This week, felt I had to do it again. I went on CNN Newsday with Alisyn Camerota, and, and I had to do it again because I'm so frustrated that we're exposing some of our nation's greatest treasures, our healthcare professionals, to this virus without making them feel safe or protected in any way. And I said, "Look, if a significant number of healthcare professionals start either self-quarantining or actually getting sick, or if you have the situation where colleagues are gonna start taking care of colleagues who are very sick or in intensive care units," the term I used, "it'll be lights out." By lights out, I mean this whole thing is over. Things will unravel in this nation very fast. And you know, and I knew I was, again, being very provocative, but sometimes you have to do it to get people's attention, and now I think it's starting to register. The question is: Can we mount an efficient response to figure this out?

4. 9:40 – 12:29

   Regional Hot Spots and the Case Multiplier

   1. PAPeter Attia9:40

      Peter, you alluded to this idea of do we have a sense of how many people are infected as a function of how many people are confirmed, so the actual to confirmed case multiplier. We've been building one of these models ourselves. We've looked at other people that have built them. I've seen people estimate that, look, it can't be less than 45 to 50. Our internal estimate, which I think is very conservative, is probably closer to 25. And what it's basically doing is trying to figure out what is the assumed number of days from an infection until a fatality, and then what is the assumed infectious fatality rate? And obviously it becomes very sensitive to both of those. But if we posit for a moment that it's on the most conservative side of those estimates, in the neighborhood of 10 to 20, do you consider that a positive or negative sign? In other words, if right now there are, quote-unquote, "only" 125,000 people infected in the United States, are we in good shape?

   2. PHDr. Peter Hotez10:40

      We may or may not be, because remember, those 125,000 are not evenly spread across the country. Let's say it's 200,000, just for argument's sake. What that really means is there may be 30,000 or 40,000 cases in the New York area, and things are getting scary very quickly, and there may be another similar number in Washington or California or the couple of places where there's known transmission, and basically just a handful of cases maybe in Texas or places like that. So the question then is, if you're modeling how you're gonna do this, what you really wanna look at is a map of the US, and you're gonna see a bunch of... Let's say you use red as your color to mark the number of cases. You're gonna see a red blob, smallish red blob over New York and W- Seattle, maybe one or two other places, and it's those blobs that are gonna start to grow. And then you're going to see other small red dots appear in the country, and they're gonna start to grow. And then it's gonna be the question of whether those blobs begin to coalesce, uh, across the country. So that's how it's gonna work. It's not- The absolute number of cases in the US, you know, it's interesting because the United States is so large, you wanna look at those nodes of where there's significant levels of infection and, and see how they grow and intensify in color. And what I'm hearing from Governor Cuomo, he's really sounded the alarm in a very effective way, and that's what we're gonna be in for, for the next few weeks or months, is a New York-like situation starting to pop up in other parts of the country.

   3. PAPeter Attia12:27

      Yeah, that makes a lot of sense.

5. 12:29 – 15:33

   Testing Missteps and the Need for a Later Review

   1. PAPeter Attia12:29

      Let's go from that then on to some testing, because testing is now going to figure into this, of course. I can't get a straight answer from anybody, so I'm curious as to whether you have an insight as to why the CDC and FDA elected to go with Roche for the testing kit when they were very late to this, as opposed to using one of the companies in China that had already done literally millions of tests and had pretty robust data on sensitivity, specificity, et cetera.

   2. PHDr. Peter Hotez12:59

      I don't know how they made any of their decisions around testing. It's clear they should have gone to commercial kits from the very beginning. I'm getting asked a lot of questions about what's gone wrong in the testing, what's gone wrong in the hospital response, and I've sort of deflected the questions a bit because right now we've, we have to really focus on the matter at hand. I think what's going to happen is when we get through all this, whether it's in a year from now or 18 months from now or, or sooner, there's gonna have to be some type of independent committee to really look into the missteps. And it's not for the purposes of being punitive, it's for the purposes of trying to figure out how to fix this when a new pandemic emerges next time so we don't make so many of the same mistakes. And, and I think we'll see a number of flaws that went on with some of the agencies. I think we'll see some of the flaws that went on, on the communication between the federal and local governments and, and state governments. And that may require us to enact some new legislation to fix it. But it's just been so exasperating to see how this has been rolled out. We didn't have a lot of time of notice, but we did have time. It's not like we didn't have any idea it was coming. We had at least a month, arguably two months, to know what was going to hit the United States, and we also saw pretty quickly that this was not gonna stay confined to Central China or even China. It moved pretty quickly to Asian countries. And even when it was starting off in Italy, we were still pretty slow on the uptake. So the fact that we did not have a faster trigger is gonna be really interesting, and it's impossible to know right now where the fault lies. I have some suspicions which I could share in private with you, but I don't think it's gonna help us right now to, to start pointing fingers. But now it's a matter of figuring out how we rapidly fix this. 'Cause now, unfortunately, now that we're starting now to fix the first phase, the testing, though we still have a ways to go, we're already moved into the second phase, where health systems are already being stressed, and I'm worried it's gonna be close to collapse in a couple of weeks unless we can figure this out. New York is already reeling. We are seeing the anxiety on people's faces in the New York Hospital system, and I'm very concerned.

6. 15:33 – 22:22

   Where the Healthcare System Breaks First

   1. PAPeter Attia15:33

      Now, Peter, what do you think is going to be the rate-limiting step in healthcare delivery in an area like New York or other areas that are going to be sort of epicenters for this? Do you think it will be the healthcare providers? Do you think it will be ventilators? Do you think it will be PPE for the healthcare providers? Where do you actually think the breakdown occurs?

   2. PHDr. Peter Hotez15:56

      Well, I see the first breakdown starting to happen with doctors and nurses already exhausted, already demoralized to some extent, and people feeling that no one is really looking after them, and they're kind of on their own. So we've already had that initial breakdown of trust.

   3. PAPeter Attia16:16

      Can you say more about that, Peter? I wanna make sure I understand, what is that resulting from? Is that due to a belief that the, the system isn't providing them with the necessary equipment to protect themselves or the necessary resources to take care of patients? Where is that disdain or lack of trust coming from?

   4. PHDr. Peter Hotez16:32

      Well, I think it's coming from seeing colleagues get sick and inconsistency in what the plan is. A lot of hospitals haven't prepared for this adequately. Not seeing-- Also, this disconnect from what they're seeing coming out of the state government or federal governments when they're very worried about for themselves and their families. They're seeing colleagues start to get sick. They're hearing stories of some colleagues being seriously ill. And either it's the White House still two or three weeks behind, still having the testing discussion, or state governors not really saying, "We hear you. We know you're concerned. Here's what our plan is," is chilling actually. I think the-- As I say, the only one now, 'cause it's New York, it's higher profile and all the media outlets are in New York, the only governor I'm hearing from on a regular basis is Cuomo, and he clearly gets it and has sounded the alarm. But I'm concerned, and I'm also hearing about from parents of, of residents or residents themselves. And then on top of that, now the latest story that's come out of both MMWR, the Morbidity and Mortality Weekly Report from the CDC as well as Italy, is that this is no longer a disease of the old and infirm. It's significant numbers of young adults, people who are residents, fellows, young attending age actually now with severe illness and going into ICUs in this country. And that buzz is already catching on among young physicians, and that's highly destabilizing, and I think that's probably our biggest link right now. Eventually, it will be the lack of respirators and lack of PPE, but I think right now it's the fact that you're seeing young physicians and nurses, people in the best years of their life now getting sick and the feeling that they're feeling abandoned. And I'm getting that sense from either direct emails from nurses and physicians thanking me for speaking out and echoing their concerns, and in many cases, it's parents of resident physicians and young-- and nurses as well, and that we're starting to see that being a regular occurrence right now.

   5. PAPeter Attia18:59

      So what is the solution to that, Peter? Because we can't obviously on a moment's notice ramp up the number of doctors, nurses, respiratory therapists, hospital staff, I mean, everybody in the hospital, right? It's the people that we don't even necessarily immediately think about, the people who clean the ventilators, the people who clean the hospitals. I mean, all of these people are not gonna be trained overnight, so how do we solve this problem when going back to your earlier point, if you look at average numbers across the United States, it's very easy to be misled? This is really going to be probably about local waves of this. So is the solution that we are mobilizing physicians from geographies that are underutilized into higher utilization areas? How do we actually go about solving this problem?

   6. PHDr. Peter Hotez19:48

      Well, the problem is the areas that are likely COVID-19 are also probably underserved already by physicians. I know we're all sort of thinking out loud, and I thought about that too, but realistically, what do you do? Take a physician who's serving the entire county, an entire county in western Nebraska, and take them to New York to help out? That's probably not realistic either.

   7. PAPeter Attia20:11

      Maybe not as outrageous an example, but again, I don't know what it's like in the Houston area right now or in Dallas or other major metropolitan areas that are not New York. I mean, could one repurpose medical staff from those areas to deal with the first wave in the places that are very likely to be overwhelmed quickly?

   8. PHDr. Peter Hotez20:30

      Yeah. On the other hand, it could be, but then if you actually talk to physicians in areas where there's not COVID-19, it's not like they're not already stressed out and already overburdened with their daily activities and the electronic health records and, and everything else. So the whole system to begin with has been pretty fragile with very high rates of what some people call physician burnout, which is a term I don't like at all, but it's not really burnout. It's making these horrible, unreasonable demands on physicians and, and healthcare providers to benefit the insurance companies. So you've already got stressed out young physicians who are, are heavily under siege, and now you're gonna bring them into a, a COVID-19 area. I'm not sure. So the bottom line is I don't have, I don't have an, any obvious solution to figuring this out. One possibility that I've thought about and haven't introduced it to anybody yet is could we dramatically expand the US Public Health Service, especially with all these individuals who are at home now and in some cases not receiving a paycheck? Would there be any advantage offered to have this use a commissioned corps of the Public Health Service or even the military to bring in a whole cadre? I'm not... Highly trained individuals, but individuals that you could train like medics to help out just to provide an increase in the number of people who can help manage ventilators and, and that sort of thing. So that's one potential possibility. And then the question is, if we're not quite there yet, it's gonna be very hard to persuade Congress to take that kind of action.

7. 22:22 – 27:06

   Antibody Prophylaxis and the Blood Type Study

   1. PAPeter Attia22:22

      So Peter, what is the latest thinking you have on things that people who are presumably not infected, so either asymptomatic or confirmed to be not infected, which is a very small number in the latter category because of the dearth of testing, that things can do to sort of reduce the probability of getting infected? So the obvious one that we've discussed, of course, is social distancing, but let's say someone has already sort of adopted that posture, and now they're sort of asking the second order question, which is, "Look, I'm basically working from home. My kids are no longer in school. What am I supposed to do with my Amazon package when it arrives? What's the probability that virus is being transmitted across that?" How much insight do we have into the real transmissibility of this?

   2. PHDr. Peter Hotez23:11

      I don't think we have a lot of data. You saw this week this paper in "The New England Journal of Medicine" that measured length of time on the virus on inert surfaces, and I actually did an interview with ProPublica asking me about the US mail, is that contaminated with virus and what should we do? And maybe we know that the virus can live for a certain number of hours on cardboard. That's been looked at. But then the question is, how relevant is that really, and what's the real risk? I think for me, the priority is protecting people who are coming into contact with sick individuals, and I come back to the healthcare providers and the first responders. And you saw how the CDC has now managed it, so they came out with new guidelines this week which kind of loosened the criteria for exposure and what exposure means and basically saying you could stay in the workforce And keep doing what you're doing, depending on the intensity of the exposure. And I think it's sort of a desperation move, but it may be something that we need to do in order to keep people in the workforce. I come back to what we introduced last time we spoke, which is the antibody therapy, but not using it as a treatment, but using as prophylaxis. I think that could potentially help a lot. So the idea is when you harvest antibodies from individuals who've gotten sick and recovered, have antibodies, you aphorese their blood, you recover the plasma component, maybe isolate the antibodies. If you give a big dose of that, you could potentially treat someone who's sick. But a small dose of it, like a 5 ml dose, you could use that as a form of prophylaxis, and the antibody would last a couple of weeks so that a single injection can potentially greatly reduce the likelihood you're going to become infected as a healthcare provider or a first responder for a period of two weeks, and then you subsequently get another dose. As we discussed, it's an ancient method, but now refined using better technology. So the White House actually came out today in their press conference and actually talked about this. I brought it on national TV on CNN and Fox a week ago, and now it's out there saying that the federal government's gonna do it. What's interesting is in the meantime, over the last couple of weeks, a number of academic health centers have started to put together a network of blood banks to actually start this, and what I've heard is that none of them have actually been contacted by the federal government yet. So I think we gotta resolve that, why there's that disconnect, that this informal network that's already started is not better linked with the White House announcement today and the comments of the new FDA commissioner, uh, Steve Hahn.

   3. PAPeter Attia26:08

      What did you make of the recent study looking at blood type ABO and susceptibility?

   4. PHDr. Peter Hotez26:15

      Yeah, I thought it was interesting. Uh, I'm not sure what it means, and I'm not sure how it's necessarily relevant to developing the plasma therapy. So I think it's an interesting finding, but I'm not sure how it applies just yet.

   5. PAPeter Attia26:31

      Yeah, I mean, I think just for folks listening so they understand, it was looking at data from China and basically observing that people with A type blood had an increased risk of infection. People with O type had a reduced risk. I think the hazard ratio on the downside was more impressive than on the upside. In other words, it was more about having O blood and therefore anti-A antibodies that seemed to be somewhat protective. So again, does that really matter? As you said, maybe, maybe not. It certainly isn't immunity, that's the point, in the way that potentially convalescent serum could be.

8. 27:06 – 31:11

   Young Patients, ICU Admissions and Long-Term Effects

   1. PHDr. Peter Hotez27:06

      Since we spoke, there's been a few interesting observations now, and people are scrambling to understand it better. I think one, of course, is in parallel, the studies out of Italy and, and the younger age group getting infected and seriously ill, and the question is why didn't we see that in China? I think that is interesting, this very high number of seriously ill hospitalized people between the ages of 20 and 40. I think it's now in the US accounting for a third of the hospitalized.

   2. PAPeter Attia27:40

      Is it that high? I saw a report-

   3. PHDr. Peter Hotez27:42

      Yeah

   4. PAPeter Attia27:42

      ... today that was about 25%, and I was going to ask you the question you're posing, which is what on earth can account for this difference in the United States? It's the most disturbing thing I think I've seen today.

   5. PHDr. Peter Hotez27:53

      Yeah. So I think the number that I saw was around, about a third. First of all, half of those hospitalized are under the age of 54, which is very different from what you saw in China. And those, and about a third between 20 and 44 is the number, or 29, 30% is the number that I saw, and there was even a blip of people under 19. So that's a big question, and I think the numbers are gonna turn out to be somewhat similar in Italy. Now, it's been pointed out that those individuals are not dying, but I said this morning that, well, even if they're not dying, if they're, can imagine if they're being in ICUs and intubated, that is still a horrible ordeal for a young person to go through. And if we have that happening over and over again, that's a huge tax on the system. I don't know. I mean, the question of whether smoking is responsible or even vaping has been raised. We'll have to do the epidemiology of that and what the mechanism is. We know smoking can upregulate the ACE2 receptor for the virus. I don't know that anybody's looked at vaping, but trying to understand what it is about young people that's different in Europe and the US, or maybe it's just host genetics, some genetic factor, but-

   6. PAPeter Attia29:16

      Well, there's something different, and I'll read to you something. It's a photo that was taken and sent to one of my colleagues from someone he knows in London today. So the piece of paper is just the ages of the people they admitted to the ICU today. This is a hospital in London. I'll read them off to you: 46, 22, 68, 61, 51, 71, 32, 29, 28, 37, 34, 32. He then also showed me a picture of the 34-year-old's chest X-ray, and it is effectively a complete whiteout. So again, will these patients survive? Hopefully, most of them will. But as you said, they're not out of the woods because the long term, the tail of this on morbidity is significant. I found a study yesterday that looked at 10-year follow-up on the SARS-CoV-1 patients, the survivors, and The amount of cardiac disease and pulmonary disease in those patients was not trivial, suggesting there was some lingering effect of that virus.

   7. PHDr. Peter Hotez30:20

      Yeah, and the other interesting finding when you look at the papers on MedArchive from the Chinese experience, there's a lot of what they're calling acute heart injury, and it's not really clear what's going on there, whether that's a viral myocarditis or whether it potentially-- whether they're just having myocardial infarcts because of the ARDS and shock. But you're seeing a lot of heart injury, and I suspect that's probably accounting for a high percentage of the deaths as well. So the first thing people want to say is, "Is this virus mutating?" And I'm always suspicious when people are quick to claim it's mutation. I'm guessing not, but we'll have to unravel that. But we need really good epidemiology now on those younger patients to try to understand what the differences are.

   8. PAPeter Attia31:10

      You know,

9. 31:11 – 34:18

   Immunity, the 18-Month Projection and Vaccine Timelines

   1. PAPeter Attia31:11

      Peter, I've been asked this question a bunch, and my usual answer is probably in the short term, but not sure in the long term, and the question is, once a person is infected and recovers, do they have lasting immunity? And obviously, the convalescent serum experiments would suggest, at least in the short term, there's immunity. Do we think we have an insight into that? In other words, is, just to speculate, is this something in your mind based on other coronaviruses that looks like a seasonal virus like influenza or more of, uh, the type of virus where once you have immunity, it's largely life-lasting?

   2. PHDr. Peter Hotez31:44

      I think there's a paper on MedArchive or BioArchive out this week on non-human primates showing that once you're infected, they're immune to reinfection. Whether that's applicable to humans is hard to know, but I'm gonna work on the premise that that exposure infection will probably confer immunity. But the flu, of course, is a different story because of all the antigenic drift and variation. But then the other questions that have come up this week are around these projections from the federal government and their report that they just released saying that they think this pandemic will last eighteen months. And I'm trying to understand what those assumptions are. I think they might be out of models from an Imperial College, which look at the fact that this virus may go down in the summer but come back in the fall and then potentially be seasonal after that, until eventually enough people are infected and therefore rendered immune from the virus. And I'm guessing that's how the eighteen-month estimate is coming from. The other thing I'm hearing, and I hope it's not the case, is that I've been told that the eighteen month is because they're anticipating after that we're gonna have the vaccine ready to go. And, and I've really been downplaying expectations of having a vaccine in eighteen months or at least a rapidly deployable vaccine in eighteen months. I think we have to be more realistic about that in terms of going through all of the adequate safety. We're just now only have the first vaccine in clinical trials with a technology that's never been shown to turn into a licensed vaccine. So I think we're gonna be looking at five or six. We won't even be fully underway for a while. So even though I think we're hearing numbers like a year or eighteen months, from my estimate, I think it's probably more likely much longer than that. So I hope that the models of ending this pandemic are not depending on having the availability of a vaccine. I think we have to proceed as though we're not gonna have one in the near future. Now, having said that, I'm more optimistic about having a lot of new technologies come out, like the convalescent antibody, but we're hearing some interesting things about new drugs, especially some of the repurposed drugs, because the new chemical entities will also take a while, but not nearly as long as a vaccine.

10. 34:18 – 38:51

    Repurposed Drugs: Kaletra, Hydroxychloroquine, ARBs and Camostat

    1. PAPeter Attia34:18

       Speaking of repurposed drugs, yesterday, the New England Journal of Medicine published a paper looking at Kaletra. It was, at the top level, viewed as a negative study, but I think many people, ourselves included, have looked at that and said, "I think the only thing we learned from that is giving Kaletra to people who are on death's door is probably not helpful." How did you interpret that paper?

    2. PHDr. Peter Hotez34:39

       Yeah, it could be. You know, people often think that antiviral drugs are like antibacterial drugs, and they seldom have that same dramatic effect. I mean, clearly the HIV story is amazing, and the, and the lamivudine story for hepatitis C is amazing. But more typically, it's... you don't see that dramatic impact of antiviral drugs. So you very well might be right. I wouldn't throw it out just yet. There's been a lot of discussion about hydroxychloroquine, and there's some interesting in vitro data on showing hydroxychloroquine inhibits replication of the virus. Also, it has some anti-inflammatory effects. And then Didier Raoult from Marseille, who's, uh, I've known him for years, he's amazing infectious disease microbiologist, mainly focused on rickettsial-like pathogens, published a small study showing maybe there's some effect of hydroxychloroquine. I think people are over maybe hyping it a little much, saying we have a cure. We clearly have to do much larger studies. But if hydroxychloroquine could ever work out or have an impact, I mean, it would be perfect, right? It'd be-- It's cheap. You can make a bucket of it. It's orally bioavailable. The nice thing is you could use it not only for the US and Europe, but it'd be relatively straightforward to use in low-income countries, and especially if this virus is now in Africa, we don't even know about it, or parts of Asia. So that, if I had a, a wish list, and it would be ixnay on wishing for my vaccine, it would be, I think, around something like a chloroquine. We've also been reading about some of the ACE2 inhibitors and the angiotensin receptor blockers, and we're getting sort of a mixed picture about that depending on what paper you're reading. So, and especially around the ARBs, the ARBs as they sometimes call them, claiming that some of the common antihypertensives that we use, where they're saying, "Well, on the one hand, it has the ability to interfere with the ligand detachment of the virus to the ACE2, and therefore, that blocking effect should have an antiviral property." Others saying, "No, no, no, it's actually gonna upregulate the receptor and make things worse." And I got a interesting email, and I wound up talking to a professor at, uh, Nova Southeastern University, Robert Smith, who's in the School of Pharmacy. He's been looking at this, and he actually thinks that it could work for a totally different reason, that it actually doesn't air this-- A lot of the ARBs don't bind actually to ACE2, but other components of the angiotensin pathway, and they have anti-inflammatory effects. So, so I think we're on a steep learning curve about these class of drugs in terms of, of their effect, but we certainly should be evaluating them, especially now that we're starting to get mouse-adapted virus and maybe transgenic mice with the receptor. I think it's gonna be a high priority to look at some of these drugs.

    3. PAPeter Attia37:47

       Have you looked at all at camostat? It's a pretty esoteric drug. It's a serine protease inhibitor. I think it's only used in Japan to treat pancreatitis, but some of the preliminary work looks really interesting. It's a transmembrane protein, and it appears to interfere with the ability of-

    4. PHDr. Peter Hotez38:05

       The furin

    5. PAPeter Attia38:05

       ... the virus to gain entry. Actually, I think it sits right next to the ACE2 receptor and impairs binding.

    6. PHDr. Peter Hotez38:12

       Because there's a protease that's involved in SARS-CoV-2, and it's a, it's a subtilysin-like protease, which means it's a serine protease and known as, uh, furin, F-U-R-I-N. So I'm wondering if that molecule works by interfering with the furin. So that'll be a interesting story, and, and that's potentially a good drug target. So there was a paper that came out not too long ago about the furin from this, and it's relatively unique among the beta coronaviruses that this virus has it. And I can't remember if SARS1 has it as well or not.

11. 38:51 – 41:59

    Universal Coronavirus Vaccines and Hospital Transmission

    1. PAPeter Attia38:51

       The homology between SARS, the CoV1 and CoV2 is similar, but not enough that... I mean, there's enough commonality to them in the spike protein, isn't there? That if you had a effective target for one, you, you might have luck against others, which I guess is really less germane to the question today and more about the ongoing probability that these viruses aren't really going away, are they?

    2. PHDr. Peter Hotez39:13

       Yeah, and we're starting to think about what is the kind of vaccine that we want to develop. We have this SARS1 vaccine that looks great against SARS1, and we think it could be repurposed against SARS2. And then the question is, what should be the goal? Should we be focusing only on SARS2, or should we really start thinking about a universal SARS vaccine? And I think before SARS2 came along, we saw how all these other beta coronaviruses were emerging out of bats, and we wrote a grant to the NIH, and I don't know if that one even got scored, uh, was... But I think that's gonna be an important approach. I mean, we have to learn our lesson. Now, this is our third coronavirus pandemic in the twenty-first century, so we have to reconcile the fact that these are gonna come out on a regular basis.

    3. PAPeter Attia40:02

       Although technically, really, SARS and MERS probably weren't really constituted as pandemics, were they? I mean, they were probably closer to epidemics and, and this being a true pandemic potentially, yes?

    4. PHDr. Peter Hotez40:13

       I don't remember how they are classified. So SARS1, of course, emerged out of Southern China and, and severely affected Canada, so, uh, maybe it wasn't, uh, classified as a pandemic. And, and the MERS coronavirus emerged out of the Arabian Peninsula and then affected Korea, where it decimated hospitals in Korea, which brings us to the other point, as this is the modus operandi of coronaviruses. They tear through hospitals, causing a lot of death and destruction to hospital personnel. This is what they do. This was true of SARS1, it was true of MERS, and now it's looking like it's true of this one as well, that nosocomial transmission is a huge factor in this group of viruses. And, you know, if I were gonna design a vaccine, which we're doing in terms of the target product profile, I would say a highest priority are healthcare providers. So I think, again, to revisit this, I know we started the discussion on this, but to revisit it, unless we can deal with the healthcare provider issue and making hospitals safe places, we're gonna be in very deep trouble. So I think that has to be a national priority, and maybe the White House needs to create a specific task force around this, is what are we doing to protect our frontline healthcare providers? Is it the antibody therapy? Should we be looking at angiotensin receptor blockers? Should we be looking at other, the chloroquine for prophylactic purposes? If we can't fix this problem really quickly, I said on CNN, "It's lights out," but you know what I mean. I think there's just no way we'll be able to manage this epidemic.

12. 41:59 – 45:58

    Bioweapon Theory and Why the Virus Is So Dangerous

    1. PAPeter Attia41:59

       Speaking of designing, w-we touched on this very briefly, I think the first time we spoke, or maybe it was just on a time when we spoke, and it was not part of the podcast. But I've had discussions with some of the most intelligent people I know, and they've asked, not in a sort of conspiracy theory way, but they've asked, "Isn't it possible that this was a virus that was designed for biowarfare, that was either inadvertently got out of the lab or something?" I have my own logic for why I find that theory very, very implausible. What's your response to the implausibility or plausibility of that thesis?

    2. PHDr. Peter Hotez42:36

       Well- When the epidemic was unfolding in China and I started hearing these conspiracy theories, it was easy to debunk it. Who's gonna design a [laughs] you know, a bioweapon that's gonna kill Grandma and Grandpa? I mean, that's not, uh, an effective biowarfare strategy. But now that we're seeing-- Now I don't have that pat answer, not that it's an appropriate answer anyway, but now that we're seeing a number of young people affected, the plausibility goes up, but not by much. And I'd just like to say you don't have to. Why go in that direction when we already know Mother Nature is one of the best bioweapons producer there is? And, and we know that these viruses have been... It's not like we didn't know where these viruses were before. We've seen a whole family of these viruses that we actually call them SL viruses, SARS-like viruses in bats. And even before SARS-2, we were investigating our vaccine to see if it cross-protected against the various SARS-like viruses that were emerging out of bats, and, and it did sometimes, it didn't others. And so we knew that there was this whole family of bat coronaviruses that are emerging on a regular basis. So if you don't have to postulate a bioweapon, why do it when it's so obvious that we've got all of these viruses, the enzootic viruses that are circulating?

    3. PAPeter Attia44:07

       Yeah. I mean, my response was probably a little more theoretical, but it was the best bioengineers of the past two decades can barely get a crop to grow any better using GMO or insert gene vectors through genetic engineering into adenovirus. I mean, it's not like genetic engineering and GMO crops have been a robust success, and if that's the best and the brightest for 20 years, I don't know where they found the people that could make such a good virus.

    4. PHDr. Peter Hotez44:37

       I mean, let's, you know, first sort of being diabolical, let's think for a minute if you were designing a bioweapon, most bioweapons people would design SARS-1, right? A highly lethal virus. But we actually saw that even though it was a devastating disease in people who got it, if you were infected, you were sick pretty quickly, and you were going into the hospital, and you weren't walking around the community infecting others. So that's why I think SARS-1, uh, snuffed out pretty quickly. This one is really problematic because it's not as lethal as SARS-1, but it's number one. Number two, it's more transmissible, and number three, there is a large group of asymptomatic individuals, and that's, that's what creates a toxic mix for this virus because it quickly spreads throughout the community and infects-- It kills a small number of people, but still 5 to 20 times more than influenza. So it is that very toxic combination of not being the most lethal, not being the most transmissible, but high enough in both categories and all those asymptomatic individuals. So in some ways, it's hard to imagine one that's more diabolical. But I can't imagine anybody being that clever to think about designing it in that way.

13. 45:58 – 49:02

    Mail, Packages and Food Safety

    1. PAPeter Attia45:58

       Peter, you mentioned something on Twitter today that just assume that when your mail is delivered to your house, basically assume it's been delivered by someone who's carrying the infection, whether they realize it or not. What does that mean practically? What can we tell people who are, again, getting their Amazon packages, getting their mail, trying to limit their exposure? What actually can be done to dramatically reduce the risk of transmission through these fomites based on the study you just quoted from the New England Journal of Medicine that came out, I think, last Friday or this week, and other things we've learned just through the field of virology?

    2. PHDr. Peter Hotez46:34

       Well, we don't have a lot of data. My gut tells me that the risk is still pretty low. I mean, the things that I worry about, I just don't worry about getting the mail. So I-- right now I'm not doing anything. I think if you're concerned, you can certainly take a Clorox... Well, first of all, who gets mail anymore? I guess we get Amazon packages. So if you get your Amazon package, wipe it down with a Clorox wipe or one of the approved alcohol wipes. You could certainly do that. I don't see any, any harm in doing that. My sense is, what's your real risk? Your real risk is close personal contact with somebody with this virus. I still think that's probably the most likely mode of transmission.

    3. PAPeter Attia47:18

       What about food? A lot of people these days are in the process of ordering food. Now, whether that be if you live in a city like New York, you're doing takeout. What do we know about the temperature that is required to be confident you've killed the virus? And then what about when we were talking about groceries, things that are very difficult to wash, like lettuce or strawberries? Is this just a time to say, "Don't eat these things," or do we think that, "Hey, if you leave it out of the fridge for a couple of days, it's probably fine," although not that you'd want to eat your lettuce if it's been sitting out of the fridge for a couple of days?

    4. PHDr. Peter Hotez47:49

       Right now, I personally have not really been doing much with produce that's different from what we usually do. I mean, maybe wash it more with water. Has the CDC put out any guidance about that? I haven't even-

    5. PAPeter Attia48:03

       I have not seen it. Yeah, the only thing I've seen is from the WHO looking at SARS-CoV-1. They published some data on temperature, and again, that basically suggested that 56 degrees Celsius for 15 minutes was about required to kill that virus. And so you could extrapolate from that, hey, if you get your takeout and you at least heat it up, or if you're cooking food that you can't speak to how it's been handled or it hasn't been, you know, otherwise sitting in your freezer for a month, you want to make sure this is north of 140, 150 degrees Fahrenheit. For me, I just think it's the produce that strike me as a little bit more concerning, just because the virus is gonna survive a little bit longer in the cold based on the WHO report I saw. And again, maybe this is marginal. Maybe this doesn't matter compared to what you said a moment ago. Maybe just not being in close proximity to other people or people who are not inside your bubble is first, second, third order reduction strategy.

14. 49:02 – 55:42

    Mental Health Toll of Isolation

    1. PHDr. Peter Hotez49:02

       It also becomes a point, I mean, we're already living under such austerity measures as it is with the social isolation, gets to the point where we're gonna have such a huge percentage of the population having their mental health affected by this. I think there starts to be diminishing returns by doing this. So unless we get some clear guidance from the CDC or FDA saying, "This is what we found, and we're particularly concerned about that," at this point I'm not doing this, which gets to the whole mental health aspect. Uh, just the thought of people being in their houses day in and day out, and it's been great for my TV ratings, but quite honestly, I would not wanna be watching Peter Hotez day in and day out. It's such dreary news that I have to believe we're gonna start seeing some significant psychological impacts, and I'm worried about suicide rates. I'm worried about... And I hope we're looking out for that because especially if this drags on. So I think it's really important for the government to be a little more clear when they said it could be an 18-month pandemic, to specify this doesn't mean that you live like you're living right now for 18 months. I just don't think that's doable for a large population. So there's going to have to be some kind of assessment there, and I'm almost as worried about the mental health status of millions of Americans or people all over the world as I am the actual virus. And I'm starting to hear from colleagues and family members that it's already creating a lot of hardship. And also, people with certain categories, for instance, you know, I have a special needs adult daughter, and now she's-- her routine is totally halted now, and this is putting a huge amount of stress on her and then our family as well. So I would imagine people with special needs family members in the house are really struggling right now, and I don't think we're too consumed with the actual infection to even think about this. And should we as a nation start thinking about some kind of low-cost mental health activity? And I don't know what that would be, whether we create a network of providers, of mental health counselors who make themselves available, Mental Health Counselors Without Borders, something where people can... Maybe either it's for free or maybe just at some really low cost where they could Skype with somebody and have that discussion. I think that potentially could be a national priority as well, or have the academic health centers take this on.

    2. PAPeter Attia51:44

       I can't agree with you more, Peter. I've been commenting to my wife for the past few days that the days seem to be going by very quickly in isolation, but the overall time seems to be going very slowly, and the irritability within me is unbelievable. I mean, I'm not the most sanguine guy to begin with, but I think the lack of control, which is probably what every person on some level feels right now, I guess different people internalize that in different ways, but certainly in me it just comes out as incredible irritability, which may pose a greater long-term risk to my health than any coronavirus could.

    3. PHDr. Peter Hotez52:22

       Well, it's interesting. My reputation as being someone who never gets angry, never gets visibly upset, or seldom does, and within the last month at a lab meeting where I wasn't happy with the way things were going, I got pretty upset. And sort of a, an important meeting with colleagues, I also got very upset and reacted in a emotional way that afterwards I kind of sort of scared myself. I said, "Wow, I can't believe I did that," and sent an apology and, and I said, "What's going on here?" In my case, it's I'm not sleeping, and not sl- and not sleeping 'cause of the anxiety. I'm not sleeping 'cause we're trying to get this vaccine started through into clinical trials, and all the teleconferences and documents that we have to put together, and then all the media stuff, 'cause I'm doing a lot of early morning and oftentimes late night. And then when that happens, you're only getting three or four hours sleep, and you're doing that several days in a row. And but I think being given the opportunity by Fox News and CNN and MSNBC to talk to the country and explain things about this virus in a way that we're not necessarily hearing from our leaders, I think that's an important opportunity, so I'm doing it. But that in itself is stressful, also threading the needle, because all three of the cable news networks are fairly politically charged, and you're being asked provocative questions all the time about this and that, and trying to thread that needle to say things in a way that goes beyond the politics and really addresses the virus. So I think it is taking its toll. I'm sort of lucky because at least I have two really big activities that I'm doing that keep me occupied with my wife Anne, she's at home, and with Rachel, our special needs adult daughter. And I think and all she's got on all day is the cable news, which is so dreary, and I just imagine that happening millions of times over. This is not gonna be good for our country. And, and so one of the things I've started to do now, it's, it's a small thing, but I've been trying to, in my messaging, talking about the science, and a few times I've been doing this, I think I'm gonna be more of it, is, is to be upbeat about certain things, not to drift into the The happy talk that's not backed by data, but just talk about the fact that the United States has got this great history in times of adversity of taking on big audacious goals and, and building out new technologies for this virus is one of them, and that's where America shines is those big audacious goals and taking on complicated projects and coming out ahead at the end. I think those kinds of things I think we need to hear more about. And again, I-- it's not some people say, "Oh, does that mean you're gonna do, you're gonna do the happy talk thing?" I said, "No, I-- that's very different." I think it's, it's a realistic goal and to say that we don't have to be passive about this, simply just hunkering down in our apartments or our houses. There are-- we still can do great things, and there's probably better messages out there than just that, but I think it's gonna be important to hear more of that. But again, the psychological devastation on the United States I think is gonna be almost as big as the damage from the infection.

15. 55:42 – 1:06:26

    Reasons for Optimism and Closing

    1. PAPeter Attia55:42

       Well, on that, Peter, I wanted to... It's almost like you read my mind. I did wanna end with something sort of positive. What are you most optimistic about? I mean, we've spent a lot of time talking about things that concern us with respect to the burden on the healthcare system, the properties of the virus that make it especially troublesome if you're trying to fight it. But if you think about where we are today versus where we are a week ago even, what are you optimistic about? What's moving in the right direction? What trend do you see that you want to see continue?

    2. PHDr. Peter Hotez56:13

       There's a few things going from not very impressive sounding to more impressive things. I think just from a, not selfish side, but I think we're seeing scientists being put in higher esteem. We were trending the wrong way for a long time because of this anti-vaccine movement. But when you hear the esteem that people like Anthony Fauci have in the country because he is a scientist, I think that's kind of reassuring that in times of stress, people are looking to scientists for guidance, not only to solve problems, but also for leadership roles. And I think that could be a, a positive outcome of this. And people writing letters to our team of vaccine scientists trying to develop the vaccine. We just had this thing, I was very moved. There are vaccine scientists are still working through this, 'cause they have to, because they have to make this coronavirus vaccine. We just had a massive donation of Girl Scout cookies for the scientists, really showing that the community is out there behind us, so that for me was really positive. Also, science communication was already starting to trend in the right direction, but I think it's really taken off. The data sharing that's going on, putting things up on bioRxiv, on medRxiv, these preprint servers, has now become a routine form of science communication. It was already starting to take off, but now it's done regularly. And the fact that even the established journals like JAMA, New England Journal of Medicine, Lancet, are putting their stuff out there quickly in, in the public domain. If we keep doing this, it's gonna change the way we do science publishing. I often say our model of how we publish science was invented in the 1850s by the German scientific institutions, and it worked for a while, but believe it or not, communicating science according to the rules of 1850 Germany is probably no longer adequate. And, and I think we started to see this with SARS-1 and MERS and then Ebola, and I think it's gonna reach its full fruition through this epidemic. So the fact that scientists are being held in higher esteem, recognized as important people, the way scientific communication is done, I think... And the same is true of our physicians and nurses. I think the fact, the heroism we're seeing of physicians and nurses, and you saw those stories from Italy of the whole nation standing out in the balcony and cheering for physicians and the nurses and the healthcare professionals. I think there's maybe gonna be a new awakening of the humanity behind the medical profession that I think we're starting to hear, and, and it works both ways, not only just people standing up and cheering, but more and more doctors and nurses telling their story of sacrifice and knowing that when they go into work, saying goodbye to their kids or their significant others, knowing that they may have to be in a unique kind of quarantine after that, not knowing if they're going home or gonna get sick. I think people seeing the sacrifice that physicians and healthcare professionals and nurses make, stuff that we do every day that gets unnoticed, is now being noticed. So I think that's also gonna be a potentially very positive outcome of all this. I mean, the worry, of course, is out of sight, out of mind. We might have said some of that after SARS-1 and, and MERS. I said the whole vaccine infrastructure will change. We'll be able to change the whole vaccine ecosystem on the base of those epidemics, and really not all that much happened. A few things happened, but not much. I always think maybe this will be the one that will happen. In terms of more immediate successes that you might see, what can we look for for things that are gonna work? The one thing that I saw was last Sunday morning when Andrew Cuomo, Governor Cuomo, wrote that, what I thought was a very courageous op-ed piece in The New York Times, saying what was on my mind for a while, but I didn't want to say it, and he just said it. We're gonna need to bring in the Army Corps of Engineers, and I think that was an important piece to this, recognizing that we may need to bring in our military and maybe sooner rather than later. So we're already hearing about National Guard units being called up. I think we're going to need our military to build temporary hospitals and facilities. Maybe some of the human capital we're going to need for this is going to become an important piece to this as well.

    3. PAPeter Attia1:01:04

       Well, Peter, on that note, we've gone a little over the time I know we both set aside for this, and we've got a lot to get done even though we're sort of late in the day. But I want to thank you again for, for the time and obviously for the hat you're wearing, which is sort of being one of the important faces of this in the public. I do think it's important that people have sort of credible information, and you're speaking to a lot of people, not just to the public, but also to policymakers. For what it's worth, I'm a little bit more optimistic this week than I was last week in terms of the seriousness with which this is being taken, especially inside government based on a number of personal discussions and some secondhand discussions. So I guess that's the thing I'm personally most optimistic about.

    4. PHDr. Peter Hotez1:01:48

       I mean, there are some people on the federal side who've definitely been doing this, and people like Deborah Birx have been good, and Tony, of course, is always great, and Brett Giroir is not a household name, but he's Assistant Secretary of Health and was with us for a while here in Texas, and he's been the one assigned to finally ramp up the testing, and he's been doing that, I think, been doing a great job. To me, I think the profile that Governor Cuomo's had is the one that really woke us up and who got on, has been getting on there every day and saying, "What the hell's going on? Where are my respirators? Where are my beds? These are the projections. These are what we're going to need. This is what's going to happen to our hospitals and being overrun." So I give a lot of courage points to the governor in New York on that front.

    5. PAPeter Attia1:02:37

       All right, Peter. Well, thank you very much. I want to let you get back to work, and I know we'll be in touch again soon, and we'll pick it up then.

    6. PHDr. Peter Hotez1:02:45

       Yeah, I think what impresses me about our discussion today is how different it was compared to a week ago and shows you how quickly this thing is moving, and so always happy to do this again at some point. We'll see how this thing continues to change because I said it last week, I'll say it again this week, the stuff we're saying today may look totally ridiculous in a few days or a week because this thing is moving so fast. These virus pandemics, emerging threats set you up to make you look bad, and they do that with our federal leaders and our state leaders and even doctors and scientists that go on TV, so you continue to need to refresh.

    7. PAPeter Attia1:03:23

       Yeah, I hope they make us look bad by saying we over-responded than we under-responded.

    8. PHDr. Peter Hotez1:03:29

       I'll say amen to that.

    9. PAPeter Attia1:03:30

       [chuckles] All right. Good night, Peter.

    10. PHDr. Peter Hotez1:03:33

        Thanks again. All the best.

    11. PAPeter Attia1:03:36

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Episode duration: 1:06:26