#106-Amesh Adalja, MD: COVID-19 vs. past pandemics, preparing for the future, & reasons for optimism

1. 0:00 – 0:11

   Intro

   1. PAPeter Attia0:01

      [upbeat music]

2. 0:11 – 4:04

   Introduction and Dr. Adalja's Pandemic Preparedness Background

   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 special episode of the COVID-19 series of The Drive. Joining me today is Dr. Amesh Adalja. Amesh is a senior scholar at the Johns Hopkins Center for Health Security. He has long been focused on pandemic preparedness and emerging work on infectious disease, biosecurity, et cetera, for many years, long before this coronavirus entered our consciousness. I wanted to talk with Amesh for a couple of reasons. One, I'd heard him on other interviews, particularly the one with Sam Harris. Also, I'd seen him in interviews, read some of his work, and just found him to be a very thoughtful guy who could put the coronavirus pandemic in the context of all the previous pandemics, and not just the ones that are immediately in our recollective, uh, memories, such as SARS, MERS, H1N1, but even going back a little bit further than that. This is a very brief discussion. He was, uh, incredibly busy. We were very fortunate to get forty minutes of his time between other interviews. But we do cover quite a bit of ground, and certainly everything I was hoping to speak with, which is a bit of a, a more clear history of when this virus likely emerged, how it came here, and what we know about it relative to other coronaviruses. We talk a lot about what the plan forward should be, and we end with really what he is most optimistic about. So though this interview is relatively short for the standards of interviews that I do, like I said, it's about forty minutes, I think we cover a lot, and there's no question I would like to have Amesh back. I do think it is really just an inevitability that we will once again face a, a pandemic, and whether it's a coronavirus or another virus is probably less the point here. But, but unquestionably, um, there are things that we could do better the next time we're faced with this. So without further delay, please enjoy my conversation with Dr. Amesh Adalja. [upbeat music] Amesh, thank you so much for making time to speak this afternoon. I know you're incredibly busy, and we were lucky to sort of catch you in between interviews and television appearances, so thanks very much. I'll just sort of jump right to it. I reached out to you because I was very interested in your perspective on the historical similarities and differences between this pandemic and previous ones. Maybe just briefly tell us a little bit about your background and, and why it is that you're not just someone who came to be interested in this in the past three months.

   2. AADr. Amesh Adalja3:14

      So I'm an infectious disease emergency medicine and critical care physician who's focused his entire career basically on the issue of pandemic preparedness, pandemic prediction, infectious disease and national security, emerging infectious disease. You know, even from the time when I was a trainee, that's basically all I focused. And I work at a think tank that's devoted to this issue, and I've been there basically full-time since twenty ten or so, but had been there since two thousand eight working on this. I published on pandemic prediction, on what the characteristics of certain pathogens that cause pandemics would be, uh, H, on H1N1, on Ebola, on agents of bioterrorism. So I've really focused and tried to niche myself into this aspect of infectious disease and medicine. So this is an outbreak that had been on my radar before it hit headlines, and I've been following it almost the way people follow sports teams that they like.

3. 4:04 – 5:46

   First Impressions in December: Human-to-Human Spread

   1. PAPeter Attia4:04

      Tell me a little bit about what you thought in, call it December, when we, at least in the West, saw the first report of the case in China. What was your intuition at the time?

   2. AADr. Amesh Adalja4:13

      At that time, I was trying to take what the Chinese were saying at face value, meaning that they had learned from the lessons of SARS about transparency and were going to do this in a different manner. And they did produce the virus sequence very quickly that allowed diagnostic tests and vaccine development to start, and we were able to identify novel coronavirus. But initially, a lot of the reports were saying this is something that was animal to human, really tied to wet markets in Wuhan, that there wasn't evidence of human to human spread. There were no deaths yet. But I did think that forty-one patients getting something from one animal at one market really seemed very odd to me, that that seemed to be too much. So I was a little bit skeptical that this was just an animal to human event unless there was something different going on or there were multiple animals that, that were infected that infected multiple people. But as soon as I saw the first paper, and that was The Lancet paper, where they showed the first case got ill on December first and he had no contact with the market, that told me that we were dealing with a transmissible human to human respiratory virus and that this was going to be a pathogen that was going to spread and not be containable, and that we were going to have to get ready. I had a lot of questions about the case fatality ratio, the hospitalization rate, which I still have, but I knew at that point when you had a virus that spreads efficiently between human to humans through the respiratory route, you really have to prepare for this being everywhere, especially when you know that this had a head start at least spreading since mid-November in China, and nobody knew about it until late December. So that gave a virus a very big head start and could have been anywhere by the time we actually knew it was-- uh, as soon as we discovered that it actually existed.

4. 5:46 – 6:49

   Was the Virus in the US Before 2020?

   1. PAPeter Attia5:46

      Based on that, do you think it's possible that this virus was in the United States, potentially even within an individual prior to December thirty-first?

   2. AADr. Amesh Adalja5:55

      This is a little bit of a controversy. I do know that with past novel coronaviruses that have been discovered, like HKU1, which isn't one that people think about, but it is one that was discovered post SARS, it was everywhere as soon as they found it. This one, it doesn't appear that at least that there wasn't widespread presence of it before maybe January. However, I don't rule out the possibility that it could have been mixed in our flu and cold season, maybe a sporadic case here or there that was mild that didn't get diagnosed. But it doesn't appear, at least from the phylogenetics, the genetics of the virus that we're seeing from both New York and, and Washington, that this was around before that. But I do think it's gonna be important to go back and look at bank samples and look at people to see if there were cases. I don't think there were a lot of them. I think we would have noticed if there were a lot of them, but I think there may have been sporadic cases that were mixed into flu and cold season. But it's an open question, and I think it's a good hypothesis, and I think it's something that deserves a lot more attention.

5. 6:49 – 8:11

   Why Containment Failed in the US

   1. PAPeter Attia6:49

      At what point, Amesh, were you becoming convinced that this was going to enter the US in a manner that was going to pose real difficulty for the country?

   2. AADr. Amesh Adalja6:58

      So I knew it was gonna enter the United States almost from the onset, as soon as we knew that this was transmitting between human to human, that this wasn't gonna be containable, just like when H1N1 appeared in 2009 and was found in Mexico, that we knew that this wasn't going to be something that would spare the United States. What I wasn't quite attuned to was how difficult it would be to contain in the United States because I, like many of us, believe that our diagnostic testing and our case finding and our contact tracing would have been really much better than it was. But the fact was we didn't know who had this, who didn't have it. Our testing made it much harder to actually do that, and we weren't even testing mild cases, and those mild cases are arguably more contagious than the severe cases. So that let this slip from something that was potentially controllable and wouldn't have been a problem or a major problem, not putting cities like New York City under the stress that they're under, to one that became completely unmanageable because we basically were allowing this virus to have about two months of unabated spread in the United States. And that's something that most of us did not think would happen because we thought that we were much more resilient to these types of infections than we really were. And I think that's-- it didn't have to be that way, but that's basically how it turned out.

6. 8:11 – 12:03

   Lessons from Past Flu Pandemics and the Avian Flu Threat

   1. PAPeter Attia8:11

      When you go back and look at the history of not just the other coronaviruses, which have gotten a lot of airtime lately, of course, most people, even if they don't remember the ins and outs of SARS and MERS, they're certainly familiar enough. But when you go back even further and look at some of the, the flus that occurred in Asia, Hong Kong in the 1950s, '60s, and of course, going back even further to the Spanish flu of 1918 to 1920, what are some of the similarities that you see with this novel coronavirus? Then, of course, I'll contrast that in a moment with what the differences are. And the point of this exercise is less about just abstract history, but more to understand what we can learn.

   2. AADr. Amesh Adalja8:53

      Sure. So if you go back to 1957 and 1968, these were pandemics that were marked by the emergence of a novel flu virus that spread around, around the world very rapidly. And if you look at the United States experience with that, 1957 and 1968, about 100,000 people died from that, which is a substantial number because on record right now, the, the worst flu season we've had outside of '57 and '68 has really been 2017 to 2018, where about 80,000 people or so may have died. So these were severe outbreaks, and, and flu has a lot of similarities with coronavirus, but there are some differences. So one thing is they both are transmitted through the respiratory route. They both have symptoms that are included coughing and sneezing and sore throat and muscle aches and pains and fever. So they have a lot of overlap clinically. And I think that because of the way they spread and their symptoms, you can look at their spread and there's a, a lot of analogies that you can draw. But what I would say is with flu is sometimes it's difficult because people have already taken flu and put it into their own risk of daily life, that they know that there's gonna be maybe 30,000 to 50,000, 60,000 people who die every year. So even during a pandemic like 1957 and 1968, most people still carried on because this was still a flu virus. And the same thing happened to an extent with 2009 H1N1, especially when we realized that its case fatality ratio was actually less than seasonal flu. Even though it infected 61 million Americans, led to a lot of hospitalizations, and put hospitals into distress, it wasn't that deadly, so people kind of took it in stride. This is something that's a little bit different because it's on top of flu. It's additive to flu. I think that's one of my pet peeves of the media coverage is sometimes they try to compare it to flu, but remember that we were already going to have 40,000 to 50,000 deaths from flu, and this is on top of that. I do think that influenza gets a short shrift by people because it's something that they take for granted and don't realize the burden of infection that it has, and that influenza still, even today, remains the biggest pandemic threat that we face. If you think about, about some of the influenza viruses like avian influenza, they have case fatality ratios of about 65%. That's too much for the world to bear. So if one of those, like H7N9, became able to efficiently transmit from humans, that's a totally different type of pandemic that we're talking about than what we're dealing with today. And I think that's important, and maybe that's why I seem a little bit more optimistic than most people or a little bit more measured when I'm talking about this, because in my mind, I'm thinking about avian influenza and what that kind of a pandemic would represent. And I used to say that this is kind of a trial run because it's only, it's less than 1% case fatality rate, maybe as low as 0.3 case fatality rate. But we didn't do that great of a job with it in terms of diagnostic testing and hospital capacity and personal protective equipment. So that's magnified this, and that's the human factor that's magnified what the virus could do, and I think that's an important point to make. And that's how I would kind of leave it, is it that you have certain ways to think about this using flu as an analogy, but I do think that I'm a little more worried about our pandemic resiliency based on how badly we've handled a 1% case fatality rate pandemic virus, where you've got cascading decisions by governors in states and countries all around the world that really have magnified the damage that the virus has done.

7. 12:03 – 15:22

   Waves, Seasonality, and a Fifth Seasonal Coronavirus

   1. PAPeter Attia12:03

      One other question I want to ask before we leave the historical, which is the sort of ebbing and flowing recurrences that occurred back in some of these other pandemics where it's easy to sort of think of them as this was the impact on the United States, but not realizing, well, actually it had a different impact on this city versus that city, and they were not just different In terms of the strain they put, put on the healthcare system or even the mortality rate, but even temporally they could be separated by quite a period of time. Is that something that also applies here, in your opinion?

   2. AADr. Amesh Adalja12:35

      I do think so. I-- We have this tendency to think of a pandemic as a homogenous wave over the whole world or even a country, but it's actually many small outbreaks together, and everybody's on a different timescale based upon when the virus was introduced into that area, what their population density is, what their hospital capacity is, what demographic got infected. So you aren't going to see synchronous outbreaks. They're going to be a little bit staggered, and there's gonna be differences on, for example, when did somebody do social distancing, when did someone not do social distancing, how do they vary between this state and that state. That's also going to impact the trajectory of the outbreak. You might see places, like I'm sitting here in Pittsburgh right now, which hasn't had a bad experience with this virus yet, but we've had the opportunity to learn from New York and Seattle and San Francisco, and that's gauged the way that we've dealt with testing and hospital capacity. So our outbreak is gonna be different because we've learned from them, and we don't have the population density issue. So I do think there is gonna be ebbing and flowing, especially with social distancing varying and maybe lifting in certain places of the country and not lifting in other places, and you may find that this virus is going to have some degree of seasonality. I don't think it will have complete full seasonality because there's so many people that are susceptible to it, but you may see this come back in successive waves. And remember, there are four other coronaviruses that circulate every year and cause about twenty-five percent of our colds. This is something that I suspect will be w- the fifth one that does that, and it looks like it has an intermediate severity. It's not as severe as SARS, for example, which has a case fatality ratio of about ten percent, but it doesn't seem to be as mild as the other four coronaviruses. So I do think you're gonna see ebbing and flowing, especially as social distancing changes across the country, until we have a vaccine.

   3. PAPeter Attia14:13

      And is it your view that this will now be a fifth coronavirus that will fit into the mix, and it's never really going to go away in the way that at least SARS and MERS, because of their severity, they don't really factor into that recurrent cycle we see every year?

   4. AADr. Amesh Adalja14:29

      I do think this is gonna be the fifth seasonal coronavirus, and I would say with SARS and MERS, it's not just that they were more severe, which they are, it's that they're poorly transmissible from human to human. They are mostly zoonotic or meaning animal-to-human transmission, so SARS from p- palm civet cats, Middle East Respiratory Syndrome, or MERS, from camels. So that's something that's really limited th-their spread. It's only those individuals who are in contact with those animals that are really at risk. And when you look at their outbreaks, they're very specialized. They're happening in healthcare facilities with poor infection control, and it doesn't really sustain itself in the human population. Whereas if you look at the other four coronaviruses, the ones that cause common colds, they are ubiquitous. They transmit very easy. They have a mild spectrum of illness, which allows people to go about their daily life and spread. And this new novel coronavirus does appear to be more like them in terms of their transmissibility, so that's why I think that this will be a, the fifth seasonal coronavirus until there's a vaccine.

8. 15:22 – 16:27

   Prospects for a Coronavirus Vaccine

   1. PAPeter Attia15:22

      Do you think a vaccine is going to be specific to this coronavirus, or do you think that it will be more geared towards all coronaviruses to cover not just this one, but perhaps others that will potentially emerge, you know, a SARS-CoV-3 that's five years away?

   2. AADr. Amesh Adalja15:40

      Right now, vaccine development is premised on making something specific to the s- the specific immunogenic protein that the immune system recognizes for this virus. So it will be specific to that, but I do suspect you might see some cross-reactivity between the vaccine for this SARS-CoV-2 and other related coronaviruses. Maybe the SARS-CoV-2 clusters in something called the beta coronaviruses. Maybe the vaccine will work against all beta coronaviruses, but it would be great if it worked against all coronaviruses, and we had a pan-coronavirus vaccine. We might get something like that because coronaviruses are different than, for example, influenza, which has been very hard to make a universal flu vaccine. The coronaviruses, in general, tend to be much more stable, even though there's some diversity among them, and we might have cross-protection, which would be useful to take other threats like Middle East Respiratory Syndrome and the original SARS off the table as well.

9. 16:27 – 18:20

   Estimating the True Case Fatality Rate

   1. PAPeter Attia16:27

      When H1N1 hit, you sort of alluded to this briefly, the case fatality rate was initially deemed to be much higher. It was only once we appreciated how prevalent it was that the case fatality rate came so far down. I, I believe in the end it's less than point one percent, correct?

   2. AADr. Amesh Adalja16:43

      Yes. Yeah, definitely.

   3. PAPeter Attia16:44

      What is your real assessment now, and again, this is, you can only be speculating at this point, I understand, but what do you think is the true case fatality rate of SARS-CoV-2 specifically? And if you wanna answer that, by the way, in terms of, "I think that the CFR is gonna be this for people over sixty and this for people under sixty, and it blends out to this," I mean, answer it any way you see fit.

   4. AADr. Amesh Adalja17:07

      So the CFR has been really hard to calculate because we have a severity bias because testing has been so heterogeneous around countries. So what I do is try to look at a place that's tested extensively and use that as kind of a barometer. And right now, it used to be South Korea that tested, and now it seems to be Germany is doing the best testing, and you're also looking at modeling studies. So some of the modeling studies from Imperial College put the case fatality ratio at zero point six six percent. Germany looks like it's at a zero point three something percent.

   5. PAPeter Attia17:34

      Yeah, I think zero point three seven this morning, yeah.

   6. AADr. Amesh Adalja17:37

      Yeah, doing antibody testing to try and understand. So I do think it's probably in that range, probably in the zero point three to zero point six six. I say that with some confidence, but it may drift lower or higher depending upon how much severity bias is in the samples, and it's very hard. We probably won't truly know until we do retrospective studies looking at antibodies to understand how prevalent it is. And there's differences amongst that because that's an average number. If you're above eighty, your case fatality ratio may be as high as fifteen percent. If you're eight years old, your case fatality ratio may be zero percent. So I think it's important to remember that these are average numbers, and it's not every person carries that risk. Some people will have much, much higher risks, and some people will have lower risks, and I think that's sometimes lost in the nuance when you try to come up with one number.

10. 18:20 – 22:27

    Critiquing Early Epidemic Models

    1. PAPeter Attia18:20

       Absolutely, yeah. Blending that is... You know, there's lots of glib examples of how you can drown in an average of three inches of water, of course, if you're walking across a river that has vacillating depth. Because you're, again, kind of a veteran of this, what do you think was sort of the Over/underdoing of some of the predictions that came out in the sort of gen one models that showed up in sort of February where they were saying, "Look, this is something that is going to infect 200 million Americans. It's going to kill two to four million Americans." Do you think that that type of modeling historically has ever shown to be accurate? Or do you think that, yes, that was accurate, and it's the measures that are in place that are going to hopefully prevent that from happening? Because I... It seems less likely now that we're heading in the direction of those types of doomsday scenarios. But again, it's hard to know how much of that is in response to the measures that have been enacted versus predictions that were predicated on poorly understood things, including what the R0 was.

    2. AADr. Amesh Adalja19:28

       I think that models, you have to realize, have assumptions built into them, and you have to look at those assumptions because just a small difference in the assumption can lead to a big change on the end of it. And what I would think, at least from my understanding of many of the models, is that the hospitalization rate was probably overstated. Because we know, for example, that the diagnosis that we're talking about in any given city or town are likely understated by a factor of at least maybe 10, and I can say that from my own practice when I order the test and don't order the test. There's many patients I think have the disease, and I don't order the test. So there clearly is a severity bias in who gets tested. And then I think you see this idea of 15 to 20% getting admitted to the hospital. I think that that doesn't necessarily mean everybody, of the people that get infected, maybe that's 40% of the population over time, that 15 to 20% of those individuals get admitted. It's more like of the 40% of the population that get infected, the ones who go to an emergency department, 15 to 20% get admitted. And maybe the real hospitalization rate is 5%. If you look at, for example, Westchester County's data, which I haven't looked at lately, but the last time I looked, they did a lot of heavy testing in, in that part of New York State because they had that outbreak in New Rochelle, and their hospitalization rate was around 5%, a little bit less than 5% the last time I calculated it. And that changes, that gives you a major change from going down from 20% to 5% in terms of what your ventilator needs are, what your ICU bed capacity needs are, and what the case fatality ratio is going to be if you look at what the hospitalization rate is. And I think that that's at least one of my criticisms of some of the models, the hospitalization rate was set too high, and that they were taking too big of a fraction using the wrong denominator, I think, to come up with what their case fatality ratios are, what their ICU bed needs would be, and what their mechanical ventilation needs would be. And that happens because models have lots of assumption in them, and they should be used as tools. They're not ironclad, and I think that sometimes that gets lost in the press reporting of them. They get looked at as if they are the truth, and they need to be revised. And when you have real data from real hospitals and real people, it should supplant what you're using with a model. So if your model's not matching reality, then I think you need to either change the assumptions on the model or actually look at reality. These are tools, and all models are going to be wrong. Some of them are going to be useful, and some of them are not going to be useful.

    3. PAPeter Attia21:47

       I agree. I think it's, unfortunately, the press sometimes views corrections of models as a sign of weakness as opposed to a necessary part of the evolution of utilizing the tool as you described it. We've talked a little bit about this being a dress rehearsal for what is coming unquestionably at some point, very likely in our lifetimes, which is another pandemic, another virus, and potentially one that could be much more devastating. You used an example of viruses that are typically transmitted only from animals to humans that can potentially be much more catastrophic. But if those viruses ever figure out how to go human to human, they spread much more.

11. 22:27 – 27:32

    Federal vs. Local Roles and the Testing Failures

    1. PAPeter Attia22:27

       What is your view on the role of local versus central government in dealing with that? Can't imagine there isn't a role for both, but I feel personally very confused when I try to... You sometimes play the game, "If I were czar for a day, what would I do different?" But the reality of it is it's easy to play armchair quarterback. I'm not really sure I know what the federal government should be doing in this situation versus the state governments and local governments.

    2. AADr. Amesh Adalja22:57

       So this is something that's pretty unique to the United States because we have a system of, of a federal government with states and locals having most of the power, and it's especially true in public health because most of the public health powers are vested at the local and state level, and the federal government is more of a coordinator. Even the CDC can't actually get involved in something unless they're asked by a state. So you will often see differences and heterogeneity between recommendations from maybe one county to the next or even, and definitely from one state to the next. And sometimes that can be confusing. I do think that I'm generally supportive of local health departments being the ones running it because they actually know their community, they know their capacities, they know where their gaps are, and they're able to really be on the ground with the people and able to do great things when it comes to stopping an outbreak. But often what we find is local health departments aren't appropriately resourced, and you've got one person doing four different roles in a small town's health department, and that can be very constraining. And what you need to really do is have those local health departments actually operating the way that they should be and thought of as part of the whole pandemic response apparatus, whereas many people think of just the CDC, the NIH, and parts of the Health and Human Services Department as the main pandemic apparatus. But it's actually the local health departments that do all that case finding and, and isolation and, and talk to the public and deal with hospital capacity levels. It's the local health department. So I can't overstate how important local health departments are. And I do think that that system works well, but you do need to have federal leadership to kind of guide the nation as a whole on what to expect and what's going on. And I think that's sort of been missing a lot during this outbreak compared to other outbreaks. And you've, because of that, you've seen governors At state health departments take on roles that they usually haven't taken, where they've deferred much more to federal experts. Not the powers, but the guidance and, and looking to them to set the tone. And I think now we're finding governors basically stepping into that role for the most part, and even mayors in some places. And I think that can be confusing to a member of the general public because they don't know who to believe, especially if there's conflicting information. You have a press that's constantly trying to pit one governor against another governor or against the federal government, and that makes it much harder. But I do think that when the process works well with local, state, and federal government all in step, all doing the appropriate roles, I do think it works pretty well. You have a locally managed, federally coordinated response, which I think is the best way to think about how it would be ideally done.

    3. PAPeter Attia25:17

       Is it safe to say that testing is really something that, like, if you go back in time and maybe change one thing, if we're sitting here and it's January 12th and we now have the sequence of this virus, would that have potentially been one of the more important things for the federal government, for that centralized piece of government to have put in place? The CDC could have said, "Look, we're gonna make this the highest priority." Because it strikes me as that's something very difficult to be done in a decentralized manner.

    4. AADr. Amesh Adalja25:44

       Right. So what happened was the CDC put out guidance on who should be tested, which basically was taken as gospel by the state health departments, and that included only people that had traveled to China in the last 14 days, as well as someone had had to have lower respiratory tract symptoms. You couldn't have just had a sore throat. You had to have evidence that maybe you had pneumonia to be tested. So we weren't testing mild cases, and we weren't testing people that hadn't come to China. That was a federal decision, and I think that could have been done better and allowed much more latitude. 'Cause you can remember that first case in California that didn't have travel to China, they, the hospital had to actually fight to get that test run, and there were many cases like that all over the country. And if you look at New York's epidemiology, their introduction of the virus was not from China. It was from Europe, and that slips through the type of testing algorithm. So I do think that there could have been at the beginning an idea that somebody could have said, "This is a respiratory virus. It has many overlapping symptoms with common colds and flus. You should think about this in your patients, and we are going to allow testing to be done if you have certain risk factors for this, and they shouldn't just be restricted to you having severe disease or having traveled to China." That would have changed the way that the general public and clinicians would have thought about this. The other thing is, is that there were bureaucratic wrangles that paradoxically, once a public health emergency was declared, they were unable to make diagnostic tests as freely available as would have been if there wasn't a public health emergency made. So, for example, you had university labs and big commercial labs not being able to make a test. Even the CDC's test had to go through FDA emergency use authorization before it could be distributed to the states. So there were a lot of bureaucratic hiccups that created a problem that compounded the testing protocol with the scarcity of tests and a delay in getting testing kits everywhere. And then we still have shortages of reagents and nasal swabs, and we're still not to where we need to be with testing.

12. 27:32 – 30:23

    Will Pandemic Preparedness Be Remembered?

    1. PAPeter Attia27:32

       And not to get too far ahead of ourselves, but do you get the impression that the response to this is serious enough that it will now be taken more seriously to have kind of that type of emergency response ready five years from now when people have long forgotten about this?

    2. AADr. Amesh Adalja27:49

       I hope so. I think this is something that's going to leave a mark on society. This hasn't happened in modern times, not during the '68 or '57 pandemics. And it did happen in 1918, but that's not in anybody's living memory anymore. So I do think that this is something that people will remember, and they will remember the cost that they personally had to incur, filing for unemployment for the first time. All of that type of stuff is gonna hopefully push the public to demand that pandemic preparedness be taken seriously so this doesn't happen again, and that this should be a priority. This should be something that's in, in a candidate's campaign literature. "This is what I think about pandemic preparedness," and it always should have been. But we've gone through this cycle for a long, long time. You can think about anthrax in 2001, bird flu scares in 2005, the H1N1 pandemic in 2009, Ebola in 2013, 2014, Zika right after that. We've had multiple types of episodes, and you get this cycle where everybody runs to fund this reactively, and then it goes from the, it disappears from the headlines and no one remembers it, and then the same cycle happens. They cut positions at the National Security Council when there's nothing going on. They do lots of things that make us less resilient to pandemics, not realizing that this is a perpetual threat, just like any other national security concern, that you have to be prepared for this at all times, and you have to actually think about it that way and fund it that way and have the proper personnel, even between pandemics and between outbreaks.

    3. PAPeter Attia29:09

       But you are optimistic that this time, I mean, just based on the economic consequences of this, even if not one more person were to die in the United States, which means, frankly, let's be clear, if not one more person died in the United States as of today, this would not be a major source of mortality. This would still be a rounding error compared to influenza. But you're just saying the economic consequences of this have been so severe that you're optimistic that we're not gonna walk away from this one in 18 months and sort of forget about it and do all the wrong stuff all over again.

    4. AADr. Amesh Adalja29:40

       Yeah, I do suspect we're gonna have m- many more deaths, probably closer to that 60,000. I do think that the fact that this outbreak touched people personally in a way that Ebola did not, the way that Zika did not, the way even that H1N1 did not. H1N1 actually engendered complacency because only about 12,000 Americans died, and then people said we ov- all overreacted to H1N1. So I think this is actually something that every American is feeling right now because of the economic shutdown, the stay-at-home orders, all of that, the fact that they had to adjust their entire life. This is something that's been extremely disruptive, and I think that hopefully the public remembers that when they vote and when they ask their policymakers about what their plans are for the future, that pandemic preparedness becomes something that is a platform issue now.

13. 30:23 – 34:11

    Reopening Strategy and the Risk of Mass Gatherings

    1. PAPeter Attia30:23

       Based on where we are, what do you think is the right strategy in, for example, a place like New York versus a place like, you could pick any city you like, whether it be Pittsburgh, Houston, you know, cities where it's been nowhere near that? I mean, how would you start to think about changing any of the policy, or is the answer, until we have more testing, we can't make any more decisions?

    2. AADr. Amesh Adalja30:47

       I do think based on modeling, if you, if these symptoms are valid and what's going on in the ground in hospitals, you can start to see this heterogeneity across the country, and not every place is going to be New York City. Not every place has that population density or hospitals that are at the brink all the time. So I do think that there are places where you can start to think about relaxing some of the social distancing recommendations as well as the economic shutdowns, especially things like elective surgeries at hospitals and opening clinics at hospitals. I think that already needs to happen, especially so in places where they're not inundated because you're going to get other health consequences that are not captured by the models, which are really measurable and we'll pay for down the road. I do think you can look right now at the governor's lists of what is an essential or a life-sustaining business and what is not, and look at who they're granting exemptions to and try to be a little bit broader about that. Think about looking to see what your school system is like, and can you open schools in a safe manner right now based on what the conditions are in your area because even the whole closure of schools was very controversial and not supported by everybody in my field. So there are things that you can do, and I do think it's not going to be one size fits all. It's gonna be dependent on what's going on locally, how much transmission do you have, what is the antibody status of your population, what's your hospital capacity, and what is your ability to do diagnostic testing? Do you have the new rapid test available in many different places? All of that can help condition how we get back to normal or a new normal because I do think that things like mass gatherings are gonna be very hard to have for some time until we have a vaccine because I think a mass gathering is kind of can put a, a town over the edge if they get multiple episodes of transmission at a mass gathering. But I do think that we can start taking steps, and I hope that we start doing it because this cost is something that is measurable, and it increases every day. And I do think that there are going to be consequences that are not captured by our models, which are really only focused on coronavirus.

    3. PAPeter Attia32:36

       Yeah. It's an interesting point you raised there with respect to mass gatherings. I mean, I think the German data, which just came out basically last night, would suggest that it's really the mass gatherings that are disproportionately driving the spread versus two people having dinner at a restaurant. Is it your view that there's really something quite devastating about concerts and live sporting events that is not necessarily captured in going to the grocery store?

    4. AADr. Amesh Adalja33:03

       Yeah. A, a mass gathering brings people from wide geographic areas. If you think about I live in Pittsburgh, and there are Steeler fans that come from everywhere in the country to watch a Steeler game, and then they go back to their hometowns. That's a way you can disperse things. And sporting games are not people sitting quietly with just one person. They are social gatherings where people are yelling and screaming and eating and drinking and all types of things that a virus would look at as an easy way to get from one person to another. We know that when people shout and scream, they make particles come out of their mouth. That can transmit. We've seen this at choir practice, for example, with this coronavirus. Just think of that inside a football stadium, and you can imagine how these types of things can transmit. I do think that mass gatherings, because of the density, because of the fact that people come from different geographic regions and then dis- disperse, are a particular problem when it comes to communicable infectious diseases. And we see this every year with, for example, religious pilgrimages to Saudi Arabia, where they make sure that you have this type of vaccination. They have a whole division of the World Health Organization devoted to mass gatherings because we know what their role is in spreading infectious diseases, and I think that's gonna be something that's going to be a challenge to have until there is a vaccine.

14. 34:11 – 39:19

    HKU1, Sweden's Experiment, and Masks

    1. PAPeter Attia34:11

       And I wanna go back to something you said about HKU1. Tell folks a little bit more about that coronavirus and the concern it gives you.

    2. AADr. Amesh Adalja34:18

       It's less of a concern that it gives me now, but it's more of understanding what happens with coronaviruses. So go back to two thousand three, and SARS is the first coronavirus that really hits the map as a pandemic threat before they're thought of as common cold viruses. Now everyone's on the lookout for any new coronavirus. And what they do is they, in Hong Kong, HKU stands for Hong Kong University, they find a novel coronavirus in some individuals that had pneumonia. When they start looking, they find more. They actually look at bank samples that were negative for SARS, positive for HKU. They look in other countries. They find HKU1. They actually find it in Cleveland. In the proportion of patients that were hospitalized for coronavirus, HKU is disproportionately found even in patients who died or were on ventilators, and it was basically everywhere you looked. That's interesting because it kind of flew under the radar because no one knew it was there because we do such a poor job at testing for respiratory viruses. Many times people go to the doctor, and they say, "Oh, you've got some virus. We don't know which one, but you're gonna get better." And that's even the case for pneumonias because most people don't get a specific microbiologic diagnosis of their pneumonia. So we really have this biological dark matter everywhere. And I initially thought maybe this coronavirus was around hidden in our cold and flu season. It clearly was hidden in China's cold and flu season since at least November. But it doesn't appear, at least from what I've seen now, that there was much burden of that in the United States prior to twenty twenty, that this might have been something that really only began in earnest in January. But I would not be surprised if you find a bank sample that there were cases in December that were mixed in just like with HKU1. But I do think we would have noticed if there was a lot of these people getting really ill and ending up on ventilators and were flu negative and not negative, and negative for everything else. Somebody, at least enough of them would have raised some alarm bells, I would hope. But I do think that's an important lesson to think about with a virus that can spread surreptitiously, and you don't know about it because our diagnostic curiosity is so bad for many infectious disease syndromes.

    3. PAPeter Attia36:11

       Yeah, that's a nice way of putting it, uh, poor diagnostic curiosity. Have you been following the sort of natural experiment that's going on in Sweden? Natural experiment meaning there's no randomization, but rather Sweden has sort of elected to not shut down to the extent that other European and Scandinavian countries have. Have you paid attention to the transmissibility in Sweden, or do you have any comments on it?

    4. AADr. Amesh Adalja36:33

       I've looked a little bit at what Sweden's doing, where they're trying to pursue a herd immunity strategy, and I do think that you're gonna see more cases there, which is what they're aiming for. I'm just worried because their per capita ICU bed numbers are not very high, and that's what we're really worried about is do you put an ICU into crisis? Do you have problems with ventilators? And I think it will be really instructive to see if they can get through this because I know they have a steep curve of infections, but it's all gonna depend upon who's getting sick and how well they can sequester their high-risk groups, which I think is very daunting and challenging. I'm all for cocooning the elderly and those with other medical conditions, but I know it's very challenging because they have to interact with other people to get their food, to do other things, and, and that can be really challenging. So I do think that everybody's eyes are on Sweden to see if this type of thing can work. But I'm worried about how challenging it might be for them because there is that group of people that are gonna get hospitalized and could put a hospital into crisis.

    5. PAPeter Attia37:24

       Last thing I want to ask you is what role do you think masks are going to play as we start to slowly ease restrictions in the coming months? Do you think that we kind of got off to a bad start on understanding the potential benefit of an N95 mask for people in public who are otherwise at relatively low risk?

    6. AADr. Amesh Adalja37:42

       So this is controversial in my field, and I tend to be someone who's not someone supportive of masks by the public, and especially not N95 masks, which I think are in short supply, unclear whether the public can actually bear wearing them for a long period of time because they're not comfortable to wear. And really what we saw in the beginning was a recommendation to not wear masks for the general public because it wasn't going to protect you from getting infected to one that's transitioned to wear a mask so that you don't infect other people. So I would say if someone is sick, if they have a cough, if they have a fever, if they're sneezing or a sore throat, they should be wearing a mask when they're out in public. Question is, are people who are asymptomatic, having no symptoms, how transmissible are they if they don't wear a mask? And this is an open question, but the CDC made a recommendation for people to use homemade masks in that event. And I'm not sure how well those homemade masks prevent you from spreading it if you are one of those asymptomatic persons, because they don't even stop the coughs and sneezes very well based on some studies that have been published. So I'm someone who doesn't necessarily think that these masks are going to be very beneficial and they could be paradoxically negative because people may then refrain from washing their hands as much. They may not social distance as much. They may contaminate other people with their mask if they don't store it properly or wash it. So I have a lot of concerns about masks, but I think that this is a, a decision that's going to be made on a political basis. And there is enough scientific controversy that I think politicians may use it as a way to move forward in a way that allows us to open schools, open businesses up if they have people wearing masks. But I'm not sure if we'll get much benefit from them. But it is something that's going to be an object of controversy for some time in the field.

15. 39:19 – 44:23

    Reasons for Optimism and Closing

    1. PAPeter Attia39:19

       What are you most optimistic about today?

    2. AADr. Amesh Adalja39:21

       I would say that I'm most optimistic about the fact that we have seen plateauing in New York, Seattle, California. We've heard about, for example, California actually taking ventilators and giving them to other states. We've heard about Washington State dismantling their field hospital that they made that did not see any patients. We've heard about Washington returning ventilators to the Strategic National Stockpile. All of that makes me very optimistic that we will be able to meet the challenge of this virus without putting any of our hospitals into crisis, that this is going to be a severe challenge for this country, but it's not something that, that is going to break the country, and it's not going to be cataclysmic. So all of those types of things, which are not well reported, the fact that ventilators are going back to the stockpile or that field hospitals are closing, I think that makes me optimistic because there is a narrative that's rightly focused on areas like New York and New Orleans and Chicago and Detroit. But you also have to tell the good stories, that there are places that were preparing for a surge, and now they're downsizing their nursing staff because less people came. So I think that that's an important part to know, that it's not going to be doom and gloom in every place, and that we need to help New York and New Orleans and Detroit and Chicago get through this. But not every city is going to have that experience, and we're going to learn from those experiences, and I think hopefully we'll get to a better pandemic resiliency position after this. So I am generally more optimistic than most people in my field, I think.

    3. PAPeter Attia40:38

       Amesh, thank you very much for all your insight today. I'd like to reserve the right to sort of invite you back when the dust has settled and we have much more time to talk about what a true preparedness strategy would look like because I, again, I do have a significant fear that as visceral and palpable and disturbing as all of this is today, both in terms of the physical suffering, but the fear, the economic devastation, that we're a species that is relatively hardwired to have remarkable amnesia. I don't know. I think it would be an unmitigated disaster if two years from now we're sitting here and this is not at all a topic of discussion and someone like you is not able to command the type of audience of policymakers to do what's necessary. So, so anyway, I hope that we can have that longer discussion when there are fewer fires burning, but when I think the stakes are equally high.

    4. AADr. Amesh Adalja41:30

       Thank you. I hope so too.

    5. PAPeter Attia41:33

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Episode duration: 44:23