WEBVTT - The Future of COVID-19 with Marc Lipsitch 0:00:15.396 --> 0:00:33.676 Pushkin Pushkin from Pushkin Industries. This is Deep Background, the 0:00:33.716 --> 0:00:36.916 show where we explore the stories behind the stories in 0:00:36.956 --> 0:00:41.796 the news. I'm Noah Feldman. Before we start today, I 0:00:41.836 --> 0:00:43.516 want to let you know that this is the last 0:00:43.556 --> 0:00:47.796 episode in our season about power. After this, we're going 0:00:47.796 --> 0:00:50.716 on a hiatus for the next few months to work 0:00:50.796 --> 0:00:54.116 on our next season. If you have thoughts or suggestions, 0:00:54.516 --> 0:00:57.076 please let me know. You can find me on Twitter 0:00:57.396 --> 0:01:00.476 at Noah R. Feldman, or you can reach me on 0:01:00.516 --> 0:01:04.876 my website Noah Dashfeldman dot com, where I also have 0:01:05.116 --> 0:01:07.436 a newsletter which you can use so that we can 0:01:07.516 --> 0:01:11.036 keep in touch while I'm off the air. It's been 0:01:11.076 --> 0:01:13.516 a joy to explore behind the headlines with you all 0:01:13.596 --> 0:01:15.916 these last two seasons, and I want to take a 0:01:15.996 --> 0:01:19.556 moment to thank you for joining us on this journey 0:01:19.796 --> 0:01:24.436 over the years. Okay, on with the show. For our 0:01:24.516 --> 0:01:27.436 last episode of the season, we're returning once more to 0:01:27.516 --> 0:01:31.756 the biggest story of them all, the global pandemic. Joining 0:01:31.836 --> 0:01:35.276 us once again on just about the exact second anniversary 0:01:35.556 --> 0:01:38.956 of his first time on the show, we have Mark Lipsich, 0:01:38.996 --> 0:01:43.556 the brilliant and influential epidemiologist from Harvard University's School of 0:01:43.636 --> 0:01:47.196 Public Health. Mark is a professor of epidemiology and he 0:01:47.276 --> 0:01:51.396 directs the Center for Communicable Disease Dynamics. It's no exaggeration 0:01:51.476 --> 0:01:54.796 to say that Mark has been the go to person 0:01:55.116 --> 0:01:58.916 for interpreting the trajectory of the COVID nineteen pandemic and 0:01:59.076 --> 0:02:06.076 indeed for trying to make sense of its future. Mark, 0:02:06.116 --> 0:02:09.116 thank you so much for joining me. It's almost exactly 0:02:09.276 --> 0:02:12.276 two years since we first had a conversation in the 0:02:12.356 --> 0:02:15.396 very early days of realization of what was having with COVID, 0:02:15.396 --> 0:02:18.476 and we've checked in periodically since. And I would like 0:02:18.556 --> 0:02:21.396 nothing better than for this to be a valedictory conversation 0:02:21.436 --> 0:02:23.436 on the topic, so that next time we could talk 0:02:23.436 --> 0:02:26.356 about some other aspect of disease dynamics. But somehow it 0:02:26.396 --> 0:02:29.676 won't quite go away. So how many more times are 0:02:29.716 --> 0:02:31.316 you and I are going to do this? I mean, 0:02:31.396 --> 0:02:33.676 but put another way, how many more letters of the 0:02:33.716 --> 0:02:35.876 Greek alphabet are we going to need to learn? Is 0:02:35.956 --> 0:02:40.436 this is the variant process, one that is probabilistically likely 0:02:40.556 --> 0:02:44.516 to just come back again and again and again. Well, 0:02:44.636 --> 0:02:49.436 until we see a protracted period without new variants, we 0:02:49.556 --> 0:02:52.916 have to assume they will keep coming. What their characteristics 0:02:52.916 --> 0:02:56.916 will be we can make some speculations about but those 0:02:56.956 --> 0:03:02.756 speculations would not have probably included omicron in the form 0:03:02.836 --> 0:03:05.716 that it had, so we should be humble about our 0:03:05.756 --> 0:03:08.996 speculations as well. I mean, I think when you have 0:03:09.676 --> 0:03:13.196 tens to hundreds of millions of people infected in any 0:03:13.236 --> 0:03:17.116 given a short period of time around the globe with 0:03:17.276 --> 0:03:21.156 a virus, there is an opportunity for natural selection and 0:03:21.916 --> 0:03:26.716 genetic drift to play their tricks and for new variants 0:03:26.756 --> 0:03:32.076 to evolve, and our immune systems impose selective pressure. Our 0:03:32.116 --> 0:03:36.836 transmission behavior impose a selective pressure. So the ingredients are there. 0:03:37.156 --> 0:03:41.836 We all knew sort of intellectually that variants were a possibility. 0:03:41.916 --> 0:03:45.436 There was some hope that maybe the evolutionary rates were 0:03:45.436 --> 0:03:49.396 a little bit lower in coronaviruses, but that has not 0:03:49.516 --> 0:03:51.756 turned up to be true. And in fact, the big 0:03:51.796 --> 0:03:56.476 puzzle in some of my friends minds right now is 0:03:56.956 --> 0:03:59.796 why is omicron so different from from the last one. 0:03:59.876 --> 0:04:04.476 So I think we're going to be at this COVID 0:04:04.556 --> 0:04:09.756 game for a long time and the real question what 0:04:09.956 --> 0:04:13.676 the impact of that on health is and what the 0:04:13.716 --> 0:04:16.756 properties of these variants are, which is I think the 0:04:16.796 --> 0:04:19.836 hardest thing to predict other than likely being more and 0:04:19.876 --> 0:04:24.516 more transmissible, and the easier thing to predict but still 0:04:24.556 --> 0:04:28.036 not certain, is what is the state of us in 0:04:28.116 --> 0:04:32.276 terms of our immunity and the level to which vaccine 0:04:32.516 --> 0:04:38.116 and prior infection confer on us lasting immunity. I would 0:04:38.116 --> 0:04:41.556 love to learn more in our conversation Mark about what 0:04:41.676 --> 0:04:45.316 are the kinds of logics that you and your colleagues 0:04:45.396 --> 0:04:48.756 use when trying to talk about what those properties might be, 0:04:48.996 --> 0:04:52.836 understanding that they're not perfectly predictable. So you mentioned transmissibility, 0:04:52.876 --> 0:04:56.196 that seems like the obvious one. What are other criteria 0:04:56.356 --> 0:05:03.596 of fitness that you usually ascribe to viruses that would 0:05:03.716 --> 0:05:06.316 lead one to make any kind of speculations? And it 0:05:06.476 --> 0:05:07.956 might be interesting just to hear some examples of what 0:05:07.996 --> 0:05:12.996 you expected to happen how omicron differs from those. Yeah. Well, 0:05:13.076 --> 0:05:19.196 so transmission for the virus is sort of, roughly speaking, 0:05:19.756 --> 0:05:24.316 a two part job. It has to find new naive hosts, 0:05:24.476 --> 0:05:27.636 and as those become less and less common because more 0:05:27.676 --> 0:05:31.196 people are immune from prior infection or vaccination or both, 0:05:31.556 --> 0:05:36.676 it also needs to transmit to immune hosts. So one 0:05:36.716 --> 0:05:41.796 sort of generalization is that initially the selection is for 0:05:41.956 --> 0:05:45.836 more transmissibility. When almost everyone as naive, and as more 0:05:45.876 --> 0:05:49.636 people are immune, it's always good to be more transmissible. 0:05:49.676 --> 0:05:51.916 But there's more and more of a premium on being 0:05:51.916 --> 0:05:59.236 able to escape immunity, particularly for infection and transmission, Meaning 0:05:59.556 --> 0:06:03.996 there's not direct selection to escape immunity against severe outcomes 0:06:04.476 --> 0:06:07.596 that may happen as a side effect of selection for 0:06:08.156 --> 0:06:12.116 immune escape. That's not the primary goal of the virus. 0:06:12.836 --> 0:06:15.476 So I mean market for one quick second, I mean 0:06:15.956 --> 0:06:19.076 it's never the primary goal of a virus to make 0:06:19.116 --> 0:06:21.876 you very sick. It's just that the virus will do 0:06:21.916 --> 0:06:24.556 whatever it takes to make more of the virus, and 0:06:24.596 --> 0:06:26.756 if it happens to be then making you very sick, 0:06:26.836 --> 0:06:30.876 does that the virus will do that at least in 0:06:30.916 --> 0:06:32.516 so far as it doesn't kill you and therefore make 0:06:32.556 --> 0:06:35.156 it harder to spread to more people. Right, That's right, 0:06:35.196 --> 0:06:39.276 And that's why everybody's watching very carefully to see whether 0:06:39.396 --> 0:06:44.556 the immune escape of omicron, for example, is to one 0:06:44.596 --> 0:06:50.196 extent it also escapes the immunity to severe disease that 0:06:50.316 --> 0:06:53.356 people have, and it's less but to some extent it 0:06:53.396 --> 0:06:57.516 does escape even that level that type of immunity. Okay, 0:06:57.556 --> 0:06:59.356 so sorry interrupted, but go go ahead back to what 0:06:59.436 --> 0:07:03.636 you're saying. So as you say, the virus wants to 0:07:03.676 --> 0:07:06.436 make more copies of itself once in an evolutionary sense, 0:07:06.436 --> 0:07:08.996 to make more copies of itself. There's been a long 0:07:09.196 --> 0:07:14.836 standing discussion in the evolutionary biology community and parallel, mostly 0:07:15.036 --> 0:07:19.996 separate discussion in the medical and public health community about 0:07:20.156 --> 0:07:23.956 what that does to the severity of viruses. And in fact, 0:07:24.036 --> 0:07:27.116 that was what I wrote my PhD thesis on long 0:07:27.156 --> 0:07:31.876 time ago, was making models of that interaction between the 0:07:31.916 --> 0:07:35.796 severity of the infection and the direct targets of selection, 0:07:35.836 --> 0:07:39.716 which are more transmission. So in the old days, people said, 0:07:40.556 --> 0:07:44.636 in a sort of hand wavy way, without much quantitative reasoning, 0:07:44.716 --> 0:07:47.076 that if you kill somebody that you in fact then 0:07:47.116 --> 0:07:51.276 you can't spread if you're a virus, And so viruses 0:07:51.916 --> 0:07:57.276 try to become over evolutionary time, less harmful to their hosts, 0:07:57.276 --> 0:07:59.916 and at the same time the hosts become immune. It 0:07:59.996 --> 0:08:05.356 was then, on sort of conceptual grounds, noted that that's 0:08:05.396 --> 0:08:08.876 true up to a point. But if a virus is 0:08:08.876 --> 0:08:11.436 trying to grow in a host and does so so 0:08:11.516 --> 0:08:13.876 weakly that it doesn't make more copies of itself, that's 0:08:13.916 --> 0:08:17.356 the other extreme. So killing the host is too much growth, 0:08:17.356 --> 0:08:21.036 and not even making many copies of itself to transmit 0:08:21.636 --> 0:08:25.036 is the other extreme. And so the notion of that 0:08:25.316 --> 0:08:28.636 viruses evolved to an intermediate level of virulence to their 0:08:28.676 --> 0:08:32.916 host was sort of what many models predict, and then 0:08:33.356 --> 0:08:37.436 factors that can modulate that include how it's transmitted and 0:08:38.036 --> 0:08:41.316 the relationship between how many copies of itself it makes 0:08:41.756 --> 0:08:46.436 and the transmission rate. So the old idea they always 0:08:46.476 --> 0:08:50.556 try to become more mild is not widely held by 0:08:50.596 --> 0:08:52.596 people who know what they're talking about, but is widely 0:08:52.636 --> 0:08:57.396 held by the general public. Right, yeah, So is it 0:08:57.436 --> 0:09:01.556 correct even to say that, as a probabilistic matter, of 0:09:01.596 --> 0:09:04.476 the viruses we know about, they are more likely to 0:09:04.676 --> 0:09:08.996 evolve to being less harmful over time, or is even 0:09:09.196 --> 0:09:11.956 that which I've sometimes heard as a fallback statement, Is 0:09:11.996 --> 0:09:16.756 even that not empirically observably true. I don't know if 0:09:16.796 --> 0:09:21.836 we have enough of the history of viral virulence to 0:09:21.916 --> 0:09:25.356 look back at and watch. The most famous experiment was 0:09:25.396 --> 0:09:29.556 the release of mixomatosis, a disease of rabbits caused by 0:09:29.716 --> 0:09:32.916 maxomavirus in Australia, which was done as an effort to 0:09:33.116 --> 0:09:37.796 kill off the Australian pest rabbit population, and indeed that 0:09:37.956 --> 0:09:42.236 started out as an exceedingly virulent virus and did evolve 0:09:42.316 --> 0:09:45.716 to become less harmful beautiful. Experiments done by Frank Fenner, 0:09:46.196 --> 0:09:50.716 who was better known for a smallpox eradication, he showed 0:09:50.916 --> 0:09:54.236 very conclusively that it did become milder. It didn't become mild, 0:09:54.276 --> 0:09:59.156 it became milder, and the counterbalancing problem was that if 0:09:59.156 --> 0:10:01.916 it became very, very mild, it just couldn't grow in 0:10:01.956 --> 0:10:07.476 the rabbits. So that's probably the best documented example of 0:10:08.356 --> 0:10:12.356 watching evolution in practice, because rabbits and that virus both 0:10:12.876 --> 0:10:15.476 reproduce quickly, so you had a lot of generations each year. 0:10:16.276 --> 0:10:19.636 There is also a sort of mechanistic consideration that seems 0:10:19.636 --> 0:10:22.876 to be true in flu viruses and might be true 0:10:22.916 --> 0:10:28.396 also for omicron, which is that replicating deep in the 0:10:28.516 --> 0:10:34.316 lungs is a different property from replicating further up the 0:10:34.316 --> 0:10:38.636 respiratory tract. Replicating deep in the respiratory tract down in 0:10:38.676 --> 0:10:42.116 the lungs is more likely to cause severe disease, and 0:10:42.236 --> 0:10:45.156 replicating up at the top of the respiratory tract is 0:10:45.196 --> 0:10:47.996 more likely to spread. So to the extent that that's 0:10:47.996 --> 0:10:52.876 a tradeoff. There might be some selection for transmission that 0:10:52.996 --> 0:10:56.596 is indirectly selection for mildness. But you can imagine a 0:10:56.596 --> 0:10:59.356 situation where that's not true. Is it fair to say? Then? 0:10:59.396 --> 0:11:01.676 So I'm trying to get what one should say around 0:11:01.756 --> 0:11:04.276 educated people. Somebody says, well, you know, the great thing 0:11:04.276 --> 0:11:07.436 about omicron is that it shows you that, like all viruses, 0:11:07.476 --> 0:11:09.836 this is getting more mild. I mean, the first thing 0:11:09.836 --> 0:11:13.236 to say is that's an old view and it's not 0:11:13.436 --> 0:11:17.236 on conceptual grounds. Is not necessarily true. And then there 0:11:17.276 --> 0:11:21.716 are certainly counterexamples of viruses that have not evolved to 0:11:21.876 --> 0:11:26.436 be substantially less virulent. Are there any that come to mind? 0:11:26.476 --> 0:11:28.956 What happened with smallpox? By the way, which you mentioned, 0:11:29.076 --> 0:11:31.876 my layman senses that smallpox was still pretty virulent up 0:11:31.916 --> 0:11:34.556 to the time when it was eliminated. Yeah, that's right. 0:11:34.716 --> 0:11:38.276 What's difficult is that proving a negative is hard, and 0:11:38.876 --> 0:11:43.716 we didn't see the initial emergence of most viruses when 0:11:43.756 --> 0:11:46.916 they became human pathogens or pathogens of whatever organisms they 0:11:46.956 --> 0:11:50.396 In fact, that's why Maxsoma introduced into Australia was such 0:11:50.396 --> 0:11:53.356 a great example. You could watch the whole time course. 0:11:53.916 --> 0:12:00.116 But I think it's hard to settle the history, especially 0:12:00.156 --> 0:12:02.996 because we usually also can't separate the changes in the 0:12:03.036 --> 0:12:05.916 host from the changes in the virus. In other words, 0:12:05.996 --> 0:12:08.596 as we become more immune, even the same virus will 0:12:08.636 --> 0:12:12.076 cause less severe disease. Mark we want to warn readers 0:12:12.236 --> 0:12:15.356 not to generalize for the mixed homa case to thinking 0:12:15.396 --> 0:12:17.956 that's true of all viruses. Tell me again so that 0:12:18.036 --> 0:12:22.596 I understand it. The conceptual reason that we cannot assume 0:12:22.716 --> 0:12:25.556 the way people did in the old days through hand waving. 0:12:25.596 --> 0:12:29.996 As you said that overtime virulence would necessarily be reduced. 0:12:29.996 --> 0:12:36.676 In this kind of Dayton picture, virulence is selected along 0:12:36.676 --> 0:12:41.036 with transmissibility to maximize transmissibility. And so when there is 0:12:41.036 --> 0:12:45.516 a trade off between making more copies of the virus 0:12:45.676 --> 0:12:51.316 and harming the host, the virus will choose making more 0:12:51.356 --> 0:12:55.356 copies of itself. When there's a reinforcement between making more 0:12:55.356 --> 0:12:58.156 copies of itself and harming the host, the virus will 0:12:58.196 --> 0:13:01.476 choose making more copies of itself. So what it does 0:13:01.516 --> 0:13:03.596 to us, as you said at the beginning, it doesn't 0:13:03.596 --> 0:13:08.396 really care. It's trying to maximize its own function. It 0:13:08.556 --> 0:13:13.236 is true, I think where there have been observations of evolution. 0:13:13.956 --> 0:13:16.836 The virulence has gone down in several examples, and I 0:13:16.876 --> 0:13:19.836 can't think of an example where it started mild and 0:13:19.916 --> 0:13:23.756 became more virulent that we can really document, but that 0:13:23.796 --> 0:13:26.276 would be hard to see. If it did happen, we 0:13:26.356 --> 0:13:28.836 might just see when it jumped out. So I think 0:13:28.916 --> 0:13:31.236 the thing to say is that there are some examples 0:13:31.276 --> 0:13:34.276 where viruses have become more mild, and there are some 0:13:35.356 --> 0:13:40.916 reasons why that might happen, But more mild and completely 0:13:40.956 --> 0:13:44.636 harmless are very different things, and that really the part 0:13:44.636 --> 0:13:48.636 that we can control is our immunity. We can control 0:13:48.716 --> 0:13:52.476 to some extent, and that is almost always a beneficial 0:13:53.356 --> 0:13:56.876 thing in terms of virulence of the virus. So that's 0:13:56.916 --> 0:13:59.476 the part where at least we can do something about it. 0:14:00.316 --> 0:14:03.116 You mentioned that one thing that variance want to do 0:14:03.236 --> 0:14:05.356 is of course they want to find new naive hosts, 0:14:05.356 --> 0:14:07.756 but over time that gets harder and harder, and so 0:14:07.876 --> 0:14:10.516 then they want to be able to get around sound immunity. 0:14:11.076 --> 0:14:16.076 Omicron seems to be pretty good at getting around immunity. 0:14:16.356 --> 0:14:18.556 Is there a sense a clear sense now of how 0:14:18.596 --> 0:14:22.116 it does so? And if so, is that a strategy 0:14:22.116 --> 0:14:27.516 that is likely to be replicated in future variants. Yeah, 0:14:27.556 --> 0:14:29.836 I mean, I think what's striking about omicron is that 0:14:29.916 --> 0:14:33.396 it not only has some mutations in its spike protein, 0:14:33.756 --> 0:14:36.836 which is a major target of antibodies, but it has 0:14:36.836 --> 0:14:39.316 a lot of mutations, more than it should given the 0:14:39.316 --> 0:14:42.156 amount of time that's passed if it were a typical 0:14:42.836 --> 0:14:48.236 virus out there. So I think the mechanism is still 0:14:48.276 --> 0:14:52.356 being understood in detail. But pridly speaking, the shape of 0:14:52.356 --> 0:14:55.596 its protein is different from the shape that the antibodies 0:14:55.636 --> 0:14:59.356 recognized which we're generated to previous variants, and so those 0:14:59.396 --> 0:15:02.756 antibodies don't bind as well, they don't neutralize as well, 0:15:03.076 --> 0:15:06.716 and therefore don't work as well. Any sense, people must 0:15:06.756 --> 0:15:08.756 be theorizing about this. You must be theorizing about this 0:15:09.116 --> 0:15:12.076 out why the jump seems to be as big as 0:15:12.076 --> 0:15:16.076 it is from earlier variants. Yeah, the evolution was faster 0:15:16.196 --> 0:15:23.316 than is typical in typical humans, and so the two 0:15:23.596 --> 0:15:27.716 leading hypotheses are it happened in a not typical human, 0:15:27.996 --> 0:15:31.116 meaning a human who perhaps had an immune system that 0:15:31.276 --> 0:15:36.316 was just good enough to exert selection but not good 0:15:36.396 --> 0:15:41.076 enough to end the infection. Part of why evolution doesn't 0:15:41.076 --> 0:15:44.516 happen too much during a typical infection is that there's 0:15:44.516 --> 0:15:46.516 a lot of selection to escape it, but not much 0:15:46.556 --> 0:15:50.636 time before the virus is gone, and dead viruses don't mutate, 0:15:51.116 --> 0:15:54.516 so once you clear an infection, it doesn't have the 0:15:54.596 --> 0:15:58.956 chance to evolve further. Immuno Compromised people in various forms 0:15:59.196 --> 0:16:03.956 often have much longer infections. If they're deeply immunocompromised, then 0:16:03.956 --> 0:16:07.156 they they may not exert much selection on the virus, 0:16:07.156 --> 0:16:09.556 and they may not survive for very long because they 0:16:09.596 --> 0:16:11.876 won't be able to control the virus. But if they 0:16:11.876 --> 0:16:14.956 are then this is just speculation. I mean compromised in 0:16:14.996 --> 0:16:17.956 some particular way that allows the virus to persist, but 0:16:18.156 --> 0:16:23.196 maintains that selection pressure that could accelerate. The other class 0:16:23.196 --> 0:16:27.076 of explanations is that, as we've seen, the Saris Kobe 0:16:27.156 --> 0:16:30.196 two can infect other mammals. For example, there was a 0:16:30.196 --> 0:16:33.316 lot of interest in the white tailed deer being infected. 0:16:33.356 --> 0:16:37.636 They were minks in Denmark that were infected earlier in 0:16:37.676 --> 0:16:42.076 the pandemic. So entering a new host species is often 0:16:42.156 --> 0:16:45.636 a trigger for accelerated evolution because the virus has a 0:16:45.676 --> 0:16:48.796 lot of new problems to solve to get good at 0:16:48.796 --> 0:16:53.996 infecting that host and So those are the two major 0:16:54.076 --> 0:16:58.556 hypotheses that people have thought about. We'll be right back. 0:17:08.756 --> 0:17:12.436 Mark word that one hears more and more is COVID 0:17:12.476 --> 0:17:14.396 is on its way to being endemic. Sometimes you hear 0:17:14.436 --> 0:17:18.196 people getting fancy and talking about a state of endemicity. 0:17:18.356 --> 0:17:21.876 My question is, first of all, what's the working definition 0:17:22.116 --> 0:17:25.636 that epidemiologists use for that? So what does endemic actually 0:17:25.716 --> 0:17:29.276 mean to an epidemiologist? And the second is in practice, 0:17:29.596 --> 0:17:31.516 what does that mean if and when we are there? 0:17:33.036 --> 0:17:36.596 I think we're The dirty laundry of the epidemiology community 0:17:36.636 --> 0:17:40.436 continues to be aired, and different people use these words differently, 0:17:40.676 --> 0:17:43.836 but I think the core idea of endemicity is that 0:17:43.916 --> 0:17:48.236 an infection is present at some level, almost constantly in 0:17:48.316 --> 0:17:52.836 a population, and it may go through say seasonal swings, 0:17:53.356 --> 0:17:57.596 and sometimes you call that seasonal upturn an epidemic, and 0:17:57.676 --> 0:18:01.276 sometimes people call averaging over the whole year to be 0:18:01.476 --> 0:18:05.396 endemic an endemic state. But it's a situation in which 0:18:06.196 --> 0:18:11.356 most people, by the time they reach some reasonably young age, 0:18:11.796 --> 0:18:15.476 have been exposed to the infection. That's an important characteristic, 0:18:15.596 --> 0:18:22.156 and where the swings are either very small, as with 0:18:22.436 --> 0:18:25.716 some infections that are just sort of pretty similar all 0:18:25.796 --> 0:18:30.516 year round, like some respiratory bacterial infections that are a 0:18:30.516 --> 0:18:33.756 little bit seasonal but basically kind of always there at 0:18:33.796 --> 0:18:38.436 similar levels, or they're predictable swings that are every winter 0:18:38.636 --> 0:18:41.756 or every summer or something like that. So it has 0:18:41.796 --> 0:18:47.036 aspects of predictability of most people having prior exposure. And 0:18:47.116 --> 0:18:49.556 therefore the reason why it's sort of a comforting word 0:18:49.796 --> 0:18:54.076 is that the two things that have really been miserable 0:18:54.236 --> 0:18:58.396 about sarskovi two have been the very large and unpredictable 0:18:58.436 --> 0:19:01.516 swings in the number of people infected, and the fact 0:19:01.516 --> 0:19:04.196 that it's preying on a population of us that is 0:19:04.236 --> 0:19:08.036 mostly naive to it and therefore at greater risk of 0:19:08.116 --> 0:19:12.116 having bad outcomes then we will be when we've all 0:19:12.476 --> 0:19:17.676 had the infection and or vaccination. The upshot that if 0:19:17.716 --> 0:19:20.916 I understand you correctly, is that even though endemic and 0:19:20.956 --> 0:19:24.396 epidemic are obviously etymologically related in terms of their relationship 0:19:24.476 --> 0:19:27.596 to the public, they're not in any very very sharp 0:19:27.836 --> 0:19:31.876 relationship to each other. Because something can be endemic and 0:19:31.956 --> 0:19:36.716 yet there can be epidemics that are seasonal. Is that right? 0:19:36.756 --> 0:19:38.396 So that those two and yet or you can have 0:19:38.436 --> 0:19:40.676 an epidemic that is not endemic, or you can sending 0:19:40.676 --> 0:19:42.476 it is endemic and is not epidemics. So it seems 0:19:42.476 --> 0:19:44.876 to have almost all the possible logical relationships. But I 0:19:44.916 --> 0:19:49.956 think I think the more helpful contrast probably is pandemic 0:19:50.036 --> 0:19:54.916 versus endemic. So the signal features of pandemics, although these 0:19:54.956 --> 0:19:58.196 are also revised as we as we have more of them, 0:19:58.236 --> 0:20:01.076 because they're each one is special. But the signal features 0:20:01.076 --> 0:20:06.636 of pandemics are a very naive population that is experiencing 0:20:06.676 --> 0:20:13.556 something for the first time, and being very widespread and 0:20:13.876 --> 0:20:16.716 having large swings and incidents and prevalence because of those 0:20:16.756 --> 0:20:21.076 two things. Yeah, so that's super helpful. I mean, that's 0:20:21.076 --> 0:20:23.436 super helpful because one can sort of think a pandemic 0:20:23.676 --> 0:20:26.596 nobody has it at first, then lots of people get 0:20:26.636 --> 0:20:29.916 it in bunches, and that's the pandemic endemic. Everybody's been 0:20:29.916 --> 0:20:31.476 exposed to it from the time that they were pretty 0:20:31.516 --> 0:20:34.356 small children, but it's still out there in the population. 0:20:34.436 --> 0:20:38.156 That seems to be very, very helpful. The thing that 0:20:38.316 --> 0:20:42.476 is a bit confusing to me at least is if 0:20:42.516 --> 0:20:45.716 we think about the relationships, say of omicron, to the 0:20:45.756 --> 0:20:50.636 earlier versions of COVID, it seems like even though in 0:20:50.716 --> 0:20:53.076 principle we should be moving to a place where almost 0:20:53.076 --> 0:20:57.196 everybody has been exposed or vaccinated one of the two 0:20:58.236 --> 0:21:01.636 that lots of people who were previously exposed to those 0:21:01.636 --> 0:21:05.036 other things or were vaccinated are getting o macron because 0:21:05.076 --> 0:21:10.036 of its capacity to evade immunity. And if that's the case, 0:21:10.156 --> 0:21:11.916 do you guys start thinking of it as though it 0:21:11.916 --> 0:21:15.356 were a separate disease and so therefore it doesn't really 0:21:15.396 --> 0:21:18.676 matter if let's say it becomes endemic. Let's say omicron 0:21:18.756 --> 0:21:21.316 becomes endemic, but something a new variant comes along that 0:21:21.356 --> 0:21:25.676 evades immunity, then aren't people sort of a naive population 0:21:25.716 --> 0:21:30.996 again with respect to that new variant if they're evading immunity, Yeah, 0:21:31.036 --> 0:21:35.716 that is the big question. The reason why omicron has 0:21:35.796 --> 0:21:39.396 been bad but not worse than it was is that 0:21:40.276 --> 0:21:45.636 the combination of somewhat lower severity and growing amounts of 0:21:45.676 --> 0:21:49.316 population immunity to severe disease, which still to a large 0:21:49.356 --> 0:21:53.556 degree though not perfectly hold against omicron, has meant that 0:21:54.396 --> 0:21:58.236 there are enormous numbers of cases, but not correspondingly many 0:21:58.716 --> 0:22:02.916 deaths and hospitalizations. And that's a kind of new thing. 0:22:03.036 --> 0:22:07.196 We haven't had a flu experience that's quite like that, 0:22:07.756 --> 0:22:10.356 and we haven't had a far as Kobe two experience. 0:22:10.436 --> 0:22:13.476 It's quite like that. So this is a new combination 0:22:13.556 --> 0:22:18.556 of properties to deal with. One way that I find 0:22:18.556 --> 0:22:22.516 it helpful to think about what's ahead in the next 0:22:22.556 --> 0:22:29.596 few years is that, as you say, the bad option 0:22:29.836 --> 0:22:34.436 will be if new variants continued to come and they 0:22:34.956 --> 0:22:40.556 really are either so good at escaping immunity and transmitting 0:22:41.156 --> 0:22:45.116 that the cases go shooting up, as they have with Omicron, 0:22:46.356 --> 0:22:50.036 or they are really good at escaping our immunity to 0:22:50.116 --> 0:22:53.756 severe disease, which was not that high at the beginning 0:22:53.796 --> 0:22:57.516 of Omicron, should be higher after Omicron, we hope. But 0:22:57.596 --> 0:22:59.996 if they're good at escaping our immunity to severe disease, 0:23:00.036 --> 0:23:02.996 then even modest numbers of cases could be a problem, 0:23:03.716 --> 0:23:07.316 and that would be like almost like a new flu pandemic. 0:23:07.356 --> 0:23:11.476 It would be an evolutionary jump that is highly consequential 0:23:11.556 --> 0:23:14.676 and is what we used to talk about with flu pandemics. Right. 0:23:14.676 --> 0:23:16.636 It's the reason that the flu vaccine, it's a good 0:23:16.676 --> 0:23:18.276 thing to get it, but it doesn't guarantee that you 0:23:18.276 --> 0:23:20.716 won't get the flu, right because the variants comes so fast. Right, 0:23:22.076 --> 0:23:25.036 partly and partly because they just aren't fully protective even 0:23:25.236 --> 0:23:27.436 against what they're supposed to talk and nearly as good 0:23:27.436 --> 0:23:29.916 as these these vaccines that I say, I kind of 0:23:29.916 --> 0:23:33.716 categorize like the two possible futures are that we have 0:23:33.836 --> 0:23:37.116 changes like the usual changes between years of flu, or 0:23:37.156 --> 0:23:39.956 we have changes like new flu pandemics that just are 0:23:40.036 --> 0:23:44.596 more frequent, And those are the two broad categories that 0:23:44.676 --> 0:23:47.476 we really really hope the first happens, but we have 0:23:47.516 --> 0:23:51.156 to consider the possibility in the second. Mark I'm trying 0:23:51.156 --> 0:23:54.756 to figure out what the right kinds of policy responses 0:23:54.756 --> 0:23:57.316 are at this moment, partly in order to get sense 0:23:57.356 --> 0:23:58.996 of what they're going to look like going forward if 0:23:58.996 --> 0:24:02.756 we have more variants. So, for example, at our mutual employer, 0:24:02.916 --> 0:24:05.956 Harvard University, on the one hand, we have classes at 0:24:06.036 --> 0:24:08.876 least at the law school in person, but we are 0:24:08.916 --> 0:24:11.036 all told not just to wear masks, but to wear 0:24:11.116 --> 0:24:14.196 a ninety five masks and possibly to wear two masks. 0:24:14.236 --> 0:24:17.316 And there seems to be a heightening of concern about 0:24:17.516 --> 0:24:20.876 transmission because I guess of the great transmissibility of omicron. 0:24:21.356 --> 0:24:23.756 On the other hand, we're in person, which we weren't 0:24:23.796 --> 0:24:27.916 obviously at an earlier stage, and What's more, everyone is 0:24:27.956 --> 0:24:32.676 mandatorily vaccinated and boostered, So what's the policy logic if 0:24:32.716 --> 0:24:37.556 you can reconstruct it behind that kind of heightened prevention 0:24:37.716 --> 0:24:43.836 coupled with diving right in and having classes. Well, another 0:24:43.876 --> 0:24:46.356 part of it, at least at our school public health, 0:24:46.636 --> 0:24:51.236 is that contact tracing is basically now left to the individual. 0:24:51.276 --> 0:24:56.836 There's no centralized contact tracing. So putting that together with 0:24:57.076 --> 0:25:03.396 what you just described, my interpretation is that people are 0:25:03.436 --> 0:25:08.676 trying to do the things that are efficient and relatively 0:25:08.756 --> 0:25:16.356 low impact that reduced transmission, while reallocating resources from very 0:25:16.436 --> 0:25:22.116 very costly in terms of time efforts like contact tracing, 0:25:22.756 --> 0:25:26.556 and trying to return to doing as much of what 0:25:26.596 --> 0:25:29.236 we're supposed to be doing as a university as possible. 0:25:30.156 --> 0:25:34.316 So that's my interpretation. And an environment where let's say 0:25:34.356 --> 0:25:37.876 almost everybody or everybody has been vaccinated and boosted, then 0:25:38.316 --> 0:25:41.636 the goal would be try to avoid too many people 0:25:41.676 --> 0:25:44.196 getting omicron so that they have to miss class and 0:25:44.356 --> 0:25:48.676 stay home and give more people omicron, but nevertheless still 0:25:48.676 --> 0:25:51.516 try to push forward with as much normalcy as can 0:25:51.556 --> 0:25:54.396 be mustered under these circumstances. And I guess the question 0:25:54.476 --> 0:25:56.796 that leads me to is and It's not that I 0:25:56.836 --> 0:25:58.476 think either has the answer to it, but I want 0:25:58.476 --> 0:26:01.916 to talk about it. Is this the new normal? Right? 0:26:01.996 --> 0:26:04.356 I mean, is there any reason if people can bear 0:26:04.476 --> 0:26:06.476 going to class in masks or teaching in masks? Will 0:26:06.476 --> 0:26:08.356