WEBVTT - The Second (and Third, and Fourth) Wave of COVID-19 0:00:15.356 --> 0:00:22.076 Pushkin from Pushkin Industries. This is deep background to show 0:00:22.116 --> 0:00:25.476 where we explore the stories behind the stories in the news. 0:00:25.916 --> 0:00:30.236 I'm Noah Feldman. As states begin to reopen, we're all 0:00:30.276 --> 0:00:34.476 desperately trying to figure out what is going to happen next. 0:00:35.236 --> 0:00:38.316 What are the possible courses of COVID nineteen, what are 0:00:38.316 --> 0:00:40.956 the possible outcomes if there is a vaccine, and what 0:00:41.036 --> 0:00:43.836 are the possibilities if indeed we don't get a vaccine 0:00:44.196 --> 0:00:48.516 or a therapeutic treatment that actually changes things. Joining me 0:00:48.556 --> 0:00:51.836 to discuss these issues is doctor Jonatan grad. He's an 0:00:51.876 --> 0:00:55.516 assistant professor in the Department of Immunology and Infectious Diseases 0:00:55.716 --> 0:00:58.516 at the Harvard chan School of Public Health. He's also 0:00:58.556 --> 0:01:01.396 an attending physician in the Division of Infectious Diseases at 0:01:01.396 --> 0:01:07.036 Brigham and Women's Hospital and Harvard Medical School. You know, Tom, 0:01:07.076 --> 0:01:09.476 thank you so much for being here. I really hugely 0:01:09.516 --> 0:01:11.876 appreciate it. And the first topic I want to ask 0:01:11.916 --> 0:01:14.316 you about is a paper on which you're one of 0:01:14.316 --> 0:01:17.556 the co authors, that was published in Science magazine. That 0:01:17.756 --> 0:01:21.556 is a model or a series of models, among other things, 0:01:21.596 --> 0:01:24.796 of what could happen under conditions of reopening if a 0:01:24.876 --> 0:01:28.636 vaccine is not yet available or potentially not available at all. 0:01:29.436 --> 0:01:32.916 Would you start by just describing at the core what 0:01:33.036 --> 0:01:35.476 predictions you and your co authors were able to make 0:01:35.756 --> 0:01:42.036 about the patterns of covid resurgence that are potentially out there. Sure, 0:01:42.596 --> 0:01:44.996 there really seems to be only a couple of ways 0:01:45.076 --> 0:01:49.436 in which a pandemic ends. One of them is elimination 0:01:49.476 --> 0:01:53.236 of the virus. If you're able to control the spread 0:01:53.276 --> 0:01:58.036 sufficiently towards the beginning of the virus emergence, you can 0:01:58.076 --> 0:02:01.356 perhaps contain it to the extent that you can eliminate 0:02:01.396 --> 0:02:05.596 its ongoing transmission. That I think is what happened with 0:02:05.676 --> 0:02:09.396 the experience of stars in two thousand to three. I 0:02:09.436 --> 0:02:13.156 think that this possibility for ending the pandemic now is 0:02:13.196 --> 0:02:16.996 extremely unlikely, given how globally we've seen the spread of 0:02:16.996 --> 0:02:21.316 SARS CoV two. The second way to end a pandemic 0:02:21.516 --> 0:02:27.116 is through population immunity or herd immunity, when enough of 0:02:27.156 --> 0:02:33.156 the population has acquired immunity to the pathogen that you 0:02:33.236 --> 0:02:37.876 don't see ongoing epidemic spread. This can happen either with 0:02:38.876 --> 0:02:42.956 a vaccine that can confer sufficient immune production or through 0:02:43.116 --> 0:02:48.396 natural infection, where that infection elicits immunity. A key to 0:02:48.516 --> 0:02:52.836 thinking about HERD immunity, then, is understanding what fraction of 0:02:52.836 --> 0:02:56.916 the population would have to be infected and recovered from 0:02:56.996 --> 0:03:00.156 infection with immunity in order for the pandemic to end. 0:03:00.516 --> 0:03:03.796 That gets to the notion of the basic reproductive number, 0:03:04.076 --> 0:03:08.676 a sense of just how transmissible the virus is. Estimates 0:03:08.756 --> 0:03:12.916 of this number for Sarryscoop two place it around three, 0:03:12.956 --> 0:03:16.516 although there have recently been some estimates that are considerably higher. 0:03:16.556 --> 0:03:19.516 There was one published last week at five point seven. 0:03:20.236 --> 0:03:22.676 But let's start with just the notion of this are 0:03:22.796 --> 0:03:26.596 not or the basic reproductive number of three. What this 0:03:26.716 --> 0:03:30.716 means is that on average, an infectious person will infect 0:03:30.836 --> 0:03:35.916 three other people. To prevent these ongoing transmission chains, then 0:03:36.236 --> 0:03:40.156 two out of three people would have to have immunity, right, 0:03:40.196 --> 0:03:42.556 so we would have to get to a point in 0:03:42.556 --> 0:03:46.556 which roughly sixty six percent of the population was immune 0:03:46.596 --> 0:03:50.996 in order to see that transmission would diminish. We then 0:03:51.196 --> 0:03:58.276 became interested in asking, given the broad based quarantine for 0:03:58.396 --> 0:04:01.916 communities that had been introduced through these social distancing measures 0:04:01.956 --> 0:04:05.716 and lockdowns, both in China and in elsewhere, what the 0:04:05.996 --> 0:04:10.036 impact would be of these social distancing measure of different 0:04:10.116 --> 0:04:14.716 durations and different effectiveness. We wanted to know if we 0:04:14.716 --> 0:04:20.236 were to have lockdowns or social distancing with effectiveness of 0:04:20.356 --> 0:04:24.556 say twenty percent so mildly effective, forty percent more effective, 0:04:24.596 --> 0:04:26.476 or sixty percent on the order of what was seen 0:04:26.516 --> 0:04:29.796 in China, what would happen and what would happen if 0:04:29.796 --> 0:04:32.876 it were four weeks, eight weeks, twelve weeks, twenty weeks, 0:04:32.916 --> 0:04:38.116 or for a long period. The key intuition here gets 0:04:38.116 --> 0:04:40.556 back to what I was describing about the fraction of 0:04:40.556 --> 0:04:44.556 the population that would have to be immune the extent 0:04:44.676 --> 0:04:49.756 to which we are successful in preventing spread. So that's 0:04:49.876 --> 0:04:54.916 the intervention. These lockdowns really diminished transmission, would maintain a 0:04:54.956 --> 0:04:59.036 susceptible population in the community, so that when you stop 0:04:59.636 --> 0:05:03.596 that intervention, when you lift the restrictions, now the virus 0:05:03.596 --> 0:05:07.356 would have the opportunity to spread again through the susceptible population. 0:05:09.236 --> 0:05:12.236 To the extent that we are successful, we will then 0:05:12.236 --> 0:05:16.916 see the resurgence of the virus. And that was really 0:05:16.916 --> 0:05:19.316 one of the main findings in this paper for that 0:05:19.756 --> 0:05:24.996 one time social distancing interventions. As there are susceptible people, 0:05:25.796 --> 0:05:28.876 the virus has no memory, it doesn't care what we've done. 0:05:28.996 --> 0:05:32.356 It just carries if there are susceptible people around that 0:05:32.476 --> 0:05:34.716 it can infect, and so we would expect to see 0:05:35.036 --> 0:05:38.276 a resurgence of the virus. So that resurgence is a 0:05:38.356 --> 0:05:41.196 version of what people call the second wave, and I 0:05:41.236 --> 0:05:43.596 take it the way you're saying is that that second 0:05:43.596 --> 0:05:45.556 wave is going to be a lot bigger than perhaps 0:05:45.756 --> 0:05:50.076 people might assume, given the success of social distancing measures 0:05:50.116 --> 0:05:51.916 that reduce the number of people who are exposed. So 0:05:51.956 --> 0:05:53.996 this is sort of the downside of flattening the curve 0:05:54.356 --> 0:05:57.116 is that fewer people have been exposed, and so when 0:05:57.196 --> 0:06:00.036 the time comes that they are exposed, potentially a lot 0:06:00.076 --> 0:06:03.276 of them could be exposed. Imagine a scenario and I 0:06:03.276 --> 0:06:05.756 think you do imagine this in the paper where then 0:06:05.876 --> 0:06:08.476 the government responds to that by saying, Okay, we have 0:06:08.516 --> 0:06:10.996 a second wave coming. We see it rising, we see 0:06:10.996 --> 0:06:12.876 the number of cases going up, in the number of 0:06:12.956 --> 0:06:15.676 deaths going up, and so now we're going to reimpose 0:06:16.036 --> 0:06:19.276 social distancing. Any reason to think that you wouldn't get 0:06:19.396 --> 0:06:22.196 similar effect of that social distancing in the second time 0:06:22.236 --> 0:06:24.316 as you did the first time, and then similarly the 0:06:24.356 --> 0:06:26.036 third and the fourth, and however many times you need 0:06:26.036 --> 0:06:28.516 to do this, that's right. So it gets to the 0:06:28.556 --> 0:06:31.316 question of why are we doing social distancing in the 0:06:31.356 --> 0:06:35.556 first place. If this virus were benign, we would just 0:06:35.716 --> 0:06:38.356 let it run through the population, right because there wouldn't 0:06:38.356 --> 0:06:43.116 really be a downside to that. But because this virus 0:06:43.156 --> 0:06:46.636 causes the extent of disease that it does, we worry 0:06:46.756 --> 0:06:52.116 about the impact it has on the healthcare infrastructure. So 0:06:52.316 --> 0:06:56.916 the reason for enacting social distancing and putting communities in 0:06:56.996 --> 0:07:01.996 lockdown is to not only try to save lives directly, 0:07:02.236 --> 0:07:05.556 try to diminish the spread so that fewer people are 0:07:05.596 --> 0:07:09.356 getting infected and dying from the disease, but also from 0:07:09.356 --> 0:07:12.716 the effect it would have on our healthcare infrastructure. What 0:07:12.916 --> 0:07:16.556 was seen in Uhan and then replicated in northern Italy 0:07:16.756 --> 0:07:20.036 and more recently in New York is that when we 0:07:20.076 --> 0:07:23.636 see this large fraction of the population infected all at once, 0:07:24.116 --> 0:07:28.756 it overwhelms the healthcare system, and then we see things 0:07:28.836 --> 0:07:33.036 like rationing ventilators, and also that people who would normally 0:07:33.036 --> 0:07:35.756 be able to come into hospitals to get care for 0:07:35.836 --> 0:07:39.036 their heart attacks or strokes were not coming in, so 0:07:39.076 --> 0:07:42.236 there would not only be death from the virus itself, 0:07:42.476 --> 0:07:45.036 but from our inability to properly care for people who 0:07:45.116 --> 0:07:48.996 have the virus and the inability to care for people 0:07:49.036 --> 0:07:52.796 who have other conditions, we would see extensive excess mortality. 0:07:53.476 --> 0:07:57.836 That led to this effort to flatten the curve. Once 0:07:57.876 --> 0:08:01.076 we stop and see a resurgence of virus, as you say, 0:08:01.596 --> 0:08:04.156 we would expect that if we are still being guided 0:08:04.196 --> 0:08:07.476 by that principle of trying to maintain the healthcare infrastructure, 0:08:07.796 --> 0:08:10.716 then to the extent that it threatened by this resurgence, 0:08:10.716 --> 0:08:16.596 we would imagine reinstituting social distancing measures. This led to 0:08:16.756 --> 0:08:19.756 our consideration of, well, for how long would we have 0:08:19.836 --> 0:08:23.476 to do that? Assuming no other intervention, And that's the 0:08:23.556 --> 0:08:25.916 question I think everybody is so focused on. You know, again, 0:08:25.916 --> 0:08:29.196 assuming no other magic bullet solution, how many times are 0:08:29.196 --> 0:08:31.476 we going to have to run this same cycle of 0:08:31.596 --> 0:08:34.036 up and down and up and down. It looks like 0:08:34.196 --> 0:08:37.076 from our models that this could take a couple of 0:08:37.156 --> 0:08:40.996 years of cycles, and that may be influenced by a 0:08:41.076 --> 0:08:46.076 variety of factors. Those factors include whether we can expand 0:08:46.236 --> 0:08:49.476 our critical care capacity. So really what we were thinking 0:08:49.476 --> 0:08:52.876 about in this paper was can we titrate to some 0:08:52.956 --> 0:08:57.316 extent the turning on and off of social distancing to 0:08:57.956 --> 0:09:01.676 optimize the number of people were caring for in hospitals 0:09:01.756 --> 0:09:04.796 or in the healthcare infrastructure, and that really seems keyed 0:09:04.916 --> 0:09:08.796 to our critical care capacity. So the goal, then, from 0:09:08.836 --> 0:09:13.316 a intervention perspective, would be to try to find the line, 0:09:13.356 --> 0:09:15.796 which is how many cases we can handle in our 0:09:15.836 --> 0:09:19.036 critical care facilities in the hospitals, and then to just 0:09:19.236 --> 0:09:21.516 bring the number of infections up to that line as 0:09:21.556 --> 0:09:24.796 close to that line as possible, and then back down again, 0:09:25.356 --> 0:09:27.196 and to do that as long as it takes, And 0:09:27.196 --> 0:09:28.676 of course how long it will take depends on how 0:09:28.716 --> 0:09:30.756 high you can make that line, because that's the question 0:09:30.796 --> 0:09:33.116 of how many people you can manage to infect. But 0:09:33.156 --> 0:09:36.716 it sounds like making fairly reasonable assumptions about how high 0:09:36.716 --> 0:09:39.676 that line could be set. You're suggesting that we could 0:09:40.036 --> 0:09:42.116 end up having to do this again and again into 0:09:42.156 --> 0:09:46.996 twenty twenty two. That's right, And it could be that 0:09:47.316 --> 0:09:50.716 those numbers are adjusted by a variety of different factors. 0:09:50.756 --> 0:09:55.156 If we find an effective therapeutic that diminishes the need 0:09:55.516 --> 0:09:59.836 for hospitalization, or if a person is hospitalized that diminishes 0:09:59.836 --> 0:10:03.916 the need for critical care, that effectively increases our critical 0:10:03.956 --> 0:10:07.996 care capacity, right, So it's mathematically the same essentially as 0:10:08.236 --> 0:10:12.316 increasing our capacity, so that can help shorten the duration 0:10:12.396 --> 0:10:15.156 with which we'd have to go through these cycles. It 0:10:15.196 --> 0:10:19.836 could also be impacted by seasonality, which is another aspect 0:10:20.156 --> 0:10:24.236 of the projections that we evaluate in this paper. We 0:10:24.396 --> 0:10:30.356 don't really know yet whether there is seasonality in transmission 0:10:30.796 --> 0:10:35.996 of SARS CoV two. For some other respiratory viruses, we know, like, 0:10:36.196 --> 0:10:41.116 for example, for influenza, that seasonality influences transmission such that 0:10:41.196 --> 0:10:44.076 it is more transmissible in the winter than it is 0:10:44.116 --> 0:10:47.676 in the summer. We see as well for a couple 0:10:47.716 --> 0:10:52.316 of the other human coronaviruses that circulate in the US 0:10:52.396 --> 0:10:57.156 and cause common cold type symptoms, that it appears they 0:10:57.236 --> 0:11:02.836 also have seasonality. Using those as a basis for seasonality 0:11:02.916 --> 0:11:06.196 for SARS CoV two, assuming that whatever factors influence the 0:11:06.236 --> 0:11:10.316 other coronaviruses would also influence this one, we would see 0:11:10.316 --> 0:11:13.436 that there would be less transmission in the summer, and 0:11:13.636 --> 0:11:16.756 then transmission would pick up in the fall and peek 0:11:16.756 --> 0:11:21.076 in the winter. That could also influence the deboration of 0:11:21.516 --> 0:11:27.876 lockdown and release from social distancing interventions. So if COVID 0:11:27.916 --> 0:11:31.196 nineteen does turn out to be seasonal in similarity to 0:11:31.236 --> 0:11:35.476 these other viruses. That would suggest that we ought to 0:11:35.516 --> 0:11:38.716 try to reopen going into the summer rather than going 0:11:38.756 --> 0:11:41.036 into the winter. And that part sounds like good news 0:11:41.076 --> 0:11:43.556 insofar as most of the openings up that are happening 0:11:43.556 --> 0:11:47.036 now are going into summer months. That's right, And I 0:11:47.076 --> 0:11:52.596 think it does raise further concern for the possibility of 0:11:52.716 --> 0:11:55.956 augmented transmission in the fall and the winter. And I 0:11:55.956 --> 0:12:00.756 think it's of concern for two reasons. One, it overlaps 0:12:00.836 --> 0:12:05.796 with the increase in transmission of influenza, which we already 0:12:05.876 --> 0:12:10.316 know creates stress on our healthcare infrastructure. So to see 0:12:10.436 --> 0:12:15.796 both flu and COVID nineteen coupled together increasing together, I 0:12:15.796 --> 0:12:19.116 think that is something that we all worry about. The 0:12:19.156 --> 0:12:22.636 second reason is actually just one of domestic politics, right. 0:12:22.676 --> 0:12:27.396 The importance of this election in November is one where 0:12:27.756 --> 0:12:30.836 seeing a rise in cases and a second wave that 0:12:30.916 --> 0:12:33.796 overlaps with the election, I think is something that people 0:12:33.836 --> 0:12:37.676 have to be aware of and be concerned about. So, 0:12:37.836 --> 0:12:40.676 just to understand what you're saying, what you're saying very politely, 0:12:40.716 --> 0:12:42.556 but it sounds like what you're saying is you could 0:12:42.556 --> 0:12:45.436 see a moment where over the summer, as reopenings occur, 0:12:45.556 --> 0:12:49.116 we actually don't get a huge spike because the virus 0:12:49.196 --> 0:12:53.036 is more seasonal. But then starts getting colder, people start 0:12:53.076 --> 0:12:57.476 going inside. It's October, and the case rate might actually 0:12:57.476 --> 0:13:00.876 begin to go up pretty rapidly, and then boom. We 0:13:00.956 --> 0:13:02.876 have an election in the first week of November, as 0:13:02.916 --> 0:13:05.036 mandated by federal statute, and the president may think he 0:13:05.036 --> 0:13:07.516 can change that, but he can't. So it's going to 0:13:07.556 --> 0:13:10.876 happen in early November one way or the other. Is 0:13:10.916 --> 0:13:14.196 it cold enough in October to have this seasonal impact 0:13:14.236 --> 0:13:16.116 before the election? I mean, I hate to ask such 0:13:16.116 --> 0:13:19.916 a crudely political question, but it seems relevant. How does 0:13:19.996 --> 0:13:23.316 flu do or how do these other coronaviruses do in October? 0:13:23.396 --> 0:13:24.916 That's really the key timing. By the time you get 0:13:24.916 --> 0:13:28.076 to November, the election will have happened, right. I expect 0:13:28.276 --> 0:13:32.316 there to be an increase in transmission. The seasonality is 0:13:32.316 --> 0:13:36.236 not an on off process. It's one that fluctuates with 0:13:36.276 --> 0:13:39.556 the season. So as we start to move into the 0:13:39.596 --> 0:13:42.076 fall and winter, I do worry that there will be 0:13:42.156 --> 0:13:47.556 increased transmissibility and arise in cases. And I think even 0:13:47.716 --> 0:13:51.116 as this is an issue that we can't know for 0:13:51.196 --> 0:13:55.876 sure at this point, it is nonetheless one worth preparing for, 0:13:56.236 --> 0:14:00.716 just in case. It's concerning enough that being able to 0:14:00.796 --> 0:14:05.036 have the option to vote by mail seems critical for 0:14:05.556 --> 0:14:08.956 an election where there may be risks as we've seen 0:14:08.996 --> 0:14:11.996 in Wisconsin and the primaries to standing in line when 0:14:12.116 --> 0:14:16.276 there are serious respiratory viruses in circulation. There's a fascinating 0:14:16.276 --> 0:14:18.876 counterintuitive result of this, which is there's been a lot 0:14:18.876 --> 0:14:21.316 of talk about what Donald Trump tried to delay the elections. 0:14:22.076 --> 0:14:24.756 If Donald Trump were to listen to this podcast and 0:14:24.796 --> 0:14:28.116 read your paper, he ought to not, under any circumstances 0:14:28.116 --> 0:14:30.676 even think about delaying the elections, because if you delay 0:14:30.676 --> 0:14:33.396 the elections, there might be a lot more COVID nineteen 0:14:33.436 --> 0:14:36.316 cases as the weather gets colder, Whereas in the first 0:14:36.316 --> 0:14:39.516 week of November it's entirely possible that that might be 0:14:39.556 --> 0:14:41.836 going on, but we wouldn't have seen it yet. I 0:14:41.876 --> 0:14:45.636 think it's so tough to speculate even months out at 0:14:45.676 --> 0:14:49.516 this point. Frankly, I think with all of the variation 0:14:50.436 --> 0:14:56.556 in social distancing interventions across the United States, it's very 0:14:56.596 --> 0:15:00.076 hard to predict what the prevalence will be, and with 0:15:00.116 --> 0:15:04.476 the risks for recurrence will be by community. Different states 0:15:04.476 --> 0:15:08.676 and different regions have taken very different approaches to how 0:15:08.716 --> 0:15:12.676 to manage the response to COVID nineteen. Some seem to 0:15:12.716 --> 0:15:15.836 have adopted the Boris Johnson phrase take it on the chin. 0:15:16.876 --> 0:15:20.156 Others are trying to flatten the curve, and yet others 0:15:20.196 --> 0:15:22.796 are trying to crush the curve. And by crush the curve, 0:15:22.876 --> 0:15:27.076 what I mean is really prevent any transmission through a 0:15:27.116 --> 0:15:32.876 combination of social distancing interventions, contact tracing, and other means. 0:15:33.236 --> 0:15:36.196 So it's hard for me to say exactly what the 0:15:36.276 --> 0:15:40.516 dynamics will be come September, October, and November, because those 0:15:40.596 --> 0:15:43.156 in part depend on the fraction of the population that 0:15:43.196 --> 0:15:47.236 remains susceptible, and that right now is just so hard 0:15:47.276 --> 0:15:59.796 to predict. We'll be back in a moment you're not on. 0:15:59.796 --> 0:16:01.956 One of the findings that really struck me in your 0:16:01.956 --> 0:16:06.396 paper was the finding that if immunity two stars COVID 0:16:06.476 --> 0:16:10.876 two is not permanent, is likely to enter into regular circulation, 0:16:11.236 --> 0:16:14.276 sort of like the flu comes around every year. There's 0:16:14.316 --> 0:16:16.876 something a little terrifying about that because the idea that 0:16:16.916 --> 0:16:19.036 we'll have stars CoV two with us in this form 0:16:19.076 --> 0:16:22.876 for a long time is kind of world changing. But 0:16:23.356 --> 0:16:26.076 hidden in there is a fascinating assumption that I think 0:16:26.116 --> 0:16:28.276 opened something that I did not understand at all, and 0:16:28.276 --> 0:16:29.756 I wonder if you would share with us, And that 0:16:29.876 --> 0:16:31.996 is what does it mean to say that if the 0:16:31.996 --> 0:16:36.156 immunity is not permanent? I tend to think I think 0:16:36.156 --> 0:16:38.196 a lot of non physicians tend to think that either 0:16:38.956 --> 0:16:41.756 you do become immune after you're exposed to something I 0:16:41.756 --> 0:16:45.436 have antibodies, or you don't become immune. But I'm sensing 0:16:45.516 --> 0:16:48.396 that that's not the right way to think about it. Immunity, 0:16:48.596 --> 0:16:52.036 we like to think of, is something that is lifelong, 0:16:52.396 --> 0:16:57.676 sterilizing protection that you get infected with something, you develop 0:16:57.716 --> 0:17:02.956 immunity to it, and you are protected against infection with 0:17:03.076 --> 0:17:06.796 that particular pathogen for the rest of your life. This 0:17:06.916 --> 0:17:10.596 is one of the concepts we think about for vaccines generally, 0:17:10.916 --> 0:17:14.716 and it's in some ways how they're pitched. Although you 0:17:14.756 --> 0:17:17.516 know from your own experience, if you go in for 0:17:17.676 --> 0:17:21.476 all of your recommended vaccines, as one should, you might 0:17:21.796 --> 0:17:24.876 have wondered why it is that for some vaccines you 0:17:24.916 --> 0:17:29.596 get several doses. Right, So every ten years, for example, 0:17:29.596 --> 0:17:33.036 you're supposed to get an updated tetanus shot right, So 0:17:33.756 --> 0:17:36.716 it gives a sense even just the fact that that happens, 0:17:36.836 --> 0:17:42.476 that immunity is not an all or nothing, It is 0:17:42.516 --> 0:17:45.796 not a one or zero. It is something that can 0:17:45.876 --> 0:17:50.116 change over time. And also that it is not necessarily 0:17:50.836 --> 0:17:54.196 as if you have some kind of invincibility shield. We 0:17:54.236 --> 0:17:56.956 can think of immunity as being in a few different 0:17:57.276 --> 0:18:01.396 categories of things. And does immunity prevent you from getting infected? 0:18:02.036 --> 0:18:08.116 Does immunity prevent you from developing severe manifestations of infection 0:18:08.556 --> 0:18:12.556 should you happen to get infected, And could immunity or 0:18:12.716 --> 0:18:16.716 different elements of immunity help prevent ongoing transmission so make 0:18:16.756 --> 0:18:20.036 you less infectious to others? These are also the different 0:18:20.036 --> 0:18:22.996 ways in which we think about the potential outcomes of vaccination. 0:18:23.756 --> 0:18:28.436 So for SARS CoV two, what we wondered about was 0:18:28.476 --> 0:18:32.436 whether immunity might wane over time. There was a study 0:18:32.676 --> 0:18:38.356 with one of the common cold type coronaviruses where military 0:18:38.396 --> 0:18:41.956 recruits were exposed to one of these viruses and then 0:18:41.996 --> 0:18:47.436 a year later exposed again, and they could still become infected, 0:18:47.436 --> 0:18:50.396 although they had less symptoms. So it seemed as though 0:18:50.756 --> 0:18:54.236 even if they were able to recover and develop an 0:18:54.236 --> 0:18:57.396 immune response to the initial infection that let them clear 0:18:57.476 --> 0:19:01.476 it That immune response was not of sufficient strength and 0:19:01.756 --> 0:19:05.556 duration that they could not a year later again become infected, 0:19:05.676 --> 0:19:08.556 although it was for many of them enough to limit 0:19:08.716 --> 0:19:12.996 the end of symptoms. We see this with many pathogens. 0:19:13.156 --> 0:19:15.796 One of the reasons why influenza is such the challenge 0:19:15.836 --> 0:19:20.196 that it is is in part because immunity to flu 0:19:20.356 --> 0:19:24.956 seems to change. Flu itself seems to change, so the 0:19:24.996 --> 0:19:28.596 pathogens themselves may evolve in response to the immune pressure 0:19:28.676 --> 0:19:31.756 from the human populations. We don't know whether this will 0:19:31.796 --> 0:19:35.196 be the case with sarscoby two. That is yet to 0:19:35.236 --> 0:19:37.676 be determined as well. So there are a variety of 0:19:37.756 --> 0:19:42.756 factors at play, both in the dynamics of the human 0:19:42.796 --> 0:19:47.356 population and individual level immune response, and in the evolution 0:19:47.396 --> 0:19:50.996 of the pathogen as well. So the takeaway then is 0:19:51.036 --> 0:19:54.556 that if exposure to the virus creates an immunity that 0:19:54.676 --> 0:19:58.476 is time bound or that is not capable of completely 0:19:58.476 --> 0:20:00.716 eliminating the chances that you get the disease later on, 0:20:00.796 --> 0:20:04.356 but just weakens the case that you get, or if 0:20:04.356 --> 0:20:06.836 a vaccine does either of those same sorts of things, 0:20:07.636 --> 0:20:11.956 then we're going to get very possibly an annual COVID 0:20:12.036 --> 0:20:16.796 scare and that could last. I take it indefinitely, because 0:20:17.516 --> 0:20:20.716 if we're not talking about total immunity, then herd immunity 0:20:20.756 --> 0:20:23.956 is in a sense a misnomer. The herd will never 0:20:23.996 --> 0:20:26.196 be completely immune because no one is, on this theory 0:20:26.516 --> 0:20:29.916 completely immune. They're just partially or immune in some time 0:20:29.916 --> 0:20:32.076 bound way. And then it will have to become something 0:20:32.116 --> 0:20:34.636 that we're going to have to manage going forward without 0:20:34.876 --> 0:20:38.836 particular end, even if there is a vaccine, again, depending 0:20:38.836 --> 0:20:41.596 on how the vaccine operates. Yes, so if we get 0:20:41.596 --> 0:20:46.036 a vaccine, and I want to add a note of 0:20:46.996 --> 0:20:50.636 caution here that it is not a given. Even with 0:20:50.716 --> 0:20:54.276 the recent positive news from the phase one of the 0:20:54.316 --> 0:20:57.396 Maderna trial, it does not seem to me a given 0:20:57.476 --> 0:21:01.996 that we will have an effective vaccine for sure. I 0:21:02.156 --> 0:21:05.436 just point out using the example of HIV, a very 0:21:05.436 --> 0:21:09.076 different virus to be sure, but nonetheless a cautionary tale. 0:21:09.116 --> 0:21:11.196 We have been trying to get a vaccine for HIV 0:21:11.396 --> 0:21:14.396 for thirty years and we still don't have one. So 0:21:14.916 --> 0:21:17.676 just to keep that in mind, I hope we get 0:21:17.676 --> 0:21:20.916 one for SARS CoV two, and get one quickly. That 0:21:21.076 --> 0:21:26.196 is highly effective and that does induce long lasting sterilizing immunity. 0:21:26.276 --> 0:21:29.596 But if we don't, then you're absolutely right. We are 0:21:29.676 --> 0:21:33.396 going to be looking at dealing with SARS CoV two 0:21:33.516 --> 0:21:39.316 as another of the seasonal respiratory viruses. It will join 0:21:39.396 --> 0:21:44.436 the ranks of influenza para influenzas once or for respiratories, 0:21:44.436 --> 0:21:48.596 and sitial virus, man aneuma virus, the other coronaviruses, rhinovirus. 0:21:48.596 --> 0:21:53.876 They're a whole panoply of respiratory viruses that cause everything 0:21:53.916 --> 0:21:57.956 from common cold to very severe outcomes including death, that 0:21:58.036 --> 0:22:00.516 come through the human population regularly, and it may be 0:22:00.716 --> 0:22:04.476 that SARS CoV two will join that group. Is there 0:22:04.516 --> 0:22:07.276 any way to know whether a particular type of community, 0:22:07.316 --> 0:22:11.476 whether it's naturally occurring or whether it's vaccine induced, will 0:22:11.556 --> 0:22:15.796 last over time other than waiting over time to see 0:22:15.836 --> 0:22:18.356 what happens? I mean, is there any way to prefigure 0:22:18.396 --> 0:22:22.956 that out? Yeah? No, not that I know of. I 0:22:22.996 --> 0:22:26.156 think it is something where it really takes time to 0:22:26.196 --> 0:22:28.396 figure it out. Part of it is, you know, what 0:22:28.556 --> 0:22:32.876 is the robustness of the immune response, and then watching 0:22:32.916 --> 0:22:35.716 what happens even over short periods of time to see 0:22:35.716 --> 0:22:42.236 whether antibody levels rapidly decay or are maintained. What am 0:22:42.236 --> 0:22:45.876 I not asking you? What are major points that you 0:22:45.956 --> 0:22:50.196 think are not being sufficiently discussed in public right now? 0:22:50.316 --> 0:22:52.916 About broadly speaking, the issues that we've been talking about. 0:22:53.276 --> 0:22:59.756 I think that there are a few key points that 0:23:00.076 --> 0:23:03.716 we haven't discussed that we should be thinking about. One, 0:23:04.436 --> 0:23:07.516 we've talked about vaccines, but we have not talked about therapeutics. 0:23:08.076 --> 0:23:14.836 I think therapeutics really give us the best and probably 0:23:14.916 --> 0:23:21.836 closest off ramp. If we had effective drugs that could 0:23:22.756 --> 0:23:28.036 diminish the possibility of severe disease, that could really treat 0:23:28.156 --> 0:23:31.916 and cure infection with stars CoV two, the need for 0:23:31.996 --> 0:23:36.556 a vaccine would go down tremendously. We could manufacture these drugs, 0:23:36.716 --> 0:23:39.516 especially if they were oral drugs. Of course, there are 0:23:39.516 --> 0:23:41.836 all the issues with resistance, and I'll just say the 0:23:41.876 --> 0:23:43.556 reason that I haven't asked you about that is that 0:23:43.956 --> 0:23:46.556 we've talked about this extensively on the show on other occasions. 0:23:46.996 --> 0:23:51.236 Remdesivir does seem to be producing some appealing results, but 0:23:51.316 --> 0:23:53.276 the numbers that are reported thus far, at least in 0:23:53.316 --> 0:23:58.116 the NIH study, were not world transforming. It was mortality 0:23:58.156 --> 0:24:00.516 from eleven point six percent to eight percent, which is 0:24:00.556 --> 0:24:05.196 meaningful but is not fundamentally transformative. And reduction of time 0:24:05.196 --> 0:24:08.436 and hospital by some number of days also great, but 0:24:08.596 --> 0:24:10.956 not formed of an I understand that this could be 0:24:10.956 --> 0:24:14.436 combined with other anti virals and potentially something could be 0:24:14.436 --> 0:24:16.476 cobbled together. So or not ruling it out in any way, 0:24:17.356 --> 0:24:19.556 but it seems as though some of the initial enthusiasm 0:24:19.596 --> 0:24:21.196 that we would find a therapeutic that would be the 0:24:21.276 --> 0:24:24.676 magic solution has waned in recent weeks. I think that 0:24:25.276 --> 0:24:32.516 enthusiasm should needs. It's too easily swayed and endurance and 0:24:32.676 --> 0:24:38.476 a continued investment is required. We should not expect that 0:24:38.516 --> 0:24:42.276 our first shot on goal will go in. We will 0:24:42.356 --> 0:24:46.356 need to continue that investment. If anything, I would say, 0:24:46.436 --> 0:24:49.396 there's encouragement that we were able to take a drug 0:24:49.476 --> 0:24:53.596 off the shelf and show that it has some anti 0:24:53.716 --> 0:24:59.836 viral activity that is clinically meaningful. Investing further in finding 0:24:59.836 --> 0:25:03.196 other drugs that have more specific activity or that are 0:25:03.276 --> 0:25:07.156 more clinically effective, I think is hugely important. What about 0:25:07.196 --> 0:25:10.516 monoclonal antibodies. We had a Kiko Iwasaki from now on 0:25:10.556 --> 0:25:12.036 the program and she said, you know, no one is 0:25:12.076 --> 0:25:15.196 paying sufficient attention to this, and she even expressed some 0:25:15.236 --> 0:25:19.116 puzzlement about why more people aren't focused on monoclonal antibodies. Yeah, 0:25:19.276 --> 0:25:25.036 I think monoclonal antibodies most likely given in combination, So 0:25:25.196 --> 0:25:28.836 not just one anti saris COB two antibody, but several 0:25:28.876 --> 0:25:32.036