Pandemic: Coronavirus Edition

Omicron, the Tesla of Variants...

• Dr. Stephen Kissler and Matt Boettger • Season 1 • Episode 91

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Matt Boettger:

You're listening to the pandemic podcast. We equip you to live the most real life possible and the face today's crisis. My name is Matt Boettger, and I'm joined with my one good friend once again, Dr. Stephen Kissler and epidemiologist at the Harvard school of public. From one us citizen to another happy Thanksgiving.

Stephen Kissler:

Hello? How are you? Hello?

Matt Boettger:

Good, good, good. How was your Thanksgiving? Was it splendid full of Turkey, stuffing, gravy, everything to make you go into a coma?

Stephen Kissler:

It was splendid and we did go into a food coma. A little bit unconventional though. There's so we stayed in Boston this year. We just had two friends over, so it was a pretty small Thanksgiving. So the bird was fittingly smaller too. We ended up doing chicken instead of Turkey. And yeah, but otherwise it was a.

Matt Boettger:

Awesome. Yeah, we're here. We had a wonderful Thanksgiving and got to see Nana. The boys were just incredibly excited. It's been all day. We had planned not to cook that much on Thanksgiving and to try to be with Nana and the boys. But in fact, we cooked all day. So a big that's one of our regrets where next year we're doing. So

Stephen Kissler:

that's the way to do

Matt Boettger:

it is so those of you who have family and have little ones, you know what, probably the feeling I'm guessing if you have to cook the whole meal yourself with like kids under eight or seven. But it was a wonderful time. It's still been a wonderfully warm weather here in Colorado, which is a great, but also. Fearsome with the mountains. It's pretty dry. We went to go cut our tree down. We go down to the Mount, we go up to the mountains and cut her own Christmas tree and we don't have there. And there was no snow anywhere to be found, which was our first year going up with nothing. So, hopefully we get some precipitation soon. Now we're giving a gearing up for Christmas. So during this time, Stephen, something really just percolated quickly. I couldn't believe this. And so well, you know what, before I do that, let's just quickly say. If you can support us, pay a patrion.com/pandemic podcast, this is a$5 a month can help or a one-time gift, a PayPal Venmo in the show notes. And then also before I get into the craziness with OMA Cron and the variant, there were two reviews that came in that were wonderful. Let's see here. I'm trying to look at the first one here. My notes are going, oh yeah. So we're going to go and skip that for now because it just skipped all over, but we had two great reviews. Thank you so much. Keep them coming. Let's see if I can get this one going. Here we go. I'm very happy to discover this podcast. I've been listening mainly in the last couple of months. I really appreciate the scope of the information. What is discussed is backed up by the most recent data in a rapidly changing environment. It is really helpful to have data, to make informed decisions about behaviors this week, which was probably a couple weeks ago. For example, they provided concrete ways to help make family gatherings more safe. Thank you for your work. You're doing that. It's awesome. That is from counts 11. So love those usernames. So thank you so much north woods or wherever your name is. I'm assuming that's not your real name. But thank you so much for that. And there was another one. I won't read it now, but we'll get into this, but I just want to pick your brain for that. Another five-star review from dragon wings, one to 1 21, but this person, he or she works in the jail. So apparently he or she has written a public service and talking about how this idea of like, wait a minute. It seems as though in the jails, it's oftentimes the first to hit away. And so why not use this as an indicator of what's to come? And has this been something that's been looked at among your colleagues or at least maybe not jails, but in general, like different little pockets, information, pockets by which seemed to get Kindle faster before other places.

Stephen Kissler:

Yeah. So this is a great question and absolutely something that we've been thinking about and working on over the course of the pandemic. So, Earlier on in I guess this was probably like mid 20, 20. I had a, a series of conversations with a reporter named Deborah Becker at WBUR here in Boston. And among the things that she reports on his his, his presence. And she had been doing that pre pandemic as well, but really, especially once the pandemic hit, there were a lot of questions about the role of the pandemic in prisons the extent to which prisons were equipped to handle outbreaks and sort of what we can. Well, we can infer from what's happening in prisons for, you know, for the wider population and vice versa, what, you know, how we can manage the spread of COVID in prisons based off of what's happening in the wider community. So it's true that in a lot of cases That in I'll say more generally that these sort of congregate care settings or, or places where lots of people are living together in close proximity. So prisons of course, but also nursing homes long-term care facilities and places like that even schools to some extent although many of those were closed early on in the pandemic. Are definitely places where the virus can often gain an early foothold. I think one of the clearest examples of that with some of the the first major wave, which happened in the summer in Arizona one of the initial indicators of that was a major prison outbreak. And so, it's absolutely true that that in many cases These places where lots of people are in close proximity. And prisons is of course, one of the, one of the key examples of that that we see early spread, but it's not always the case because a lot of times these places are also places where there's less interaction with the surrounding community. And so oftentimes what we see is that COVID will. Spread rapidly through one of these communities. And on average, they're probably on the early end, but sometimes they're not you know, sometimes they get spared to some extent until later on in the wave. And then they see their major surge. And one of the difficulties with prisons both was protecting the prison population itself. And with sort of inferring, you know, what might be in store for the rest of the population is that. You know, oftentimes their testing is really frankly, not up to snuff. That's been one of the real difficulties is getting solid information about the number of COVID cases in prisons, because as you can imagine, there tend to be pretty underserved. And there's not a lot of interest in, you know, testing doing surveillance within prisons, even though frankly, there really should be. And so, In a lot of cases, prisons are places where absolutely there's a lot of COVID transmission happening. But a lot of it, we just don't know an awful lot about. And so there's been a lot of effort there for prison rights advocacy which, you know, and I think that this you know, gets towards a much larger sort of principle of the overall pandemic, which is the, you know, we, we are all in this together, you know, rich, poor In prison out of prison, you know? And and it's easy to adopt the sort of protectionist mindset and to sort of only pay attention to what's happening in our population and the people that we normally see. Even speaking from just an epidemiological perspective, that's a foolish thing to do. Because the virus is going to spread everywhere and, you know, none of us is healthy or safe until all of us is healthy and safe. And the, and so I think that that really, really strongly advocated. Better surveillance, better care in all of these vulnerable populations including the prison population. So very great point, definitely something that we're looking at, but also something that we need to do a lot more work on to both protect the prison population as such and to then, you know, have a better sense of what's happening in those communities so that we can have a better sense of the broader community, both what's to come and what's already happened.

Matt Boettger:

Great. That's perfect. And thanks for making that nuance between like, like the descriptive and the prescriptive, like it's one thing to describe what's going on in prisons and how that might be able to tell us what's coming in the future. But at the same time, that's not the point because they're not meant to be a series of lab rats to let us know what's coming. And in fact, there's a prescriptive element by which the it's like, it's going back to way back in March of 2000, we talked about that great CS Lewis quote. The rats and the seller. And when you quickly turn on the light too, you see the rat and he's slowly being around. They go away, but the light didn't cause a lot, the rats it's the suddenness. And so the suddenness of this pandemic has really revealed some of the areas by which we have. We are weak in participating in helping those who need that assistance. And so we need to use that as a prescription to make things better. So we don't have to use this as a scarily as a way to protect ourselves, but let's continue on. Before we get to Alma Cron. Let's talk about the flu because you know, it's been, I've been out of a week. I've been trying to take some time off family. I haven't really been participating in looking at the news on the flu that much and selling to get your analysis of like what you've heard or seen it right now with the flu compared to last year. Is it re raising its ugly head is it's it's it's you know, where are we at when it comes to flu? Yeah. Compared to last year, but last year, but in general.

Stephen Kissler:

Yeah. So, flu is spreading here in the United States and around the world. And currently in most places across the U S it's still at pretty low levels which is not terribly surprising. Usually our flu season starts to come in, you know, maybe around now, but oftentimes it's skewed a little bit later towards January, even February when we start to see a lot of high levels of flu transmission. So it's a little early to say it does look like some places in the mid and mountain west. Actually New Mexico has quite a few cases right now. It seems. But a lot of the rest of the country is. So bad at the moment. The main flu strain that we're seeing in the U S right now is H three and two. So with flu, we have a couple of different strings right now is sort of the two major ones are H one N one and H three and two, and every three or four years, they sort of trade off. So you'll have three or four years of age, three and two, and then three or four years of age one-on-one they differ a little bit in terms of how infectious they are, how severe they are. But for the most part, they're pretty interchangeable. And so, the, the fact that it's that particular strain circulating is more of sort of a epidemiological curiosity and something that I'm paying attention to, but it's not necessarily something that will affect our day-to-day lives. So right now transmission mostly seems low across most of the. And is roughly in line with what we expect to see around this time of year on average. But we're watching it closely because there's definitely flew around and cases are starting to tick upwards in line with how they would normally tick upwards. So I do expect there to be a flu season this year. And it's impossible to say at this point how bad it will be. One of the things, of course we've been thinking about a lot now, too, is that, you know, especially with the news about the Omicron variant you know, the question is now to what extent will these things be superimposed on top of each other? And that of course could cause some issues as we move forward. But right now there's not a lot we can say about what exactly is in store.

Matt Boettger:

Then you made a segue perfectly to Omicron. So this was crazy Stephen, because like, you know, it was funny. On Thanksgiving. I was talking to my sister-in-law, you know, and she's like, you sound like an epidemiologist to make it because I hang out with one. So I'm just the messenger. She was wanting information about like, you know, the booster, this kind of stuff. And then I was just talking about, oh yeah, we're. You were talking about how, you know, we do think that some point in time, hopefully relatively soon that these variants are going to like level your time. And, you know, I wouldn't even look at the news. I literally, as I'm probably telling her, this is probably now blowing up all over in the media. Cause I was not checking. Then that night I checked in like, oh my gosh, just so I was telling her about this story. This blew up and it's like, literally overnight. And I want you just to go and go every direction you want to on this. But like, you know, my questions are, first of all, like how did this become a sensation overnight? And where are we at with this? How bad could it be? I know we're still in the woods. It's still early on. But the who came out with stuff, Pfizer is talking about it with journeys, talking about it. Gosh, it's probably gonna be on Sesame street next week. Right. So

Stephen Kissler:

where are we? Does the Greek alphabet.

Matt Boettger:

So where, where are we in this? And. Yeah, let's start with that. Before we talk about how this might change our game plans for the next three weeks or so as we gear up for Christmas.

Stephen Kissler:

Oh boy. Yeah. So, I can maybe start by talking about my own experience, learning about the variance. So similarly, you know, we'd had Thanksgiving. I was none the wiser and it was largely away from my phone. And it wasn't until that evening that I sort of checked in and noticed that a lot of my colleagues were already starting to talk about this new variant which at that point didn't even have a name. It only took about a day for the world health organization to give it the name of Omicron and classify it as a variant of concern which is unbelievably rapid. And so one of the things that I want to talk about as we move forward to sort of like why. So quick. And so, yeah, so I, I tried to learn as much as I could about it in the next hours and days, basically. So basically everything I'm going to spread back to you all are the things that I've been studying up on over the last few days and the sorts of things that my colleagues have been talking. And we've, we sort of find ourselves in, again, this situation that we've so frequently found ourselves in where you know, we, as the scientific community, as well as the broader public are trying to make sense of something where the pieces just aren't quite adding up yet. And eventually we'll have the right mental model to understand what's happening and why all of the things that we've observed have happened. But it's really interesting because I don't think that it's often that we get to see. As sort of, you know, as the human population sort of putting together knowledge on the fly. And we've gotten that opportunity a lot of times during this pandemic and here's here's yet another one. So after we talk a little bit about sort of the, the speed with which this gained attention, I also want to talk about some of the unknowns what we know, what we, don't, why we don't, when we will. And those sorts of those sorts of questions as well. So, You'll notice them. I'm also clearing my throat a little bit. I I I got boosted this past Saturday, and so I'm still feeling slightly under the weather. I think that my lymph nodes are still draining, so that's way too much information for all of you on the podcast, but I just want to be, I just want be sure. With with what's going on over here. I can talk about that experience too, because I think that actually one of the big questions with over is, is the question about vaccines and boosters and will they hold up. So, as I forget all of these different points that I've just made please remind me because I inevitably will. Right. So, so I think that one of the things that has been especially Remarkable about this variant. And this is true for me as well as for many of the people who aren't specialists. So I've spoken with just how quickly this variant has gained attention. So like what happened here? I think there are a couple of things behind this, so first and I think probably most importantly it was a lot of very swift and responsible efforts on the part of the south African public health administration. They detected that something strange was going on, they were seeing, you know, South Africa has just made it through a major Delta wave of infection. And then they started to see an increase in cases in particular, one of the things that raised. Is that they're PCR tests, which we talked about a long time ago, usually have three different targets. So basically your, your tests, your PCR tests will try to detect three distinct parts of the virus. And they noticed that in a lot of cases, they were getting positives on two of those parts that a negative. If you cast your minds way back to the beginning of this year, that's the same thing that happened with the alpha variant, where there was this target failure this SG and target failure or ESSA dropout that was happening with the alpha variant because the, the spike protein of the virus was mutated in this one part that the PCR tests detected. So the tests were still turning positive. It's not that they weren't. But they noticed that we're sort of, Groundhog day style repeating this, where, where all of a sudden there are these dropouts again. And so they're like, well, what's happening. So they very quickly got on it. They started sequencing some of these samples and noticed that what they were sequencing was really pretty different than a lot of what they had seen circulating before. So more on that in a moment, but they they detected the variant and very quickly held a press conference. We're very clear about what they knew, but they didn't know and shared this information with the world which is exceptional. That's exactly what we want. And so. As opposed to a lot of other situations in which it's taken a lot longer for these things to be detected. There were a couple of strokes of luck and a couple of strokes of genius. And that got us into this situation where we detected this thing very quickly, very early on. And so it was really able to spread the information was able to spread very quickly around the world to the great, great credit of the south African scientific community and political community as well now. Yeah. So I think, I think I'll leave that there for now. We can sort of circle back to a broader discussion

Matt Boettger:

on that in a moment. Quick question on that. So then just so you know, you said the alpha, did the Delta not have that because, so then, so then it didn't have that kind of, so it was gone for a while and then it raises its ugly head again. Okay. Exactly. Continue to get that narrative.

Stephen Kissler:

Yep. Yup. And so, you know, that's, that's an interesting point because I think the next thing that You know the question of like, why is there so much attention around this? You know, we've had, we've had multiple other variants. We've had, you know, the mew variant and the Lambda variant. And in a lot of previous podcasts, we sort of talked about these and it's sort of like, yeah, these are like issues for certain parts of the world. But like ultimately, you know, none of them have shown this really at the ability to out-compete Delta. And so, you know, something to pay attention to you, but, you know, Delta's the thing. So why, why this one now? And so there are a couple of reasons. So first while South Africa actually has a relatively low vaccination rate compared to The U S in many European countries, although a high vaccination rate relative to many of its neighbors in the African continent it has also had a lot of spread. And so despite relatively low vaccination rates there out to be a pretty high level of previous of immunity from previous infection. So already starting to see an uptick in cases with a new variant is a bit of an alarm and actually begins to point towards something that looks like maybe immune evasion. So that's, you know, sort of the first alarm bell that started. So as they sequence to the virus we were able to sort of get some more insight into what might make this variant special. And so the second thing that was super alarming was the, just how mutated to this virus is. It really is carrying a lot of mutations relative to anything that we've seen previously. And so. It's really hard to pinpoint where exactly it came from. I mentioned that it has this SG and dropout, and so in some sense, that kind of makes it sound similar to the alpha variant. And maybe it's more closely related to that, but it really seems like this is something that evolutionarily has kind of diverge pretty profoundly from previous things that have been circulating and has picked up a lot more mutations and things that we've seen previously. A lot of these mutations. Spike domain of the V of the virus. And so what that points to is that it's been sort of actively selected for and that these aren't just a bunch of random variants or a bunch of random mutations, but actually that they probably, you know, and I'll talk more about the implications of that in a moment. And then, yeah, and then a lot of the mutations that we've seen There've been laboratory studies previously that have looked at the effects of different single point mutations. So you can take you, you can sort of deconstruct the virus and pull off its different segments, including the spike protein so that the virus is no longer sort of infectious. It can't spread, but then you can do these laboratory experiments. That look at how how well that spike protein binds to different human cells and how well the antigens that are produced by that protein are, are, are neutralized by human antibodies, for example. And so you can do a lot of experiments that can then implicate different mutations of saying like these particular mutations. If they show up in nature would be. It turns out that the OMA variant contains a lot of those mutations, both mutations that have been implicated in better binding to the human receptors. So probably a greater transmissibility and places that tend to be immunogenic. So places where we expect there, if there are mutations that it might get around some amount of of our immune response. So that's another reason why it gained so much attention so quickly is because it was like, wow, this is really sort of, you know, coming out of it's unlike things that we've seen before, and it's really carrying a lot of these mutations that at least in theory could give it a lot of these concerning characteristics. So I think that those, those things combined are part of why it's risen so quickly to the general attention. And so now we're sort of. Frustrating situation where we have this variance, we know that it's grown in one part of the world. We know that it's been detected in other countries. We know that it carries these mutations that could make it concerning, but we don't yet know how those actually play out in the real world. And that's, you know, one of the big issues because one of the big challenges with genetic and microbiological studies. You know, as, as such, you know, with viruses and with everything, is that we're beginning to get a good sense of what happens when you mutate sort of one small part of the genome, but things get much, much more complicated when you mutate multiple parts together because the, the protein structures interact with each other in ways that aren't really very well predictable. And how those then interact with human physiology is also very unpredictable. And so it's really unclear sort of how this constellation of mutations is going to play out in the real world. And the only thing that we can use to know for sure is actually observing what happens. And so we're in this sort of frustrating waiting period where we we don't know exactly how it's going to behave. So what do we do? Well, I think one of the useful things is to think about is we do have a rough timeline for when we expect to have more information about these different characteristics. And so the three characteristics that we're usually interested in most with new variants are immune escape as the first transmissibility as the second. So how infectious is it and severity is it more or less severe than, than previous variants? And so, I think that that's sort of the order in which we can expect to understand new information about this. So in terms of immune escape one of the nice things. In some sense about that is that we can continue to do these laboratory studies with the Omicron variant and look at neutralizing antibody Sera from so, so parts of the blood that generally neutralize viral infections, and we can see sort of in the laboratory to what extent are previous immunities, both from vaccination and or from previous infection, stand up against the Omicron variant. We can also look at Epidemiological evidence from people who have been vaccinated, who had been previously infected and see whether or not they become infected again. So these studies are underway and I think that that's probably the first thing that we'll get information on probably in the next one to two. Okay for transmission, that's going to be a little more on the order of two to four weeks, because we actually have to see this thing spread in multiple contexts to understand sort of, to what extent did it just happen to gain a foothold in South Africa versus to what extent is it sort of more broadly transmissible in other populations with different age distributions, with different levels of immunity across the population with different types of interventions in place and masking, et cetera. So that'll take a little bit longer And so I think that probably something realistic for a very clear estimates of the transmissibility is two to four weeks. Severity is much more difficult. So there've been these reports from one of the doctors in South Africa who was saying that like, you know, it, it seems like these infections that I've been seeing are actually pretty mild generally, and that, you know, that's very good news if that's truly the case. But I really want to caution against using anecdotal evidence too much. One of the things we know is that it takes a while for severe cases to become severe. And we haven't really been paying attention to this variant for a very long time. And because of that you know, because it can take weeks for a person to really become severely ill with COVID-19, it's going to take probably on the order of one to two months to really understand the degree to which the severity of the Omicron barrier differs from the severity of previous various. Now, with all of these things. I don't know if I can say it's a good thing or a bad thing, but the more severe Omicron is on any of these axes, the sooner we'll have information about it. So if the spread is absolutely explosive, if it's really got a much higher reproduction number we'll expect it to take off much more quickly in different places. And we'll know that a lot sooner. Similarly, with the severity, if it causes symptoms sooner, or if it causes much more severe symptoms, then we'll probably know that pretty quickly. So in some sense, the longer we're waiting to answer these questions the better. And so, that's, you know, that's one thing to keep in mind as we move forward, but that's, you know, that's, that's some of the complexity that's facing us is that, you know, there's, there's so many people, both scientists and nonscientists out there sort of trying to make these projections and, and assessments about the data and what is, and what isn't. And right now it's just like, We just don't and can't possibly make some of these conclusions yet because the data just doesn't exist and we can sort of hazard some guesses in some direction, but, oh boy, it's going to be a little while. So I think we just have to hang on.

Matt Boettger:

Yeah, that's helpful now. Okay. So there's a number of questions and we'll talk about the booster in just a second. But looking back so far, you know, we haven't seen anything in the U S but I think I was looking at your Twitter feed, which I think is a great trigger for you to follow. He repeats a lot of great people, great scientists. So like it, see. Among the scientific community. That's probably here in the U S somewhere. It's just that we aren't as good as South Africa and the places are to actually do the genetic or whatever we, the, the sequencing and actually see if it exists. Is that, should we just kind of assume it's probably on some level in the U S by now, already?

Stephen Kissler:

Yeah. So I would assume that we probably have some cases here in the U S Some of the, you know, some of the fact that we haven't detected it may have to do with with sequencing, but you know, we've actually, in the last few months, we've actually done an awful lot to ramp up our sequencing capacity. And so, while we may not be sequencing as high of a fraction of of cases as for example, the UK we've really made up made up a lot of ground in that area. And frankly, I'm actually a little bit surprised that. Detected any of them yet? Especially because we know that we can detect this variance with PCR as well, not just through sequencing. So we're definitely looking for this variant, both through sequencing, but also through this S gene target failure. And we haven't detect. Either to my knowledge in the United States. So while I do expect that it probably is circulating here already given how many other places in the world it is. I do think that the fact that we haven't detected it yet suggests that it's not, you know, rampant. And that really probably what we have in the U S has mainly dealt.

Matt Boettger:

Okay. So then now take into like, what do we do in this situation? Because now, okay, so now there's this Alma Cron, you know, we're a little bit afraid. There's a lot of unknowns. Granted, there could be some information coming soon. Maybe we don't want it to come soon. Like you said, we want to come later. Give us a little bit insight. This, this falls, you know, right before the holidays, we just got into a holiday. We just had family. Now we have a little gap and now we're going to get ready for the holidays again. So what, what do we do in this situation? So let's come back to the booster as one, one solution and talk about to what extent can we put some hope that the booster and the vaccine may, if not completely address this Omicron variant at least offer some level of

Stephen Kissler:

protection. Yeah. So, You know, the, the definitive evidence about the vaccine's effectiveness against Omicron, like everything else is going to be sometime in coming. But I think we do have good reason to believe that our best protection that we currently have against Macron is still the vaccine. And that's because the vaccine has largely held up pretty well. Again, in terms of severe disease and hospitalization and death against all of the variants that we've seen so far. So even though it was originally formulated against the founding strain, essentially It's in terms of those most severe complications that tell a pretty well against alpha against Delta. And so, chances are, it will still provide a decent degree of protection against our McCrone as well. Going back to some of our earlier discussions in previous podcasts about the immune system there are multiple arms of the immune system and it seems like with The SARS, cov two the T cell immunity, which is harder to measure it seems to be really key to these responses. And it seems to be in many ways sort of what the vaccines elicit that really protects us from the severe disease. And so. While a lot of the antibody studies that have been circulating about the Macron variant have sort of been alarming in the sense that, you know, it has all of these mutations in these immunogenic sites. A lot of those are still oriented towards this B cell type immunity, the things that you can measure very easily in in the plasma and that. And so I think that we're going to have to wait even longer to understand sort of what the T cell type response is against Homa crown. I Relatively optimistic that the vaccines will still hold up. I do think, you know, frankly, I do think that Omicron will take probably a bigger hit on our previous immunity and vaccination immunity than any of the previous variants that we've seen before. Just because it's so heavily mutated in the spike protein. So I do think that there'll probably be more breakthrough infections even than we've seen with Delta. I do think that there will probably be more symptomatic infections even in vaccinated and previously exposed people. And I think we need to ready ourselves for that, but I do also think that the vaccines will probably end almost certainly before. A good and currently our best protection against the worst outcomes from from the variants. So I would still highly recommend getting boosted. I, as you mentioned before, I can't remember if this was while we were on air or previously, but some of the vaccine manufacturers are already starting to talk about updates. And again, this is one of the great benefits of using the RNA vaccines because they can. Quickly be updated and ramped up to to account for these antigenic shifts. These, these changes in the, in the surface of the virus protein. My biggest concern about that is actually not so much the scientific hurdles, but the regulatory ones. And so it'll be interesting to see how long it takes for those things to be approved to be tested in the ways that they need to be tested before they can be. But some of that will also depend on how much of a issue the Democrat variant becomes because we may reach a scenario where you know, if, if it is really spreading rampantly and it is, you know, a serious issue, then it will have to start considering these emergency use authorizations again, for some of these updated vaccines as well. And for just a point of reassurance about that, I think it's worth remembering that we update our flu vaccine every year too. And there's an expedited regulation process for that. Really there's, there's an existing paradigm for this, that we do this already. And so my hope is that we'll be able to sort of slot this into the same sort of update vaccine update paradigm that we have already existing. But that's way beyond my pay grade. I have no idea what that's actually gonna look like.

Matt Boettger:

I'm sure. You know, I remember hearing, gosh, a year ago, two years ago, maybe it's urban legend, but that like, oh, with the MRI and a vaccine, things can be more quickly adapted and put out there, like without. All the regulatory hoops that you have to jump through. Is that, do you remember hearing something like that or is that just like an urban legend that I read a couple of years ago, that there was some hope that it could be tweaked faster and just put right back out?

Stephen Kissler:

Yeah. So, again, you know, from a, from a molecular and a scientific point of view, that's absolutely true. And that's the big, the big value, but I think the regulatory steps are just a whole different beast and I have no idea what goes into those. So.

Matt Boettger:

And then you taking a couple of things I want to go back to. So you have the Omicron, which is highly, you know, has all these different kinds of mutations, right? Uh it's it's, it's one of those things where I'm thinking my mind. Not every mutation, right. Is, is a benefit. I would imagine. Like, I, I guess this is, this is the complexity, right? When you have smaller amounts of mutations, you can, like you said, you can measure if you're out to how, how, you know, how much worse is going to be, but it's not unimaginable, unimaginable to have a series of mutations that. Not great, but in an orchestrated reality, they actually begin to, to go against each other on some particular kinds of this mutation by itself. It's really great. But with this mutation, it actually neutralizes that and make it not effective. Is that also just part of the complexity of knowing how these actually work together with our own own immune

Stephen Kissler:

cells? Exactly. You know, and related to that is you know, also a lot of our uncertainty about sort of what the virus does to our bodies. We have a decent sense of, for You know, what, what leads to infection. We know that there's this ACE to binding and viral replication within the cells, but what actually makes the virus clinically severe is still a pretty big mystery, frankly. And so, we don't have a good sense of what different mutations do and how those might affect clinical severity. And that's, that's why that's sort of one of the big questions right now because this whole constellation of mutations. We know it might be implicated in immune escape and they might be implicated in increased transmissibility. We have no idea what they would do to clinical severity and it could go either way, frankly. I, I'm glad that you brought that point up because you know, there's been a lot of sort of speculation, especially, you know, amongst sort of the, the general public and even politicians on Twitter, sort of, suggesting that the natural way for pathogens to evolve is for them to become more transmissible, but less. And it's not entirely true. So absolutely pathogens evolve to become more transmissible, you know, that's, that's what they do that is, that is, you know, a natural selection at its vice. Severity is often just sort of a unintended and unfortunate side effect of just pathogens doing what they do now, if there is a pathogen that where severity limits its ability to spread. So for example, if you show severe symptoms before you ever become contagious, then yes. All of a sudden that severity is under evolutionary pressures. Decrease so that the pathogen is able to spread before. You know, before you know that it's there pathogens want to be sneaky. Right. But with the case of SARS, cov, two, most of the spread happens before any of us know that we're infected in the first place. And so its severity is not really under selective. At all. And because of that it's kind of anybody's guess which direction severity might go. And so, yeah, so I think that with this particular virus, we don't necessarily expect the severity to decrease just based off of evolutionary principles. It could happen, but if it does happen, it's, it's by having.

Matt Boettger:

Yeah, great. That's really helpful. Now I want to go back to another thing was one of the tweets that you shared with the what's that lady's name again, if you want

Stephen Kissler:

to follow up. Yeah, so there's Dr. Emma HOD Croft is the one I think she has been doing some really excellent work on The viral genomics understanding sort of like what's going on with, with this variant and how it stacks up against the others that we've seen so far. And

Matt Boettger:

so one of the things she mentioned was this kind of goes a little step above just virology and that kind of stuff, but policy, right, as soon as the Alma Cron happened, there was all of these kinds of like travel bands and, you know, see, she said, look, basically I'm paraphrasing. Travel bands have never worked to actually stop the transmission and plus it just punishes those people and you know, which I could kind of see it now. Cause now you even have articles with South Africa. It's like, now you're punishing us because we were so good. And then of course, now I'm thinking, oh my gosh, now, now our other countries, when we want to hide their variants, because they don't want to have a travel ban because now there's this pressure. Like, no, I don't want to be the first one to say it because then guess who's going to put me on the bad, the naughty list for Christmas or whatever, you know? So. You want to talk, you know, maybe speak in a little bit, because in my mind I'm thinking, oh, travel bands are like a, an aggregate mask, right. It's like, you know, we're gonna put up, it's like six feet of distance. This is now, you know, 6,600 miles of distance. Right, right. We put a mask on and so just wait, just like it should. It should help, but maybe that's it, or maybe it might help, but it doesn't actually, he doesn't actually complete prevent. Can you tell a little bit about how the, the history of traveled band and if it doesn't work, why we got to this point of just like immediately, like you're, you're no longer, you're no longer able to come here or we can.

Stephen Kissler:

Yeah. Yeah. So, you know, broadly, I really agree with what Dr. Hopcroft was saying about these travel bans and the they can be helpful in some circumstances. So what travel bands tends to do is they buy you some time. We haven't really ever been in a setting with a respiratory pandemic infectious disease where travel bands have totally prevented the introduction of a pathogen. Especially, you know, especially with SARS, cov two, like it always comes at one point or another travel bands can slow that down. So with the travel ban, you always need a very clear plan for what you're going to do with the time that you're buying yourself. The travel ban can never be a policy unto itself. And further to that, once there's clear documentation of. Within country transmission, that's a widespread, then the vast majority of your cases are likely going to come from that. And then it doesn't really make sense to maintain the travel ban because travel bands are extremely disruptive and they interrupt both the economic links between countries, but also the scientific links. It becomes a lot harder to share samples and to share knowledge about about the very thing that we're trying to. Prevent the spread of here. And like you said, it also imposes these very strong incentives for countries to not report things that are of international importance. And so I think that, you know, travel bands do make sense in some contexts but they need to be imposed swiftly with a plan for what to do with the time that you've gained and they need to be. Loosened immediately, as soon as it's clear that there's the uptake of spread within a country simply because they're so, so disruptive. You know, so I think that there's, you know, there's room for argument around these things. A lot of people have really been coming out sort of very strongly against or strongly for travel bands. And, you know, as is the subject of this entire podcast, right. There's like a lot of complexity and nuance here. But that's precisely because, you know, travel bans like masks are only effective when done in. Tandem with a number of other interventions. And so, with these travel bands, we really need to be thinking about, okay, what do we want to do with the maybe week or two that we're going to buy with this extra time? Because realistically that's, that's all that's going to be.

Matt Boettger:

Yeah. That's helpful. Great. Thanks for sharing for that. Let's go back to quickly the boosters, before we wrap this up. Just, you know, Stephen, you were talking about this, Madonna announced a strategy to address Omicron, which is really hopeful. So just for those who are listening, I'll put the show in, I'll put the link in the. They have three steps by which they're going to address Omicron, which is really great. First Madrona has already tested a higher dose booster of Emma MRI. Now, if you guys think back, back in the original, the first vaccine one of the things that made Medina more effective and granted I'm just a messenger, that's all stuff that Stephen and Marcus told me. So I'm just spitting it back out to save Stephenson words. And that is basically it was, I think almost like twice a dose of Pfizer. And so. That's what made it so powerful and Pfizer had less dose and from what I have read, partly so they could slip in and get FDA approval faster because with, with a lower dose, you'd probably have less side effects and those kinds of things. So that helps to get approved faster. So it sounds like the booster from a dhurna, it's kind of like right. The Pfizer one where it's half it's, half the dose of what Madonna was going through. Is that correct? Stephen? Yep. The current booster. And so now they're looking at a higher, that's a booster that's twice. I guess that's twice as much in it. So that's their first one. Second modern is already studying to multi-view Vaillant booster candidates in the clinic that were designed to anticipate mutations such as those. So that's, that's hopeful. It's already been in third, maternal will rapidly advanced an Omicron specific booster candidate. So that's our three steps that are going on. Pfizer also had a promise basically of if it is warm, Th th within a hundred days to have an Omicron booster shot with an advisor. And of course, as you just stated, that's the actual clinical side of things. The other side, the policy, the safety, that's a whole other beast of its own. It does not mean right. That in a hundred days would have a vaccine in our arm.

Stephen Kissler:

Yeah, that's my understanding. So

Matt Boettger:

great. Last couple of things on here, when it comes to boosters there was an article that came out. I saw, I read about cover boosters with children and how we don't know yet. Of course, cause everything is really new, but there is a possibility that you may not, our little kiddos may not need a booster because their immune system is so. Good. If you guys would go back maybe six months ago when they were doing clinical stuff on the original vaccine, just how much more effective it was, like almost pretty much a hundred percent with, with kiddos because of their, their, the response was so great. And oh yeah. I think I said anything. Any last words

Stephen Kissler:

for you, Stephen? I think that's it. Thanks for the whistle stop tour.

Matt Boettger:

That was awesome. Oh yeah. One last question we had at the home as we prepare for Christmas. Any, any, any tips on what we should do? For example, my mother-in-law again, I'll I can use the, my own personal story. Sorry guys. But hopefully some of this resonates with you. She's 87 years old. She has the maternal vaccine. She does not have a booster. Don't know if she's going to get one. When she's going to get one, Christmas is revving up. We have some people wanting to invite us to their home next week to have dinner in their house. They're all vaccinated. Right. But they're all, but they also have high school children that go to public school. Right. And so is this something that we should, oh, it's okay. They're all, we're all vaccinated. Our kids are not our little kiddos. Aren't. So is that a safety thing that it's okay. Go head, go have dinner next week. And then that's plenty of time before Christmas to have your mother-in-law in, even though she is flu vaccine, but then the booster you see other complications, or should we begin to like, you know what, let's play it safe. You know, Colorado we're in a particular place where we have a high amount of transmission right now. Do we begin to just kind of offer the level of safety, just kind of quarantine two weeks before or still entertain these events? Any, any, any ideas of dealing with

Stephen Kissler:

complexity? Oh boy. Yeah. It's really difficult. I think that you know, there's, there's a lot of different levels on which you can make these decisions, but I think that, you know, again, Getting vaccinated, getting boosted as the, the best thing that we can do making plans to do that now, especially if you would like to have it by the Christmas new year period of time. Because by the time we get it scheduled and by the time you give it the two weeks to sort of come into full contact, full effect, it's you know, it's, it's Christmas kind of do kind of, kind of got to do it now. So, yeah, so I think that, you know, thinking about that and then Otherwise, it's just you know, in the interim just doing everything that we already know prevents the spread of COVID. So, if you're gathering inside, keep your windows cracked. If people are willing to wear masks, absolutely do it. And I know her don't Thanksgiving. I was especially saying that like, With vaccination and testing and ventilation that you can really sort of not have to distance and mask. But again, it's sort of like, you know, this, this risk budget that we've talked about a couple of times before to where you know, for a holiday like Thanksgiving, that you can often really derive a lot of value from having an unmasked and distanced sort of gathering But if there are sort of, you know, less important, but still valuable gatherings you might be having. In the meantime, it might be worth sort of saving a little bit on that risk budget before the holiday season by wearing masks, by meeting outside, if you're able to. So, really just thinking about these next few weeks, you know, six to eight weeks as a collective unit, and sort of thinking about where you want to spend your COVID risk and where you want to save on it. It's probably the best. Great.

Matt Boettger:

Thanks, Stephen. Good to see a buddy. Likewise, for those of you who want to get in contact with Stephen, you can do that on Twitter. S T E P H E N K I S S L E R. I'd really recommend following him. He's got great tweets, retweets, all these guys. He follows the best people, a great place to be informed and get the right news. If you want to support us patrion.com/pandemic podcast, please do so$5 a month as little as that can help us one time gifts, PayPal, Venmo, all in the show notes. And please leave a review if you can, and inspires us, keeps us going, and we will see you all in a couple of weeks. Take care and.