Pandemic: Coronavirus Edition

Is natural immunity better than the vaccine, and is Moderna the best vaccine?

• Dr. Stephen Kissler and Matt Boettger • Season 1 • Episode 85

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Matt Boettger:

You're listening to the pandemic POS podcast, where we equip you to live the most real life possible in the face of these crises. My name is Matt Boettger and I'm joined with one great friend of mine. Dr. Stephen Kissler epidemiologists, the Harvard school of public health. How are you?

Stephen Kissler:

Fine, sir? Hello, I'm doing all right. It's happy post labor day weekend. Yes.

Matt Boettger:

Happy post labor day. Everybody who celebrates labor day in the U S here. We will make a quick announcement if you notice where we're kind of starting to go to every two weeks. Maybe we'll go back to every week. It's not because there's not any news. Obviously it's just that life is just crazy for Stephen, myself, mark, and to get us all to rally and be every week has been a little more difficult than usual. So we may go back to once a week. At some point in time, we may stay every other, every other week as such, you know, we're here. We want us to continue to be here, but we're trying to navigate being present and available to all of you. And navigate our own crazy lives, right Stephen?

Stephen Kissler:

Oh yeah.

Matt Boettger:

Oh yeah. Well said, well said, so if you, if you can leave us a review, even if we're going every other week give us a little shout out and let us know how we're doing. You can do that on apple podcasts and think there's another other platform you can support us that would help us tremendously. Maybe even get us to be a little more often just to help us get the support. We need an offset. It. At patrion.com/pandemic podcasts as little as$5 a month can help a lot as well, as well as one-time gifts at PayPal or Venmo and both they're all in the show notes. So there you go. Okay. So I feel like we have a lot to talk about. There's some things I think we'll try to just breeze right over. Just talk about it. And then Stephen and I talked before we start recording, there's a couple of things that seem really fascinating, and I want to really unpack it with Stephen. I want to learn a lot more. But before I want to get started with this, I saw this article, Stephen, and I don't know, kind of surprise me. Not really, but this article is Biden said, he'd follow the silent side science to experts. He's sometimes fallen short. Now, when I kind of dove into this expert, we're not going to talk about politics per se, in that area. But when I dove in his article, it seemed like the focus of all things. And they talked about teachers being vaccinated and that might've been not following CDC guidelines. But the meat of this whole article was really about boosters and how he didn't follow the science. So I want to pick your brain because you're an expert. So, and we've talked about this before about boosters. Should we, should we not? And is it good? Is it ethical? And is he falling the science. With the idea of wanting to advance boosters for the U S is he not following science or is this more than just science? Is it policy? And this is just some kind of switch bait headline that we need to just ignore completely altogether. Sure.

Stephen Kissler:

Yeah. So, I mean, there's, I think there's two layers of complexity to this. So the first. The thing about it is that, I, I, and many of my colleagues were w were taken off guards to some extent when the when the administration first said that, we'll, we'll be having boosters for Americans by X date, whatever. And, and they've actually sent, sort of walked back from that a little bit. And there were two reasons why we were surprised by that. The first is that there was. Absolutely emerging evidence at that point that that the third dose of the MRN vaccines could be beneficial towards giving you a better immune response, a longer lasting immunity. And this will make sense off of what we know about immunology too. Many of the multidose vaccines that we get as kids are also separated by, on the order of six months to a year and that separation can be really critically important for giving you the long lasting and unity. So. Since, and there was some emerging data suggesting that that might be the case, but we still absolutely, at that point, hadn't reached what we like to call a scientific consensus. There were some studies that were supporting this, but one, one or two studies does not make proof or does not make, a, a really compelling story. The, the whole practice of science is sort of steering this massive ship of human knowledge. And one, one little study isn't going to do that. Really. We need lots of corroborating evidence from different angles. So. What we were waiting for as scientists. And that's why, when this announcement first came out, right. Maybe a little premature, even though it's probably pointed in the right direction. So, now that said, in the meantime there, a lot of that corroborating evidence has come through and it does suggest that a additional dose of the MRA vaccines can be very effective at giving you higher levels of immunity, longer lasting immunity, unity. So, so now the, in some ways the science has kind of caught up. And so now it makes a lot of sense, but, but the timing of it was was surprising. The second thing is that Generally political administrations are not the people who make these announcements. Right. Like this is, this is something that should be coming from the FDA. It requires, at this point again, a careful evaluation of the evidence a careful deliberation amongst experts who know about many different types of vaccines and about these vaccines in particular, which is what the FDA exists for. And so that was another thing. So it was like, why, why are we getting this announcement from a the, the white house and not from the FDA? And so it, it, it was sort of like putting the cart before the horse. And so, so that was another one of the more sort of policy side with scientific overtones that, that caused some surprises. And now the last thing of course, is that in the midst of this now, even though the science does seem to be suggesting that a third dose of MRN vaccines does seem like it will probably be a very good idea at some point there's still a lot of really thorny policy questions as to how to organize the rollout. How do we, yeah. Giving third doses in the United States versus first doses in much of the rest of the world. How, how does this work? How do we keep track of things? Frankly, probably many people have already gone out and gotten their booster shots because in many places you can just walk up and say, I want a vaccine and she can get it right. Which is not at all, something that I would recommend at this point, but as possible. Sure that people have done it. And so, one of the big issues now is that we, we don't have very good record keeping around who's gotten which vaccines and how that plays together, which makes doing research a lot more difficult. It makes setting policies a lot more difficult. So there are a lot of really thorny questions in here that, that aren't just science to that I think we really urgently need to get sorted out. And I think that, that seems to be what this article was pointing.

Matt Boettger:

Okay, that makes sense. So now is the booster shot? Nothing more than the same? Shot given at the beginning. It's not like this new revised one that's tweaked for the Delta. The heap hearing about has been under undergoing this is just the same one that's originated. There's a third

Stephen Kissler:

version third. Yeah. Currently it seems like that. Which, which again is an interesting choice too. I know my, my colleague, Michael Mina has been very outspoken about the fact that like, w w we have the capability of updating these vaccines, we might as well give something that's more closely related to the Delta. And one of the reasons why not is because that might be subject to a more stringent safety and efficacy review, which might delay, how long it would take for that to actually get rolled out. So again, there are very practical reasons why we might use the original dose, but right now that that is the case that it's the original Formulation that is currently being used for for these third doses. Now I imagine some of our listeners will probably notice that I've been sort of steering away from calling it a booster and been calling it a third dose of the series as well. And part of that is because It's splitting hairs a little bit, but and, and definitely, booster your shot is, is the thing that has really been prevalent in the media. But I think really what we're trying to do here is to understand, what should the actual series of COVID vaccination be? And when you think of, when you think of something like tetanus, we get booster shots every 10 years or so. Right. And you need that for life. And so what a booster shot implies is that it's sort of something that's ongoing in perpetuity, but we're not sure that that's going to be the case for COVID right now. Really what we're trying to do is work out, how long should the series be and how far apart should they be? Sequenced it's it's possible. We might need it. COVID shots, as booster shots, sort of like we do the flu, it's sort of like we do for tetanus. But I'm actually hopeful that maybe actually what we need is like a two or three dose series and then we're done. And so that's part of what we're trying to work out too. And we're just not sure what you mean. Settings we're going to be in, so it, okay. That's not to say that we shouldn't be using the term booster, but that's, that's sort of why I've been steering away from it. It's cause we're not really sure about that yet.

Matt Boettger:

That makes sense. And for those of you listening no, Stephen is not next to a dentist office for the drilling somebodies teeth. It's actually construction work outside and we have no choice, but he's got the

Stephen Kissler:

window closed. Yeah. Sorry about that. No, it's okay. It's like right outside. So

Matt Boettger:

living in the city life, man city life. Okay. So let's get straight into it. The reason why would be one booster is why we're talking about boosters because there's so many variants. And so I want to get caught up to speed with you, Stephen. So we know about the Delta. This has been the headlines forever. I like to get the status from on your end. Now there's a C1 to have no clue why he doesn't have a Greek letter, but maybe you can explain why maybe it's too early or whatever. That seems like something to be aware of. Can you talk about that? And there's the mu these two seem to be really kind of percolating to the surface and the media outlets I heard about Mo maybe evading the vaccine immunity. Where are we at in this? Where do you expect it to go? I, I heard about with Moo at one point in time, the U S was the only place in the world by which it was rising. Sounds like that's different now. So that's maybe good news, but guest cuts to speed. Where are we at and where should we be concerned?

Stephen Kissler:

Yeah. So, first a point on the naming. So, these different virus lineages all have the Sort of long mouthful letter plus a whole bunch of numbers, plus a whole bunch of dots. And, and that, when we were talking about and B 1 6, 1 7 0.2, all of these things that's, that's still going on under the surface and, and, and those those names are very useful and informative for those of us who are, frankly nerds and are interested in, like figuring out how all of these things are related to one another. So the first thing that one of the virus gets is, is one of those associations, but then once it becomes classified by the CDC or the world health organization as a variant of interest or a variant of concern, meaning that we've seen a major outbreak of this particular variant in a location and. No genetic markers that suggest that it's something that we ought to be paying attention to. And then we give it a Greek letter. So C1 two, hasn't gotten a Greek letter yet because it hasn't quite crossed that threshold of concern yet. Whereas new and alpha beta gamma, Delta, et cetera have all sort of crossed that level of concern at some point. And so that sort of gives us a shorthand for referring to these different. Got it. Nope. You're right. We've been hearing a lot more about both the variant, the new variant and yeah, and I think, rightly the question is like, how concerned should we be? So, as with most of these variants, in some ways it's the same old story playing itself out again in that So we have a variant they've each been increasing in particular geographic locations. And so that's 0.1 of concern, because if, if a variant is able to increase in prevalence, then that suggests that it is for some reason more transmissible than whatever is spreading at the current moment in that particular location. So, That's sort of 0.1 0.2 then is, okay. So does the variant contain the genetic markers that we know to be associated with things that we might be concerned about? So there are different ways of testing for this, for example, in laboratories you can sort of tweak the structure of different parts of the virus. Remaking the virus itself. And then you can expose that to different antibodies and see if that has the ability to get around some of our immune response. And so we know what some of those mutations are, even if they haven't yet emerged in nature. And so when we start to see those things emerge, we can say, okay, well this, this at least has one of those markers that could make it get around our immune system or could make it more transmissible. We don't know for sure if it does, but it's, it's definitely something worth being concerned about. And, and for the, for the mew in particular, that's something that we've seen where it's, it has some of these mutations, but we haven't yet seen how that plays out in the real world. Totally. So, the key thing about both of these variants and really about everything that we've seen since the Delta has come out and you were alluding to this during the introduction to this bit So far, it doesn't seem like anything has really been able to out-compete Delta. Even the mew, get emerged. You can see the sort of ebb and flow of different variants sometimes because sometimes a viral strain will get lucky. It will reach a community and there will be a couple of super spreading events and it will rise and prevalence. And all of a sudden we'll say, oh, here's something that we may be out to be concerned about, but the real concern. As happened with alpha and as happened with Delta is when you see that outbreak, like we saw in the UK, like we saw in India, and then it starts recapitulating itself in many different places, because that suggests that there's this robust ability to out-compete whatever is there in the first place. Whereas it seems like these variants so far, wherever they have emerged, they've kind of been driven out again by Delta. And so no matter what mutations, no matter what. Functions. We call them phenotypes. These, these viruses have if they're not able to spread in the context of another spreading virus, then they're never going to really take off. They might cause small outbreaks, but they'll eventually be driven away by the thing that is more transmissible, which is currently the Delta. And so right now it really seems like. Delta's the thing, that, that is the thing where consistently wherever Delta is spreading, nothing else has really been able to hang on for long. And so that's the upshot. And so there's, there's, definitely a lot of chatter and, and these are things that we need to be paying attention to you. But right now, the thing that's on my mind is Delta. Yeah.

Matt Boettger:

And then it kinda reminds me of Lambda where I remember early on talking about Lambda was in south America. There was a lot of worry about this and then it just never really could get an edge, because of the Delta. And so it's clearly it seems to be possible. The variant could evolve. The dad's actually is maybe more dangerous. Can bring people quicker to hospital could be so, so changed that it evades even vaccines, but then just dies off. But that doesn't, it doesn't have the capacity to compete with Delta, which might not be as dangerous, but it's just so vibrant and so contagious that it just dominates everything else. Is that true? That you could have worse variants in the sense of hospitalization? But because they don't, they're not quite as V that viral ENT, so to speak, they just can't compete with Delta. So Delta keeps it at bay,

Stephen Kissler:

right? Yeah. And just to note on terms, and this is super confusing, you would, you would think that, viral, it means contagious, but actually viral int is usually what we use to describe the clinical severity. And so, yeah, just just a point to our listeners. So, so actually, right. So, so. Amend that statement for what I think you were saying. Was it just that there might be more violent or more clinically severe strains that sound very concerning, but if they aren't as contagious or transmissible as the Delta, then they're not really going to be able to take off. And so that's, that's the real concern is that generally an increase in contagiousness or transmissibility is usually a much bigger. Okay.

Matt Boettger:

Great. Thank you for that clarification. I'm the lay man that I'm an expert on the show. Okay. Yeah. So let's, that sounds good. Like hopeful news, at least when it comes to the one too. Now I'm guessing because it's C going from B to C, that means there is a stronger change. Is that how it goes? Like a, B, C it's it's it's more, it's changed more dramatically. So

Stephen Kissler:

now it's a new letter. Yeah. Thankfully, somehow there's actually something that makes sense about this whole thing that intuitive. Exactly.

Matt Boettger:

Great. Good to know. Okay. So I want to make a quick just bookmark this. We're not going to talk much about this. I read this from the Atlantic, the masks were working all along. I know every once in a while we come back, we talk about this, but this seems to be an incredible study done in Bangladesh. Probably the best study done yet on the ethicacy of masks. We're not going to talk about this, but I'm going to put in the show notes. It's a great read. Just proves the point of how powerful and really good mass are to help keep COVID at bay. Again, not the only tool in our toolbox, but another one that's just really great along with all the other ones as well. So please check that out in the show notes. So we have two big subjects we want to talk about that I think are really interesting. I saw this Stephen and a handful of article. Banging over and over this drum, this idea, this came from Israel, the study in Israel that's that, that, that apparently showed that natural immunity is more effective than the vaccine when it comes to the Delta variant. Now, is this true? Or how, how do we navigate this

Stephen Kissler:

terrain? Yeah. So, th first of all, it seems like. This study, it was pretty well conducted. So I'm, I'm inclined to think that this is probably the case. And and part of that too is because it also aligns with what We might think from from just the theory of immunology. So one of the things that happens in our immune systems is that we our immune system is great at identifying things that we've been infected with. And one of the ways that we get better and longer lasting protection is to be exposed to lots of very slightly different things. And that sort of helps us, learn in, in the case. SARS cov two, it helps us sort of learn the shape of the virus in our immune system. And so when we've been exposed to just the vaccine we learn about what that vaccine, spike protein looks like, but of course, the vaccines just contain sort of the, the. Elements of and the structure of just one part of the virus. It's a very critical part. And it's the one that our body probably recognizes most easily, but it's just one part. Whereas the virus contains, these little spikes, which the vaccines capture, but also there's a surface and there's all sorts of little nooks and crannies that that our immune system is going to respond to. So when we have a natural infection, the immune system is probably going to identify parts of the spike in parts of the other bits of the virus. And we'll give you a an immune response that is different than the one that we get from the vaccine. So. When you have natural infection and vaccination, you've been exposed to a couple of different things. And so that sort of gives your immune system sort of this wider breadth of things that it can identify. And so it makes sense that natural infection plus vaccination might be better than just two doses of the vaccine for providing broader protection, especially against the variants that have emerged since the vaccines were originally formulated. That's not to say that, the vaccines are useless and we should all just, we should have all just gotten natural infection, the great Barrington declaration people were. Right. Because to get that natural infection, it's a very costly thing, you had to have about, of COVID in the first place. And. That's not good. So the vaccines prevent you from getting COVID in the first place, which is the point altogether. And even if there is a bit of an edge in the amount and the really, I think the, the big thing is like the duration and the breadth of protection that you get from natural infection plus vaccination versus just vaccination alone. You know that that difference is still very small compared to the difference in somebody who's totally immune naive and somebody who's been vaccinated. So, absolutely. You get the vaccine, it's, it's still makes an awful lot of sense. But I think, what, what this is doing is it's helping us to learn about how the immune system works. And I think it's making a case for adjusting our vaccine formulation because that would help do. What this natural infection plus vaccine is doing for us in the first place. Yeah. So all of that is to say that it's, it's sort of a complex landscape, but I, but I do think that that's probably the case. Yeah. Now what does this mean for policy to, you could also envision a world in which the traditional course of vaccines consists of two vaccines, but if you have a previous confirmed PCR infection, then maybe, maybe all you need is one dose of the vaccine. After that, we don't know for sure. But I, definitely I know that Eric Topo has been sort of arguing for that saying that that probably makes a lot of sense. And so, this is part of the conversation that's happening right now. So this, this study and these kinds of findings do have really practical Outcomes in, in, how we, how we deal with the vaccine. Great.

Matt Boettger:

Now to rewind this, just so I could, there's a couple of pieces that are missing for me in light of what we spoke about maybe eight months ago. And I think I can reverse engineer this. I'm going to do this as a layman, and then you can correct or modify whatever I'm saying is wrong. Because right now we're saying now, particularly in the Delta variant, that it could be true, that natural immunity is better than the vaccine, but you kind of give all the cab caveats of, that doesn't mean the vaccines. Now we right, eight months ago, we said the vaccine was better than natural immunity by large amount. So what seems to be a contradiction? I think I'm going to reconcile and say, because the vaccine, I think you just said it already, the vaccine originally was made for particular strain of coronavirus, which actually made it more effective than natural immunity, but because of the Delta on the scene now, which is obviously we couldn't prophecy in the future, we had no idea about variants. We had this crazy Delta. Natural immunity may now have an edge because it had a particular complexity about it. That's not in the vaccine that may give it a slight edge to handle the particular variant. So both can be true because what I said.

Stephen Kissler:

Exactly. And there's, there's one additional point to that too, which is the time that has elapsed. So when you get vaccinated, you're that, you're, you're getting dosed with this thing that like your body is, it goes, it's PR it's perfectly formulated so that your body mounts, this massive immune response. Right. And so oftentimes your body will now. This year, I produce tons and tons and tons of antibodies after a vaccine that is orders of magnitude much, much higher than what you get from a natural infection, but those antibodies also decline over time. And so at some point, do they sort of converge at similar levels? And so then what you were talking about kicks in as well. So maybe for the first couple of weeks after vaccination, the vaccine is actually much better than natural infection at protecting you, but then at home, The antibody levels converge. And then you have this additional protection from natural infection by having this broader response as well, that causes the natural infection to give you the slight edge, some number of weeks out. So all of those things are kind of in play. Thanks for bringing that up. Yeah.

Matt Boettger:

Great, man. If it's complicated, speaking of complication, let's talk with you. You did the best segue ever, Stephen, because you talked about antibodies. So this is the other big stuff you want to talk about. There's two articles. Unreal. And I'm going to bring them together and I want Stephen to help understand. So this first one says that RNA vaccines seem to produce very different antibody levels. Now I'll put this in the show notes. The one thing I want to highlight is this idea that it talks about how Madonna kind of Madrona has been this kind of in the spotlight recently as being this kind of this winner right now of, of, of, of running the race on the, on the various. That it mentioned that like the Moderna antibody response was significantly more than the Pfizer when you compare them at the same time, like two orders of two to three times more. Right. So you would think, oh my gosh, Madeira might be two or three times more effective than five. Of course, this article then made the caveat, wait a minute, wait a minute. We still haven't done this yet, but we need to look at another level of not just antibodies, but neutralizing antibodies, and that could bring the dirt and Pfizer on the same playing field. We don't know, but it could. So that's one article that I want to highlight. I want you to talk about the other article, which I think is related is this article is what Pfizer scientists consider the biggest surprise about their COVID-19 vaccine. And I'll read this because this is important. This came from I'll put in the show notes, the aspect of Pfizer's coronavirus vaccine that really stunned the company. Scientists was the fact that vaccinated participants in the, in the phase three efficacy trial had protections against the pathogen by day 12, a time at which there was barely any antibody response, stat news reports. That that was the biggest surprise. Now then the next next paragraph says it's possible. He suggested that's more important to measure cellular immunity than look for robust antibody response. So I want to repackage all of this, but during the huge antibody response, it's better. Maybe we need to look at neutral antibodies and then that'll bring it down. Wait a minute. Maybe antibodies are somewhat irrelevant. So maybe it's something else we add in this mix. What's going on? How can we parse and put this all together?

Stephen Kissler:

Oh man. Th these are, these are great, great, great questions. And I, I really want to empathize with the, with the complexity of this. So I'm, I I, I spend my time thinking about these kinds of things all the time, and it still makes my head spin. I've got a textbook on immunology. That's like sitting out here right now that I'm trying to read it so that I can learn about these kinds of things, because they still confuse me all the time. So, so we'll try to walk through this and and see see where we get. Right. So Pfizer and Medina as you say, they're good, a couple of studies that suggest that Madrona has sort of been holding up a little bit better than Pfizer has in, in the face of the new variants. And as time has elapsed since vaccination. So, a first of all, to the extent that that's true, like you said, there's potentially a higher antibody response and, and it does seem like it may provide elevated protection against Symptoms, further out from the vaccine as well. So there, there are some studies that, that are actually looking, not just at antibody levels, but at actual physical correlates of protection. And, and it seems like Medina might have the edge there too. So Y we had sort of thought about these vaccines as virtually equivalent. Well, The two key differences between the majority and the Pfizer vaccine, or is that first, the Medina has a longer span of time between first and second dose. And that's one of the big questions about the third doses that we've been talking about too, is that, not only do the doses matter, but the amount of time between them does too. And generally the longer you have between the doses, the more durable your immune response is going to be. So it's possible that even just that one week makes a bit of a difference. The other thing is, and that. I'm inclined to think that this might actually be a bigger thing, is that there's the Madrona dose is actually just bigger. You just get more? Yeah. I think it's like two to three times you get on like almost twice or three times as much stuff injected into you with the maternal vaccine is what the Pfizer my hunters that, that might make a difference too. And so, okay. Yeah, so there's, there's that too. So, so that might help us start to understand some of these differences between the two, but you bring up an important point that, we've been looking a lot at antibody levels. And is that what matters? So, here again, the answer is yes and no. So absolutely. The antibodies that you can measure in a person's blood stream. Generally correlate with the amount of protection that you get from infection, but it's not, it's not equivalent to protection. One of the key differences is that the relationship between levels of antibodies in the blood and protection from infection is not linear. Just what we like. So basically what that means is that if you have, If the difference between, say your antibody levels in some random units is 10 versus 20, that might be different than the difference between 20 and 30 and 30 and 40. Because really maybe what we need is some baseline level of antibodies in our system. And that if you're below that, then you have a chance of getting infected. If you're above that, you're not going to get infected. And so if both vaccines are giving you these astronomical antibody levels, Then the differences between those antibody levels. It might not matter as long as you're past that threshold. And that, that actually seems to be a pretty good mental model for how immunity works. So that's one reason why we haven't been too concerned about, these differences in antibody levels, because they can be really hard to interpret, especially when both numbers are very high. Furthermore, the immune system is very complex and what these antibody levels are measuring is really just one arm of the immune system. And in fact, it's the arm of the immune system that for much of the pandemic we've thought to be is maybe not the most critical one. Oftentimes we think about antibodies as these B cell antibodies, but we've also been thinking about, T cells, which seemed to be the really critical element of the response which is just a different, a different part of the immune system. And so that also offers a different type of protection as well. So definitely, higher levels of antibodies. Probably on average lead to better protection, but that difference might be very, very slight. Last thing. So you had mentioned to this study that if Pfizer was looking at their clinical trials and we were 12 days in and they were, people were already starting to show an immune response, that's crazy. They, they hadn't had that many antibodies in their blood, so, so where is this protection coming from? And I think that what this is getting at is something that I'm, again, still learning lots about, which is that, our, our bodies are not just bags of cells. We are these incredibly diverse. And complicated biological landscapes and immunity sort of plays out on each of these different levels in different ways, in really important, different ways. So for example, you think about the way that you get infected with a respiratory virus and generally it enters through your mouth or nose and it fuses to your epithelial cells. And And once it's able to do that, then it gets into your cells and starts to proliferate, and then it can sort of migrate down in your throat and into your lungs. And then it can maybe cause a systemic infection. And so there are all of these different stages, but one of the critical things that can prevent you from getting infected in the first place is if you, if you get a good immune response in those. Cells and those epithelial cells, which are already really chockfull of immune stuff. And so, and so getting a vaccine probably does give you some amount of immune protection from that first layer of defense that you might not be able to measure in your bloodstream yet, because it takes just a longer period of time for those antibodies to Mount up in your, in your blood system. Right. You know your body in all of its brilliant wisdom, sort of preferentially allocate some of that protection towards the places where you're, where you're going to need it first. And so that might be part of why we've been seeing some of the protection, on day 12, that doesn't really seem to make sense if you're just measuring bloodstream antibodies in the first place. Now of course, w w the long lasting protection also seems to be reversed in a sense where actually that, that epithelial protection, that sort of first layer of protection might actually be much more temporary and your bloodstream protection might be much longer. And so that might be part of the reason why we're seeing very good protection against severe disease, which is when you want lots of antibodies circulating in your blood, but why we're starting to see lots of breakthrough infections, because they're able to get into the nose and cause that initial infection. Proceed further. So not only are there different places in the body where the immune system acts differently, but the duration of immunity in those different places is probably different. And all of this sort of plays into this constellation of things that we're starting to see here very complex. So again, I always want to try to bring this back to like, what does this imply for us? Well, first of all, Do you seem to be good again, they're protecting against severe disease which is great and that's really what we want. But we would also like something that prevents us from getting infected in the first place. And they do that too. They, they do lower that probability, but not quite to the same degree. There's some suggestion that Nasal spray vaccines might do a better job of that. And we already have things like that for flu. Especially for kids. Kids will often get a nasal spray flu vaccine rather than an injection. And so we might start to think about that. Get immunity in the parts of the body that need it most to protect us from infection at these different places. And so I think that's a really interesting area for further work too. So I wouldn't be surprised if at some point we get a nasal spray COVID vaccine that's suggested maybe even in addition to the injections to give us sort of this broader spectrum of response in the different, our body that need it,

Matt Boettger:

man. That is fascinating. Stephen, number one, do you, do you play music? Yeah, I do. Okay. Because. I like hearing you talk on this whole epidemiology immune. And like, it sounds like a beautiful orchestration of music, the way like the first starts with, with the nose and the other, and then it goes to the, then, then it hands over to this other kind of major player in the, in the, so I thought, man, totally not. I think. Ironic that you are, you play music, but yet you're an epidemiologist. I think they're both just like beautiful orchestration, so

Stephen Kissler:

fast. Thanks. And I think there's something inherent to it too. There's one of the things that has attracted me to infectious diseases in the first place. And actually some of the math that I've done too, is that there's, there's a certain poetry to it. That's, that's sort of inherent in the thing itself. And so, yeah, there's, there's a real beauty to it that yeah.

Matt Boettger:

It was gorgeous. Yeah. Thank you for the explanation. And so then this may be going a little bit too far. You talked about the nasal spray and he talked about, and I know there's other nasal sprays were like natural nasal sprays. Are these things that, I mean, clearly I'm not advocating a replacement. I'm not like that, whatever that index, whatever that stuff is, that, that horse stuff, I'm not trying to say this stuff and saying like, is, does this show whilst like nasal sprays are, can be. A nice extra bonus of doing, because that is an area of entrance, that those things could help a little bit with the protection as well, in general, not just COVID, but just like cold and that kind of stuff. Is that why we have nasal sprays as a protection? Or is it more of just like, ah, to keep them keep them wet?

Stephen Kissler:

Yeah, it's right. So. I think that, for, for the nasal spray vaccines, that makes a lot of sense because it's basically sending the, sending the antigenic stuff to the places that that's going to get exposed to the virus first. Now there are, of course, other nasal sprays that sort of help keep your nasal passages wet. And, and that probably helps to some degree. Not so much through the immune response, but as one of the hypothesis, why why respiratory infections are more common in the winter months is partly because it's just drier. And so one of the ways you might protect against that is by making your nasal passages a little bit more tropical. And one of the ways to do that is through a nasal spray. Right. And so, so, so that's sort of more of like a physical and physiological thing. I, I haven't done the research into, to, to like compare rates of infection in different people who have used a nasal spray or not. So I can't, I can't speak intelligence, but sure. It would make sense. And it would be a different mechanism. Similar idea that basically you're, you're sort of paying attention to the part of the body that is exposed first. And if you can prevent an infection from happening in the first place, then you save your body a lot of trouble down the

Matt Boettger:

line. Yeah, absolutely. No, thanks for sharing. That was great, Stephen. Yeah. One last thing I'll just mention here. Why I didn't talk to Stephen about this? I just saw this article. I'm always interested in about how COVID and children. Cause I have three little boys run facts, but they didn't, who knows when that's going to be available. But I saw this article, most children with severe post COVID 19 condition in fine health year later. So just a study following kids after a year who've had severe, it looks right. Is promising that these like either long holler, what are you going to call it resolve over time, right? Naturally or back to their norm. Healthy reality. So just a little drop of hope for that as well. Thank you again, Stephen. This was awesome. I learned a lot and I guessing our listeners learned a ton as well. If you wanna support us again, patrion.com/pandemic podcast,$5 a month. One time gift Venmo, PayPal on the show notes. S a S T E P H E N K I S S L E R. And Twitter. You can follow him, Stephen. You can reach out to me, matt@livingthereal.com drop a line. If you have any questions, we'd love to answer them. And I think that is it. I hope you guys have a wonderful week and we'll see you probably and two weeks, maybe one who knows no more than two take care and have a wonderful week. Okay. Bye bye.