The complicated world of the AstraZeneca vaccine

We apologize for the brevity of this episode after two weeks off. Both Matt and Mark got new computers that had some glitches, and Mark was recording while all the children were streaming virtual class. This created quite the series of complications! We hope to be back next week with a normal length episode!

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Things Discussed on Episode:

• AstraZeneca Faces More Vaccine Questions After Manufacturing Error

Transcript

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Matt Boettger 0:00

You're listening to the pandemic podcast. 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 my two good friends, Dr. Steven Kissler and epidemiologist at the Harvard School of Public Health and Dr. Mark Kissler, a doctor at the University of Colorado Hospital. Hey guys, happy belated Thanksgiving.

Stephen Kissler 0:17

How's it going? Hey, it's good to hear from you guys.

Matt Boettger 0:20

Oh gosh. It's been forever. How are you, Mark?

Mark Kissler 0:22

Good. Happy Thanksgiving. That it's nice to be back. It is.

Matt Boettger 0:26

It is good to have you back. Did you guys have a traditional Thanksgiving or kind of this like pandemic? Let's just do this totally different

Mark Kissler 0:32

style. We had a pandemic Thanksgiving over here. We, I I was, that sounds, it sounds more grim than it was, it was really festive, but we did it on a, on Saturday. Cause I was working a little bit this week. and I cooked, an entire, I've never cooked a full Turkey before, by myself. And so that was an adventure. We got the, we ended up with like a 20 pound Turkey. So we're going to eat Turkey soup for three months.

Matt Boettger 0:57

I didn't know. At 2010 turkeys existed, once they were all cut up. That's amazing. Good work. So, what did Steven what'd you have for Thanksgiving?

Stephen Kissler 1:04

it was, and it was also a pandemic Thanksgiving over here too, but similarly, you know, you had a lean cuisine, right? That's right. That's right. Just pop that in the microwave and go, no, we kicked it a ton of food. I mean, since we were staying put, there was no travel associated, so. we actually had a lot more time to do cooking. So, we, yeah, we just made a bunch of things, just kind of picked and chose from each of our families, what we traditionally have, but just pick the things that we like the most and go to those. And it was great. So, Yeah, it was kind of like the greatest hits.

Matt Boettger 1:35

That's awesome. That is actually really good. That's what you need right now. We need a greatest hits album in our life right now for 2020 to keep us motivated. It's awesome. I mean, it might be a short hit list, but nonetheless, you're still motivated. Listen that sucker all the time. Stay inspired. Oh man, we are Thanksgiving. It was totally a different non-thinking non traditional. I'm not a big Turkey fan unless he did douse it with gravy and mashed potatoes and stuffing to the point where you don't even see it or case anymore. So we went live at different. We just did it like some tacos, but we had a kind of a medical, issues, the day before Thanksgiving. So that thwarted, our, our Thanksgiving a little bit. So it was really extra low-key it was going to be low key, but then it was really low key, but the good news is we went to the woods. Out in the forest or the mountains and we shopped around Christmas tree down. So that was pretty fun. And the boys loved it. So that was our highlight of the week. So if you haven't done that, those who were listening, this is the best thing. It's the best pandemic way to do it as well. Don't go to a tree farm or a bunch of places go out to a forest chapter and treat legally by the way, legally just don't shut down random ones, but, get your permit. It was a fun experience. The boys loved it. so that was, that was our highlight of the week. So let's get started. It's been a couple of weeks that we've been together. there's a lot going on. I know we see a huge increase in cases it's just nonstop. the death rate is going up. I know for me personally, this is the first time. the mortality rate is actually affected me in some, in some remote way. we'd hear the news, that kind of stuff, but I've had two people have friends, my good friend from high school and growing up, he, they babysat me. His father passed away of COVID. after 24 hours of getting it, and that was a big shock to everybody's system. And that was a big setting to hear from my friend. And I have a person too. I know in Boulder, whose mother got COVID as well in the same week and passed away two days later. So this is my first time hearing it, in like close circles. So it just feeling the weight of this and hearing this increase. I want to throw up to you guys, start with you, Steven, of just talking about what you're seeing right now, with increased cases and what. Might be to be expected, which doesn't, it doesn't seem like it's going to be necessarily a great thing in light of the Thanksgiving holiday.

Stephen Kissler 3:46

Yeah. I mean, at first, I just want to say, sorry to hear that. you know, it's, it is a really difficult time and it seems like, with every passing week, it's closer and closer to home. and, yeah, it's it. I think these, these next few weeks we'll probably continue to be, w w difficult in many ways, We've talked so many times about how there is these delays between the rises in cases and then, how they subsequently lead to hospitalizations and deaths. And so, the unfortunate thing about that is of course cases across the country have largely been on the rise. and that. Obscures a lot of variation that there is at local levels. We've seen in many places that actually many States have been able to turn their, case counts around or at least level them off somewhat. but, nevertheless sort of averaged across the country they're going up. And so that's, that's again, continuing to lead to these increases in deaths. And, that will probably continue, for the next couple of weeks, because in a way those are already sort of, You know, those infections have already been triggered. and so there's not a lot we can do at this point. It's just sort of the, the people moving their way through the course of infection. so I, and I think it will probably continue to get worse before it gets better. But like you said, also I think that this is really, really affecting a lot of people. And so, I'm hopeful that we'll be able to, you know, a lot of this is, is still. In our hands and, and there are things that we can do to continue to turn cases around. And I I'm hopeful that we'll be able to do that over the next couple of weeks.

Matt Boettger 5:09

Yeah. It keeps seeing. The mask research key, win for them further how great it is and how much it helps to reduce. And I know the, my, my friend whose father passed away, I mean, they don't know where he got it, but they, it sounds like from what he's been kind of talking about that it probably, it came from an, an unmasked individual, you know, just in, cause he was around mass people and then he was masked and it was, it was, it was going well for him up until that, until that moment, I knew one thing before I throw it barcode. Chat with you in a second about the hospitals, but this one last article, I talked about this idea of doubling the amount of deaths in the next 10 days. is that something that you guys are talking about? That's a real possibility. Is it that quickly increasing the death toll?

Stephen Kissler 5:48

well, you know, it, it could, you know, so what that, what that is reflecting is that we've seen the cases double over the course of about 10 days. And so it's exactly that, that if, to the extent that the number of cases that we're observing. leads to a proportionate number of deaths and that's, that's really just sort of projecting forward the number of cases we've already seen. so I don't know if it'll be exactly doubling, but, but it could very well be on that order.

Matt Boettger 6:12

And I would imagine, like, it's not going to be necessarily like the fall, the fall. We, we kept seeing you Mark brought it up a number of times. Like we're still not seeing increase in deaths. We're still not seeing increase deaths. And then. Steven, you kind of gave the caveat. Well, this is a little bit nuanced and you gave it multiple caveats because it was happening to the younger generation and the younger kids, college students. And then that had to get to older students. I would imagine the effects of Thanksgiving would probably come sooner than the fall. Is that a, is that a correct way of thinking about this?

Stephen Kissler 6:42

Yeah. It's you know, of course only time will tell, but, but you're right. I think that there, it seems like there are probably more opportunities for direct transmission to people who are at higher risk groups. So that delay might shorten some

Matt Boettger 6:52

yeah. Mark, what about you? Like you've been even out, we haven't heard from you from a few weeks and even in the hospital, I don't know if you've been on the, the COVID rounds and that kind of stuff. What's been your experience at the hospital and the increase of volume there.

Mark Kissler 7:04

Yeah. You know, so we've seen, as we've expected over the last couple of weeks, we've seen a big uptick in cases. and there's always the interesting, you know, discrepancy, I think between, how geographic it is. And then also sort of the feeling of life inside versus life outside the hospital. one thing that's been on my mind a lot has been, our, you know, our. where our parents lived on in Pueblo, Colorado has been hit really, really hard over the last couple of weeks. and that's one of those instances where they were relatively spared during the first phase of the pandemic, or that first wave in the spring. And we just kind of see different areas, you know, being affected in different ways. fortunately in Denver, So far, we've had, enough resources to help to relieve some of the other outlying areas a little bit with patients when they get overwhelmed. we're starting to see, and we have seen a significant increase in our patient counts. Absolutely. Over the last couple of weeks. And I think everybody's, from, from just sort of a subjective standpoint, everybody's holding their breath a little bit to see what happens, through Thanksgiving. you know, it's, it's, it's funny because there's just such a sense, you know, if everybody's. Feeling good. And, you're not seeing the cases kind of personally from day to day. I think there's a sense of like, you know, is this, how, how bad is it? You know, there's even now there's questions of like, is this really is as big of a deal as we think it is. And while I would say that, you know, in the hospitals, we. At least here in Denver, we're able to manage the patient volumes. Fortunately, we have a lot of additional volunteers who've been coming in to help out, from other divisions of medicine in our, you know, clinical operations folks have been working really tirelessly to, to ramp up our, our ability to be, to kind of. Take care of patients in the safest way possible. we have seen, you know, it is, it is definitely going up, you know, we're seeing a lot more cases. and so it's something that's just on my mind. Well, it'll be, we'll just see how the next couple of weeks go, but I think that we will see. How well we did with social distancing over Thanksgiving within the next week or two

Matt Boettger 8:58

for you, Mark. I mean, I don't even know, like when it comes to capacity, where are you guys at at capacity right now? You guys still like, Oh, you're you're at 25% or do you guys kind of measure that or where you're at right now versus how much room you have to grow and spare. Okay. Sorry for the disruption. We have to modify a couple of things because a good old Marc, he's got a household full of streaming individual children. Who are, actually learning remotely. So it's caused some hiccups, right? So we had to move. We

Mark Kissler 9:23

are, we're doing our best we're we're we're at least, hopefully they're not moving backwards. Everybody's everybody's home now. It's been it's, it's pretty crazy. We everybody's home now, post Thanksgiving, we're fortunate. They were in, you know, as long as, as they were. And, you know, everybody stayed healthy, but, we're we got my, my wife's finishing a PhD and like the kids are streaming and everybody's got meetings go in here and there it's it's. Everybody knows everybody's listening has lives like this, you know, or there's something crazy going on.

Matt Boettger 9:53

And so, yeah, so all this is going on. And so Mark's has to go because the place is melting down. There's a lot going on and we got him on. So it sounds, he sounds totally different now because we had to patch him in through the cell phone because his broadband is just tapped. But I wanted to ask him one last question in light of this, just with your experience of the hospitals, like where is it at a capacity right now? Is that something we're like, Oh, we're only at 25% and you have a lot of room to grow or is that something where you guys are feeling the weight and starting to feel getting close to a threshold, or what's your experience with that kind of area of the hospital?

Mark Kissler 10:26

Yeah. Well, I mean, I think the big thing to say to that question is that our governor asked all of the Colorado hospitals, I think just last week to submit a plan for how we would operate at 50% above capacity. and so the indication being, you know, we're, we're not there yet. but that we need to have it. Sort of operations plans in effect, so that we can just drop into that if at some point between, you know, now in the, in the new year, we end up at 50% above capacity capacity is kind of a tricky thing at times because it's, it's not always beds. It's also personnel. and as we saw in the first wave of the pandemic, As elective procedures and other types of hospitalizations have decreased, we've been using those beds and some of that personnel for COVID patients. And so there's a little bit of a, it's, it's always a little bit of a moving target. I would say, you know, right now we have, we already have extra teams with lots of extra ICU teams from what we have had, You know, in the, in the previous months, and we're seeing a lot of increased hospitalizations. I don't have the specific numbers here in front of me. but, that being said, I do think that our in-hospital mortality, is we've talked about previously is lower than it was during the first. phase of the pandemic as well. And so we're seeing length of stay, at times be a little bit shorter. but especially our in hospital, mortality is a little bit lower. And so even though we're hitting numbers, as high or higher than our April peak, right now, we still, you know, for the time being are feeling okay. And, feel like we have a plan. To go ahead.

Matt Boettger 11:57

Thanks for sticking around a little bit longer, Mark. I really appreciate it. I know you've got to go have a wonderful day and then hopefully when all the technology glitches get resolved, we can come back in on full stereo flavors. Sound good? That

Mark Kissler 12:08

sounds great. All right.

Stephen Kissler 12:09

Great. All right.

Matt Boettger 12:11

Take care. Bye-bye. All right, Steven, back to you, dealing with the vaccine, we've had a few things show up lately. We have, AstraZeneca, a little bit of information that can you give us a little bit of information what's going on with that? I'll I heard it in the news was something about how they're going back to another round of trials, because either have a mishap or discrepancy in data, or maybe hiding some data. But what do you know about AstraZeneca, where it's at, where it's going right now?

Stephen Kissler 12:38

Yeah. So it's been an interesting story on, my information about it as only partial too. But from what I understand, it sounds like, there, there was a mistake, in the trial, in which a number of the trial participants who got the actual vaccine, only got a half dose of the vaccine for the first of the two doses that are required for it. I'm not entirely sure how that ended up happening. but, you know, this is, these are, these are the complexities of, of running vaccine trials and record time. And, so, but one of the remarkable things about this is that. in their two arms of the trial. So they, they compared to the data that was, thankfully they had good documentation of who was in which group and who only got a half dose on the first time. and remarkably the people who got a half dose for the first vaccine and then a full dose for the second one, according to their analysis, had. Quite a bit higher vaccine efficacy. Now, the people who got the full dose on both shots, w the difference being on the order of between like the, the lower efficacy was like on the order of like 65% and the higher was on the order of like 90, which makes it comparable to the, to the Pfizer and the Moderna vaccines. So, there's been a lot of head-scratching as to both. You know what happens to bring this about, and then also why this discrepancy now some of the discrepancy could just be chalked up to, small sample size. So there's some uncertainty there. And I think that's why the trial is now continuing to try to see if this is a true effect or if they just got this high efficacy by chance. a couple other explanations have been proposed. one is a biological one. Which is that by having a half dose the first time around, and then a full dose the second time, essentially, what that does is that allows your immune system to get primed to the virus, or not to the virus, but to the vaccine, which, vaccinates against the virus the first time. But if you get too big of an initial dose, then. your body is sort of, and, and this is again, speaking about immunology, which I know not nearly as much about, I feel like I should put that asterisk at the beginning of every one of these things, because now I'm speaking about things that I don't actually am not an expert in, but, but basically some, some speculation that maybe with a really big dose, your body doesn't actually Mount as good of an immune response to it because it, it just so completely. all of its alarm bells go off and it just like neutralizes it before. It has a chance to really, develop the, sort of immune memory that you'd need, to fight off further infection. So that's what I do. Okay. Another contributor that's been proposed, is more of a behavioral one, which I think is really interesting, which is that, so these vaccine trials work so that, some people get the vaccine and some people get a placebo, basically. I think, The, the placebo has either been just a shot of saltwater. or sometimes people get a, a different vaccine. but, one of the concerns is that the people who got the real vaccine, but only got a half dose. Didn't develop the side effects that you get, because it, since it was a smaller dose, you wouldn't have gotten the side effects. And so part of the concern is that, for, for those people, then they would have assumed that they'd got the placebo. And so they would have continued being very cautious in their behavior. Whereas people who did develop side effects would have been like, Oh man, I got the real thing. I got the vaccine, you know, so maybe they're going to let down their guard a little bit and lead to a lower efficacy there. So there, there could be a behavioral explanation for part of this as well. And I think that's why they're continuing these trials just to really pin down what exactly was going on. I

Matt Boettger 15:56

didn't even think about that version, man. This is complicated, Steven.

Stephen Kissler 16:01

Yeah. It's, there's, there's so much going on.

Matt Boettger 16:04

Just talking about side effects. Let's go there. Cause I heard a couple articles about Moderna and Pfizer and of course AstraZeneca about side effects. Our next big challenge. And I know, weeks ago we talked about this as being, Oh, there's really not much of a side effect. Are there any updates, particularly with Pfizer and modernists since they're the ones really going to be coming out any week now that are, that we should be concerned about.

Stephen Kissler 16:26

So from the, from what I can, so there are no side effects that we really need to be concerned about. it seems like they're, so both vaccines can lead to side effects for sure. and those side effects can make you feel like you've been infected with a virus for a short period of time. and so, you know, but this, this makes a lot of sense because in a way you are being. Injected with a foreign body and your, your own body is doing what it does when that happens. and so all of the side effects that you're feeling, which include fever and sometimes fatigue, come from your body's immune response. So it's really an indication that the vaccine is working. and part of the trade-off that we might have for these very, what seemed to be very effective vaccines are these, maybe slightly higher profile of side effects, than you might get for other types of vaccines. like maybe the seasonal flu vaccine, but of course recall that the seasonal flu vaccines efficacy is usually between 40 and 60% and this is upwards of 90. So, so that there may be that trade-off for sure. but of course the key here is that, these vaccines seem to be very good at preventing severe illness. So even if you feel it, you'll probably be less sick than you might be, if you actually got COVID and crucially, you know, these things are also likely to be public health tools, so it'll be to prevent you from spreading the virus to other people. and so, yeah, so, so that's, that's sort of, what's in play there. So there, there are symptoms for, or there are side effects for sure. that are worth being mindful of. I'm not totally sure, like what the severity of those tends to be. I have heard that they can usually you feel it when you get one of these shots, for maybe a couple of days afterward. and I think that makes good sense, but I think is not a reason to be. Concerned about that, that is in fact, an indication that they're doing their job,

Matt Boettger 18:07

any updates you were just kind of looking to this. Cause we were saying it's about this time, maybe next week about Moderna and Pfizer and, or we'd know whether to, what, to what extent does it prevent transmission and does it, you know, those, those complications of how is it actually effective? Has that been released yet? Or is that still up in, not quite

Stephen Kissler 18:23

public yet. To my knowledge, that's not public yet. And I think that it will be a while, especially the question about how will they prevent transmission. that I think is probably not something we're really going to know for sure until, we start rolling these things out, to the broader population and then doing some epidemiological analysis, but in terms of preventing severe illness. So, I think it was just this morning that Madonna. put in there, request for emergency approval from the FDA. and that was based on them completing their trials and showing, both a statistically significant decrease in the total number of cases. And, basically in their trial, there was a complete absence of severe illness in the vaccination arm, which is very good news. Now that doesn't mean that. Getting the vaccine makes severe illness impossible. It could just be a very, very low probability event, but still, if it's a very low probability event, that's a very good thing. We'll

Matt Boettger 19:11

take it. We'll take it. And then one, probably one more question. And we'll probably wrap this up with all our technological difficulties. We've had this this week and we'll be back on a, on a better schedule next Monday. you were mentioning about how with this Pfizer Madrona, that potentially because of its different than uniqueness and also its response, 90% effective that yeah, there might be some, a little bit more of a side effects and ones that have. 40 to 60%, all different kinds of complications. Now I've been hearing. This in small little circles, I just wanna bring it out into, to the forefront discussion of saying, Oh, this is a terrible idea. This is a whole different kind of vaccine. This changes your entire DNA. And this is going to change you who you are. It's an, a, you're gonna be more susceptible to all these different things. Is there any truth this, or am I just in a different world of what I'm reading right now?

Stephen Kissler 19:55

Yeah, so, these are everything that you've just mentioned are, arguments that have been leveled at various times against, all the different vaccines that we have available. So they're, they're pretty consistent arguments that, at least the ones that you've mentioned, I think are not. based in, scientific reality. but it, it does make sense to me that, like why there would be some concern about some of this, because on the surface, so on the surface, essentially what you're doing is you're injecting, A short sequence of RNA, which is, genetic material. It's different than the genetic material that we use as the basis of our genomes, which is DNA. but we inject this genetic material. that's basically coded in these, fat particles. and these go into your body. they get taken up by, Basically immune cells that circulate in your skin and in your muscles. and then those immune cells do what they do. Anytime you get a foreign body that invades, and they express basically chopped up portions of the proteins that are encoded by that RNA on their surface. So then your immune system can Mount a response. So RNA is really interesting. It's, it's a very unstable molecule, biologically speaking. So once it gets into your body, it's really not. it doesn't take long for it to completely degrade. and so in that sense, it has a really pretty low, Like, it's just not going to be circulating for very long. It's going to get taken up by your ear immune cells and then it's going to be these sort of, it's. I mean, it's already neutralized. It can't replicate it. Can't, it can't integrate into your genome. our genomes aren't even based on RNA or genomes in code RNA, which then encode proteins, but this isn't. Like doing anything to our genomes or making us different organisms or anything like that. that there's just, there's no, there's no biological process that could make that happen. now that that's actually different than, Viruses, which some viruses actually can integrate their genomes into our, our, our DNA. So viruses are pretty crazy things, you know, and we, there's to my knowledge, I mean, I think that there's like the human. DNA sequences do contain quite a bit of viral DNA too, just cause we've had viruses for a long period of time. So, and, and we see that because, you know, there are viruses, that can lead to cancer. HPV is the canonical example. Right. And that's part of what's going on there is they, introduce, Sort of mutations into, in our, genome that great can lead to the development of cancers. so, so viruses to me are much more concerning than these vaccines because these vaccines don't have the possibility of replicating or integrating, but viruses do both. so in that sense, scientifically speaking there, Everything that I've seen into that I can reason through suggests that these things are, are a lot safer than getting infected by the thing itself

Matt Boettger 22:37

to the great irony of it. That in fact, it's potentially the exact opposite about tending the vaccine. You're lowering your chances to actually change your DNA and not increasing your chances. The change your DNA. So, hopefully that goes a little bit of a word to those out there who may be a little hesitant and until they get it to be the first round, I'm an early adopter. As I mentioned, I would take it on the very first day. If once it came out, I don't think it's going to be available to me in my particular class of where I'm at in my age group. And my family wants me to wait a little bit, before I, before I become the early adopter, but I'm excited for it to come out. I hear it's going to get it right in a couple of weeks. Maybe that the first round might be coming out.

Stephen Kissler 23:14

Yeah. I think so they're probably going to start with people in, Long-term care facilities and healthcare workers, and then just keep on going out. So I think, I think we'll probably see the first people in those facilities start getting vaccinated within the next couple of weeks.

Matt Boettger 23:25

And the new, the new end is insight. And I'm so excited to see how this turns out. We're going to end there just because we've had a lot of technical difficulties and I'm going to have quite the job of editing this son of a gun. So, someone has some time working on that today. so we're leaving, we're there. Mark he's gone, but I'm thankful that he was able to join us for a little bit. Steven, thank you so much for coming back on and just reconnecting has been a couple of weeks and, for all you out there, if you can leave a review and didn't mention at the very beginning, please do, you can do that on, through, Apple podcasts and on the show notes as well. reviews are hugely helpful for us to kind of rise and give this information to people who need it. And, if you can, At all offer any kind of financial benefit as little as $5 a month helps keep this going. You can do that at pet patrion.com/pandemic podcast. Okay. just an FYI, my computer melted down two weeks ago. And so that's been part of the problem. Mark got a new computer we're just in technological bliss and also uncertainty. Just so we'll get these things worked out and we back next week have a wonderful week. I hope you had a wonderful and great Thanksgiving. We'll see you next Monday. Take care. Bye-bye.