COVID Vaccine Update 2/5/21 w/Dr. Paul Offit

Dr. Z: Hey everybody, “ZDoggMD Show.” P. Diddy, Paul Offit, welcome back.

Dr. Offit: It’s good to be back, and I love being called P. Diddy.

Dr. Z: I see you got dressed up for CNN, because you never dress up for me, man.

Dr. Offit: That’s correct, that is absolutely correct.

Dr. Z: So let’s launch into it. Since I told people you were coming on the show, you’re the vaccine expert, everybody gets a lot out of what you teach, we have a lot of questions. So I mean, we’ll just launch into it. Let’s start this way. What do you, what’s burning in your mind that you wanna tell people about right now? Because there’s been so much news on the multiple vaccines, and everything, and the rollout. Just hit me with where you think we need to start.

Dr. Offit: I think the thing, I think we can get on top of this virus. I think vaccines are our way out of this. The variants do worry me. And so, it’s the variants that are on my mind. And I guess, to make it simple, you know an important line has been crossed if you start to see people who have been fully immunized with, say, two doses of the Moderna or Pfizer vaccine, that nonetheless are getting hospitalized with one of these variants, most prominently the South African or Brazilian variants. If that happens, that’s a bad sign. That hasn’t happened yet. To date, it looks like, from the Johnson & Johnson trial, so you know that Johnson & Johnson has now submitted for approval through Emergency Use Authorization. Our committee, the FDA Vaccine Advisory Committee, will be meeting on the 26th of February to discuss that. But at least from their top-of-line data, which is to say their press release data, it does, although the vaccine was only, was less effective in South Africa than it was in the US, sort of 72% effectiveness in US, 57% effectiveness in South Africa, it did protect against severe disease. All the hospitalizations, all the deaths in that trial, including South Africa, were in the placebo group. That’s good. So as long as that, you just want this vaccine to keep you out of the hospital, keep you out of the ICU, and keep you out of the morgue. When it stops doing that because of the variants, that’s a problem.

Dr. Z: Yeah, and I think one of the things that had been mentioned when J&J’s results came out is everyone was freaking out that, oh, it’s only 57% effective against, you know, in South Africa against this variant, but in terms of severe disease, still 85%, and it may improve over time, right?

Dr. Offit: Yeah, that’s right. I mean, you’ll, we’ll see what the effectiveness data looks like, meaning not just the efficacy in the study, but the effectiveness data. There are advantages to this vaccine. It’s a one-dose vaccine. It’s refrigerator stable. It hasn’t been mass produced a lot. I think they only have about 6 million doses available at the time of launch, but assuming it gets approved. But it’s, everything, any weapon that you have in the fight against this virus is of value.

Dr. Z: And it’s an adenovirus vector vaccine, which means it’s using a human adenovirus to deliver the double-stranded DNA, correct, that then, so this is something that came up. This double-stranded DNA then does enter the nucleus of human cells and gets transcribed to mRNA, and then translated into protein in the cytoplasm. Are you concerned about incorporation of double-stranded DNA into human DNA, insertional mutagenesis, and some of the other theoretical concerns that have come up with this?

Dr. Offit: I mean, we have other DNA viruses that infect us that don’t do that, so no, the answer is no.

Dr. Z: Yeah, because the natural viruses that do this don’t cause massive problems the way you would-

Dr. Offit: Including adenoviruses. I mean, adenoviruses are common cold viruses among other infections, but they don’t do that either, and those are replication competent viruses.

Dr. Z: Correct, right, and these adenoviruses that we’re using in the J&J vaccine are replication deficient. So you give a bunch of adenovirus, it doesn’t replicate, but it injects the instructions to make spike protein, correct?

Dr. Offit: Exactly right, yeah.

Dr. Z: Now, how does this differ, and we’ll get into variants, but how does this differ from the Novavax approach, which is a purified protein, spike protein, with an adjuvant?

Dr. Offit: Right, so that’s made in a manner very similar to Flublok, which is to say, use a baculovirus expression system to express one protein. So now you’re giving the protein. You’re not giving the gene that makes the protein. You’re giving the protein itself adjuvanted with an adjuvant actually very similar to one of the adjuvants used in Shingrix. So we’ll see. If you asked the question sort of at the beginning before you knew anything about efficacy data, or effectiveness data, what vaccine seemed to induce the highest titers of virus-specific neutralizing antibodies, it was this vaccine, the Novavax vaccine, which, you know, looked promising at preventing mild, moderate to severe disease at the level of 90% was their data. But again, all press release data. They haven’t submitted for approval, so we’ll see when we get to look behind the curtain. One other thing I’d like to say, though, is that the FDA process is remarkably open. I mean, we will get two documents. We’ll get the submission by the, in the case of the Johnson & Johnson trial, we’ll get the 100-page submission from Johnson & Johnson. The FDA will also put together 100-page, you know, review of all their data. So those 200 pages will end up on the FDA’s website before we meet. Our meeting is open to the public. It’s available for public comment. So you get to see the data just like we see it.

Dr. Z: Got it, yeah, makes a lot of sense, and I got to say one thing before we go on, but, ’cause I wanna talk about variants, I wanna talk about the two-dose Johnson & Johnson trial that’s ongoing, et cetera. But I got to say this, so I’m now 48 hours out from my second Moderna dose, and I got to say, Paul, man, about eight hours after that second dose, my ass was kicked, and I couldn’t sleep. I had fevers, rigors, body aches, headache, I mean, full-on man flu, like the kind where my wife makes fun of me, because she got the same thing, and had a mild headache, and I’m just man flu-ing away. I mean, is there anything you can say about this? It’s really about the immune response, this sort of B-cell clone army firing up, and inducing interferons and cytokines, right?

Dr. Offit: Yeah, this is just your immune response responding. You know, I too, I had Pfizer, and after the second dose of the Pfizer vaccine for 48 hours I had fever and fatigue-

Dr. Z: Yeah.

Dr. Offit: Which I handled, by the way, by constant whining. I recommend this. It works well. My wife really appreciated it.

Dr. Z: You know, women are so used to men whining about man flu, you know, that this was nothing. You know, it’s interesting though, did you reframe it in your mind, instead of like, “Oh, I’m infected now,” you know, it was more like, “Oh, this is actually a good thing,” so I’m still gonna whine, because I’m a man, but you know.”

Dr. Offit: Yeah, well, actually, you know, that reaction is less common in people over 65, so I’m over 65. So I’m thinking I’m not gonna really suffer that, but I did, so I’m thinking this is a good sign.

Dr. Z: Yeah, that’s wonderful. So back to this thing, so the variants, you wrote a JAMA piece recently that I thought was really fascinating about how we can think about new coronavirus variants in relation to the vaccines. Can you kind of walk us through a little on your thinking, and why you’re concerned, or not concerned about it?

Dr. Offit: Sure, so just sort of in general, so this is a bat coronavirus. This is not a human coronavirus. It has never really adapted itself to the human population. It did initially in Wuhan. Then the first variant arrived. Either it started in China, or it started in Europe, but that was the first variant. It doesn’t have a city or a country name. It just has a letter-number designation, which is the D614G variant. That’s the common virus. That’s the one we, that Tony Fauci will refer to as wild-type virus. That’s the one that’s predominant in the United States, and most of the world. That was variant number one. Then it, as this virus continues to adapt to growth in people, it will continue to create variants. And so, the critical question that you have to answer is not whether variants will be created. Of course, they’ll be created. The question is will they be functionally different, meaning will they be more contagious? Will they be more virulent? And most importantly, will they escape recognition by vaccine-induced immunity? That’s what you really worry about, because our way of getting herd immunity population immunity is only with a vaccine. And if the vaccine, if the virus truly escapes that, that’s a problem, and flu does. I mean, flu essentially does that every year, which is why we need a yearly vaccine. Think about how hard it’s been to mass produce and mass distribute and mass administer this vaccine. Imagine if we had to do this every year for an entire adult population. It would be hard.

Dr. Z: Yeah, really difficult. And so, this idea of how do we measure, so the variants, if they produce mutations within the receptor binding domain of the spike protein that is more the action area of where these neutralizing antibodies work, how are we gonna know when that happens? How are we gonna measure it? What are these neutralizing antibody assays? How are the companies kind of monitoring this, and the government?

Dr. Offit: Right, so what you do is you take, you have so-called polyclonal sera, the kind of sera that’s generated if you’re naturally infected, or the kind of sera that’s generated after you’re vaccinated. And then when you isolate these variants in the laboratory, you can then see whether or not you can neutralize that virus with these antisera, or not. And so, with the UK strain, the UK strain was still sort of fully susceptible to neutralizing antibodies generated by natural infection or immunization, so people didn’t worry about the UK strain escaping vaccine-specific immunity. But that wasn’t true with the South African strain. The South African strain was less capable of being neutralized by those antisera from natural infection or immunization. So then that, then people were frightened. Will this escape recognition in a real-world situation, meaning once people are immunized, and then that, then infected with the South African strain? And so far, probably the data that are best on this is the Johnson & Johnson data, where they did a study in South Africa, where the South African strain, not shockingly, is predominant, and found that were protected against severe disease. That’s good then as well, because, remember, there’s this, so this protein is 1,173 amino acids big. It’s got a lot of different epitopes on it. And so, you have to really affect all those epitopes. Now, that said, the South African variant is pretty much resistant to the Eli Lilly or Regeneron monoclonal antibodies. So now you’re just looking at one little epitope, and if that’s changed, then you’ve lost for your monoclonal antibodies. But that’s the advantage of polyclonal sera. I mean, you’re recognizing many different epitopes, and so, and then the critical question is how many epitopes need to change, meaning immunologically distinct regions, before polyclonal sera don’t recognize this anymore? And that to me matters in the real world, that you’ll know that it’s critical when people like me, who’ve gotten two doses of vaccine, are hospitalized if I’m exposed to the South African strain.

Dr. Z: Okay, I’m gonna try to unwind this a little bit, so I understand. When you say polyclonal sera, you’re talking about antibodies to multiple, when you say epitopes, you’re talking about little sites on that protein, and polyclonal antibodies can be generated by natural infection, or by vaccine. Monoclonal antibodies are just single epitopes, and that’s like the Regeneron, and things like that, and what you’re seeing is it’s probably easier to escape, for a virus to escape, from a monoclonal antibody, ’cause it’s just one site that needs to change, as opposed to the robust immunity you get from spike protein-generated antibodies that are polyclonal from vaccine and natural infection. And the idea is you can then see, all right, are we gonna start to see hospitalizations, because that’s the business end in doubly vaccinated humans, because again, what we’re seeing in the trials is severe disease, hospitalizations, et cetera, actually prevented in Johnson & Johnson, in Novavax, and in presumably the Moderna and Pfizer, correct?

Dr. Offit: Correct.

Dr. Z:  Yeah.

Dr. Offit: And that’s, I think that’s really good news. There was another thing, by the way, Dr. Fauci said on TV the other day, and it was scary the way he said it, but if you look a little closer, it’s actually not that scary. He said, “If you look in South Africa, “people can get infected twice “with the South African strain,” that natural infection didn’t appear to protect against reinfection. But if you really look at those data, what really happens is when you’re first infected, you know, you can have mild, moderate, or severe disease, but on the second infection, you invariably, at most, had mild disease. That’s all you care about. You just want natural infection to protect against moderate to severe disease, and as long as you can do that, then you can mimic the immune response caused by natural infection to protect you against moderate to severe disease. That’s true of many viruses, actually, where the first infection, you know, will cause more severe disease, but the second one won’t, and that’s all you care about here, and that was true of the South African, in South Africa as well.

Dr. Z: So I really need to double down on what you’re saying, because this is where I think the press loves to make us feel terrible, and you’re an optimist, I’m an optimist. I think we’re seeing the end of this thing. And what you’re saying is, yeah, okay, let’s say you can be reinfected with the virus, but the second infection is going to be mild. It’s the same, that second Pfizer, or the second Moderna dose I got made me feel symptoms, right? But I’m not, if it were a virus, I probably would have brushed it off quickly. I would not have been hospitalized, and that’s what we care about. If we can vaccinate, or naturally expose, which we don’t wanna do because of all the downside of that, the entire, you know, herd immunity levels of population, then the thing is done as a concern for the most part, right?

Dr. Offit: Right, exactly.

Dr. Z: Yeah, so let me then get into some things. So these ideas of we don’t have enough vaccine, we’re concerned about it, should we be delaying second dose? You know, Marty Makary came on the show the other day, was talking about some ideas about delaying it, just in terms of the public health implications of harm reduction. What are your thoughts on this from the immunological side?

Dr. Offit: Right, so a lot of people have weighed in on this along the lines of let’s just give one dose, and then we’ll eventually get to that second dose, because that way we can prevent more, we can protect more people. I mean, major people, people like Stanley Plotkin, who is, you know, the inventor of several vaccines, and is the editor of the book “Plotkin’s Vaccines”- Tobin’s spirit guide, yeah.

Dr. Offit: Halsey, Ashish Jha, Bob Wachter, you know, from UCSF, I mean, you know major smart people have weighed in on this, and here’s their thinking, and I’ll tell you why I think the thinking is flawed of Stanley Plotkin, who was my boss for many years, and who if I’m disagreeing with him, I’m probably wrong, just so we’re clear. But the thing is, okay, you have a theoretical million people, you have a million doses, if, of one of the mRNA vaccines. If I gave two doses to 500,000 people, then 95% will be protected, or said another way 475,000 will be protected. Or I can take a million doses, and give it to a million people. And if, and the statements that have been made by these folks is that it’s 80% effective. So not 95%, but 80% effective. And so, 80% effective, a million people, that’s 800,000 people who would be protected. 800,000 is bigger than 475,000, therefore you’re doing good. The problem is where did that 80% figure come from? It comes from the fact that in the Moderna trial specifically there was a period of time between dose one and dose two where people got sick. And so, the question is were they more likely to get sick if they got placebo than vaccine? Yes, they were. And so you were, there was an 80% efficacy in that four-week period. I wanna emphasize that four-week period. So you don’t know, because everybody got a second dose, how was how that would last. But you do know from the Phase I data that you had a much bigger, more vigorous response after the second dose, far greater quantities of virus-specific neutralizing antibodies, and you develop the T-cell response, at least the detectable T cell response, which suggests immunological memory, or said another way, two doses of the mRNA vaccines will, without question, give better, longer lasting immunity than one dose. Now, everybody who has stood up for this one-dose strategy says that. Nobody’s arguing that this is anything other than a two-dose vaccine, and the CDC, to make some room for this, has said, okay, you can get your second dose six weeks after the first dose, as long as six weeks after the first dose, in sort of extreme circumstances, or said another way, three weeks longer than you would for the Pfizer vaccine, or two weeks longer than you would for the Moderna vaccine. That’s fine. I mean, if you wait a few extra weeks, that’s fine. But when you do this, when you send out this message, and I can tell you I just got an email from somebody from NBC that tells me this is already happening, some people are gonna hear one dose, 80%, two doses, 95%, yup, close enough for me, I’m good, you know?

Dr. Z: Right.

Dr. Offit: And plus, you know, I had some symptoms with that first dose, and so-

Dr. Z: Exactly, yeah.

Dr. Offit: heard that it’s worse for the second dose. Why don’t I just stay where I am? And then you’re gonna have a lot of people out there who’ve just gotten one dose. It’s also hard to get back for the second dose. You know, even the shingles vaccine, which is a two-dose vaccine, times zero, then two to six months later, 25% of people don’t come back for that second dose. So let’s assume that that’s gonna be at least true here because it’s hard to get this vaccine. It’s not that hard to get the shingles vaccine. So now you’re gonna have a lot of people out there who are partially immune for a shorter period of time. That is a great way to create variants. That’s the way you create a variant in the laboratory. You give a lower quantity of neutralizing antibodies, thus sort of crippling, but not killing the virus, allowing it to escape, in a sense. And when it escapes, it escapes by mutating. So I just think it’s a way of increasing variants. I think it’s a way of having a lot of people out there who aren’t gonna get that second dose, and I think that is a major mistake. It’s a messaging problem, more than anything else.

Dr. Z: So this is great, because these are two different spins on harm reduction, the Paul Offit spin and the Plotkin spin, and I think this is, it’s great for people to be informed on this, ’cause one of the interesting things that’ll happen is you’ll have people that are singly vaccinated with a two-dose vaccine, and then you can see some months later who is hospitalized, if people are hospitalized, and if they were single dose, double dose, or unvaccinated, and we might get more information in a few months too that’ll ultimately answer, at least go some way towards answering this question. But you know, one of the other questions, Paul, is people are saying, “Well, what about mixing vaccines, “and what about do a Pfizer first, and a Moderna second “if we’re short,” or even, heaven forbid, what if you do a, one J&J, if J&J gets EUA, a J&J after a Moderna, or something? I mean, is, what’s the thinking on that?

Dr. Offit: Well, the thinking is there’s no data. I mean, I think what the CDC has said, and this is, shows you the desperation we’re at now, because we just don’t have enough vaccine, some people are saying, “Look, I got a Pfizer vaccine. “Where I am right now, “I can’t get a second dose of Pfizer vaccine “but I can get a second dose of Moderna vaccine. “Should I just wait ’til the Pfizer’s available, “or should I get the Moderna?” Now, there’s no data on this, but they’re both mRNA vaccines, and they are different molecules. I mean, they’re given at different doses, which tells you they’re different molecules, one at 30 micrograms, and the other at 100 micrograms. But the CDC figured this is probably not a leap here. You’re probably definitely gonna get a response, you know, boosted response. So we’ll say under extreme circumstances, you can do that. I, this, it just, what worries me in this, it’s not, Dr. Plotkin is my hero. I mean, he’s just the smartest person I’ve ever met in my life. I’ve never seen anybody who was so good at analyzing data, and it’s the only time I have ever disagreed with him in my life. Well, now, we have talked about this on the phone, and we both agree it’s a two-dose vaccine. I just think, I think he’s wrong about messaging. I think he thinks way too much of the American public about yeah, we’ll eventually get the second dose. The minute you say that to them, many of them are not gonna get that second dose. That’s the way it works.

Dr. Z: Well, you know, so this is a good lead-in to a question I have, which is messaging on post-vaccine life. And I have opinions on this, and others have too. I’ve had Vinay Prasad on the show talking about this. It seems that we’ve messaged that you can get your vaccine, but still have to distance, mask, do all the other things. In other words, life doesn’t change until everyone gets vaccinated. But what, I mean, what’s your take on this?

Dr. Offit: Well, you could take sort of the selfish or altruistic view. The selfish view, which most people are willing to take, is the vaccine is not 100% effective. It’s 95% effective. So you can wear, you can assume that you’re one of those 19 people, but you might be one of the 20 people, that one in 20. You might be that one in 20. And so, protect yourself while this virus is still raging. You know, wear a mask, social distance until we get on top. Also, just it’s interesting, these was a study done in Norway in 1999, 2000, and it’s gonna sound counterintuitive, but when you think about it, it’s not. Obviously, you were least likely to get measles if you were vaccinated living in a highly vaccinated population, but you were more likely to get measles if you were vaccinated living in a relatively unvaccinated population than if you were unvaccinated and living in a relatively vaccinated population, meaning the more likely you are to be exposed, the more likely you are to get sick, because no vaccine is 100% effective. And so, or you could take the altruistic view, which is I still might shed virus, and so, I’ll wear a mask to protect others, because most people don’t care if they’re asymptomatically infected.

Dr. Z: Oh, man, that’s really interesting. Yeah, yeah, I guess, yeah, that it’s a question of too how do we get back, how do we really motivate people to get vaccinated when some of them just don’t see the value, because either they’ve, oh, and actually, that becomes an important question. People who’ve had COVID, now, you know, should they be de-prioritized in the rounds of vaccine, even if they’re at high risk, or should they be getting it just as the same as everyone else, since they probably have some neutralizing antibodies?

Dr. Offit: Well, the recommendation is that everybody gets vaccinated. I mean, everybody who’s in those groups, you know, 1A, 1B, 1C, as we move along, gets vaccinated. The sort of worst case scenario, you get a boost. I think, you know, you could probably make, again, no data for this, but you could make a reasonable argument if I’ve already been naturally infected, wouldn’t that first dose serve as a boost? Do I really need a second dose? And again, no data, but that is a perfectly reasonable thing to say. But there actually are starting to be some data on this, and that is a reasonable thing to say. It’s just that that is not currently the recommendation. There actually was where there was a little data on this in the Pfizer trial, ’cause the Moderna trial excluded people who were previously infected, but the Pfizer trial didn’t. So there were people who were naturally infected who then got sick. And so, the question is were they more likely to have received vaccine or placebo? And the answer was they were more likely to have received placebo. So there were actually eight, it was only just a handful of patients, were eight patients, but seven of them who had previously been infected were in the in the placebo group that got sick, and only one was on the vaccine group. So it showed you that there was a benefit to boosting. But you could argue one dose might’ve been enough.

Dr. Z: Right, so again, more data we need to have before we can really say that. You know, what you said about measles was really interesting that if you’re vaccinated against measles, but you’re surrounded by a bunch of measles, you’re worse off than if you’re unvaccinated against measles and surrounded by a bunch of vaccinated people, which again, speaks to the value of community immunity, and vaccinating as many people as possible as quickly as possible for this. Now, here’s a question that I have. Wouldn’t vaccination, let’s say we suddenly could wave a magic wand, Paul, and vaccinate 80% or 90% of the population with the coronavirus two-vaccine regimen, 95% efficacy, theoretically, in like two months. Why wouldn’t that put enormous pressure on the virus to generate variants beyond, you know, a slower approach or something?

Dr. Offit: Well, so the goal is to eliminate viral replication, not to lessen viral replication. So if you have a very strong neutralizing antibody response, you will virtually eliminate the capacity of that virus to replicate. The degree to which you have a lesser immune response is the degree to which the virus still limps along, and has the option of escaping. So the quicker we get on top of this, the better. I think the most interesting thing to look out for is whether these variants escape immunity regarding serious infection. That’s the key thing to look out for, because if that happens, and you start talking about second-generation vaccines, it’s been hard enough to give the first-generation vaccines, and it’ll be nightmarish.

Dr. Z: Yeah, it’ll suck. Well, hopefully, we can get ahead of it first, and you know, relating to that, so there’s this two-dose J&J trial. So the longer, let’s give a second dose, I don’t know how far apart they are, tell me about whether you think that’s gonna work, because you’re using an adenovirus vector, and the second dose of a viral vector, wouldn’t you mount an immune response to the vector, and it would never be able to get that DNA into cells?

Dr. Offit: Right, so that’s why they’re doing this study. It’s interesting, they did both a one-dose and two-dose trial, which is not usually the case. The two-dose trial presumably will be done in the next couple months, and this is the advantage having a country that is on fire with this virus is that you can do those trials more quickly. And so, it would be interesting. I mean, if you, you know, we know that one dose, at least US, was at least top-line data, again, press release, 72% effective, and highly effective against serious disease, if you give that second dose, it may be, mimic more serious, more what you saw with the mRNA vaccines. We’ll see, in which case you can just get a second dose. So you never need to start the series again. I mean, you’re already primed. So that’ll be interesting, but you’re right. I mean, the UK data also uses a replication defective virus. It’s a simian adenovirus. And so, they tried different things in Phase III. They tried let me give a half dose for the first dose, and then full dose for the second dose, the thinking being I’ll have a lesser immune response against the vector, so that the vector can still work on the second dose, and then the other strategy was let me just give it three months later, let that antibody response settle down against the vector, and then see that, which is what they argued made for a better vaccine. But that should have all been done in Phase I. I mean, the fact that they did that in Phase III was, made for a very confusing Phase III trial, and that’s why they’re doing their own Phase III trial in the US, separate from that.

Dr. Z: And you’re talking about AstraZeneca’s vaccine?

Dr. Offit: AstraZeneca, yeah-

Dr. Z: Yeah, what’s your gut on that one? Because you know, I’ve had messages from people asking me to ask you, you know, they’re in the US Bahamas, and they’re expecting to get AstraZeneca, and they’re wondering if they should fly to the US to get Moderna, Pfizer, or if J&J gets approved. I mean, what’s your gut on AstraZeneca’s data so far?

Dr. Offit: Well, I think it’s probably a valuable product, I do. I just wish they’d proven it. There’s every reason to believe it will be valuable. My suggestion to your friends is get what you can get is my feeling about these vaccines.

Dr. Z: And that’s important. Why, ’cause we have, what is it, almost five now, and we can even talk about Russia’s Sputnik vaccine, and the Sinovac, and all that. What’s your take on those couple?

Dr. Offit: Well, the first dose of the Russian Sputnik V vaccine is the J&J vaccine. It’s the same thing. It’s a replication defective Ad6.

Dr. Z: Ah.

Dr. Offit: Same thing, same thing as the J&J vaccine, and then their second dose is a replication defective Ad5, the thinking being just what you said, that you won’t have a response against the vector, so I’ll give a different vector, and that’s it. And they, so they submitted for publication. It’s about 92% effective against all manner of, against disease, and it’s, and across all age groups. So it looks good. If you believe the published data, it looks good.

Dr. Z: So you-

Dr. Offit: So that’s good.

Dr. Z: You’re saying Boris and Natasha Russian technology very advanced is what I’m , you know, we used to have a character, Paul, in med school we used to do. He was Dr. Sergei Panzsdropov of the Panzdropov Institute of Technology in Russia, and all trials were placebo versus placebo. Interestingly, big difference between placebos. I’m digressing. So relating to this, you have this population of vaccines. All of them seem to have pretty decent effect. What might explain differences in efficacy in the trial data for, say, Novavax, J&J, and the Moderna stuff? Do you think it’s artifactual, or you think these are real differences?

Dr. Offit: You’re right, I mean, how do you define efficacy? Are you saying efficacy against mild, moderate to severe disease if you’re, whereas another may just be moderate to severe? How do you define moderate to severe disease? I mean, and it’s interesting, you just look at the Moderna, Pfizer trial, they do define severe disease a little differently. One group has 30 patients with severe disease. Another group, the other trial has five patients with severe disease. I mean, it’s, that difference wasn’t how they defined it, although, thank you for making the reference that only people who watched Bullwinkle and Rocky J. Squirrel would know, right? I mean, it’s like Boris Badenov, which I assume was an Alexander Godunov reference, but who knows.

Dr. Z: Well, yeah, when I used to round at Stanford with the residents, I would always, I would abuse the new millennials with my Gen X memories, and I would refer to them, you know, one of the interns or med students as squirrel. “Listen, squirrel, did you round on bed five yet?” They did not like that. Speaking of children, Paul, since we were talking about millennials and Gen Z, so a lot of people have now talked, and I had Vinay on the show the other day, and we were talking about this idea that I think some people are pushing that we ought to be now studying the vaccine in children, expanding the reach of the vaccine, and then not allowing schools to start until children get vaccinated. I mean, what’s your thinking about this coronavirus vaccine in children, any of the vaccines?

Dr. Offit: Well, so it is being studied in children. I mean, now the first wave will be children down to 12 years of age, and I think it’s not gonna be an efficacy trial for practical reasons, more than anything else. I mean, children, there aren’t enough children who get sick-

Dr. Z: Right.

Dr. Offit: That would enable you really to do an efficacy trial, unless you were looking at large numbers of people. So I think what you’ll see is a 2 – 3,000 person trial, where you’re making sure that you’re getting the dose ranging trial, that you can induce a consistent immune response safely. And then that, it’ll be just essentially an immunobridging study. It will say look, I can induce the same neutralizing response that was seen in the Pfizer trial, or seen in the Moderna trial, and so, I think I can vaccinate children. Certainly this to me has nothing to do with going back to school. I mean, I feel the same way about teachers. I think teachers are right. I think that they’re essential workers, and essential workers need to work, whether it’s, I mean, the feeling, and this is why I’ve been getting just a ton of hate mail-

Dr. Z: Oh, me too-

Dr. Offit: ‘Cause I’ve said as much on TV, on CNN, actually. They, somehow, they find my email. They certainly find my email, and they’re so mean, but in any case, the, I think that if you, if you’re a teacher, it’s, you know, kids, virtual learning is not the same as on-site learning. I mean, certainly in the Philadelphia area, for many kids, this is the only decent meal they get during the day. I mean, it’s where child abuse is often picked up. We need to go back to school. Children are getting depressed. And certainly for young children, virtual learning is very hard. I mean, it’s a little easier for the older high school student, but not the young child. So, and so, I mean, everybody else is going back. I mean, firefighters, you know, police department, utility workers, grocery stores, so they’re not waiting ’til they get vaccinated before they go back. They’ve got to go back to work because they’re essential workers. And so, I feel the same way about teachers. You’re not helpless here. You know, wear a mask, and social distance the best you can, and try to get to the best you can. Now you have this antigen test, you know, which is a 15-minute test, which can be really effective to identify things quickly. So I just, you know, I just feel that it’s time to go back to school.

Dr. Z: I couldn’t agree with you more on this, and I think a lot of the guests I’ve had on my show are of similar mind, and it may be that I’m just, I have confirmation bias, Paul, but the truth is, you know, and we’re doing, you know, like my kids are doing okay outside of school, because they’re reasonably, they’re a little older, and they’re proficient at it. But I think about kids who aren’t, and how that’s gonna affect society, and our overall health moving forward. And so, here’s a question though. You know, they’re talking about even vaccinating kids under than 12, under 12, and studying it, and so on, and I feel like wouldn’t the concern be, look, you vaccinate a million kids, you even have, you know, 14,000 of them that have bad fevers, and muscle aches, and all that other stuff, and they’re out of school for three days, and you know, for a disease burden that is minuscule-ly small, another number needed to treat may be a million to save a life, I mean, what are your thoughts on this?

Dr. Offit: Yeah, so you’re right. I mean, the people less than 21 make up 26% of the population, but 0.08% of the deaths. I mean, it’s the rare child who dies. I won’t say rare, but there’s many children died of COVID-19 last year as died of flu. I mean, around 150, 160 children roughly-

Dr. Z: Right, right.

Dr. Offit: Last year, 150. So, although I should make a point about flu in a second, but it can cause suffering. I mean, it can cause this multi-system inflammatory disease. It does occasionally cause death. If you can safely prevent children from getting this virus, then prevent it, I’m all for that. I don’t think we’re gonna go down to less than six years of age. I mean, the less than five-year-old is really unlikely to get infection, mostly because they don’t have that ACE2 receptor. The other thing that’s interesting here, by the way, and I’m sure it’s not gonna affect our behavior, but it should, is that typically 150 to 200 children die every year of flu, children less than 18 years of age. This past year, this year, one so far, one death from flu. I mean, this is the advantage of social distancing and masking.

Dr. Z: Do you think, so, Paul, let’s ask about that, because I did a show recently about this trying to tease out what happened to flu. Is it all social distancing, masking, lack of travel, closed schools, or is there also a component of viral interference, where you have a dominant respiratory virus now, COVID, and but which doesn’t really infect children, so why would that explain, I mean, is it just overall suppression, is it all of the above? What do you think as a virologist?

Dr. Offit: I think it was all of the above.

Dr. Z: Yeah.

Dr. Offit: I think it’s just this simple stuff. I mean, this was also true in Australia. It was true in South America, where their flu seasons precede ours. They too had a really mild flu season. So I think it’s just that, social distancing, masking, and so you could argue, you know, why not mask every winter? I mean, which is what they do in Japan, for example, or Korea are more likely to wear masks. I mean, when I go to the Eagles games, I should wear a mask, but as you know, it is hard to boo through a mask, and that’s why I don’t do it.

Dr. Z: I can boo through anything, Paul. I’m an equal opportunity hater. There’s nothing that can stop me. Yeah, one other question, follow-up question, because I succumbed, I have to say my flesh is weak, Paul. I’m real wuss. After 30 hours of suffering after the second dose I finally gave in, and took, you know, a gram of Tylenol, ’cause that’s the only thing that ever works for me. I’m like a Tylenol-seeking patient. I’m like, “You know, the only thing that works for me “starts with a T,” Paul, and it’s 1,000, you got to give it 1,000 milligrams, and push it with Benadryl. But at that point I finally took it, but I let the fever ride for, you know, the good rest of those 30 hours. Are you still thinking people, if they can, don’t treat fever during the vaccine response as a way of boosting potential immune function?

Dr. Offit: Actually, I thought you were going for “The Music Man” reference there when you said starts with T. I thought you’d go rhymes with P, and that stands for Paul. … trouble right here in River City. So I think the data, there are no data to answer the question about treating after you’ve already had fever. There are data in studies looking at flu vaccine in Australia, and then a variety of pediatric vaccines in the Czech Republic that pre-treating with antipyretics does lessen the immune response. The question is if you’ve already starting to have this, the symptoms of your immune response essentially, does treating it that point make a difference? So it’s don’t know. My advice though is not to do it. I suffered, I didn’t take Tylenol, I just whined, and that worked.

Dr. Z: Whine-ol, Whining-ol, yeah.

Dr. Offit: Hey, yeah.

Dr. Z: Yeah, I find whining has a very, it’s an anti-substance P kind of effect. It makes me feel better. I get attention. You know, yesterday I went home after I, so I did an interview in person with Dr. Vinay Prasad, and we were sitting here, and the whole time I was doing the interview, my head was throbbing, and I was trying to get through the brain fog of this thing. And so, I crawl home having rigors, and my nine-year-old daughter, who’s vastly more empathetic and compassionate than I will ever be, puts an electric blanket on me, and gets me a little ice pack, and it’s the full, I mean, the full sick role theater, you know, the whole thing. I never felt so joyous in my life, Paul. It was a wonderful experience. So I wanna be respectful of your time, ’cause I know you’re, yeah, you got dressed up for CNN. You’re probably exhausted. Were there any other sort of parting things you wanted to say that you can’t typically say in your soundbite media appearances?

Dr. Offit: No, I think, I really do think things are heading in the right direction. I’m always a little uncomfortable when you look at these sort of national television shows, and they just hang crepe. I mean, it’s like the variants, and you know, and it’s this, and the we can’t get vaccine out there, and these people are having side effects, and it’s just like we’re all gonna die, I mean, just crawl in a hole and die. And I just, I mean, there’s so much, I think there’s so much reason to believe, or so many reasons to believe that we’re gonna get better, but you have two vaccines to work. You have three vaccines coming on the market. You have the, you know, we list it as 26 million people infected, but that’s just people who’ve been tested, and found to be infected. I mean, we do antibody surveillance studies. That number’s off by at least a factor of three. So it’s at least 75 million people. That’s 20% of the population that’s already essentially immune. We’ve already got more than 3 1/2 million doses out there, and that’s another 10% of the population, I’m sorry, 35 million doses out there, so that’s 10% of the population, which at least we are getting some immunity. And so, you know, you’re already starting to build up immunity and it’s gonna get warmer, and you have an administration that cares about things like, you know, modeling good behavior on social distancing, and masking. So I think there’s every reason to believe that things are just gonna get better and better, I do. But again, as I said earlier, I’m an Eagles fan, so you’d probably have to-

Dr. Z: You’re doomed. We’re all doomed, Paul. You know, and again, I think it’s the media loves, I watched some actual TV news the other day for the first time ever, and was shocked at how they would say, “Well, you know, it appears death rates are dropping “around the country, but the worst of the pandemic “may yet be to come,” and then some mumbling about variants. It’s really too bad that positivity doesn’t sell, Paul, because I think, honestly, I think if none of us ever watched the news for the whole pandemic, our mental health would be vastly better. We probably would’ve gone on with business, and would have auto-regulated our behavior in a way that would have improved outcomes, but I may be crazy. Man, P. Diddy, every time you come on the show I get this rush of dopamine, and so does the audience. I really appreciate it, man. Anything you’re doing for fun these days in quarantine?

Dr. Offit: No, God no! Not at all! I mean, it’s just, this is nightmarish. I mean, and I just found out right before I came on your show that I was supposed to do this course next week for the medicals and fourth-year medical students, where it’s two hours a day for five days. I had completely forgot about it. I don’t think I have two hours in any day, actually, for five days, and I wrote back, and I said, “I just don’t think I can do this. “I mean, I’m on the FDA Vaccine Advisory Committee. “I have these other commitments that I’ve got too.” He said, “No, you can’t get out of this. “You have to find some two hours somewhere in the day.” So now I’m trying to figure out how to do that. It’s-

Dr. Z: Oh my gosh, dude.

Dr. Offit: That was the worst news.

Dr. Z: You know what you need, Paul, is an animatronics version of you that sits in the suit right there, like in the Disney Hall of Presidents, and it’s just like, “Vaccines are safe and effective,” with the little fake motions. Paul, well, thank, you know, I know your time is so valuable. I so deeply appreciate it that you give it to our audience, because they benefit from it. I can’t tell you how many emails I’ve gotten from people saying, “Your interviews with Paul “have convinced me to look at that vaccine and get it, “and I was very skeptical,” and skepticism is great, and it’s good to be able to talk about it, and get past it. So-

Dr. Offit: Yeah, first of all, this is my most fun interview. Anybody who makes a reference to Rocky J. Squirrel, or Bullwinkle Moose, you know, wins my heart.

Dr. Z: Was placebo versus placebo, squirrel. Guys, I love you. Share the video, become a Supporter, or don’t. Thanks to Paul Offit, and we are out, peace. Oh man.

Dr. Offit: Take care.

Dr. Z: Thank you, Paul, appreciate it.

Dr. Offit: That was fun …