In the Bubble with Andy Slavitt: Our Shot

Delta: What to Worry About and What Not to (with Eric Topol)

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Andy calls up physician, scientist, and author Eric Topol for a can’t-miss, in-depth conversation on the Delta variant. Andy and Eric cover why it’s taking over, what vaccinated people should be thinking, and whether there’s more variants like it to come. They also discuss the latest vaccine data out of Israel and why the FDA hasn’t fully approved the COVID vaccines yet. Plus, a sneak peek at Andy’s interview with Pfizer CEO Dr. Albert Bourla.


Keep up with Andy on Twitter @ASlavitt and Instagram @andyslavitt. Check out In the Bubble’s Twitter account @inthebubblepod.


Follow Eric Topol on Twitter @EricTopol.


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Andy Slavitt, Eric Topol

Andy Slavitt  00:18

Welcome to IN THE BUBBLE. I’m your host, Andy Slavitt. Everything you need to know about the Delta variant and all other variants. This week, which you be worried about what should we be worried about? looking at today, looking at what the head that’s what this week’s gonna be all about. It is the everything you need to know week. It begins today with Eric Topol. Eric Topol has been a guest on the show before. He is a preeminent physician, scientist and author. He’s founder and director of the Scripps Research Translational Institute. And is amazing and interesting. We had him here, the very day that Pfizer’s vaccine information came out on his first vaccine back in the fall. And he’s back again today. And he did a really good job sorting things out. And then Wednesday, the first part of our two-part series with Albert Bourla, the CEO of Pfizer. He will be answering your questions, questions that I gleaned from asking all of you about what are some of the most important things on your mind and what you need to know?

Andy Slavitt

What is the data telling them about the vaccine and its effectiveness? And if it’s waning? What is it implying about when we might need boosters? What do we know about vaccinations for immunocompromised? The timing of vaccines for kids? What do we know about combining Pfizer with other vaccines like Johnson and Johnson? What does he see around the world? And what other research are they doing into other variants and preparing the vaccine for other variants? Part one, on Wednesday, Part two, next Monday. It is everything you need to know, the conversation with Eric today will really set that out well. We’re going to talk about in addition to delta, you’re going to hear us get into it about the FDA. And Eric published a piece, saying that the FDA needed to immediately approve the COVID-19 vaccines. And we’re really gonna get into that topic as well.

Andy Slavitt

This is gonna be a fascinating conversation. I love talking to Eric, I think you’re gonna love listening to it. Before I get into the sermon on this episode, I want to talk about this notion of how vaccinated people should be feeling and what is our ability and what is your ability to get your life back as a vaccinated person versus to feel like you’re still very much in the middle of this pandemic. And I will say, you hear on the show have, you know, delta variant has changed things a bit. But it’s something that just changed and some things that haven’t changed. And it’s very confusing if you look out their stories. So what’s changed the country in the last few weeks? We got a significant growth in cases there’s no doubt about that. 40% of its coming from three states, most of its coming from unvaccinated locations.

Andy Slavitt 

And so far, the growth is largely among unvaccinated people. There are plenty of breakthrough cases as you’d expect. But serious cases are almost entirely among unvaccinated people. In fact, many of the positive cases of COVID detected and people who are vaccinated are what’s called Incidental Testing, testing when somebody gets admitted to the hospital for something else, or when they are tested on a routine basis because they’re traveling or they’re part of a sports league. But we can hope for is despite all of this growth in cases, that there will be a lower death rate, because many of the people that are older and that are more unprotected, are now protected. So we’re going to live through this wave. I’m not sure how long this wave is going to last, it’s going to be largely waved with the unvaccinated.

Andy Slavitt  04:19

It will say that in India, this wave was very quick. It had a very steep ascent and a very steep descent. That means something we’ll talk about that with Eric on the show, why is that. I would be clear, I think, as we talked to Eric today is that there are slightly higher risks even for vaccinated people. Those risks come from there being more people who have COVID that you’d be around and those risks come from the Delta variant being about 10% more aggressive. So there’s no question that things are a little bit worse. And you know, what does that mean for us? What does that mean for all of you, will explore with that on this episode. But what I can don’t talk about as much as sort of the psychology of you know, what does it feel like to be think we’re done and then be trapped, wrote back in again and then be uncertain about whether or not this is really severe or serious.

Andy Slavitt 

And it’s hard, but you got it like stick as much as possible with the data until we know better data. And we know that 99.3% of people who died from COVID were unvaccinated. That may get a bit worse, they may become if it’s 10%. Worse, it may be 98.5%. Generally speaking, it’s the same people we need to be worried about as we’ve been worried about before. So your chances of being vaccinated and getting sick with COVID are still very, very low. They’re not zero, but they’re very, very low still. So it’s worth taking precautions, particularly if you are in contact with people who were maybe unvaccinated in particularly indoors. More if you’ve got a high amount in your community of COVID. Sure, wearing a mask is like when it’s raining out do you add a raincoat to your umbrella to keep yourself dry? Not a bad idea.

Andy Slavitt  06:12

There’s other factors here that I know people are concerned about. Can even if they don’t have symptoms, can they pass those symptoms along to others? That’s something that Eric and I talked about today. And we know what’s right for us in our lives. And I’ll tell you what, I think for those of us that have been vaccinated, the feeling of safety after a year of fear is a vital psychological respite. So it’s hugging our families, or friends, returning to some of the normal rhythms of life. Those are important, I think a vaccine, even in the face of Delta affords us that ability doesn’t mean we shouldn’t take additional precautions, we should, when and if we feel it’s appropriate. But it shouldn’t rule our life if you’ve been vaccinated. You’ve done the right thing by being vaccinated, you’ve got a risk to manage, still, but I think we can manage it well.

Andy Slavitt

But we also have to acknowledge that we’re living in a world where we’re going to see unvaccinated people in particularly hospitalized and sick. And there’s no reason we should lose our compassion for them. There’s no reason why we shouldn’t feel like, hey, we’re not out of this until the vast majority of us are out of this, not just here in the US, but abroad. So let’s get back to our lives as many ways as we can plus, let’s also acknowledge that these other things were feeling and experiencing that are making us concerned or cautious or empathetic or real. No doubt about it just says anything in life that we have to live with. It’s unpleasant. This is in that category as well. All right. I’m really excited for you to hear this conversation with Eric. It’s a great conversation. It’ll answer a lot of your questions here goes.

Andy Slavitt  08:14

First of all, it’s great to talk to you again. You’re one of the people I both respect, and enjoy talking to you most of all my interactions with people in health care. You were on the show before and I don’t know if you remember this. But it was the exact day that the first research findings from the Pfizer vaccine came out, right?

Eric Topol 

Right. I do. Yeah, big day.

Andy Slavitt

And we’ll play a little clip of how we’re feeling that day.

Andy Slavitt 

So there’s a lot of things to be excited about. But for those who don’t know, we’re talking about news this morning, out of Pfizer, and a German company that I think is called BioNTech. How excited were you this morning when you hear it? First of all, tell us what the news is? And then tell us what you felt like when you heard the news?

Eric Topol

Well, I woke up this morning, it was about 5am. And I’m looking at my emails and I’m saying oh my gosh, Pfizer is announcing 90% at least, 90% of efficacy. As you know, Andy, we’re looking at they were looking at 60% we’d be happy even met 60%. So the fact that it was 90 plus the fact that it was 94, rather than 32, which was going to be their first interim. It was enthralling. It was definitely the kind of news we need right now. Because things are overall looking so bleak. And this is the beginning of the turnaround. This is a day of inflection.

Andy Slavitt

So from then to now, it’s been seven, eight months. We were reacting then to something that was incredibly exciting news about how effective the Pfizer vaccine is against COVID-19. Up till that point, we really just didn’t have any idea. So if we reflect on the time from then and now, what has it felt like? Has the vaccine lived up to the euphoria we felt then? And what have been the good things and disappointments?

Eric Topol  10:12

Well, Andy, that was for me the most memorable day perhaps of the whole pandemic, because it came as a kind of shock. Great news, we were hoping for anything over 50% efficacy. From the full trial of Pfizer completed. And that would have been fulfilling FDA criteria, and it came out at 95%. And that is of historic significance, there’s only one other vaccine that has that level of efficacy. So this was a momentous advance. And thinking about it, I remember we talked about how, you know, we went from 10 months from the sequence of the virus to completion of the largest vaccine trials in history, and then they have this extraordinary level of safety and efficacy. So, you know, I look back, I say, we could have squashed the pandemic, we could have, if we had rolled that out, you know, throughout the world, not just in the US, we wouldn’t have had alpha, beta, gamma, delta and whatever else.

Eric Topol

So, you know, we just, especially in the US, it’s surprising since Pfizer, and Moderna, US based companies, even though Pfizer was using a German based BioNTech ingenuity, but they’ve been basically, this was advanced through the efforts of very extraordinary clinical trials. And the proof was, is gotten only one thing, also, just to reflect, Andy is that, you know, usually efficacy trials, there’s a drop down from that to effectiveness. Yeah, as you know, the real world isn’t as good as the clinical trials that are pristine, right? And here, we’ve seen that maintained, just, you know, amazing, so, probably the most. So it’s…

Andy Slavitt  12:09

So it’s lived up to what we saw on the lab? What we saw in the trials, we’re now seeing in the real world.

Eric Topol

Yeah, that’s a good way to put it in, you know, also flanked by everything previously, in vaccinology. And infectious diseases. This is perhaps, you know, just in biomedicine general, the greatest success story and so the disappointing part about that is actualizing it into, you know, putting the brakes on the pandemic, and stopping the toll of deaths and hospitalizations, and long COVID and everything else.

Andy Slavitt

So let me break that down a little bit. In terms of the effectiveness of the vaccine for people who’ve been vaccinated, and who get vaccinated. Are you as enthusiastic as you were that day, we talked or a little less so, a little more so, given particularly given the presence of the variants.

Eric Topol

Yeah, I think the Delta variant is the only really substantial challenge. You know, the vaccines held up very well against the, what was used to be called the one B117 now Alpha variant that was found in the UK. And then the other two, you know, Beta from South Africa. And Gamma from Brazil, at least that’s where they first were identify. The vaccines held up well, the mRNA, in particular. And then today, we have data from the UK, the Public Health England, where there’s like five- or six-point drop against any infection from what was 95% to, you know, 88% to 89%. So, you know, they’ve held up well, even against delta, delta is the most formidable challenge. But you know, overall, this is extraordinary. And the problem we have is lack of full acceptance. And, you know, the ability, that’s just any infection protection, the ability to protect from hospitalization and deaths are, you know, 95%-96%, it’s amazing.

Andy Slavitt  14:21

So it’s been as advertised, we have this little Delta variant, and you’d say to people who are vaccinated, they should feel very confident that they’re going to be protected. I’m putting words in your mouth now. So please feel free to correct me. They’re going to be protected from something serious. And you know, while it’s not quite as strong, it’s certainly possible that they can get an infection. a mild infection, still, relative to all the vaccines we’ve seen throughout the course of the world is still pretty darn good.

Eric Topol

Yeah, I mean, I think what I’ve called is the Delta stress test. And what we don’t want to do if you’re vaccinated is to try to put your status, your immune response status into a stress test with this variant, this version of the virus we know has more than 1000-fold viral load in people who are carrying it, then the original ancestral strain. And so you don’t want to be indoors without a mask and people who you know are potentially unvaccinated or, you know, we know that people vaccinated can carry this. And although it’s rare, they can transmit. The point here is that we have to until we get through this wave, Andy, we’ve got several weeks to get through the Delta wave, we got to get back to just any time you’re going to be indoors, any prolonged period, or even if you’re going to be outdoors, and you’re going to have an extended contact, direct, close contact, somebody singing, yelling at you, you know, these are things that are not good, because if still, you don’t want to be one of those rare, significant breakthrough illnesses.

Andy Slavitt  16:04

So, mask indoors?

Eric Topol 


Andy Slavitt 

Can you help people understand what exactly 1000 times the viral load means? It sounds like a lot. To the untrained ear, though it sounds like 1000 times as likely to get sick, is that 1000 times more contagious? Is 1000 times more deadly? What does that really mean?

Eric Topol

Yeah, no, it’s a very careful study that came out of China. Just a week ago, one of the best studies about Delta to explain why we’re having such a rough time with it. And basically, what it showed is that the viral load basically what we harbor in our, our nose, our upper airway, particularly in the nasal mucosa. That the viral load, and it’s reflected in a couple of ways. One is if you do a PCR test, the so-called cycles threshold CT, the lower that is the more viral load, essentially, it’s the number of copies of the virus that are sitting in your nose if you want to get down to the simple explanation. And the point here is that this version, delta, the strain is so good at getting in cells through the upper airway, that it is you know, as the cells become hijacked, and they are the factories, and they’re just making 1000 more copies that are replication competent, that are transmissible. So this is the issue why the Delta wave that you know, the UK is, of course, grappling with the Portugal, those are good well vaccinated countries and you got places like Indonesia and Russia and Bangladesh, South Africa, you know, they don’t have vaccines, and that’s why it’s such a rough road right now for those countries.

Andy Slavitt  18:08

Right. Right. Okay. So what you’re saying is that 1000 times the viral load is what makes the virus about twice as transmissible as the 2020 version, right? Is that what 1000 times translates into about twice as transmissible?

Eric Topol 

Exactly. The transmissibility is the most important feature. It has the other side feature of this so called “immune evasiveness”. Whereby it has ways to evade our natural immune response or even the vaccine immune response. So it has some features of both ways that make it more challenging, yeah.

Andy Slavitt

the strange thing I noticed, in India, that it rose incredibly fast, incredibly high. And then it seemed to drop incredibly fast and incredibly low. Is there something about Delta? Or is there a feature of Delta that makes it such?

Eric Topol

Yeah, well, that’s, I think, it was horrific what happened in India. But in many respects, it’s also a favorable thing to see. This variant is so good at finding hosts, it rips through the population, it gets as many people as it can get. And then it just basically comes right down. So the accent of cases in India was as rapid as the descent. And basically, the whole thing took 8 to 10 weeks. And we’re starting to see that in the UK right now. It’s had a very rapid ascent. And hopefully, we’re starting to see the accent that the sooner that happens, as soon as we can take a breath of relief that that’s going to be replicated. It may start to happen right now in Russia. But the point you’re getting at is a really important point. We are going to get through this delta wave. It’s just a matter of time. Unfortunately, a lot of people are going to become new hosts of this dammit virus, but it will run its course, it basically it’s kind of like using timber in a wildfire, you know, it can only burn through so much.

Andy Slavitt  20:13

Now when people talk about a stream being more lethal, that’s always a complicated thing to me because by definition to me if it’s more transmissible, it’s more lethal. But to me, something else is implied with that, which is that there’s something about it that hits people harder, it kills more people and sends more people to the hospital. Are we seeing any of that with Delta?

Eric Topol  20:34

Well, there have been people that have said it’s more deadly. But it’s tricky to interpret that as you’re getting at. Because there’s two big confounders. One is when you’re so highly transmissible, well sure, more people are going to die more, we’re going to get really sick, it’s just getting to a lot more people quickly. The other is the vaccine effect, which modulates it. So let’s say you’re in the UK, you vaccinate or Israel, you vaccinated so much of the people who are vulnerable of advanced age. And now that people are coming in, they’re much younger, and the case fatality rate goes down a whole order magnitude, you know, less than 1/10. So it looks favorable. But it’s because there’s different kinds of people that are getting infected.

Eric Topol

So, it’s really tough to say the only thing that would make it look more deadly. If you look at places like Indonesia, and Russia, their death toll is the highest ever in the pandemic. But again, that could be explained even though they don’t have much vaccines because it spread more than any prior strain. So it’s a tough one. I would say, you know what, we got enough problems with this damn Delta. We don’t need to add to it deadly. You know, we got danger, we don’t need to be doomed. I just don’t see enough to convince me yet that this is truly more deadly by itself, per se. But it’s very confusing to people because they don’t understand that at all more people dying must be more deadly. No.

Andy Slavitt  22:06

Right. Okay, can we just take 30 seconds just to explore the counterfactual. I mean, just for the fundament. And you alluded to this a little bit when you talked about Indonesia, and some other countries, but can you imagine going through this without a vaccine? Can you imagine Delta being here now and what this wave would look like in the US if we had no vaccines?

Eric Topol

You know, it’s funny you mentioned that, Andy, you know, I was looking few days back about, you know, the 1918 pandemic, flu pandemic, and how they were three big ways. And it was, you know, for over an 18 months, this has already gone on longer. And we have another major act to follow here. And in thinking about what it would be doing right now in the US had we not had vaccination, watching what’s going on in Indonesia, which is the fourth largest country in the world after us, where is profoundly devastating. It’s as horrific as was India, countless number of deaths and suffering. So we will be going through that, because we’re defenseless, and we’re tired, you know, we don’t want to wear the mask, we, so it would be the worst wave ever. But here we’re going to have a wave, at least it’s going to be blunted, it will have lots of cases, but we won’t have the deaths and hospitalizations or anything like that monster, third wave, you know, that is a vaccine story that’s played out already in the UK, Israel, other countries and is going to be playing out here.

Andy Slavitt 

You know, it’s a really important thing to do. One of the things that I really think you and I need to cover and I’ll go there in a minute, is that some of the anecdotes that are creating misperceptions about the vaccine, and I want to get into that with you in a second. But I have a couple technical questions first, that I think people will want to know to help them understand just the basic inner workings of the vaccine so far and against the variance. Is there any evidence that you’ve seen, either in Israel, or here, that we’re starting to see any waning of the effectiveness over time and the lower durability? I have, I should tell you that I think you know, we, you know, you and I talked about, I have Albert Bourla, the CEO of Pfizer coming on the show on Wednesday. So just two days from now, and we’re going to talk about that. But anything, anything you think we’re seeing that suggests that there’s a waning and that there will be boosters needed in the fall and winter?

Eric Topol  24:42

Yeah, this is of course stirred a lot of people because of the idea that potentially everyone’s going to have to come in for a third shot who’s gotten two mRNA vaccines or, you know, get additional boosters. The Israeli data hasn’t been published or even in a pre-print. It was I guess, discuss with Bourla and some of your Whitehouse friends, of course CDC, FDA, etc, recently. What was put out today by Ministry of Health in Israel suggests that if you were vaccinated in the early part of their campaign January, and you were, of course, you were be among the elderly and most vulnerable, that here in recent weeks, you are more likely to have one of the breakthrough infections and potentially get ill. But it’s very difficult to interpret that Andy because they’re also the most vulnerable people and we don’t really have controls.

Eric Topol 

So right now, there’s a preliminary sense that this this kind of waning immunity as they’re calling it, it might be real, but also to over interpret that for everyone. Just because we do know that neutralizing antibodies come down over the course of a few months. But at the same time, memory B cells kick in on demand T-cells are going, you know, as our reserves. So whether we’re going to need boosters from this limited data is unclear. But if we do at least the first part of this is about elderly or highly vulnerable people, not across the board. That’s kind of where I see it. Now, obviously, Bourla has a different view on this, getting more billions of people to take a vaccine is in their interest. But we have to be careful before we buy into that because their booster at this point is just another version of the same original.. I want to see either a Delta multi valent vaccine that takes this one on specifically, it’s very different than the original strain, or even better a pan Coronavirus vaccine, which we should have soon. So going through the booster, and this kind of one more dose of an already, you know, antiquated version of the vaccine. I’d like to see something better than that.

Andy Slavitt 

Well, it’s one of the questions I’ll ask him on Wednesday. And I understand from talking to them, that they’re doing research into all of those. And at least so far, the recommendation is that if they do a booster, that it’d be the same. And I do think that, as you said, it may just be for older people. But I also think if I were going to give them more of the benefit of the doubt, I’d say they’re getting prepared for every scenario possible. The federal government should and is getting prepared for every scenario possible. And we when I was there, I made sure we had enough vaccines in case boosters are needed. But neither their application nor that advanced purchasing means they’re going to be needed. And I think the CDC and FDA will need to do their work and make their call.

Eric Topol

I totally agree that we got to be ready. And you know, the more vaccines they can make and have contingent plan for boosters, the better I am in full agreement with that, I just think that before we get people all worked up out there, that we should have better data to be confident. And also, you know, when they initially file, or say they’re going to file the UA, they didn’t say we’re going to be specifically interested in the elderly. It gave the sense at all. Here we are, you know, 160 million who showed up already, for two are going to have to come back. So I think we just want to be careful on the communication about who and I’m glad that if it turns out, that’s what their  tension is. That’s much better.

Andy Slavitt  28:44

Yeah, I think so. I’ve tried to follow the money a little bit and just given the purchase of vaccines have already been made, you know, I can’t really, look, I’ve been, as you know, a big critic of the pharmaceutical industry pricing for a long, long time still am and very outspoken about it. in this situation. I don’t think that given that they’re going to sell billions of vaccines around the world. That will end up being a couple of what will end up being just a couple 100 million boosts in the US. I don’t know if that’s a big stock price move. Right? Do you think that Albert, and it’s gonna be interesting to talk to him views his role is to figure out how to help build trust and communication around the vaccine. They haven’t always gotten it right. And I think they know that. But I will say this when we came in Eric, Pfizer and Trump administration, any terrible relationship, a lot of mistrust.

Andy Slavitt

Trump thought Pfizer was playing politics in terms of when they were delaying their application after the Trump was pissed that they didn’t join Operation Warp Speed. So there’s a lot of mistrust. So nobody knew what was going on in their factories when we got there. And when we came in, we said look, let’s share all of your challenges and we will help you in over a reasonably short amount of time. We built a lot of trust, give general partner a lot of that credit, and we helped the goals, the vaccines precisely because we were able to do that together. So I’m hopeful that despite all of the things as you know, that the FDA and CDC is sending a message saying, hey, we’re in charge here of looking at the data, you guys submit an application. And hopefully that message came across.

Andy Slavitt  30:19

Right? That’s good to know, really.

Andy Slavitt

So there’s 100 million people in this country who have either not been vaccinated, nor have they been infected with COVID. Is it safe to say that the majority, the vast majority of those 100 million people one way or another, will get immunity from COVID? If presumably, they survive? Or is it going too far to say that?

Eric Topol

Well, you know, people have put that out there. I think that’s a little strong. You know, everybody in India, a billion people didn’t get COVID or get antibodies, and obviously, a limited number of unvaccinated from Delta. Our biggest challenge yet no, I think what we’re going to eat, we know, we have 160 plus million fully vaccinated, we got another, whatever, 20,000,00 million that have had one dose. But that other figure about natural immunity from having an infection. We don’t know that too well, because we have over 100 million were at some point infected. We know that much, we can extrapolate. But did half of them get vaccinated? What proportion got vaccinated So you know, if you add them all up, you got maybe, you know, let’s say we have that’s 230, who had some type of immunity. And as you say, that leaves 100 million, that includes children who wouldn’t be at this point below 12. That you couldn’t vaccinate, and we don’t have a way to do it.

Eric Topol  32:06

So yeah, there’s a lot of people out there, but I don’t think all those 100 million are going to get COVID in this Delta wave, I think that a lot of them, for whatever reason, are going to be able to evade it. You know, either because, you know, it can’t travel long distance, right? it’s got to be, you got to have some contact, you got to be in the room, you got to be in the car or the bus or whatever. So people will evade it, we won’t be fully, you know, the problem is we need like, 90%, to have immunity of some kind, to really get that population level protection. And, you know, we’re not going to get it even through the Delta, this is just going to still be plenty 10,000,000 are not going to, they’re fortunate enough that they’re not going to get hit.

Andy Slavitt

So another way of saying that is it isn’t our last wave?

Eric Topol

I wish it would be I hope still, I’m a crazy optimist. You know, I do think that it’s, you know, recently I wrote a paper in Nature Medicine with my friend Roberto Burioni from Italy. And we posited that this is peak fitness, that, you know, it has still hasn’t evaded our vaccine. And, you know, I think what the Delta wave is going to do, and if we do ever get the darn full approval, the FDA will get up there more on the vaccine immunity, we’ll get more through the Delta wave infections, we’ll get closer. But if there is another, more transmissible stream ahead, there’s a lot of debate on that most of the virologist and evolutionary biologists, Andy, think there’s gonna be worse to come? There, they actually think I’m hoping that we will not see something that will evade our vaccines or natural immunity plus vaccines. So we’ll see. But I’m hoping that we get through Delta we get through September, and things start looking good again.

Andy Slavitt  34:09

So these evolutionary biologists would say what? That we just have an ongoing competition between our medical technology and the virus for you know, the foreseeable future?

Eric Topol 

Well, what they are saying is, you know, the first three variants of concern, Alpha, Beta, Gamma, they all kind of fall out a succession of specific mutations in the spike protein in the internal domain, and then this one was a detour, Delta. And so it basically and of course, as Lambda out there, we don’t know that one also took a detour. So the point here is the concern is that there’s new paths for this virus to find by its random mutations that are occurring as it propagates through populations. It sustained; it will find potentially other mutations not yet having been actualized to make it even more transmissible. But you know, it’s gone through so much more contagiousness from its original strain. You wonder what is a limit? I think hope, and I’m you know, this may be a fantasy is that we won’t see something worse than Delta. But there’s many, I would say the majority of the cognoscenti are saying, no, no, it’s going to get worse.

Andy Slavitt

Okay, now I’m gonna say something that I don’t even understand. So if you say to me, Andy, what are you talking about, I really have nothing to respond. But one of the things that I’ve heard is that there is some limitation, because of the way the virus works, to how aggressive it can get. In other words, if it gets much more aggressive, it means that it alters the spike protein and its variability to attach to ourselves. And if it does that too much, it becomes way too difficult to attach to ourselves. And the virus has almost kind of a self-governing state that keeps it in a more of a happy medium, then it’s something that becomes too invasive to the vaccines. And so it ultimately means that the virus will be vaccine a ball. Another way to say that is if it does something to completely evade the vaccine, it would make it much less likely to attach and therefore not evolutionary progressive. So is there anything what I said that makes sense?

Eric Topol  36:33

Yeah, actually, there is, Andy, there are pathogens that have evolved to the point where they are much less of an issue. They’re less pathogenic, they’re less disease causing, they’re, they’re less efficient in getting in to hosts and people. So that’s the hope is that, you know, we got to always keep our hopes up there. But, you know, I think there’s a reasonable chance we’ll see that here. And, you know, this has been going on quite a long time now. I mean, it’s had many chances to evolve. And there’s only four, so far versions of this virus that have been significant among, you know, 1000s of different lineages that really have essentially developed over time. So let’s just hope that the next major version is not going to be one that causes so much trouble. I think it’s certainly possible.

Andy Slavitt

Well, yeah, it seems the variants that cause more trouble for the vaccines like Beta, which were not as contagious, so they were out competed pretty quickly. So it feels like you’re either going to have a fast one or innovative one. And if you do, the fast one’s going to be the evasive one. And that’s actually good news, and helps the vaccine in a weird way. If you’re vaccinated, Delta is sort of your ally, because it’s sort of eating up the variance that the vaccine can’t eat up.

Eric Topol  38:01

Yeah, no, I think that’s a very good point you’re making really.

Andy Slavitt

So let’s talk about some things that are spooking vaccinated people for a second, and then I want to talk about the FDA. There are a few phenomenon that people observe and write about that get people worried. For example, this statement that there are more and more younger people in the hospital, for example, I hear a doctor telling me a month ago, I would get a call of a breakthrough case, every couple days. Now I get like five a day, or five yankees tested positive or 60 people in the Olympic Village tested positive for Covid, none of whom had symptoms. And it causes people to go, Whoa, maybe this vaccine thing isn’t working so great. Now, this information without context can scare people. But of course, we know why there’s more young people in the hospital relative to old people, because old people are protected, as you said, why are doctors seeing more breakthrough cases?

Andy Slavitt 

Well, there’s more vaccinated people. It’s like, if everybody was seven feet tall, we’d say, wow, there’s more tall people getting COVID. So all you have to do is look at the math. But it’s hard to do that because you never quite know what the denominator is. We don’t know the number of people getting breakthrough cases, and it applies that may be the vaccines that are working as well as we thought, or, you know, people are testing positive, when in fact, they could be testing positive, because the vaccines working in fighting off the virus, but you could get a positive test result. So can you help people understand these phenomena out there? Are they being translated to the public? Indeed, is there something to be concerned about? Or are these exactly the kind of things that we would expect to see based on the data?

Eric Topol 

Yeah, and I think there’s a lot of misunderstandings as you’re getting out here. The point is, is that as you get an increasingly large and majority population who were vaccinated. Of course, as infections continue, among that group, there will be more but it’s still a tiny fraction of the group of vaccinated people. But you’ll hear about them specifically, they’re skewed because they’re not expected. But they should be expected, of course, because we know Delta our best data is, you know, 88%-90% best protection, that’s not 99, 99.9, 100, it’s 88. That means is a significant fraction who still are susceptible vulnerable to infection. That’s one thing. The other thing is, you know, we’ve had breakthrough infections, I hate the term because it sounds something alarming breakthrough infections, but we’ve had these post vaccination infections fully vaccinated beyond two weeks or whatever.

Eric Topol  40:42

And we’ve had them you know, for months, but they weren’t that many. They’re more with Delta, we have to acknowledge that. And the reason is, is because the vaccines were holding up still at 95%. Until now, and the drop down of 6%-7%, that’s enough to see. So you know, I think whereas we’ve been hearing about only 99.6% of people who’ve died, you know, we’re unvaccinated. That number is going to drop to, you know, 99.1, or 98.7. Because delta is more formidable. So, there’s a lot of different parts of the story. One of it is understanding the math. The second is, you know, appreciating that we have a lot of skewed reporting and experience, because we have a significant proportion who haven’t vaccinated. And then third is, hey, we really do have a little more of a challenge than ever before.

Andy Slavitt

Okay, I love that answer. Because your answers yeah, it’s a little bit to do with things getting a little bit worse, explains a small drop off, as you said, you know, seven points off 95 is not nothing, you see, you know, 8, 9, 10% more than you would have seen otherwise. And likewise, some of that will translate into hospitalizations, and deaths, and so forth. But that’s a very small element. And you look at the CDC’s decision not to publish information on breakthrough cases, because these are literally cases that would go largely unrecognized, because people aren’t in a protocol where they’re getting tested. So it’s not clear that they matter that much. But still, we don’t have all the data that allows us to answer some of these questions. So, you know, these are people amounting an immune response and immune response triggers a positive test result, in some ways, it feels a bit like a false positive, although I don’t know that that’s quite accurate.

Eric Topol  42:39

Yeah, I think the point here, if we tested like at the Olympics, or like the NBA, or if we tested everybody, every day, we’d see a lot of people who are vaccinated and had COVID in your nose, Delta in their nose specifically, there’s a lot more out there than then we are testing. In fact, our testing in this Delta wave is going down rather than up. And of course, our sequencing isn’t at the high levels it ought to be but the key here about the if it’s just harboring as a carrier, and it’s not transmitting to people, no one’s getting sick. It’s not a problem, right? What is the problem if you’ve had vaccination, and you wind up in the hospital, it’s also a problem, I have to admit, if you lose your sense of smell and taste, which some people are, they’re not sick to the go to the hospital, but they’ve had a local invasion.

Eric Topol 

They don’t get pneumonia, it doesn’t get into their, you know, bought the rest of their body. But locally, it can do that. And that’s obviously a very, you know, that’s not something you want to have happen. So, Delta will do more of that. We have to be ready for that. That’s why I think that you know, indoor masks are a good thing. Don’t stress the vaccine protection, because it isn’t as good as it used to be. But it’s damn good. Just not at where we were when Alpha was circulating.

Andy Slavitt  44:02

Right. And of course, it’s still possible, although it’s not the most likely thing in the world, it’s still possible for someone to give it to me, me to feel no symptoms, and then me to give it to someone else who does feel symptoms.

Eric Topol 

Yeah, I think the chances are low, because if you get Delta, you’re more likely to know it. But yeah, we don’t have enough really good data on asymptomatic status with Delta. But we do know from the athletes, like in the Olympics and other recent testing that if you do systematic everyday testing, you will find people are harboring Delta have no idea. So yeah, the question though, what you’re getting is can you give it to someone in that state and that is unknown. It’s probably rare.

Andy Slavitt 

It’s probably rare and it’s also not necessarily a bad thing for you to have an asymptomatic case of COVID-19. The reason I say that is because it tell people if you hadn’t vaccinated decades would have likely been a hell of a lot worse. And so what you’re seeing is the vaccine working and people use this analogy, it’s not unique. But it’s like when you carry an umbrella, and you go outside in the rain, you know, generally speaking, you may get a little bit wet, but you’re not getting soaked, and the umbrella is doing its job. It’s not like you throw out the umbrella because you know, your shoes got a little damp. And well, you know, Delta baby is a little more slanty rain, so maybe you get a tiny bit wetter. So maybe the umbrella doesn’t do quite as perfect a job, but you’re still damn glad to have it.

Eric Topol

Well, you know, I think there’s another point here, which I’m not something I’m advocating at all. But if you are fully vaccinated, and you have a Delta a case, it’s usually obviously either asymptomatic or mild, guess what? You benefit from that. Because you do amount, even more of an immune response. So not suggesting that people have Willy vaccinate get because you don’t know how you’re going to wind up get Delta COVID. But the point is, is that we know now that the super human response to COVID is if you’ve had an infection, and you get one dose mRNA. That’s even better than two doses of the vaccine. So you get through your vaccine, and you get Delta. Oh, man. So the next wave of immune response studies actually is going to be that interesting. It’s going to be what happens when you are fully vaccinated, and you get exposed to delta. But I’m not recommending that to anyone, just to be clear.

Andy Slavitt  46:32

Interesting. Okay, got it. So let’s talk about solutions. And let’s talk about the FDA. You wrote a piece that got a lot of attention. Eric, it sparked a lot of dialogue, which I think was probably one of the purposes, it has become kind of a mainstay reference point from when you said, hey, FDA, you really studied this thing. We got billions and billions of people have been taking this thing. I know you’ve got your processes. But what the heck are you waiting for? Now, I know that’s a little shorter version, or maybe a little bit colloquial version of what you wrote.

Eric Topol 

Yeah, the near times might not have gone with those words. But anyway, yeah. So as you know, I’ve worked a lot with the FDA over the years. You know, I know Janet Woodcock for 35 years. I’ve been on an advisory committee. So I’ve also has spoken to a lot of people at the FDA throughout the pandemic. And I understood something that was unusual. This key thing is that, normally a full licensing application, which is 100,000 plus pages, they got to bring in with a truck with all the boxes to review. Normally, that takes a year to review, all right? Or more. This was a very special case. So when Pfizer, and I don’t know when you have Albert Bourla you might ask him about this. But when Pfizer and Moderna put in their full application, it was annotated by seven months, they were sending in sections, because this was a pandemic special situation.

Eric Topol  48:14

So they’ve review of the so-called biologics licensing application, the full approval story is not just safety and efficacy. I think we know that. But it also includes plan inspection, the preclinical data, the manufacturing, all the specs, production, all these other issues, you know, the things about cold freezing refrigeration, all that stuff is reviewing all the data to give it final approval. Now, the problem here is that the FDA has essentially had seven months, not a few weeks. So when Pfizer went in the first week of May, and Moderna on June 1, they already had lots of feedback from the FDA. So if you talk to the people in the know about how the FDA works, they’d say in June, this should have been done, in June. But moreover, if we didn’t have Delta and we were everything was kind of peachy keen and we were just sitting down there with just keep coming down, down down. And we had containment, it’s wouldn’t be an urgent matter but it is. And if the FDA gave full approval, the impact would be profound. It’s our only big coupon to get 10s of millions of more Americans vaccinated right now, we have yet no other we pulled out all the stops, Andy, when you were with the White House, you did it all and we have no nothing left to go except FDA full approval.

Andy Slavitt

And I happen to have some insight into when the timing of this as expected and not knowing anything, not having your training. Having been as close to the FDA as you have been. It feels to me like it’s a little too long. So I wonder what are the T’s are crossed? And what are the eyes they’re dialing? Like, is this really impractical stuff? Or is it stuff that has meaning or instead of losing the forest from the trees, are they really seeing that if there’s things that they don’t do now, it would come back to haunt them, because people would have pointed them and diminish their work. Do you have any insight into it?

Eric Topol  50:22

Yeah. Well, you know, I try to put the pieces together. You have last week. Dr. Woodcock saying that it will be done by January. Well, that doesn’t give us a whole lot of sense of relief. And it could be sometime any time before then well, there’s no transparency as to what’s holding out from the FDA. So if they were to say, Well, you know what, we’re making really good progress. But we waiting for Madonna and Pfizer to get you know, this to us, that to us? We’re missing some piece. Now. We don’t get that. Now, my understanding is that, as you know, when Janet Woodcock said it’s among our top priorities. Well, you know what, it shouldn’t be among the top priority. There isn’t anything more, you know, the FDA is responsible in so many respects for the health of the public and what could be more urgent in this. Now, the part of the story here is that the FDA has been preoccupied with the Alzheimer’s drug approval, which is probably in my view, the Nadir of the FDA’s record for all my career, 35 years.

Eric Topol

I’ve never seen anything so egregious as this. Approved a drug, overrule that the advisory committee […] or a drug that we have no clinical benefit? The two trials were stopped with the futility and somehow out of a rabbit out of a hat that, you know, Biogen works with the FDA very irregular front page in the New York Times today. Previously story broken by stat news, it’s a really bad looking thing. And they’re defending that. And by the way, that’s a biologic, vaccines are biologics. The point being here is if you were the leader of the FDA, you would take every one of those 20,000 employees, as many as you could and say, work on this BLA and get it done. Whatever it takes, get it done right. No one wants to have it done you know, short cut, you would do that. But it’s not happening. My intelligence..

Andy Slavitt  52:22

And BLA stands for biologic licensing agreed. That’s the final approval what we’re talking about.

Eric Topol 

My intelligence tells me that that hasn’t been done that Peter hasn’t given that mandate, or Janet Woodcock to the people that are doing the work. And meanwhile, we’re watching disarray, because you don’t have an Alzheimer’s drug approved in the middle of this mess. Until you get that, you know, that’s just and by the way that was defended by you know, Dr. Woodcock, and, you know, I just really, this shows a dysfunctional FDA to me, that’s my diagnosis

Andy Slavitt

Let’s skip ahead and say, okay, in this intervening period, when we’re really just seeing a trickle of new people vaccinated, I think there’s an opportunity for us to begin to do the work to make sure that the approval lands as it should land, and to begin to have a conversation. And I’m going to have one with obviously, you know and with folks in the business roundtable, presidents of universities and others say, we’ve got to talk to the public and say, look, many of you wanted to wait and see what happened. You wanted to wait for the jury to come back in on the vaccine before you decide whether to get vaccinated. Okay, fine. The jury is now in. The jury took a long time, and the jury did all the work for you. And they did not prebake the answer. And you have these 15 questions. Well, they went and answered all 15 of those questions. In fact, they answered 15 more you didn’t have. So therefore, here’s what you’re going to do, whether your municipality, a government agency, an employer, a venue, you need to be thinking through what the steps you can take, and we’ll take when we have a fully approved vaccine, so we can make the most of it.

Eric Topol  54:10

Yeah, you know, I think, obviously, we’ve seen more of this, with passing days, like the University of California system, and some more health systems, we’re seeing that trend, but it’s still, you know, in the single digit percent, and the readiness to have that ready. I’ve talked to General Counsel, not just where I work, but many other places and they are waiting for that full approval. The problem I foresee Andy is the Delta wave will go through us before that’s going to happen. And then the urgency of the requirement will be relaxed because well, we will get through this, this darn wave. And it won’t take that long. I mean, we’re starting to get well into it. Now. It certainly parts of the country and it’s going to go through the rest in a matter of time, so, you know, I’m not optimistic that when we are there, when the damage is done, the full approval won’t be nearly as important, you know, even if they had approved in June, as you will know, you got to go through two doses and another couple of weeks, and it takes time. So every day that we missed this opportunity, we’re not confronting our challenge our formidable foe, namely delta.

Andy Slavitt 

So my last question is, what’s the most optimistic but realistic thing you can tell people from where we sit today? And I’m not asking you to lie to people, I’m asking you to put things in perspective of how people should be thinking about the next period of their lives.

Eric Topol

Well, I mean, you know, we are exceptionally lucky not to be living in, you know, perhaps the worst pandemic in history, especially in context of modern medicine. It is. But we are exceptionally lucky because we have powerful, safe vaccines that are protected even against the most formidable version of the virus yet Delta. And that people should be confident if they’ve been vaccinated, that they’re going to hold up well, and they shouldn’t, you know, try to give it an acid stress test, you know, and be still be vigilant about it. But we will get through this. And hopefully, this is the last bad wave. That’s my view. I mean, we certainly we’re not going to eradicate Coronavirus, COVID. From the planet. It’s going to circulate, we got plenty of parts of the world, we still have more to come. But the point is, is that if we took more advantage of the vaccines and the tools we have, we could be fully contained, namely, less than one case per 100,000 people maintain that containment, we can get there.

Eric Topol  56:49

And I’m confident of that. But it takes more solidarity. It takes less conspiracy theorists and anti Vax and anti-science, which we need to confront. And by the way, you know, when I spoke to Vivek Murthy, about this needing to confront misinformation, in May, May 11, by the way, I was gratified to see him last week roll out that this, you know, taking on misinformation, but still not aggressive enough. So, if we do that, counter that misinformation, if we get the full approval, and we just use the tools that we have right now we will achieve containment and I’m excited about that. And I’m excited about getting practice pre-COVID life, because I’ve had enough of this. And I know all your listeners have had more than enough of this stuff.

Andy Slavitt 

Yes, well, they have. But they haven’t had more than enough of you because you’ve been amazing. You’d been one of our favorite guests I’ve had on the show. It’s fun to have you twice. And the first time it was a day that I think both of us will remember forever. Today’s a day, I think when people could really use help in figuring out what this new dance partner Delta mean, it will mean, I think he provided a lot of light on the topic. And combined with my conversation with Albert Bourla from Pfizer on Wednesday, hopefully, we will have some more things figured out. But you’re great. And I truly, truly appreciate the friendship.

Eric Topol  58:13

I want to just say one thing, I want to thank you for 140 days what you did, the White House, which were I think was in many ways managing the communication, the vaccine rollout, which was exemplary got up to four and a half million vaccines a day, many times. It was a blowout what you did, I think it’s just, you know, something that is a legacy that, you know, not only should you have to be proud of, but we’re indebted to you. So that’s outside the bubble. That’s just want to say, I know, I acknowledge that, you know, least through Twitter, but we’re indebted to, you know, leaving your family leaving your home and making Washington DC and the craziness there for a protracted period of time. And you’re good timing for when to get back home. Kudos to you.

Andy Slavitt 

Thank you, man. Let’s do this again.

Eric Topol 

Great. Thanks, Andy.

Andy Slavitt

Thank you, Eric. I think that gave everybody a helpful understanding of the state of play with the Delta variant. And now let me tell you about what’s coming up on Wednesday, we begin our two-part conversation with the CEO Pfizer, Albert Borla. We’re going to start with diving right in to where we just were.

Andy Slavitt  1:00:36

So we’ll get Albert’s thoughts on everything from the Delta variant to how they will keep up with future variants to what they’re seeing in terms of the need for boosters, to what the data is telling them on the success of the vaccine to the timing for children and other approvals to how they’re thinking about vaccinating the globe. And there’s so much good information that we’re going to start with part one on Wednesday. And we’re going to continue with part two, this coming Monday. Hey, everybody, have a great couple days. Look forward to having you tune in on Wednesday.


Thanks for listening to IN THE BUBBLE. Hope you rate us highly. We’re a production of Lemonada Media. Kryssy Pease and Alex McOwen produced the show. Our mix is by Ivan Kuraev. Jessica Cordova Kramer and Stephanie Wittels Wachs still rule our lives and executive produced the show. And our theme was composed by Dan Molad and Oliver Hill, and additional music by Ivan Kuraev. You can find out more about our show on social media at @LemonadaMedia. And you can find me at @ASlavitt on Twitter or at @AndySlavitt on Instagram. If you like what you heard today, most importantly, please tell your friends to come listen and please stay safe, share some joy and we will get through this together.

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