In the Bubble with Andy Slavitt: Our Shot

Breakthrough Infections — and Boosters — Explained (with Jennifer Nuzzo)

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So you’ve been vaccinated. And now you’re hearing that you could get infected? Or be contagious? Andy gets to the bottom of this when he calls up one of the clearest explainers he knows, Johns Hopkins epidemiologist Jennifer Nuzzo. They discuss why although you may get infected with SARS-CoV-2 eventually, vaccinated people are still unlikely to get COVID-19, and what that means. Plus, Andy breaks down the new recommendation about boosters.


Keep up with Andy on Twitter @ASlavitt and Instagram @andyslavitt.


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Andy Slavitt, Dr. Tony Fauci, Jennifer Nuzzo, Winston Churchill

Dr. Tony Fauci  00:00

You know, I think the first thing we should do is that clarify the word breakthrough, because that really has quite a negative connotation. No vaccine is 100% effective, even vaccines that are really quite effective, like the mRNA vaccines, which are 94% to 95% effective. But if you look at what that number means, it means effective against clinically apparent disease. So people who get infected, despite the fact that they’re vaccinated, generally fall in the category with some exceptions, of course, of either being minimally symptomatic, or not having any symptoms at all. They’re categorized as a breakthrough infection.

Andy Slavitt 

Welcome to IN THE BUBBLE. I’m your host, Andy Slavitt. Let’s acknowledge the week we’ve had. The tremendously emotional conclusion to our time in Afghanistan. The images in the reality of the lost time, lost lives, lost treasure, lost money. What will soon be the heartbreaking loss of a civil society, to girls and women and to many there. let’s acknowledge a UN report that is telling us that our climate is beyond even what we believe to be the case that the next three decades are baked in. And we’ll see one and a half if not two degrees of temperature change, which means the summer we’re experiencing now will be considered the good old days very soon. And let’s acknowledge that COVID is as a reality, with Delta, something that feels is a new introduction to this world into our world that’s here to stay.

Andy Slavitt  02:40

So why do I start this way? Because these are challenges that impact our psyche. And that impact on our psyche is the real challenge that I think many of us face how to react to these things. Now, I want to play for you two clips. They’re both really the inspiration behind this show. The first was recorded in June 18th, 1940. In the House of Commons, when the first images of the Eiffel Tower were seen with Nazi flags hanging from the rafters in the foreground, France had capitulated to the Nazis. And it was very clear that England was going to be next. And Winston Churchill took to the floor of the House of Commons.

Winston Churchill

The whole fury and might of the enemy must very soon be turned on us. Hitler knows that he will have to break us in this island or lose the war. If we can stand up to him, all Europe may be freed and the life of the world may move forward into broad, sunlit uplands. But if we fail, then the whole world, including the United States, including all that we have known and cared for, will sink into the abyss of a new Dark Age made more sinister, and perhaps more protracted, by the lights of perverted science. Let us therefore brace ourselves to our duty and so bear ourselves that, if the British Empire and its Commonwealth last for a thousand years, men will still say: this was their finest hour.

Andy Slavitt  04:53

This isn’t the first time we’ve had faced tough times and Churchill, you’re basically the way that speeches, written in history, called on, England called on the whole British Empire, called on his allies as well, we would take another year or so to really join the war for Europe to our finest hour. And I think the difference between saving the world at that point in time was whether or not we had our finest hour, or whether or not we gave in, as we had just seen in France. So if that clip reminds us, that we faced tough times before, and we’ve gotten through them, the other inspiration for IN THE BUBBLE sends us another message.

Speaker 4 

You are my friend, you are special. You are my friend. You’re special to me. You are the only one like you, like you, my friend. I like you, in the daytime, in the night time, any time that you feels the right time, for a friendship with me, you see.

Andy Slavitt  06:24

That’s of course, Fred Rogers, and who’s my other hero. Because sometimes, you know, the tough times comes down to a hug, or some other kind of support. That is just so personal and basic. And, you know, maybe we all do need a hug right now. So the theme of this episode, really, is to try to get a handle on what it is that people who are vaccinated, who felt that we were winning the war, who felt that we’d done all the right things, avoided risks, are still facing as school begins, etc. And I’m not going to load it up with sappy emotion from Fred Rogers, or inspirational speeches from Winston Churchill. I’ll loaded up with really plain clear, simple, helpful facts from Jennifer Nuzzo. Jennifer is an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, and a senior fellow for Global Health at the Council on Foreign Relations. Now, it is a really interesting conversation because we get to the truth of breakthrough infections, and what they really mean how they really work. And it’s not a sugar coating. It’s an explanation.

Andy Slavitt

So we have to continue to look at it and focus on facts and the truth. We could take breaks from it from every now and now and then and do the things we enjoy. But we have to know what’s going on. Because we have to make tough decisions. And one of those tough decisions, which I hope we face with a fair amount of Winston Churchill inspiration and Fred Rogers compassion. And Jennifer Nuzzo’s knowledge is this decision around boosters, and what it is we need to do with boosters in this country? Because that question is upon us, as the government is now saying here in the US that after eight months, people will be eligible for a booster. So here’s the plan. It’s a little bit unusual, it’s a little bit different. I desperately want you to hear from Jennifer Nuzzo. And then after that, I’m going to come back and record my own thoughts on the booster shot, and the pros and cons and tradeoffs of the booster shot and what that means.

Andy Slavitt  08:55

And I think we’re all about to be a lot better informed by listening to Jennifer Nuzzo. Talk about what actually happens with these breakthrough infections. What does it mean? And you take that analysis, plus the analysis of long COVID. From Monday’s episode, I think it paints a picture. And it’s a picture with no easy answer. We are making decisions in times of scarcity. We are in London in 1940. And we don’t have the munitions for the fight. We are outnumbered, but we can’t quit. And we sure can’t quit on each other to what’s right for us. But also what’s right for others, which I hope we take into account what’s right for bringing this pandemic to a close and saving more lives. There we are, are we up for the choice? I think we need to be, so let’s go to Jennifer Nuzzo.

Andy Slavitt  10:09

Let’s put these vaccines in the proper perspective. You know, this is an audience that I can’t imagine there’s a single person listening that’s not vaccinated. So, you know, this is an audience where we need to persuade people that the vaccines are good, that they protect people against the most awful things that can happen when they do it incredibly well, and that we’re very lucky to have them. But I think it’s a moving picture, right? It’s a moving picture, because the vaccines work differently against Delta. It’s a moving picture, because we’re now hearing that not only can you get asymptomatic infections if you’ve been vaccinated, but you can get symptomatic infections, you can get disease and you can even pass it along to other people. And you can even pass it along without knowing it. So could you help us demystify what some of the facts are about how the vaccines work and don’t work and how often they’re doing their jobs well, and when they’re not?

Jennifer Nuzzo 

Sure. So I think the basic facts haven’t changed, which is that the thing that we’re using these vaccines primarily for keeping people out of the hospital and preventing death haven’t changed, the vaccines are still really good at that, with some very small exceptions. What we have seen in the trials in terms of their abilities to prevent serious illness is matching largely what we’re seeing in the epidemiology of real life.

Andy Slavitt

Can I just pause quickly to just clarify one thing? Has that changed over time from say, March, April, May to June, July, August?

Jennifer Nuzzo 

Not really. I mean, I think what we’re starting to see is that there are a very small number of people who are not fully protected from the vaccines. And the best data that we have is probably coming out of the UK and Israel where the surveillances is better. And I think the take home from that is that of the people who are hospitalized for COVID, because there’s clearly a lot of that happening right now. It’s a very, very, very small percentage that have been fully vaccinated. And those people are, by and large, from the epidemiologic studies that have gone on people who have underlying health conditions. And that is why you are seeing now a move to potentially offer a third shot to people who may not have been protected enough from the vaccine.

Andy Slavitt  12:29

Okay. But we don’t think that picture is appreciably worse in August than it was in March?

Jennifer Nuzzo 

I wouldn’t say appreciably worse. No, I think what we are now seeing differently, because we didn’t have time to see it before is that getting vaccinated. Well, doesn’t prevent you from being infected, which we actually did know, I think we were just maybe sloppy in our language around that. But what is probably different for people is just seeing people develop some symptoms. And they may not feel great when they develop symptoms of COVID. They may feel lousy, but they by and large, don’t go to the hospital, which is why I say the facts fundamentally haven’t changed, that the vaccines are doing exactly what we need them to do. Because if we had never, if this virus never had the capability of landing people in the hospital of killing them in large numbers, most people would never have heard of this virus. So by that metric, which in my view is still the chief metric, the vaccines are still doing a superb job.

Andy Slavitt 

Got it. So what has changed? I mean, I think nobody would dispute that who’s listening to this, which is not to say that someone will listen to this and try to take something you say out of context. So it’s important for you to say what you just said, it’s the right baseline. But if we’re gonna explore the limitations of the vaccines, do we know what for example, what percentage of people are getting actual infections, even though they keep them out of the hospital? And Do we know how that differs by each of the different vaccines?

Jennifer Nuzzo  14:05

We don’t really and in part because we’re not really tracking anything other than serious illness. There are studies coming out looking at that, but their studies and limited populations, and they’re always limited in terms of their ability to extrapolate to larger groups. And this is why many people have pushed on health authorities. You know, they often point the finger of blame at CDC. But really the responsibility for collecting case data rests with the states and then they can decide whether to report it up to CDC. I’m sure CDC is looking at data through some of their sentinel surveillance programs. But this is why some people have been concerned that we’re not doing more to track all the people who test positive after vaccination, whether they develop symptoms or not. We are right now tracking the people who wind up in the hospital after having been vaccinated, and those numbers, you know, are the basis of what I said, which is that the vaccines are working incredibly well, because they’re incredibly small numbers, compared to the numbers of people who’ve been vaccinated.

Andy Slavitt 

We’re initially hearing your 90% protection, it feels like perhaps because of some of the data we’ve seen from Israel, and some of the suggestions that we’re seeing some waning after six months waning of the effectiveness. And because Delta is just a more powerful virus, that 90% is no longer the kind of baseline assumption, what’s your sense from the studies of what’s real?

Jennifer Nuzzo 

I think it’s fair to say that more people are developing symptoms after being infected with the virus than I think we expected to have happened. We don’t have a great number that I feel like I can really point to, to tell you what that number is. I’m sure everybody, you’ve probably heard of people. I’ve certainly heard of people. And I think when you add that, those anecdotes up, they suggest that I think vaccinated people should not necessarily assume that just because they’re vaccinated, they’re not going to develop symptoms at some point. And that’s why there’s been a push to employ other measures for the time being. I think it’s though important to separate out a few things. And one is that it is entirely possible. If you have been fully vaccinated, if you get a test, say because you are going somewhere and you need a test or your workplace requires you to be tested, if you’re tested not because you think you’re sick, but you just get tested, it is possible for you to test positive.

Jennifer Nuzzo  16:40

And that doesn’t necessarily mean your vaccine didn’t work. In fact, the challenge with tracking those mild infections, or the you know, anybody who doesn’t wind up in the hospital, is the fact that what the vaccines are meant to do is to train your body, that when your body comes in contact with the virus, it won’t know that it has come in contact with the virus until the virus infects yourselves. But the vaccine was supposed to teach your immune system what the virus looks like to respond to limit that infection, hopefully, before you develop any symptoms, but in some cases not. In some cases, you’re going to have symptoms for a while until your body eventually fights off the infection. But that’s still a vaccine success. And it’s also separate from whether you’ll be able to transmit the virus to others. So this is why it’s challenging to test people who have been fully vaccinated who have no symptoms whatsoever. Because that positive test may not be a public health of significance, but just an indication that the vaccine is doing exactly what we hope it will do and training our bodies.

Andy Slavitt 

So help us understand how that works if you have a PCR test, and let’s just take the asymptomatic case that you spoke of, and you’ve been exposed to COVID, the vaccine does its job, do you test positive because technically the virus is in your cells and PCR test picks that up?

Jennifer Nuzzo  18:12

Yes. So you know, if you remember that most people get swabbed in the nose. And that means that there’s viral RNA in your nose. Now, just from that PCR test, we don’t know if that’s viruses capable of infecting other people. That’s a separate test that we would have to do. But you could have RNA in your nose. As your body is fighting off the infection. The amount of viral RNA in your nose May at the beginning be the same as the amount of viral RNA that unvaccinated people have in their nose. But what we are seeing from other studies conducted outside the United States is that the amount of viral RNA in a vaccinated person’s nose falls off quite quickly compared to an unvaccinated person, in part because the immune system is doing what it was trained to do responding to that infection, and limiting it before the virus has a chance to continue to multiply and infect additional cells.

Jennifer Nuzzo 

We’re also seeing a difference in terms of where in the body you can find virus in people who are infected after vaccination versus people who are not vaccinated. And there’s some thought that though the virus may be in your nose, if you’re vaccinated, it may not make it to your lungs and be able to infect and multiply in your lungs, which could increase your abilities to transmit an infection to others as you’re breathing out infectious particles. That’s another hope that the vaccine will help reduce your ability to transmit by preventing, hopefully the virus from getting into your lungs.

Andy Slavitt 

And it’s the thinking that also because of that, that the vaccine reduces the likelihood does it eliminate it but reduces the likelihood that you’ll get long COVID?

Jennifer Nuzzo 

Well, that is one of the thoughts and I think that that’s even more of an open-ended question. And I think we still need to do but this is where I would probably defer to my clinical colleagues, a number of infectious disease colleagues suggest that well, we can’t rule out the possibility of long COVID. And certainly, it’s been observed in patients who have been vaccinated. The hope is that the vaccines do reduce the likelihood of that happening. But I think that’s an area where we fairly need more data.

Andy Slavitt  20:22

Got it. So if I’m trying to understand this, and the great thing about me hosting the show is if I can understand it, because I’m not as smart as my audience, then they can understand it better, is that the virus is spreading rapidly, you’re vaccinated, the vaccine doesn’t act like a shield that sits outside of your face, and says, virus, you can’t come in. The vaccine only works once the virus comes in through your nose, your mouth the same way you’d get it if you weren’t vaccinated. And then it starts to infect your cell. And that’s when the vaccine sees I’m going out on a limb here, sees the spike protein, and then take it away from there.

Jennifer Nuzzo 

Yeah, so our immune system sees the spike protein that says, I remember you, you’re no good, and starts doing what it does, which is really, you know, targeting those cells and trying to get rid of them.

Andy Slavitt 

We should make a cartoon, like a Sunday, Saturday morning cartoon. I do think it’s helpful for people to understand because, like, I remember all of us in December being like, oh, it’s 96% effective game over. And, you know, to some extent, that hurt us, because it didn’t really explain how this thing works in a way that current facts are causing enough confusion. Right?

Jennifer Nuzzo 

I absolutely agree. I think we need to explain that. I also think part of the problem is our use of the word breakthrough infection. And because it implies that infection is represents failure, when in fact, infection is, you know, first contact with the enemy, and then hopefully, be able to defeat the enemy before it matters.

Andy Slavitt  22:30

Let’s go to the occasion when we start to show symptoms. In that situation. I’m gonna go with your analogy, here, we’ve got this little swordfighter in the vaccine who’s fighting off the immune system, because it’s been told by the vaccine to prepare for this enemy to come in. It’s fighting it off. But it’s a harder battle, because there’s more of the enemy. So you’ve got a knight, and they they’ve been able to vanquish the prior. But now Delta comes and Delta comes in with a bit more of an attack and starts to wear down our brave knight. And when that happens, we start to feel some of the effect that they couldn’t run right through, because the vaccine prevented them from running right through and getting into lungs and doing all the things that it normally does. But some of it gets through is that would that make our cartoon?

Jennifer Nuzzo

So Delta complicates things I think in two ways. One is the biological way, which is that it seems like for reasons I’m not sure fully elucidated, I certainly don’t know them, if they have been people who get infected, seem to produce more virus. Now why that is, I don’t fully know. And it’s possible that it also infects more deeply in the body. Those are some things we hear. But Delta is also complicating, because of those biological traits, it makes it easier for people who are infected to spread it to others. So that means that there winds up being a whole lot more virus in a community because more people are getting infected. So now, not only do you have this virus that maybe has some advantage in terms of reproducing itself in your body, but also your probability of coming in contact with somebody who’s infected has increased.

Jennifer Nuzzo  24:14

And that I think, is probably why we are seeing what we’re calling these worrisome breakthrough infections more than we did before, in part because vaccinated people are probably have a greater probability of coming in contact with an infected person now than they did a few months ago. The case numbers are higher, in part because this virus is spreading so quickly, and we see a number of reasons why that’s happening. One is that people seem to be able to transmit a little bit earlier in their infection because the viral load peaks a bit earlier. And we’ve also heard that the incubation period tends to be a bit shorter, which means you can create generations of cases more quickly.

Jennifer Nuzzo 

But there’s another way of saying that, the vaccine works great as long as there’s no virus out there.

Jennifer Nuzzo 

Well, the vaccine again And I think it’s really important to keep coming back to what is our goal with the vaccine. And the goal is to keep us out of the hospital, if we could do that broadly. And I think rare we’re in this really challenging situation right now is that we have a subset of people who just don’t get enough protection from the vaccine. And that’s where the booster conversation comes in. And then we also have kids who are too young to be vaccinated, if we could take care of all of those populations. I honestly think our expectations about getting sick will start to change.

Andy Slavitt 

Yes, but kind of to readjust in our minds, and our thinking that you can be vaccinated. And there is some chance we don’t know the exact data, but there’s some chance you could get a little bit sick, and some chance that you could pass the virus along, and even some chance that you could not feel sick, and potentially pass the virus along. Those are new expectations with the Delta variant and as you say, with the fact that we have more spread in the community that we have to all understand as we modify our behaviors or as we go about our life or as we make decisions.

Jennifer Nuzzo  26:07

Yes. Now, I want to caveat this, because there’s one area where we are definitely missing data. I think they’re forthcoming, I hope by maybe by the time this airs, we will have more. But what we know so far, at least in the US context is that it has been observed that people who are fully vaccinated have gotten sick. It has been observed that people who are fully vaccinated who have gotten sick, at some point have potentially the same amount of viral RNA in their noses. It has also been observed that they’ve been able to culture the virus from their noses telling us that that’s a virus, that’s potentially capable of infecting others and not just a fragment of the viral RNA picked up on PCR. Those are all worrisome signs, for sure, not downplaying those worrisome signs.

Jennifer Nuzzo 

But to answer the question of how frequently in vaccinated person who becomes infected, is able to transmit the virus to others, we still don’t have what I think is really necessary, which is the contact tracing data to say, wow, we had this vaccinated person, they got mildly infected, and they infected 3, 4, 5 other people, that is actually what’s really necessary because there’s other things that I mentioned that kick in, like your immune system will kick in, and it will reduce your viral load potentially preventing the virus from going into the deeper part of your respiratory symptoms, all those things can potentially reduce the likelihood that you pass it on. So in order to answer that question of how likely am I as a vaccinated person, if I were to become infected to pass it to others say my unvaccinated kids, that’s still where I think we have enough of a question mark, that makes me just say, not quite sure yet.

Andy Slavitt 

Right. So in other words, we’re not always in a nightclub in Provincetown four days in a row in close contact with people. And it could be that with that kind of intensity, and by the way, just as to say what you said earlier from that whole event, four people were hospitalized, nobody died. So that’s your first point. But even to your bereaved point about how infectious Are you the fact that you had people in close contact with one another with multiple people indoors, often, although there was a lot outdoors as well, but indoors frequently, is a pretty intense challenge to any vaccine, as opposed to kind of what might be considered a more, more normal contact. And so to be cautious, you’d say, well, to wear a mask inside Don’t be in large crowds for too long. And that will significantly reduce your exposure. But I think what you’re saying is, it may not be highly infectious, or it may be only highly infectious for a short period of time for people who are vaccinated do I have that right?

Jennifer Nuzzo  28:51

Yeah, I mean, you know, again, we have taken some humility with all of this, which is we keep learning new things, but I just want to flag what the open-ended questions are so that people don’t necessarily feel hopeless based on what’s been observed. And, you know, even coming back to the Provincetown example, we obviously heard about a concerning number of infections and people who were fully vaccinated, we saw the very concerning detail that they had similar PCR CT values, suggesting the same amount of viral RNA in their noses as unvaccinated people, again, one point in time doesn’t take into account the fact that that number can change, hopefully over the course of illness as the immune system ramps up. But we also didn’t really know the denominator, you know, who of how many people were exposed that and this cohort of, you know, several 100 patients that wound up becoming infected. What was the denominator and, you know, again, from some of that, just public reporting, I mean, it sounds like there were literally 10s of 1000s of people involved in the weekend. And so, you know, we don’t really know what the exposure numbers were, but we also have to always couch events that we observe in the context of the events that we didn’t observe.

Andy Slavitt  30:08

What do we believe about the waning of the vaccine effectiveness? And I will just start with, you know, we had Albert Bourla, the CEO of Pfizer, on a couple episodes ago. And, you know, his commentary was, he was quite explicit in what he believed, which is what they’ve observed, both from the clinical trials, and from Israel, is that, you know, at each two-month period, the vaccine effectiveness declines. You know, and I think I’ll use rough numbers from the mid-90s, to the high 80s, from the high 80s, to the 70s, to the point where at six months, those numbers that Israel reported about the 40s and the 50s. He didn’t dispute those numbers. He believed that after that amount of time, that couldn’t be right. Does that sound consistent with what our understanding is?

Jennifer Nuzzo 

Yeah, I mean, those are the facts that we know, I mean, finding this out is always a little bit tough one, because again, are we measuring it against any symptomatic illness? Or do we care about serious illness? And in my view, that’s what I care about most. And the question is, are there other components of your immune system that will prevent you from having serious illness? Particularly your T cell response. You know, how is that affected over the long term? You know, but I think people smarter than I continue to point out that that this is probably a real occurrence. I still think that there are some complicating factors such as you know, we’ve seen different virus over this time, some of the earlier populations tended to be the people who we most worry about having waning immunity to begin with the elderly population, people who also potentially have underlying health conditions that make them more susceptible.

Jennifer Nuzzo 

So, all of those, those things factor in, you know, obviously, healthcare workers were vaccinated first, and we are seeing some subsequent infections in healthcare workers, but they are exposed to high levels of illness. So I think there are still some question marks next to this. But I think given these observations, it’s enough of a concern to say, well, you know, how do we feel about this? And what are we going to do about it? You know, does it require a third shot for everybody? I have not been convinced to that. And part of why I am not convinced of that is because I can’t answer that question without considering the global ramifications of that decision, which have relevance for all of us in terms of how likely we are to be infected by worse things in the future.

Andy Slavitt  32:43

So I’ll give you a slight counterpoint to that, actually, to two pieces. One is that if you do the analysis, the debate over whether or not really a couple 100 million boosts happen in the US, is fairly inconsequential, to what’s you know, really a 10-11 billion dose target. So I don’t think we’re gonna miss by 200 million, I do think there’s an equity issue and that those 200 billion could go to save 100 billion lives. And I don’t doubt that, but it’s not as clear a tradeoff. And I think some of the analysis I’ve shown, I’ve seen shows that but there, you’re asking the right question, which is, which is ultimately the most effective and perhaps also the right moral thing to do? And I think that’s an important question for discussion and debate.

Jennifer Nuzzo

Yeah, I mean, if you do the math for any one country, I mean, similarly to thinking of the math for any one patient, it obviously favors the decision for that one country or for that one patient. The challenge is, you know, really, to date, we’ve seen about 10 countries use more than three quarters of the world’s vaccines. So it’s not just a US calculation, it’s a, you know, will those 10 countries continue to use even more of the world’s vaccine? And, you know, a question is, it’s not necessarily should we ever do it, but when should we do it? And is now the time?

Andy Slavitt  34:03

Right, and I think just the state of affairs here in the US on that question is, well, you know, we’ve seen in Israel that they’re now recommending boosters for 50 and above, the US has made the decision that for people who have immunosuppressed and I think Tony Fauci has now said publicly what many of us have suspected, which is that I doubt we will get into the late fall and winter season without at least boosting people in nursing homes, and healthcare workers who are elderly. And I think that will beg the question, among others, where does the data say we should stop? And I can imagine people who are over 65 and people who are over 50, I happen to know someone over 50-54.

Andy Slavitt 

So I don’t think of myself that way. I think I’m 20. But nevertheless, as painful as that is, you know, you can imagine people My age, saying, well, gee, if the data says that we need to give it to seniors, and we need to give it to healthcare workers, certainly a couple months later, you know, is it called for me? And if you put aside the global moral question, which I don’t think you can put aside, but if you divorce it from that calculation for a second, feels to me, like we’ll go at least as far as the elderly, but that the next wave, the people will be pretty demanding, and that has political force behind it,

Jennifer Nuzzo 

Right. I mean, again, it keeps coming back to for me, what are our goals in terms of controlling COVID? And particularly, and how we’re going to use the vaccines and my fundamental goal in all of this is keep people out of the hospital and keep them from dying. And I think to answer some of these questions, if that’s the goal, that’s my personal one, in part because I, it’s hard for me imagine another level of control without taking very, very drastic actions. And I’m not sure if society can absorb and not even sure are working in some of the places that are taking those actions. If we’re trying to defang this virus, tame it, take off the table, its ability to put people in the hospital and die. To answer the question of whether we need to boost is who is not being protected enough from the vaccines that they’ve gotten such that we are worried that if they’re infected, they’ll wind up in the hospital.

Andy Slavitt  36:22

So let me give you the pushback on that, which I’m sure you’ve heard. You know, we had Diana Berrent interviewed her for the show. She’s the, as you know, the founder of Survivor Corp, you know, her belief. And I think these numbers may be a bit rich, but her belief is that as many as 30% of people who get COVID get some form of long COVID have some sort of sustainable symptoms. And whether that numbers 30% or 10%, we don’t need to adjudicate that. But it’s unfortunate that people will get those symptoms and, and that’s not good. That’s not pleasant. And that if you’re vaccinated, you can still get long COVID. And again, it’s an argument as to whether or not you can get it just as likely or not quite as likely. But she would question the entire paradigm of all we care about our hospitalizations and deaths and say there’s so much bad about this virus that occurs to people that are never hospitalized.

Jennifer Nuzzo 

So I’m not worried about that, for sure, I am a little bit skeptical of those very large percentages, just because I think some other higher quality studies have ratcheted down, I think our estimates, but obviously long COVID is a serious concern. I think we urgently need more research to understand not only how frequently it happens, but how frequently that really severe symptoms happen. Such you know, unfortunately, a lot of studies have this really mixed bag of a whole lot of different symptoms, some of which are much more concerning than others. But then ultimately, we need treatments. I mean, that’s regardless, we need treatments. But I’m not convinced that we are ever with a vaccine that doesn’t have sterilizing immunity going to prevent that from happening if that is what we think is happening. We don’t, I have not, if we think that vaccinated people fully vaccinated people are going to still develop long COVID in very frequent numbers. I just I’m not sure we can vaccinate our way out of that problem. At least I haven’t seen data that tells me that we can. So I’m not to diminish, of course, the concerns of people who are struggling.

Andy Slavitt  38:35

That’s a real answer. That’s a good answer, which is that at the current present state, it may be a fact of life. Now, we can always change the facts of life, as you say, with treatments, antivirals, there’s lots of tools in the arsenal, it’s not just the vaccine, but calling it out like you just did. I think it’s incredibly helpful. And saying whatever the percentage is, if it’s 10% or if its 5%, with vaccination, whatever it is, you know, it is a present problem and a current challenge. And we shouldn’t beat around the bush on that. In fact, I think the question that I think it’s as an individual question that a population question, Jennifer, so I kind of want to take it to that level as if you’re listening is There’s a lot of people who could reasonably say, you know what, I don’t care if I get COVID. If I get COVID I’ll get past it. It’ll give me some immunity. Whatever. I’m not that worried about it. Why do young people feel that way?

Andy Slavitt 

And, look, I’m not gonna say that. That’s not an understandable point of view. Because it’s the acknowledgement that this thing is hard to avoid forever. But there’s another set of people who would say, you know, what, I really don’t ever want to get COVID I’ve been able to avoid it so far. And, you know, we know that there’s 200 million Americans that have not gotten COVID and many of them are like, you know what, I just assumed not have it. Maybe not even because I have underlying health condition or because I’m older, but I just don’t want it. I don’t want the risk of long term. I don’t want it. And for those people, which I think represents a lot of people, a N-95 mask indoors during the time, when there is high frequency in your community. Is that the best bet?

Jennifer Nuzzo  40:17

Yeah. Yeah. I mean, yeah, I mean, wearing a mask, certainly. And I think, you know, some people more strongly than I feel that that the higher quality masks or even better. I think the best mask is the one that you’ll wear. And I know some people have a hard time with the N95, or the other versions of them. But yeah, absolutely. If that is you, if you’re the person who says, you know, and listen, none of us want to get it like there is nobody who’s just like, give me COVID, or at least I haven’t met those people. And I talked to a lot of people who absolutely fall on the spectrum of I don’t care if I get it. I don’t think I have yet to meet somebody who says bring it on. But none of us want it. I guess the challenge that I have, which is this virus isn’t going away, and we don’t have a vaccine that prevents sterilizing immunity. So is it likely that we will avoid it now? I think that what you sketched out as a reasonable proposal, which is like, hey, one problem and says, hi, maybe we’ll put on a mask. I will say, what is tricky about that is how much of it we ask everybody to do versus how much of it is about personal choice. And not I’m putting aside the moment that we’re in right now, because we’re still in a very urgent situation, where not enough of our US are vaccinated, where we’re still seeing dangerously high levels of hospitalizations in many places.

Jennifer Nuzzo 

But looking ahead, let’s hope that lots of people see the light and we get more people vaccinated. And we take off the table our acute worries about the virus crushing us in the ways that it has over the last year and a half. I think what is challenging about that calculation is that for the people who are like, oh, I just don’t want to get it. I just want them to know that I’m not sure there’s ever like a complete end of worry, in the sense that I expect that this virus is just going to be with us in the same way that so many other respiratory viruses are. And hopefully through enhanced vaccination, we will just have it fade into the background of things that we don’t think about day to day, like so many of the other viruses that circulate.

Andy Slavitt  42:30

Right. I mean, look, it’s 102 years later, and we’re still living with strains of the Influenza that came here in 1980.

Jennifer Nuzzo 

And we still every year are getting infected with the strain that caused a pandemic in 2009.

Andy Slavitt

Right. And we don’t talk about it’s not the headline news. You know, you and I aren’t being asked to be on TV all the time to opine on it. Because it’s a fact of life.

Jennifer Nuzzo 

And I don’t want to get the flu. I don’t want to get the flu. I get vaccinated for the flu every single year. Our flu vaccines are not as great as I wish they could be. But I’m very happy to have them to keep us out of the hospital. I’ve got young kids who have been in daycare, and I can tell you for the past few years, I’ve gotten the flu every year despite being vaccinated. It has been mild. You know, I’m only laid up for a couple of days, but I feel lousy for a couple of days. I am incredibly grateful that I got the vaccine because I know otherwise I would have had a much worse illness. And my kids largely recovered from their own infections unscathed, which is wonderful. But it’s not as though flu has gone from a concern for lice. Now I have to caution that I do believe our COVID vaccines are actually better than our flu vaccines. So I am more optimistic about COVID and our COVID future than I am about our flu future and really hope we can get a better flu vaccine soon.

Andy Slavitt 

I just want to say for the record, that I’m incredibly whiny if I get the flu. No, I’m incredibly whiny if I get an allergy. I have a rotator cuff problem right now. I’m impossible. Absolutely impossible. No, I can’t I can’t lift that. Can you and my poor wife is like she’s five foot two. And she’s like, yes, I’ll climb up on something and put that up for you dear because of your rotator cuff.

Jennifer Nuzzo  44:20

I will refrain from making a very gender-based joke right there but it’s just begging for it.

Andy Slavitt 

Don’t refrain, don’t refrain I’m throwing that out there believe that men will not be the last creature standing. You know if worse comes to worse. The strength will come from your please find a way to keep us going because it will get finished off by something very mild and very inconvenient.

Andy Slavitt 

I had to take that digression. But you were talking about the flu and getting the flu. I think it’s worth touching that comparison, and a bad flu season. About 100 people a day die. Now, we got down it COVID at a low point in the spring, to just about above that a couple 100 people a day, dying from COVID. Now, unfortunately, we’re back up because of Delta, you know, I think at a couple 100 COVID. I think we’ve barely scratched the top 10 in terms of killers in the US in terms of you know, we’ve got a lot of things that kill us at greater numbers, cancer, heart disease, etc. Is your sense, that best case that we kind of land in that sort of zone?

Jennifer Nuzzo 

I mean, I hope we can do better. Again, I think we have better vaccines and like you said, I mean, the people who are dying of flu or you know, largely the unvaccinated it’s because it’s not just the elderly. It’s also particularly young kids, and the ones who do wind up dying are largely the unvaccinated. But yes, we have better vaccines. And, you know, I think people have more of a fear of COVID than they do a flu rightly. I mean, it is a deadlier disease, for sure. But we have good tools to prevent it. My goal is nobody dies of this infection. And I think we have to figure out ways of preventing that from happening. But I think that vaccines are our best hope to do that. And, again, you know, I think our current vaccination scheme with the additional protection for people who we know right now need additional help. A third shot is going to help us greatly but to me that the biggest challenge right now is getting people vaccinated because we still have perilously low vaccine coverage in so many places.

Andy Slavitt 

Yep, yep, yep, yep, yep, yep. So we’ll be close with this. I’m so appreciative of your time. I’m a big fan of yours. And I know many people who listen to the show as well. So should be an exciting episode. I talk about, you know, kind of three basic priorities for where we should be focusing our energy right now, as you know, continuing to vaccinate the pockets of this country that where we have low vaccination levels, and everybody that has been vaccinated. Look, I’m supportive of increasingly muscular measures to do that. Second, is vaccinating the globe, which I think we’ve talked about, we’ve got a race, and we’ve got a critical 90 days. And the third is an oral antiviral, which could be another game changer, in terms of how we think about this virus and the damage could cause and the tools we have to fight it. So first of all, do you agree with those are those the right three priorities from your perspective? And are there any others?

Jennifer Nuzzo  48:06

Those are absolutely the right three, I would add a fourth […], which is, you know, treatments for the people who are continuing to suffer long COVID. But yeah.

Andy Slavitt 

Great addition. So how are you doing?

Jennifer Nuzzo 

Okay, hanging in there. We’re so fortunate.

Andy Slavitt

You got young kids. But this is your job. You got to be an expert. Does this get to you? Does it carry rough moments for you?

Jennifer Nuzzo

Oh, yes. I mean, particularly now, just looking at another school year. I mean, this is where like, I can’t divorce my role. As an epidemiologist from being a mom. And I’ve had two young kids who’ve had a relatively normal summer, they’ve had outdoor camps, and they’ve got to experience childhood. But we’re looking at a very uncertain school year, and my daughter’s entering kindergarten, and I think of her going to a completely new school under these circumstances, my son’s entering the third grade, and really, really suffered last year under virtual learning. And so I’m just really worried about them. I’m really worried about their lives. And that’s what’s rough. I mean, personally, that’s what’s rough is thinking about their..

Andy Slavitt 

Are they gonna be going to do in person learning both of them?

Jennifer Nuzzo 

Yes, that’s the plan right now. That’s the plan. I mean, I feel comfortable sending them. But, you know, like many other communities, case numbers are rising, and it’s uncertain if there’ll be interruptions,

Andy Slavitt

Right. Look, our kids are older. They’re 23 and 19. So it’s a different equation. When you say you have anxiety about your kids, which I totally get, how much of it has to do with just general anxiety about the future? Not just this one year, but like this sort of sense of how long will this go on and when can they get back to normal and will this be a part of their lives, you know, on an ongoing basis?

Jennifer Nuzzo  50:03

That’s exactly my worry. I mean, obviously, I’m not worried about the risks of COVID. I mean, nobody wants their kids to get sick ever. But I am mostly worried about the disruptions to their lives and wanting obviously to be safe and not put their health unnecessarily at risk or the health of others at risk, but it’s also a balance in terms of having them have lives that, you know, are developmentally appropriate and stimulating, etc. I mean, my daughter, who’s entering kindergarten, I mean, this is almost been half of her life. You know, she sees a ball, a spiky ball that they play with and calls it a Coronavirus. I mean, like they have been changed by this event. And you know, it’s not necessarily bad, it’s just it’s changed. And is vastly different from the childhood I have. So you can’t help but worry what that means. Maybe it’ll be great. Maybe they will be the generation that like, ends human suffering, I hope that’s going to be the case. But it’s hard not to worry what holds it will have.

Andy Slavitt 

There’s so many layers to what you just said that it’s so interesting, the fact that they don’t have the kind of carefree lives that we want for them. And that this is sort of accepted as part of the furniture, you know, as the way they grew up. But also just this, this really unknowable question of how this will change them, and also change their outlook on the world, when these kinds of things are more of a given. And the possibility that the wakeup call to the world, even if it can’t be heated as well by those that got us there, this generation will be just so markedly different because of this. And I guess I’d say that the best of all worlds is, as we get them their innocence back. Yet they have a sense of the interdependence of humanity when they grow up, that it’s just so sadly missing.

Jennifer Nuzzo  52:07

Yeah, I mean, I think it’s hard to imagine that they won’t have a sense of interdependence, because so much of their lives have been couched in the context of doing things to protect other people. So I’m hopeful that that will leave something beneficial. But, you know, when, like I said, they’ve gotten to have a bit of a relatively normal summer and just seeing them spontaneously play with strange, you know, other not strange children, but you know, children that we don’t know that they meet on the beach, you realize that that is really important, too. So I hope we can get to a place where we all feel a lot more comfortable letting that happen. Good.

Andy Slavitt

Good. Well, I could tell that your kids will grow up to be great people anyway. So that’s very clear. Well, thank you again, thanks for all you doing.

Jennifer Nuzzo 

Oh, the same top, really appreciate you, and all your contributions and service to the country and the world.

Andy Slavitt

Okay, I hope that that gave everybody a real sense of breakthrough infections, and what they mean, there’s a lot of subtleties in there the difference between an infection and actually an illness, a lot of the subtleties that I think we generally tend to skip over, but are really important. All of that, I think comes together. And one of the things that Jennifer and I were talking about, which is this decision around whether or not we should have boosters, and that’s a decision that is imminent. I think the die is cast; the scientific agencies have decided that it’s important for this to happen. That is getting announced today. So if you haven’t heard it yet, you will hear it shortly. And I want to just give a little bit of a rundown on this topic, because it’s tricky. And there are a couple of tricky elements to it. So here goes. So it’s best to help understand exactly how the immune response for the mRNA vaccine works and how supported this question. And if you take in Johnson&Johnson say what about me I had taken Johnson&Johnson, my response is simple. Go get an mRNA vaccine. That’s my opinion, not a doctor. Let’s put all this aren’t people telling me.

Andy Slavitt  54:24

So here’s how the mRNA response works is the first dose will create a big antibody response. you picture a graph with the jumps up heavily, and then you get a second booster and you get an even greater immune response. So that’s your second shot. And for a while, you have very high levels of antibodies in your system. And what that means is that if the you come in contact with SARS-CoV-2, the virus, you will be able to attack it and that’s important, particularly with Delta because It means you’re less likely to face symptoms, because delta is pretty overpowered and creates a higher viral load. Now, what happens is we know that those levels of antibodies wane over time, they decrease. So that graph where you just saw this big spike declines, declines, declines, month by month, packs lower punch, and the combination of the lower punch, and more viral attack from Delta means that those lines cross pretty quickly.

Andy Slavitt 

And when those lines tend to cross, that’s when people are more likely to get symptoms. But here’s the cool thing that happens, the vaccine does something else. Your body has these things called memory B cells and T cells. And they remember what it felt like to spark this immune response. And so it can trigger the same response. So you know how you got an MMR vaccine when you were a kid? Well, that response is sitting there in your memory B cells in your T cells. And so it reminds your body how to go find that response, even if you had the measles booster when you were a kid. But what happens is, this response just takes a little longer. And this is really an important part of the explanation, the response from the B cells and T cells takes a little longer to stimulate. And during that time, when this response is slower than your high antibodies, you are able to eventually blunt the infection, just not as quickly or as well, which means that you are going to be both more likely to have some symptoms breakthrough and more likely to pass the infection along to others sticking with me so far.

Andy Slavitt 

So the memory B cells and T cells are our friend, they were great. And ultimately, they win the vast, vast, vast majority of the time, which is why they keep us out of the hospital, is why they keep us from dying, except for people who are very sick and will get bowled over by just a small infection. But they don’t do as good a job preventing illnesses. So as the vaccines wane over time, you get to six months, eight months, the vaccine increasingly becomes a thing, which does what many would say it’s designed to do. It protects you against hospitalizations, and deaths.

Andy Slavitt 

But it doesn’t protect you against all these symptoms. And remember, remember our episode on Monday, where we showed with our conversation with Diana, if you didn’t listen to it, you should listen to it. That’s not entirely harmless. Some of those symptoms end up showing up and staying with you. And you get to keep COVID for longer than you want. That’s not great. But it is the reality. So given that, you kind of have to think about your definition of what the vaccine is supposed to do for you. If the vaccine is supposed to protect you against hospitalization and death, then you’d say, well, unless people are very high risk, there’s really no purpose of getting them boosted because you know, the vaccine shouldn’t be designed to just prevent modest infections and possibly transmissions. On the other hand, if you say, you know what, I want a vaccine that protects me even against feeling a little bit sick. If you want that, then you’d say, well, we should get a boost, because we should constantly keep our levels of immunity higher. And who wouldn’t want that? Who wouldn’t say, yeah, give me a boost. So that way, I don’t even get sick, it reduces the likelihood transmission, and it reduces the potential for long COVID.

Andy Slavitt  58:43

But there’s a catch. And if you’re sticking with me so far, I’m gonna say what that catch is, the catch is, that you increase the odds of future variants if you do that. Why? Because variants happen when they have a greater opportunity to morph and mutate against the vaccine. And if you keep vaccinating the same people over and over again, and so far 10 wealthy countries have used about 90% of the vaccine supply. We’ll keep doing that by keep boosting people, then not only are we failing people around the world, parts of Africa with 1% to 2% vaccination levels, but we’re also giving ample opportunity to the virus to continue to mutate. And even in a matter of months, even if we can speed up vaccinations by a matter of months. epidemiologists will say that it will save us a lot of potential heartache by dramatically reducing the potential for more deadly variants. Okay, so what does all this mean? And I’m sorry if this feels like a complex explanation, but what it means is that if you assume that the US is a global leader, makes a decision to boost its population. You assume also that the rest of the g7 wealthy countries do the same.

Andy Slavitt  1:00:05

You know, you’re prolonging the virus, you’re increasing the likelihood that the next thing after Delta happens, it becomes worse. So that’s the cost, in a sense. That’s the cost of making a decision to protect us from even symptoms. And it’s a very tricky equation, because I think we all as individuals, may feel like one thing works better for us. But it also runs up against a lot of problems, including the fact that we would be saying, as wealthy countries, we should go first, we should go second, we should go third, before you even have a chance to go first. So maybe the answer lies in boosting just the people that are at high risk and using those other vaccines around the globe. But it doesn’t appear that that’s the choice we’re going to make, it appears that the choice we’re going to make is not the one that necessarily leads with epidemiology and science, the one that might lead with political science call it and behavioral economics, which is that people are much more protective and care much more about themselves in general, than they do about the globe.

Andy Slavitt 

Just by what they say, people want to protect their families, and do that. And all this, of course, is much more challenging, because we can only vaccinate a part of the country here in the US. If we could vaccinate more of the country in the US, those equations would be much, much, much easier, it’d be easier, because we’d see less transmission. And we’d be less worried about needing to boost because it just be low levels back to where we were a few months ago. So how do you think about that? What’s the decision? What’s the Winston Churchill decision? What’s the Fred Rogers decision? What’s, what’s the EU decision? What’s the need decision? It’s complex. It’s complex. Here is an optimal answer for this pandemic, which is we have to vaccinate the globe first.

Andy Slavitt  1:02:26

Yet, I don’t know that as individuals, people will make that choice. Even if you agree with me, if you were offered a vaccine for a boost, and reduce your symptoms and reduce potentially you’re likely to spreading the virus, would you do it? Would you take it? Tough questions. Tough times, but we can run from these questions. Okay, let me tell you about our two episodes that are coming up. The first is with Mark McClellan, former head of the FDA, and my partner in crime on a lot of the work we’re doing to try to increase vaccination requirements in the US. We’re going to talk about the key decisions the FDA has in front of them right now we’re going to talk about the various system which is a system that has been bastardized by anti vaxxers. And we’re going to explain the truth behind that. We’re talking about what’s gonna happen with decisions or kids finalizing the vaccine approval, etc.

Andy Slavitt

Then on Wednesday, one of my all-time favorite conversations, sir Jeremy Farrar, but you can call him sir, you call him Jeremy. He is the director of the Wellcome Trust. He is one of the leading global experts on the pandemic and on public health. And remember, we just talked about why we need to vaccinate the globe more quickly. He’s going to lay out the facts behind how to do that. What’s at stake, how quickly we can move and then you’re going to hear us plot on how to get it done. So, look forward to talking to you on Monday. Have a great rest of the week.


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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