Why is the delta variant a game-changer? Abdul dissects how the delta variant has changed our approach to COVID-19—and what could be in store. He speaks with America Dissected’s resident virologist Dr. Angie Rasmussen about why the delta variant is so transmissible and how it should change our approach to COVID-19 in general.

Transcript

Dr. Abdul El-Sayed: New York City imposes a vaccine verification requirement for bars, restaurants and gyms as Delta reached over 100,000 cases a day nationwide. The WHO calls for a moratorium on boosters until at least 10% of citizens in every country can be vaccinated. The worker shortage has hit hospitals. In Arkansas, hospitals are offering a $25,000 signing bonus for new nurses. This is America Dissected. I’m your host Dr. Abdul El-Sayed.

If you’re like me, the last few weeks of COVID-19 news have been a bit of a roller coaster. First there was this:

[news clip] The CDC updating mask guidance. They are now recommending everyone, even vaccinated people, wear masks indoors in areas where COVID is spreading rapidly.

Dr. Abdul El-Sayed: And then this:

[news clip] The Delta variant surging across the U.S. appears to spread as easily as the chicken pox and may be more transmissible than Ebola and smallpox. All of this according to an internal CDC document.

Dr. Abdul El-Sayed: Our spring of hope was supposed to lead to a summer of freedom. But today, with fall fast approaching, Americans are leery about what changing mask guidelines in a new raging variant mean for our future. But this new wave, it hits a little different.

[news clip] And just in the last week, new COVID infections up 47%.

[clip of President Biden] We have a pandemic for those who haven’t gotten the vaccination.

[clip of Dr. Fauci] That it is among the unvaccinated. And since we have 50% of the country is not fully vaccinated, that’s a problem.

Dr. Abdul El-Sayed: Across the nation, hospitals are filling up again and the patients filling those beds overwhelmingly are the unvaccinated. In fact, 97% of patients in hospitals today with COVID-19 have not been vaccinated. But you could also look at it the other way. 125,000 vaccinated people have tested positive for COVID-19 nationwide. Sound like a lot. It’s not, considering the fact that 166 million people have been vaccinated. That means that less than 0.1% of vaccinated people have tested positive. Let me say that again, less than 0.1 of vaccinated people have tested positive. So the story here is not breakthrough infections, it’s the fact that people are still not getting vaccinated. Because when you look at maps of COVID-19, it’s clear that the vast majority of news spread is in communities where a large proportion of people still remain unvaccinated. That’s why when the CDC announced their new mask guidelines, they tied it to the level of spread, saying masks should be required in communities with, quote unquote, “substantial or high” coronavirus transmission. Despite all this, the idea of a pandemic of the unvaccinated isn’t quite the whole story. The most important developments from the past two weeks actually concern people who are vaccinated. The CDC’s new mask guidelines, as you’re likely already aware, recommend asking for everyone in places with substantial levels of transmission, vaccinated or not. See, vaccination isn’t usually only about protecting yourself, it’s about protecting everyone around you too. The whole concept of herd immunity is about people who are vaccinated, sealing themselves off from spreading the virus to people who are not. But new data from the CDC, the data upon which the new masking guidelines for vaccinated people is based, suggests that vaccinated people can, in fact spread the Delta variant. The CDC based their new recommendations on an analysis of an outbreak in Provincetown, Massachusetts, where nearly three quarters of the people who were infected had been vaccinated. Importantly, though, of the 931 who were infected, only seven ended up in the hospital and no one died. The vaccines are working. That said, they found that people who were vaccinated had the same amount of virus in their noses. That may explain why vaccinated people can spread the virus. But CAN spread the virus, doesn’t always mean DO spread the virus. Our understanding here is evolving. See, there was another study of an outbreak, in Singapore, that regularly checked how much virus infected people had in their noses, which found that vaccinated people cleared the virus far faster. That suggests that their risk of transmission is lower overall. Nevertheless, even the possibility of transmission means that we should do all we can to prevent it. I know that these new mask guidelines appear to be asking vaccinated people who’ve already done their part to do something even more to protect people who won’t protect themselves. But this isn’t just about protecting people who are still unvaccinated because they don’t want to be, it’s about protecting everyone who can’t get vaccinated, like my three-year old daughter, and all the other under 12s for whom the FDA still hasn’t approved the vaccines. And then there are people who are immunocompromised. For the vaccinated, this may mean that masks are the norm again. For the unvaccinated, getting vaccinated is crucial now, more than ever before. With our capacity to get to herd immunity in question, vaccination is the most important option to stave off infection for this new, more transmissible variant. What’s clear, though, is that Delta is different, it’s forcing us to rethink our approach to the pandemic and what may come next. I reached out to Dr. Andrew Rasmussen, our resident virologist, to help us understand what makes this variance so transmissible and how that should shape our approach to addressing it, after the break.

[ad break]

Dr. Abdul El-Sayed: Well, let’s, let’s jump right in. Can you introduce yourself for the tape?

Dr. Angela Rasmussen: I am Angela Rasmussen, Angie. I am a virologist at the Vaccine and Infectious Disease Organization, a vaccine research institute at the University of Saskatchewan. I am also an affiliate at the Georgetown Center for Global Health Science and Security.

Dr. Abdul El-Sayed, narrating: Dr. Angie Rasmussen has become our resident virologist here at America Dissected. We’ve had her on from time to time to help us understand how the biology of SARS-CoV-2 is shaping our experience of the pandemic. Obviously Delta’s gives us a lot to discuss, so we wanted to invite Angie back on to help us better understand what Delta could mean for the future of the pandemic.

Dr. Abdul El-Sayed: This is our third opportunity to chat and learn from you. I want to step all the way back, right, because I think for a lot of folks, understanding this whole conversation about variants is a little bit hard, right? We’re constantly hearing about these new Greek letters. Can you give us a sense of what a variant even is and what makes SARS-CoV-2 so capable of evolving new variants?

Dr. Angela Rasmussen: Yeah, absolutely. So variants are actually completely normal. It’s not a unique thing that SARS-coronavirus2, does. Variants are basically just mutans. Every time the virus replicates itself, it copies its own genetic material. When it does that, it makes mistakes. Those mistakes are called a mutation. Most of those have no effect whatsoever. Some of them have a negative effect on the virus. And so they’re under what’s called negative evolutionary selection, meaning that a virus that gets one of those won’t be able to survive and go on to replicate some more so it’ll be selected out. And sometimes those mutations, which occur randomly, happen to be in a place that gives the virus some kind of advantage. When that happens, they’re under positive evolutionary selection and those variants will outcompete the ancestral variants that were in that population. And that’s exactly what we’re seeing. So we shouldn’t think about these as outliers. They’re actually completely expected. They’re just unfortunate because they really can be prevented by bringing transmission down and by not letting the virus rip through the population out of control.

Dr. Abdul El-Sayed: So turning our attention to Delta specifically, can you walk us through how it originated? For some time, they were calling it the double mutant. So can you speak to us about what makes Delta, Delta, and why it’s so transmissible?

Dr. Angela Rasmussen: Yeah. So the double mutant part just refers to two mutations that are in the spike protein. It actually has more mutations than just those two in the spike protein, and also has other mutations throughout the genome. We actually don’t know what most of those mutations do. We’ve been focusing for all the variants on the mutations that are in spike. So you’d be forgiven for thinking that that’s the only place that these viruses, these variants, are acquiring mutations, but they are actually acquiring them throughout the genome. And those might have an impact in terms of the virus’s fitness, its ability to replicate. And it’s not really its infectivity, that’s usually in the spike protein, because the spike protein is what binds the cellular receptor and allows the virus to infect and enter cells. So we don’t know about a lot of those other proteins. They may play a role in antagonizing the immune system, for example. They may, those other mutations may be important. But the mutations in spike, the one that seems to have the most impact, is the P681R mutation that is right at the boundary of S1 and S2. These are two different parts of the spike protein that normally get cut in half by an enzyme called a protease. In this case there in the furin cleavage side, which if you’ve been following discussions about virus origin, you may have heard about. A furin cleavage site is actually just a consensus sequence that tells an enzyme called furin that, hey, you should cut me here. Now, what this does is it exposes what’s called the fusion peptide of the virus. This is a peptide that’s usually hydrophobic, or sort of like salad dressing, you can think of oil and water. Normally the sort of water-loving amino acids are on the surface and the oil amino acids are like little bubbles in a salad dressing that you haven’t shaken up. They are inside. By cutting the furin cleavage site, that exposes this hydrophobic peptide, it allows that part of the spike protein to get in to insert itself into a membrane which has a hydrophobic core, or an oily core—and that allows the virus to enter the cell because the virus has to get through that membrane barrier that has essentially oil in the middle of it. So that is thought to be, well, that’s why the furin cleavage site’s important. Both Alpha and Delta, which have been more transmissible, have a mutation at site 681 in which a proline in Alpha is turned to histidine, and in Delta it’s turned to arginine. These are positively charged amino acids and they probably make for a more optimized furin cleavage site, meaning that there’s more cleavage there, there’s more fusion, there’s more virus that’s able to get into cells. It makes it more infective. We don’t know that for sure. There are other mutations might be contributing, but that’s the one that seems to be really important for these highly transmissible variants.

Dr. Abdul El-Sayed: Yeah. So that’s really helpful to understand. So you’ve got some change in the RNA, which codes for a different one of the protein building blocks, that then allows the sort of sticky part of the virus to be more sticky, and it helps us to get through the cells. And what a lot of folks don’t appreciate is that cells are, you know, we think of cells as being the sort of like building blocks, but really, they’re all soft. And the example of salad dressing you used is really helpful because basically every cell is like some some little oily part, right, that surrounds a watery part. And what allows you to get into the cell faster is what allows you to puncture the oily part faster. And so what you’ve demonstrated for us is that this little change in one piece of RNA fundamentally changes the biology of this particular virus and makes it so that it sticks and gets into cells faster. And you can imagine, right, you have hundreds, thousands of particles of virus and the ability for any one of them to get in faster means that more of them are going to get in, meaning that you’re going to get a higher probability of of illness.

Dr. Angela Rasmussen: That’s right. And I mean, there very well could be other factors to this, too. There is a study that that came out of China that followed people who had been exposed to someone infected, to a person infected with Delta, and then they did PCR on them every day to see when they actually became positive. The ones who did become positive had viral loads that were a thousand times higher than people who had been infected with other variants. So that suggests that, you know, there’s a fitness advantage too that can’t necessarily be explained by that furin cleavage site. And as I said, that could be due to one of the other mutations in the spike. It could be a combination of mutations throughout the genome. It could be a mutation in another viral protein, and there’s 39 proteins in SARS-coronavirus2 so it’s not just spike that’s doing stuff. So there’s still a lot that we have to learn about why Delta’s more transmissible. But certainly the mutation it at proline 681 does seem to be important for both of the variants of concern, both Alpha and Delta, that have been more transmissible, which is why that has gotten a lot of attention.

Dr. Abdul El-Sayed: Does Delta make us more sick?

Dr. Angela Rasmussen: The jury is out on that. There are some people who will tell you definitely yes. There are some people who said that about Alpha too. I’m not convinced in either case that the viruses are actually more pathogenic. And there’s a couple of reasons for that. One, we are looking at the virus spreading in different populations of people than variants that came before. So when you’re saying there’s more of a risk of hospitalization, there’s more of a risk of death, you’re also talking about variants that are infecting a different group of people who haven’t been infected yet, that may have different comorbidities, different preexisting conditions that would cause them to die, people who weren’t infected by other less transmissible variants. And then when you have increased transmission, you have more people getting infected in different circumstances. So it’s really, really hard to say for sure. There was one study done by a really great group in Japan that used a hamster model to try to address whether or not Delta is actually more pathogenic. And the data, it’s a pretty small effect size. It’s a small change in morbidity as measured by body weight. So one way that we often look at how viruses make animal models sick is by just measuring their weight every day, because if the animals don’t feel well, they won’t eat, they’ll start to lose weight, just like people do. And you can see how much weight they’re losing over the course of their infection. In this case, the animals infected with Delta versus other variants lost a little bit more weight a little more quickly. Whether that weight loss, increased weight loss in hamsters translates to more pathogenic in the human population in the real world is really hard to say.

Dr. Abdul El-Sayed: You know, we just don’t have the right apples to apples comparisons to really be able to measure that appropriately in humans.

Dr. Angela Rasmussen: I mean, I would argue that it’s not less pathogenic, so avoid getting it.

Dr. Abdul El-Sayed: That is, that is the ultimate point, right, is that it is making a lot of people sick right now and we have to avoid it. And of course, a lot of folks who are choosing not to be vaccinated right now will lean on the idea that they’ve previously been infected and therefore their bodies making antibodies to SARS-CoV-2. But Delta may not be affected by those antibodies. Can you explain how Delta has figured out how to slip our natural immunity?

Dr. Angela Rasmussen: Yea. So there’s still a lot we don’t know about this course, but natural immunity in general is really variable. So some people will have really potent antibody responses, neutralizing antibody responses and T cell responses that are equivalent to people who’ve gotten vaccinated. We know that generally, immune responses, at least that we can measure, are stronger the sicker that you are, and that’s probably because your immune system’s just being exposed to more virus. But we also know that people can sometimes not have very potent responses. And on top of this, I mean, I think that there’s a few good explanations for this. First of all, people are all different. We all have different preexisting medical conditions. We all have a different background genetically and epigenetically. We all respond to things differently. If I get infected with one virus, I might have a very different outcome than you do. And we see this certainly with the broad spectrum of disease severity that results from SARS coronavirus-2 infection as well. So some people will respond really well and have really potent, robust, probably lasting immune responses. And some people won’t. And we don’t really know how to distinguish between those two different groups. It’s also a spectrum. We don’t really know when your immune response is so kind of lackluster that you’re not going to be protected. And so we can assume that just because you had COVID that you have the same level of functional protection in the real world against Delta or any other variant as somebody who got two doses of an mRNA vaccine. And there’s another good reason for this, too, and that is when you get an mRNA a vaccine or actually one of the adenovirus vector vaccines, which are replication incompetent viruses that don’t go through a full replication cycle, you’re getting exposed to the spike protein and your immune system is responding to that. It recognizes that it’s foreign. It mounts these great immune responses. And with two doses, especially of the mRNA vaccines, you will get affinity maturation. You will get these really potent neutralizing antibody and memory responses. When you’re infected with SARS coronavirus-2, as I just said, there’s 29 proteins in this virus— some of them are immune antagonists, some of them will modulate your immune response to that infection to make it better for the virus and often that can make it worse for your long-term immunity. We also know that people who have died of COVID, who have really severe COVID, they’ve done these post-mortem experiments and looked at their lymph nodes and they have effectively no germinal centers in their lymph nodes. Germinal centers are the parts of your lymph nodes where your immune system, your B cells and your T cells, essentially go to get educated and become memory immune cells. They don’t have germinal centers, you’re not going to develop a long-lasting immune response. We don’t know if that happens in everybody because we’re not doing the lymph node biopsies on every person who recovers from SARS-2. But we know, at least in severe cases, there does seem to be a big element of the virus antagonizing and messing with your immune system, basically. So we shouldn’t assume that the long-term immunity from natural infection is ever going to be the same as from vaccination, because with vaccination, you don’t have basically a virus messing with your immune system while you’re being vaccinated and you’re mounting those immune responses to it.

Dr. Abdul El-Sayed: That’s a really helpful explanation. One thing that we’ve seen, of course, was the massive change in policy recommendations from the CDC regarding masking for people who are vaccinated. And, you know, on the one hand, we know that this, the vaccine remains the single best way to protect yourself from symptomatic illness from Delta. And at the same time, what we have seen is that the biology of Delta has changed the probability that vaccinated people could potentially pass along the virus, which really messes with the concept of herd immunity that we had been pushing to establish for some time. Can you explain why it is that even though vaccinated people are still protected from symptomatic illness to a very high degree, they can still pass along the virus, and what that means for our ability to slow the spread of COVID-19 via vaccines?

Dr. Angela Rasmussen: Yeah, absolutely. And I’m so glad you asked about this because I think a lot of people have interpreted the data about Delta as, OK, vaccinated people have a similar viral load to unvaccinated, therefore the vaccines don’t work so what’s the point? That is absolutely not true. So first of all, in Provincetown, Massachusetts, that was a weekend that was associated with a lot of events that brought people from outside the community—and Barnstable County, Massachusetts, is one of the most highly-vaccinated communities in the US—brought a lot of people in from outside who weren’t vaccinated. Clearly, Delta got brought along with them, but put people into situations that are very conducive to transmission. So you’re hanging out with a ton of people in a super crowded environment. You’re hanging out in a bar, you’re hanging out there for a long period of time, it’s not well ventilated, it’s crowded, you’re drinking alcohol, maybe inhibitions are a little bit lower, you’re not being conscious about distancing and nobody’s wearing a mask—then you are going to see people getting infected regardless of their vaccination status, because the vaccine is not a force field that causes viruses to bounce off of you when you have one. You can still get exposed. These vaccines were also not evaluated to be able to prevent infection. They were evaluated to prevent symptomatic COVID-19. Now they’re not 100% and if you have a community of mostly-vaccinated people, guess who most of your cases are going to be in? Mostly vaccinated people, because that’s the majority of the people in your community. Nobody says, oh my God, there’s no point in taking birth control pills because, you know, a couple people in my community that I know got pregnant while they were on the pill. We accept that many, all of the drugs, all of the vaccines that we use don’t have 100% perfect record of effectiveness. And that’s no exception for vaccines. These vaccines have still exceeded our expectations greatly and continue to against Delta. They are on the order, even against Delta, of 85, 90% effective at preventing symptomatic COVID-19. People in multiple countries, in the U.K., here in Canada, in the US, in Israel, who get Delta after they’ve been vaccinated, are largely not going to the hospital, they’re not dying from COVID. The people who are in the ICU, the people who are dying from COVID, it’s unvaccinated people. And that’s the basis for that masking recommendation. The danger is not transmitting the virus on to other vaccinated people who are going to have a mild case—and this is not also to dismiss long COVID. Ideally you don’t get infected at all, that’s why you wear a mask now if you’re vaccinated. But the risk here is largely not to the vaccinated people. The risk here is to the unvaccinated. And I think the, there is no evidence in that MMWR report about Provincetown or the preprint that just came out about Wisconsin that shows similar data—there’s no evidence of onward transmission and it’s entirely possible, and people should consider that viral RNA loads are not equivalent to shedding infectious virus. So we don’t even know if vaccinated people are as contagious as an unvaccinated person. They may well not be because of those immune responses that may not prevent infection, but they do control and rapidly clear the infection. And there is a new preprint from Singapore that actually shows exactly that: vaccinated people clear the virus much more quickly than unvaccinated, including with Delta, and they also have much higher titers of neutralizing antibodies. Together that suggests that vaccinated people, even though they may have equivalent levels of viral RNA if they have a breakthrough infection, are not necessarily shedding as much infectious virus that could go on to infect others. But we have to be, we have to use caution. I think it’s wise to err on the side of caution and to have vaccinated people wear masks, which many of us we’re doing anyways. I mean, I am fully vaccinated and I still wear a mask in public places. I don’t go to indoor restaurants, I certainly don’t go to bars, just until prevalence is lower—then we can start relaxing. And, you know, the thing is, people are saying, oh, herd immunity is impossible, we’re not, we’re never going to get to herd immunity. Well, you’re right. We’re not if people continue to decide not to be vaccinated. So if we get enough people vaccinated, prevalence will go down to the point the virus is just going to keep hitting dead ends because it keeps running into vaccinated people. We are not going to be seen a forever pandemic among the vaccinated. We just need more people to get vaccinated because again, the main risk here is transmission to unvaccinated people.

Dr. Abdul El-Sayed: Yeah, I really appreciate that clarification. And, you know, one of the things that I always try and encourage folks to focus on is the fact that if you just look at the map of COVID-19 and you lay it on the map of vaccination, the fact that those two things look very similar tells you what you need to know about the protection capacity of the vaccine in the real world. And evidence, right, regarding the potential risk of spread from vaccinated people is one thing, but then the question of actual risk of spread among communities where there’s high vaccination rates is another and the maps tell the story, right? The virus isn’t discriminating on anything except for the potential for people to both carry the virus and get sick and pass it on, right? And I think it is important for us not to get too drawn to the shiny object and instead step back for a second and say, well, this follows of a very recognizable set of patterns that tell us something about the efficacy of these vaccines in the real world. And so I appreciate that point about a deeper, better look at the data from which policy’s been made. One of the interesting things about Delta is that if you look at the two, two of the countries that have been hit hardest by Delta, whether it’s India or the U.K., there was a pretty rapid spike and then the spike pretty rapidly fell. And I want to, I want to get your sense of why that happened and what that tells us about the spike that we are headed into right now.

Dr. Angela Rasmussen: Well, I think in that, it’s not as applicable to India because it’s a completely different situation there with regards to vaccination. Very, very few people have access to vaccines in India and very few people did in the spring, certainly when that surge occurred, that probably gave birth to Delta. I don’t know if there’s a better way to put it than that, but Delta emerged as a result from all of that uncontrolled transmission. I mean, this is a good example of how people can misunderstand data about transmission. When you add additional measures meant to reduce exposure, other non-pharmaceutical interventions, you will see drops in transmission. You can change the viral reproduction number, you can change R-naught. So when the slide was going around last week from CDC, that was oh, my God, Delta’s just as contagious as chicken pox—I mean, do people actually, first of all, really know how contagious chickenpox is? But second of all, that is talking about essentially R-naught in the situation, the Delta outbreaks that have been described so far. That number is not static. It is dynamic, and it can change with vaccination, with overall community prevalence, with natural immunity, with other precautions that people are taking meant to reduce exposure risk. And I think that that is what we can see, as countries realize that they’re going through a surge, people stay home, they wear masks more often, they’re more diligent about that sort of thing. Then you will see cases decrease. Also, you will probably see cases decrease as people who were recently infected start to recover. And early on, at least, most people do have immune responses that will protect them from re-infection. Most people will, even if they develop long COVID, they do clear the acute infection. So we will see cases after a spike go down. In the UK, that’s a little more confusing to me only because the UK is a very different situation. They have a lot of vaccination there, but a lot of partial vaccination because they had a delayed second dose strategy there, unlike in the US. So we do know that people who’ve only had one dose of either AstraZeneca or Pfizer are more susceptible to Delta than people who have been fully vaccinated. I don’t know how much of their rapid spike was the result of that, but I certainly noticed that this big spike in Delta was accompanied by a lifting of many of the coronavirus restrictions that they had in place. And yeah, they delayed their Freedom Day, or whatever it was called, by a couple of weeks because of that spike but ultimately, they were already on the road to a very relaxed coronavirus, restrictions. So, and then they were able also to get more supplies and vaccinate more people quickly. I mean, I think that that might be able to explain it. But one thing we do have to think about for all of this is that this is very situationally dependent. So the situation is different in India, it’s different in certain parts of India from one to the other, just like in the US. It’s a very different situation in Provincetown compared to St. Louis, Missouri, where they’re running out of hospital beds because so few people have been vaccinated. So we need to stop thinking about this in terms of national numbers to a certain degree as well. We need to start thinking about this in the form of communities because that’s where the virus is spreading. It’s not spreading in the United States homogenously, across our entire huge nation, it’s spreading within individual communities at the local level when people are interacting with each other and giving the virus to each other. So that’s how I think we really should be thinking about it, as a local community level outbreak rather than a national one. Because I think that is what we’re going to continue to see in the US.

Dr. Abdul El-Sayed: That’s really helpful to understand. And spreading all the way out, right, beyond local outbreaks. This is a global pandemic. And Delta reminds us yet again that what happens around the world will affect us here at home. And that reminds us also that we have a responsibility as the richest, most powerful country in the world to do our part around not just keeping people in the rest of the world safe because it is the right thing to do—which it is—but also because it will ultimately reverberate back onto us. As we think about where we go from here, what do you think of as the probability of a yet worse variant that is potentially even more transmissible, that could potentially slip our vaccine-mediated immunity? And what does it mean for what we ought to be doing to try and get vaccines everywhere?

Dr. Angela Rasmussen: I think it’s certainly possible that we might see a more transmissible variant emerge. We might see variants that are capable of evading more of those neutralizing antibody responses. I think, though, it’s unlikely that we’re going to see a variant emerge that’s capable of evading the totality of the human immune response. I mean, the immune response—most people think about it is antibodies and like, oh my God, we get enough mutations in the receptor binding domain of spike and vaccines aren’t going to work. But that’s not true. We already know that the immune system is a lot more complicated than that. There are T cells, there are multiple types of T cells, there are memory natural killer cells and natural killer T cells that are kind of in the middle of the innate and the adaptive immune system. There’s multiple mechanisms that our bodies have to respond to these viruses. And many of those are not targeted just at the spike protein. But some of them that are, are targeted towards parts of the spike protein that the virus can’t tolerate much mutation in. So there are parts of of every viral protein, including spike, that are very, what we call conserved. That means that they’re structurally very important for how the spike protein works. If this protein doesn’t look like a spike on the surface of the cell, it’s not going to be able to do its job, because part of its job is binding ACE to the receptor and allowing that virus to get into the cell. If it has a radically different shape, it’s not going to be able to bind the receptor anymore. So certain mutations can’t be tolerated. Those are those negative mutations that we started talking about at the very beginning. Those will encode proteins that basically make the virus not viable. So I don’t think that we will see viruses emerging that have a radically different spike protein to the point that it completely gets around every single one of our immune responses. Now, that said, I think there certainly could be variants that emerge that are more capable of evading those neutralizing antibody responses that probably largely protect against infection and transmission. However, what we already know from looking at Alpha, Beta, Gamma and Delta—the four variants of concern—is that the ones that are better at evading those neutralizing antibody responses, Beta and Gamma, are outcompeted every time by Alpha and Delta. So more transmissible outcompetes neutralizing antibody evasion. And that’s probably because those viruses didn’t actually evolve to evade neutralizing antibodies. They evolved to bind better to ACE2, the receptor, their enhanced infectivity—and that just so happens that incidentally, that leads to neutralizing antibody evasion because that interaction is important for antibody neutralization. If you think about it this way, if there’s a big antibody stuck to the receptor binding domain of the spike protein, it can’t bind ACE2. So if it changes the amino acids in there so the antibodies can no longer bind, that’s going to make it better at binding ACE2 but also evade those antibody responses. But we know that, again, those don’t seem to win in a head-to-head competition against Alpha or Delta. Alpha rapidly, despite our fears about Beta or B1351, as it was called then, and P1 (Gamma), our fears at the time that those would become prominent—Alpha just absolutely smoked them all. Alpha has become dominant in almost every country in the world, and now Delta is well on its way to displacing Alpha because it’s even more transmissible. So I think we really don’t need to stay up all night worrying about completely vaccine resistant mutants emerging. I don’t think that’s going to happen. I think that there’s a reason why the people who are saying that—and no disrespect to my physician colleagues—but the reason that people who are on the news saying that a lot are not virologists or immunologists, because I think that it’s just very, very unlikely. This isn’t like an antibiotic, where a couple of mutations can render it completely drug resistant. This is something that the virus would have to fundamentally change into something new. And I think that that is really just not going to happened. It’s unlikely to the point of being impossible. I mean, it’s possible, but not very possible.

Dr. Abdul El-Sayed: Dr. Angie Rasmussen, thank you so much for joining us today and helping to clarify and help us to better understand this Delta variant, and where we go from here. Always grateful for your time and your expertize.

Dr. Angela Rasmussen: It’s always wonderful to be here. Thank you so much for having me.

Dr. Abdul El-Sayed: As usual, here’s what I’m watching right now. Last week, New York City Mayor Bill de Blasio announced this:

[news clip] New York City will be the first in the country to require proof of vaccination for those dining inside restaurants, in gyms and movie theaters.

Dr. Abdul El-Sayed: If you’ve been listening, you know, I’m a big proponent of vaccine verification. If we’re serious about taking on this pandemic, we’ve got to take away its fangs, and that means vaccinating more people. And the best way to do that: make being vaccinated easier and being unvaccinated, well, harder. There’s been a prominent, if bogus, response to this, that somehow requiring vaccinations creates two classes in society, or discriminates against unvaccinated people. If you think you’re being discriminated against for something you can change in 15 minutes at your nearest pharmacy, you simply don’t understand what discrimination is. Being unvaccinated isn’t an immutable or deeply-held fact of your life. Besides, your choice carries costs for other people. Economists call these externalities. When a choice an individual makes has consequences for other people. Take, for instance, pollution, or even smaller, smoking a cigarette in a crowded place. If you’re remaining unvaccinated hurts other people or restricts their choices, public policy has a responsibility of making sure that other people don’t have to pay for that choice, you do. Vaccine verification is good policy, and we need more of it.

In other news, there’s some evidence, heavily promoted by vaccine manufacturer Pfizer, that immunity can wane in seniors or folks with weaker immune systems. Based on this evidence, there’s been a concerted pressure campaign to offer boosters of the vaccine. But here’s the thing. Millions of people around the world have had no vaccine at all. The pressure campaign the pharmaceutical industry is mounting is all about money. They want to sell boosters to governments in high-income countries at a premium, rather than sell the same vaccines to low income countries for less. It’s a shameful outcome of the way we fail to value human lives in this world. In response, this was WHO Director General Tedros Adhanom last week:

[clip of WHO DG Tedros Adhanom] Accordingly, WHO is calling for a moratorium on boosters until at least the end of September to enable at least 10% of the population of every country to be vaccinated.

Dr. Abdul El-Sayed: This moratorium would be about making sure the most vulnerable in the poorest countries have a chance at their first and second doses of the vaccine before the folks in the richest countries in the world get their third. Lastly, if you’re a nurse in Arkansas or are willing to be a nurse in Arkansas, you can make $25,000 simply for signing a contract. That’s right, the infamous worker shortage has hit health care. But here’s the thing. Maybe it’s just the fact that for too long, nurses have been forced to bear the brunt of this pandemic short-staffed, short of supplies and short of support. And when you have to go on the front lines again, because people just won’t take the damn vaccine, maybe at some point you get tired of caring for folks who don’t seem to want to care for themselves. But what do I know?

That’s it for today. On our way out, do me a favor and go to your podcast ad and rate and review the show. It goes a long way to getting it to other folks. And if you really like us, go on over to the Crooked Media store and pick up some merch. We’ve got our new logo tees and mugs, our Safe and Effective shirts, and our Science Always Wins shirts and dad caps.

Dr. Abdul El-Sayed: America Dissected is a product of Crooked Media. Our producer is Austin Fisher. Our associate producer is Olivia Martinez. Veronica Simonetti mixes and masters the show. Production support from Tara Terpstra, Lyra Smith and Ari Schwartz. The theme song is by Taka Yasuzawa and Alex Sugiura. Our executive producers are Sarah Geismer, Sandy Girard, and me: Dr. Abdul El-Sayed, your host. Thanks for listening.