You’re listening to a press conference from the Harvard T.H. Chan School of Public Health with Yonatan Grad, the Melvin J. and Geraldine L. Glimcher Assistant Professor of Immunology and Infectious Diseases and a faculty member in the Center for Communicable Disease Dynamics. This call was recorded at 10 a.m. Eastern Time on Wednesday, December 8th.
Moderator: Dr. Grad do you have any opening remarks for us?
Yonatan Grad: Sure. Today I think there’s a fair bit to talk about, so I just wanted to try to frame discussion and then we’ve got to field questions. So I imagine with the data that’s started coming out yesterday afternoon and evening on neutralization titers for Omicron, there’s going to be a fair bit of discussion about that and the implications. I just wanted to address a few points. So with this new variant, there are questions around its transmissibility, neutralization and severity. So for transmission, the data that we have so far suggests that it appears to be highly transmissible and to some extent, that’s innate transmissibility. And then it’s also as we’re seeing now attributable to some extent to escape from immune response. And I think the implications are really important. We will see, as it seems to out compete Delta, a big wave of Omicron. At least that is the concern. So it’s also worth noting that even as that’s the concern, we’re already seeing a huge amount of transmission of Delta. So I think that it portends a difficult winter ahead. So the next few weeks and over the winter, we’ll have to address a number of issues and be prepared for what’s coming. And I think as it has been always with this pandemic, you can anticipate some of these features, but you really need to start preparing early and the whole concept of exponential growth that we’ve been talking about for two years now. And so the first issue transmissibility and second one neutralization. So the first data that we were seeing yesterday suggests a substantial reduction in neutralization titers from individuals with two doses of Pfizer vaccine and less so in those who were vaccinated and infected. In other words, those people appear to have less of a reduction in neutralization titers. And Pfizer released some press report, although I have not seen data, suggesting that much of that reduction is made up for by a booster dose or a third dose. So we see again less reduction in individuals who had three doses. But there’s a fair bit of uncertainty here, and I think we’re going to learn a lot more again over the next days and weeks when we have a chance to read the manuscript and actually see how all of this was done for neutralization titers comparing to two doses of three doses. We also know that what matters is timing. When did those people get their vaccines? When are those the sera used in these assays? Where are they from, are they from two weeks post last dose? Or is it something where they waited six months to see what the sera were? So again, these are issues with waning that we are familiar with. Neutralization is also important for monoclonal antibodies, which are a big part of the therapy for COVID-19 and their suggestion that at least one of the monoclonal antibodies seems to still have substantial activity. But there’s good reason to suspect that others do not. And that has again big implications as we look ahead to Omicron spreading and causing disease, requiring hospitalization and limited therapeutic options will pose a challenge. So first transmissibility, the neutralization, and the third issue is severity. So it is just too early to know what is going on with how severe disease will be from Omicron. I think it is reasonable to start to assume that from neutralization escape, we should start to see as well decrease in vaccine effectiveness for hospitalizations and deaths with Omicron. So there is a good reason I would say from these data and also from the precautionary principle to be alarmed and start preparing. And again, we’re in it already with Delta, with cases rising in many places. So for sure, the unvaccinated are at big risk, both the delta and then with coming Omicron. And then the other issue that I’d point out is we are seeing flu. So there is a fair amount of influenza picking up around the country. And this is, I worry, starting to look like the scenario that everyone was worried about last winter, when there’s concern for both influenza and SARS-CoV-2 spreading over the winter season. So, you know, going back to the same payments from the beginning as we were heading into last winter and the strain on hospitals and health care system broadly, I think is going to again be a priority this winter. So that was basically the prelude. Happy to field questions.
Moderator: Thank you very much, Dr. All right. First question.
Q: Hey, thanks so much for the time. I have a couple of questions related questions, if that’s OK, tied to kind of what you were saying about transmissibility and how you’re thinking about that with Omicron. And I guess so to start, like, how are you thinking about its transmissibility as it compares to Delta? I mean, maybe what you’re seeing in South Africa or in Europe, and it sounds like you think that whatever advantage might exist could be both that innate transmissibility as well as a greater degree of immune escape.
Yonatan Grad: Yes, I think we’re still waiting for more data on neutralization, but from, and again, this is still a bit early. We’re going to get more data from South Africa, from the UK, from other places where they have great surveillance systems that will allow us to try to better estimate what the transmissibility advantage is of Omicron over Delta, but certainly the data we’ve seen so far suggests that there is some. One of the questions has been to what extent is it kind of an innate transmissibility advantage versus an advantage conferred by escape from neutralization? So, it could be components of both. And again, I think we’ll have a better sense of that, both as we get more data on neutralization and as we get more of the epidemiological data. But right now, it looks like there may be contributions from both to Omicron’s advantage over Delta.
Q: And just to follow up on that, if I like, if you don’t mind, you know, forecasting a little bit. What does that mean about like how could how epidemiologically could that transmission advantage play out in a place like the US? Because I know like when a variant enters a new place like a lot depends on whether other variants are circulating in sort of like the immune profile of that place. I think, like Fauci yesterday raised the idea that South Africa has much higher rates of HIV, so it’s harder to draw comparisons. But like is Europe a better comparison? So how could that play out in the US?
Yonatan Grad: Right. So, you know, it’s going to be influenced by all of the usual things that we’ve talked about. So one, you’re absolutely right, it has to do with the extent of immune protection in a population. So as we learn more about that neutralization from people who have been infected from people who have had two doses of vaccine from people who have had boosters, all of that will play out. I am worried about transmission in the U.S. because of the large fraction of the population that remains unvaccinated. Right. So the extent of immune protection is not substantial enough to really, it seems, make a huge dent we’re seeing spread in South Africa. We’re seeing spread in Denmark, we’re seeing spread even in the U.S., the cases are picking up here as people identify more and more Omicron across the country. So I am worried about Omicron spreading, and I say this even as we have a wave of delta now where Delta is spreading through the population. So, you know, it’s hard to estimate exactly what the patterns will be that is influenced not only by the transmissibility of the virus, but also mitigation measures we take and how much the population decides to get vaccinated or boosted. So there are things that people can do to help slow the spread. But I am certainly worried that given the fraction of the population that remains unvaccinated and both unvaccinated previously uninfected so really totally immune naive, we will see a huge amount of spread.
Q: Thanks so much. Really appreciate it.
Moderator: Next question.
Q: Hi, there. That was started with some questions I had, but I just to follow up on this idea of transmissibility real quick because I spoke to a researcher in the UK who is already said he thinks the effective reproduction number is above three there. You know, based on early data and that kind of mirrors what they’re seeing in South Africa. And I just wonder how you kind of, how you digest this, this early information and the fact that we might be seeing a similar, you know, reproduction in two very different places, you know, like the U.K. and South Africa. What could that tell us?
Yonatan Grad: Well, I think it is consistent. I mean, the data that we’re seeing in these places is consistent with each other and consistent with what we’re now seeing in terms of neutralization and what had been anticipated based on the genomic sequence of Omicron and particularly all of the mutations in the spike protein. So all of this is consistent with expectations right now. And it’s concerning. So, you know, the main issue that we have to be prepared for is not only the ongoing wave of Delta that we’re having right now, but our concern for a wave of first Delta then followed by Omicron as it will start to spread too.
Q: And just to put that in perspective, real quick, I mean, if it were to be like the initial estimate of like three in terms of reproduction, I mean, is that just how do people understand that number in terms of level of concern or relative to Delta?
Yonatan Grad: Yeah. So I mean, there are a number of ways to look at an individual level. The first observations that perhaps there’s less of a reduction neutralization in people who had boosters. Again, these are preliminary data I just want to emphasize so that, you know, we’ll have to see how this again how it appears actually in the manuscripts and in published reports. But you know, if it is the case that as we would expect it to be, that people who have additional immune protection, whether it’s from a combination of vaccination, infection or vaccination and boosters, that those people have less of a reduction in neutralization as compared to Omicron, then it really suggests that an individual level you should get a booster, get vaccinated if you haven’t been vaccinated and get a booster if you haven’t gotten one yet, because that will reduce your individual risk and also help to reduce population spread. The other factor it suggests, at least as we head into the holiday season, is that engaging in the non-pharmaceutical interventions that we’ve been discussing for the past two years again will become pretty important. So masking, masking particularly when you’re indoors, avoiding large gatherings and using or being in places where you have good ventilation or trying to improve the ventilation in the places that you enter. Those are all going to be key to help reduce that effective reproductive number. But the big concern, again, is that with an art that’s around three in populations that have a fair amount of immune exposure or at least first round of vaccination is that we’re going to see it spread pretty widely here too. And it’s, you know, hospitals already in many places are struggling with Delta. If we add on another surge to that, it’s, you know, definitely alarming and something to be worried about.
Q: OK, thank you.
Moderator: Next question.
Q: Hi, thank you very much. I have two questions, one about the past and the other about the future. Speaking of the past, I’m wondering if you have a favorite theory on where Omicron came from. Do you think it was in an immunocompromised person or an animal host? I mean, how did how did we end up with it? And my other question I’m wondering looking ahead, given that COVID is going to be with us in some form or another for a long time, do you feel that we’re prepared to deal with it in terms of having the infrastructure for testing and vaccinating and boostering and mask compliance and that kind of thing?
Yonatan Grad: No. And that also brings up another point that I regret not mentioning in discussing the non-pharmaceutical interventions in answers to prior questions. I really should have said something about rapid tests because I think rapid tests are hugely important in all of these. You know, rapid tests before you mix with people I think are key and can have a huge impact on reducing spread. So I just again, I’m sorry for not answering the previous questions from both true and kind of highlighting that so. So then going to your questions in turn. So one, where did it come from? I don’t know that anyone has a high confidence theory. I don’t know that we can have a high confidence theory right now. The number of mutations in the long branch is an indication that it was circulating somewhere for a long time before it was picked up. Now where was that? It could be that that was in some undetected human population. I think that is, meaning like a population of people and just circulated among that group and then eventually got out, I think that’s extremely unlikely given the extent of mixing among people that we would not have seen it or sampled it somewhere before. So I think a human population is unlikely. What about an animal population? Could it have gotten into, say, deer or some other animal host and circulated there for a long time and then jumped back into people had another spillover event? That’s possible. But you know, it’s a hard one to prove or disprove. What about in an immunocompromised person? Well, we know that immunocompromised people can be chronically infected with SARS-CoV-2. There have been a number of published reports on this. And it is something that we’ve seen with other viruses as well, like influenza and respiratory syncytial virus just to identify two other human respiratory viruses. So it certainly can chronically infect an immunocompromised individual. One of the things that’s interesting about Omicron is the number of mutations in antigenic sites. So those areas of the spike protein that are targeted by antibodies. And one of the things that I wonder here is rather than someone who is severely immunocompromised and unable to generate an immune response, this suggests to me a possibility that the person who is chronically infected may have had cycles of immunosuppression and so still never totally immunocompetent to be able to clear the infection and get it out of the system fully. But periods where you have enough of an immune response to actually apply a selective pressure to the virus such that it would evolve away from, say, the antibodies that we’re targeting one site. But then with immunosuppression, a virus can proliferate again. You add on another layer, you remove the immunosuppression so the person becomes more immunocompetent can develop more of an immune response. But now it’s targeting another site on the virus. You go through these kinds of cycles and you can see this extensive evolution to avoid multiple types of antibodies. So you see epitope changes many epitope changes in one virus. So to my mind, that that seems like the most plausible scenario.
Q: Why would a person’s immune strength be cycling in and out, though. What are those circumstances?
Yonatan Grad: Yeah. So that can happen in a few different circumstances. We do that to people as physicians. We treat people who have cancer with cycles of chemotherapy where their immune system will go down and then come back up. We treat people with immunosuppressive agents when they have autoimmune diseases, and so those get delivered, usually monthly basis. So Rituxan or rituximab anti-CD20 antibodies basically knocking out your antibodies. So, you know, there are ways in which we do this deliberately to people. There are also people who go on and off medications, so someone who has, I think this is less likely, but someone who has HIV and takes their medications for a while and stops for a little bit and takes time again, and it stops for a little bit, this is how you actually select for resistance mutations in HIV. But there are certainly ways in which in how we care for patients in a variety of different conditions where you would see cycling of strength of the immune response. So that’s all within one person. It could also be that this is something passed from in a small group of people where we just haven’t seen much sampling. So in three or four people, you could see that kind of thing. Again, I think I personally find the idea of it passing between three or four people to be less likely than something, you know, where it’s really incubating in one person over time. But again, these are all theories, and it’s very hard to prove or disprove any of this.
Q: Could you talk a little more about, you answered my second question with one word, which is very pointed, but can you talk about a little more? What do you see as the greatest weaknesses in our ability to respond to this ongoing pandemic?
Yonatan Grad: Yeah, I think that there are a number of things. One is, you know, we are often playing a game of wait and see when I think again, precautionary principle should dominate and it’s going to be in many ways too late. And we can anticipate what’s going to happen. So being prepared early and starting to take early action seems to me, one of the important lessons we should have learned from all of the previous waves. But it seems like we’re not acting on those lessons as yet. A second, really, which picks up on how I began my answer initially after you pose your questions, making available rapid tests. They’re incredibly useful in as a tool in our response, but we don’t really have them available right now. I know that there is or at cost, right? So I know that there is discussion about having insurance companies pay for them. But you know, I was in a CVS actually earlier this morning and listened as the person at the register answered the phone and said, nope, still haven’t received any tests today. So they’re not available in local pharmacies. So I think, you know, ramping up production and making available these rapid tests to people is another place where we have not met the challenge and need to get on it. So I think there are a number of places where it feels like we’re falling into the same traps and haven’t learned our lessons from previous waves.
Q: Anything else that we should be doing right now?
Yonatan Grad: Well, you know, encouraging vaccination, encouraging people to get boosters. You know, there are still parts of the population where, you know, we’re just not seeing it taken up. You know, I think vaccine mandates for population health make a lot of sense. And so we’re requiring vaccination and boosters because again, if the preliminary data holds up, that will help slow the spread of Omicron, and then preparing as well. And I’m sure vaccine companies are working on boosters that are Omicron specific, but that that too will be important. But for now, trying to get people vaccinated, encouraging where we can masking and all of the non-pharmaceutical interventions, many of which we’re just seeing people rebelled against because of understandable fatigue. You know, again, we’re going to see the impact of it. And I’m quite concerned, given that we are already seeing a wave of Delta that is challenging hospitals, that is filling hospital beds and we are seeing influenza pick up in this country too. So that having both a wave of influenza and waves of SARS-CoV-2, first Delta that followed by Omicron, you know, it’s going to be a huge stress on the health care system.
Q: Thank you very much.
Moderator: Next question.
Q: Hi, thanks for taking my question. This is kind of broad, but just based on what we’re seeing with the new variant and the questions about how many shots people need to get and how they should be spaced out and whatnot. Why do we still not really have a correlate of protection? Can you get into, you know, why we still have questions about how much we need to be relying on memory cells versus neutralizing antibodies? And just any clarity you can bring to that discussion, I think, would be helpful now that we’re dealing with yet another new variant.
Yonatan Grad: Well, I’m not sure I totally understand the question, are you asking why we don’t know what the right correlative protectionist yet is that? Is that a way to summarize your question?
Q: Yeah, yeah. Just it’s you know, it’s been almost two years of this. And you know, maybe it’s more complicated than I understand. There’s been so much talk about, you know, understanding what the correlate of protection is, you know, the neutralizing antibody level, but also understanding how the memory cells play into this. But it still doesn’t seem like there’s a good handle on it other than just, you know, if we boost people, their antibodies go up, and that seems to be good for now.
Yonatan Grad: Yeah, I think that is true. Well, it is true that when people’s antibody levels go up, they seem to have more protection. And I think, you know, the idea of a correlate of protection, it is the case that we have learned that antibody levels do seem to be generally predictive of the extent of protection. There is not a clear threshold where you can say above this number, you have zero risk, below this number, you have 100 percent risk, it’s a continuum. So there is there’s always risk to varying extent. And so if you imagine a graph where you have on the y axis the likelihood of infection or the likelihood of severe disease if infected and on the right you have basically, a battle of immune response or extensive antibodies, you’ll see some kind of curve, right, so you’ll be able to say that with higher levels of antibodies, you’re less likely given an exposure to be infected, but there isn’t a clear number where you can say you’re going to be totally protected or, you know, risk will be zero, it’s always going to be there. It’s just kind of, how does it how does it play out in in the middle range? We can say that with low antibody levels, you know, people are at higher risk, so that I think you can start to identify those people who are at risk if they have low titers. Now it gets even more complicated because it’s a question of what are you actually assessing with titers? Right. So many of the tests are looking at IgG levels. And then there’s the issue of neutralization. So how well does an IgG titer actually correlate to neutralization? There does seem to be from data that I’ve seen a good correlation, at least for the original founder strains, it seems like there is still a correlation, perhaps not quite as good, but still pretty good with Delta. And we just don’t know yet for Omicron. So, you know, the relationship there, we’ll have to see what it is for Omicron as well. In terms of, you know, when people go and get a test for antibody level, they’re really just looking at IgG particular epitopes. So it is possible that someone depending on what epitope is being checked, you know, someone may have very high titers, but they may be strain specific. So there is nuance here where it’s not always clear how you can go directly from a particular antibody level or titer to protection depends on what epitope is being checked, and it depends on the relationship between that antibody level and neutralization activity. So, you know, I think generally we know that a higher antibody levels at a population level, just looking across the board and looking at averages, that those do correlate with better protection, but there won’t be a strict number, it will be much easier to say people who have low antibody levels are at higher risk, but there isn’t going to be a number where you can say above this number, you’re at zero risk. It’s just going to be those people may have lower risk, but it will still, it will still be there. And then again, the nuances I was mentioning with, you know, it’s not always going to be the case that even people with high antibody titers are going to be totally protected because it has to do with what are your titers actually to? And they could be strain specific, for example. So, yeah, again, a fair bit of nuance, but generally, I think the idea that a lower antibody levels are certainly going to be an indicator of risk. Long answer, I may be repeating myself a bit there, but I hope that gets at some of what you were asking.
Q: It does, though, when it comes to memory cells there seems to be a lot of oblique references to, well, this plays into it too, but we can’t really put specifics on it. Can you address that a little bit? You know, there doesn’t seem to be a real firm understanding of how much memory cells vs. antibodies play into the responses generated by the vaccine.
Yonatan Grad: I’m going to leave that for a bona fide immunologist to speak to you. Yeah, I’ll just leave it at that.
Moderator: Next question.
Q: Yeah, thank you so much. Two questions, the first being with the new study out on Pfizer and boosters and the protection levels. What does that mean for our kids 5 to 11, who just are completing their first two doses? And should we be talking about shortening that length of time before the booster shot?
Yonatan Grad: So I haven’t seen any data from Pfizer, I just saw that press report they put out on this. So just to caution, all of this is pretty preliminary, right? So it is adding speculation onto data where or onto reports of data of it, but I haven’t had a chance to see, you know, so I think there’s still going to be a fair bit to learn and to evaluate before starting to make policy based on these things. So you know, there are going to be a few factors here. One of them is what is the extent of protection in kids? Another one is rate of waning. If people had just been vaccinated or protected, we know that over time, you know they will start off high and slowly come down. But if they’re right now in that time point that where they’re most protected and perhaps that can go to, to what extent does that carry through the winter wave? What is the optimal time for a booster in this population? I think there’s still going to be questions about that. So there’s still, I think, a fair amount to learn before making decisions on policy and what to do with this population, when to give them additional doses if we need to.
Q: Thanks so much, and my next question has to do with the testing, I know you mentioned the need for more rapid tests and just the availability of those, and there’s been a push nationally. But I have also heard from scientists saying, yeah, that’s great for stopping the spread or at least catching the spread, but we really need people to get PCR tests too, so that we can for from an epidemiological standpoint so that we can track this variant and how it’s spreading. Do you think that’s an important piece to this, that if you take an at home rapid test that you should also be going to get PCR so we can be monitoring for this variant and new variants?
Yonatan Grad: Yeah, I think that there are multiple ways of approaching this. You know, if the major use of these PCR tests or any of the rapid tests in the context of public health setting, it’s really to help people be more confident to enter into group settings where they will be at risk for transmission. I think in those settings, a negative rapid test can provide some confidence again in that setting. A positive rapid test, and you should definitely see about contacting a health care provider, whether you need to, you know, particularly if you develop symptoms and, you know, let public health officials know so that you can start to, this can be tracked. I don’t know that we are at a point where we need to worry that these rapid tests are going to so outpace or replace PCR testing. So you know, and I should say that PCR testing and epidemiological tracking of cases, has itself had vagaries through the amount of testing that’s happened in different places. And in some ways, we look to a variety of other kinds of signatures to keep track of spread epidemiologically, including hospitalizations and deaths. So there are a number of tools available, and I would not in any way point to rapid tests as undermining epidemiological observation or inference as a reason not to use them or to say this is a call for just using PCR. I think the application of rapid tests for people to be able to gather safely is still extremely important and where people are positive, there are other ways of reporting cases.
Q: Thanks so much.
Moderator: Next question.
Q: Hi, Dr. Grad, thanks for doing this. You know, I’m curious how confident you are in predicting that this virus is going to be as pathogenic as Delta or other strains that have been around. And I mean, there are these early signs, I guess, that it might not be. So given that it is incredibly, has this very high are not and that, you know, a third of the population in the U.S. or whatever is just pretty steadfast about not getting vaccinated or doing anything else to stop the spread of the vaccine. How are you going to, I mean, does it get to, I realize this isn’t exactly your lane, but do we get to a point where we’re just trying to communicate with part of the population and everyone else is on their own? Because if it’s spreading at that rate, if it starts spreading at that rate and you’re not vaccinated and you’re not taking precautions, it’s going to continue to spread. And so then it becomes a matter of figuring out what measures to take for people who care about it.
Yonatan Grad: Right, so, yes, this is why I began with the statement of just how worried I am, I am concerned for the reasons you lay out and the fact that we’re already seeing a dramatic increase in cases attributable to Delta. And so it will start to be Omicron in the next few weeks. But we’re already seeing our health care institutions challenged by Delta. And then, as I mentioned, we have flu around the uptick too. So it is it is absolutely concerning. I don’t know about pathogenicity. I think we won’t have a sense of the severe disease for some time yet. And that’s because we have to look at in which populations, as they’ve been spreading what is their age group and what is the extent of immune protection in those populations. There are a variety of questions that we’d have to answer before we can address this extremely important issue of severity of disease caused by Omicron. But I think that those data aren’t going to come for a while. In the meantime, it seems from my perspective, it’s reasonable to assume it will be like other variants and even if it’s half as virulent as Delta, that’s still as virulent as the founder strains. And so that in an unvaccinated, previously uninfected population, we saw what damage that could do back in the spring of 2020. So given the number of people a fraction population that is in that category, it absolutely is alarming. And something that you know to your question about, what should we do about it, to try as much as possible to convince people where we can and to encourage through mandates or other measures and uptake in vaccination. But you’re also right, that’s not exactly my lane and not a policymaker, and I’m not a social and behavioral scientist, so I don’t know that I have great ideas on how to present a compelling case to individuals who have been so recalcitrant how to start engaging in public health interventions that you would think for people who care not only about their individual rights, but care about populations, their loved ones, their friends and others. What would be right actions to help protect everyone? So, yeah, it’s really extremely difficult to share.
Q: Thank you. Could I ask one just small question. I don’t know that. Is there anything that, do we know enough about the structures of the virus and what they mean, I mean, we know that this has there are all these mutations in the spike protein and the binding areas and so on. But do we know enough about the structures of these of this virus to know whether certain changes have any effect on are likely? You know, where we could predict that they would have an effect on pathogenicity as well as infectiousness?
Yonatan Grad: I don’t think so. I think that’s really going to be something that we learn. I mean, clearly it can infect people, right? And so the extent of disease is really going to be something that I think is going to wait. We’ll have to wait to answer that question, and it’s probably going to be. I mean, we will get some hints, but really good solid answers are going to take a month or two.
Q: Thank you.
Moderator: Next question?
Q: Given the newness of the data regarding the Pfizer boosters effectiveness against Omicron, can you speak broadly about the importance of getting a booster? People who have had their first two shots may think they’re already all set.
Yonatan Grad: Yeah, I think even before Omicron, I think there was very good reason to get a booster. Data from Israel and from actually from the U.S., from many places now really suggest that a third dose is extremely important for immune response. So I know the CDC recently changed their statement around boosters from making them available to recommending that people get them. Now there’s discussion about whether a fully vaccinated individuals should be considered someone who’s had just that first course meaning for Pfizer, Moderna, the first two, or it should be someone who has had all three. I advocate for all three. I think that is really where we should be. So and that’s even before Omicron. I haven’t seen the data, Pfizer’s data on boosters and the extent to which Omicron reduces titers from those who have been boosted. I am really interested to see those data, but I think that just further emphasizes the point that a third dose is going to be really important. And I suspect Pfizer and Moderna and others are working on an Omicron specific vaccine, probably something that won’t be available until March, but that may also be an important feature in responding to the spread of Omicron and subsequent strains. But we’ll have to see.
Moderator: If you have any other questions just put them in the chat, and I’ll ask.
Q: Have you said anything about monoclonal antibodies?
Yonatan Grad: I’m sorry, say that again.
Q: Have you commented on monoclonal antibodies?
Yonatan Grad: I haven’t. So far as there’s some initial data, I believe from the GSK monoclonal antibody that has seen that it still seems to retain a large extent of its effectiveness. But I haven’t. I have to say I haven’t yet seen those data myself, and there is reason to be concerned about other monoclonal antibodies given the mutations in the spike protein in Omicron that they will have markedly diminished effectiveness, therapeutic effectiveness given the escape. And now that we’re starting to see data on escape from neutralization from individuals who have been vaccinated or previously infected, I am concerned about a number of these monoclonal antibodies no longer really being particularly effective. Now, one of the things to keep in mind this new monoclonal antibodies that are targeted against Omicron can be developed, but those will take some time. So the existing ones, while I believe again data for one of them may be that it retains some of its therapeutic potential that it continues to be neutralizing, I think for a number of them. We expect that with Omicron, they will have their effectiveness will be markedly diminished.
Moderator: She would like to know why patients are still dying from Delta, given that monoclonal antibodies their effectiveness.
Yonatan Grad: Yeah, they’re not perfect. And, you know, people have severe disease, so well, you know, we don’t have a 100 percent cure. Much as I wish we did. We don’t have something where you can take a drug and immediately become better. So, you know, this is Pfizer and Merck. Both have now antiviral pills that I think will contribute to our therapeutic response. But, you know, people still get very severe disease. They show up at different times in their infection course. And while the health care institutions and providers may do all they can, sometimes it is just not enough that these are the tools in our toolbox help us and reduce the rates of mortality, but they cannot bring them down to zero. I mean, it’s the same thing that we’ve seen for most of the diseases that we struggle with and in this world, in this life. Nothing is perfect, but they help lot.
Moderator: And her other question is, what might the criteria be for a whole new vaccination rollout of a revamped Omicron specific vaccine? Do you have any ideas of the breakthrough infection rate or hospitalization rate?
Yonatan Grad: Yeah. I don’t know what that we have any particular thresholds I think we will see. But again, we’re still fairly early on, but if the indications are it holds true to what we’ve seen, then I think there will be reason to try to broaden people’s kind of the extent of the immune response by targeting the antigens in the crowd. I think that if we are really at an effective reproductive number that was akin to what the original founder strains of SARS-CoV-2 had in a totally naive population, then I think there be a good call to try to vaccinate people. Something that is more Omicron specific to broaden are the antibody repertoire. So we’ll see how it plays out. I would not be surprised if in the spring we have vaccination campaigns with a specific iteration of SARS-CoV-2 vaccine.
Moderator: Next question.
Q: Hey, thanks for letting me have a second crack at this, I wanted to run this scenario by you, which I’ve heard, suppose Omicron overtakes Delta and replaces it because it’s so much more transmissible. And then it turns out that Omicron causes only very mild disease. So my question for you is, does that seem likely? And if so, would that actually be a good thing?
Yonatan Grad: OK, so yes, I don’t know how to gauge the risk of severity with Omicron because again, those are data that we’re still waiting to see. But I wouldn’t bet on it. I think again that the expectation should be that we will see it just as pathogenic, particularly in individuals who have no immune experience of SARS-CoV-2. So those who are unvaccinated and previously unaffected, I think we should still expect to see the same level of severity as we’ve seen with all of the other variants. Now one thing your question gets at is where are we going with COVID-19 in the long term? I don’t know that we should necessarily expect that the virus is going to become more mild or that, but instead that by immune experience in the population, we will reduce the severity of disease if infected. And this is what we have seen with the success initially with these with the vaccines and then with the boosters that they are effective in reducing the severity of disease and that if enough of the population, really if people just have some kind of immune experience with this virus, then the next time around, when they get exposed and infected, the likelihood of severe disease goes down. And so in essence, the amount of risk that type of disease they causes is more mild is just, you know, it is not that the virus necessarily has changed its risk in a totally unvaccinated and uninfected immune naive person, but rather as we as the population become more experienced with the virus, the amount of disease it causes is less. So I mean, that’s where we hope we are going as more of the population gets vaccinated or some kind of immune memory experience with this virus. But I would not, I don’t think it is, I think we have been caught in the trap before of hoping that a new variant is going to be less virulent. And I think it makes more sense to anticipate that it will have to be just in virulence, particularly in the people who are at risk. So, yeah, well, we’ll see how it plays out over the next weeks and months.
Q: Thank you.
Moderator: I think that’s our last question for today. Do you have any comments for us?
Yonatan Grad: No. Thanks for all the questions and the discussion.
This concludes the December 8th Press Conference.