Coronavirus (COVID-19): Press Conference with Yonatan Grad, 07/17/20


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 11:30 a.m. Eastern Time on Friday, July 17th.

Transcript

MODERATOR: Dr. Grad, do you have any opening remarks?

YONATAN GRAD: I’m happy to field whatever questions, and if I can address them, I can address them. Let’s just jump in.

MODERATOR: Great. Thank you, Dr. Grad. All right. Looks like we have our first question.

Q: Yes, hello. Thank you. My first question, to be considered as an effective vaccine, for how long should that immunity last? I mean, how long should the efficiency of the vaccine last month to month, its effectiveness?

YONATAN GRAD: So I think vaccine efficacy in these trials is really looking at how well individuals are protected. You know, it’s tough, of course, to assess the duration of protection in the context of a trial because you will only be able to really evaluate it for the time of the trial. The longer a vaccine can confer protection, the better. But is it going to be on the order of under a year, over year? Only time will tell. We want the vaccine, of course, that not only protects the most number of individuals, but does so for the longest period of time. I don’t think that that efficacy is really assessed in the context of an initial trial. Beyond the trial, you just can’t do that. But of course, you want it to be as long lasting as possible.

Q: Yeah. Another question, please. We may have at a certain point several vaccines. There are vaccines now being developed in the UK, in the US and China and Russia and Europe in general. What are the standards that countries should follow to sign a deal to get one of them? Or maybe more than one?

YONATAN GRAD: What are the standards in what sense?

Q: I mean, if in any country there are several vaccines, what are the standards that pushed me to get this vaccine, and to prefer this vaccine compared to other?

YONATAN GRAD: Right. So, I think it’s basically the same set of characteristics that I imagine everyone is looking to evaluate, the vaccines that can confer the best protection to the most number of people. So, where the ability to elicit protective immunity from the largest fraction of the population is probably going to be the most important characteristic.

The question you raised before about the duration of protection will, over a longer period of time, probably also be one that that plays a role. There’s a historical example of this in the race to develop vaccines for rubella. The first rubella vaccine that was incorporated by Merck into the MMR, the measles, mumps and rubella combined vaccination, had less of a duration of protection than one developed by Stanley Plotkin. It ended up that Merck decided to replace the initial rubella vaccine strain with the one that Stanley Plotkin had developed a few years after they first rolled out MMR. That, incidentally, is why it’s called MMR II. So that’s going to be something that will take time to evaluate.

So upfront, I think that initial characteristics of vaccines that will be important from all these clinical trials will be just how effective it is in generating protective immunity in the broadest range of individuals. There are other characteristics, of course, that are economic. It’s hard for me to speak to, right? So, how many how many doses does it take? How expensive are they? And so, things that are cheap, that work quickly, where you need little of the vaccine to generate immunity, that can be delivered in single doses rather than repeated doses. Those are all characteristics that would be ideal. So the ones that can get you to a high level of protective immunity with either the smallest dose or the less need for repeated dosing and that are cheapest are probably going to contribute as well.

Q: Thank you.

MODERATOR: Next question.

Q: Hi there. Thank you for taking my call and my question. Locally, we have seen testing turnaround times increase to 10 days or longer. The health department says that they can contact trace. I suspect that after 10 days, contact tracing stops being an effective option. Can you actually contain infection if you haven’t begun contact tracing until 10 days after a test has been submitted?

YONATAN GRAD: No. And from your question, I think you are right on track. Turnaround time matters a lot. You have to be able to identify cases quickly. Not only for the purposes of contact tracing, but really, generally, for management of an epidemic.

But, just sticking to the point of contact tracing, given that we expect individuals to be infectious, not only when they’re symptomatic, but a couple of days before they become symptomatic. And that can also be people who are asymptomatic be infected and contagious. You really need to move quickly to identify those individuals and place them into quarantine or test them. And if they’re positive, place them in isolation to work to address the spread of infection. The slower the turnaround in doing so, the less success you’re going to have. I think there was just a paper actually.

Q: Are you talking about the Lancet paper?

YONATAN GRAD: Yeah, exactly. That quantifies this. So. Yeah, exactly.

Q: All right. I’m going to have to bring this up with the local health department and the State Health Department, but in terms of contact tracing capability, they’ve always been talking about staffing, being able to staff the appropriate number of people for the state of Tennessee. I’m not convinced that staffing matters in the absence of testing.

YONATAN GRAD: Yeah, I agree with you. And I don’t know the numbers in Tennessee specifically, but I mean, it’s generally the case when you have an uncontrolled epidemic, contact tracing is going to be insufficient to put it under control. You’re just not going to be able to identify enough cases or reduce the extent of transmission sufficiently to bring it all the way under control across a state. You are going to need other types of mitigation measures in order to do so. Now, contact tracing may be a contributing mitigation measure, but it is on its own certainly not going to do it. It’s really most useful when you have a smaller number of cases.

So, when you have sufficient testing to be able to identify those people, you should be tracing. You need more pieces than just contact tracers. You need to be able to do case identification in an extensive way in order to really make it most effective.

Q: With respect to those other mitigating measures, the Center for Public Integrity just released the White House documentation that says that Tennessee Statewide is on a red list where it recommends statewide mandatory masking orders in addition to other measures to prevent public gatherings and the potential transmission events. So far, there’s no indication statewide or locally that any of these things are going to be implemented. In fact, political pressure is very strongly against them. It’s a dumb, obvious question, but that’s definitely just going to increase the number of cases in this state?

YONATAN GRAD: Yes. Cases and hospitalizations and deaths. I mean, this is not a stretch. It sounds like giving up, and just accepting that people are going to die, and not doing what you can to slow it down. It seems hard to fathom because those who argue that it’s necessary to take this approach of, as they say, “take it on the chin”, to use the Boris Johnson phrase from several months ago. That does not help your economy. We see that the economy is similarly challenged even in the absence of mitigation measures, and our health care infrastructure is threatened by a large number of cases. So it seems contrary to the public health interest to not take efforts to to mitigate. It is similarly contrary to economic interests to not try to control the virus.

Q: Thank you.

MODERATOR: Are you all set?

Q: I think so, yes.

MODERATOR: All right, great. Next question.

Q: Dr. Grad, thanks for taking the time this morning. A couple of quick questions about testing capacity in the U.S., alongside the recent surge in case growth. The U.S. obviously has increased testing capacity, while cases have been rising as well. There have been some suggestions that the increase in case growth is due to this increase in testing capacity. I’m curious what you would say to that. And also, when you look at the numbers for increases in testing and increases in cases, what do you do to sort of pick apart where more numbers of cases might be due to more and more testing and where it might be due to just increase in the spread of the virus.

YONATAN GRAD: Yes. So that claim is patently false. It’s demonstrably false. Look at the percentage of tests that are positive. We see that those are going up. So, if the disease was not spreading and you were increasing testing, then the fraction positive should stay stable or go down. But in fact, we’re seeing that the fraction of tests that are positive is going up as testing is going up. That is a clear indication that there is increasing spread of the virus. That is similarly observed in increasing hospitalizations and deaths from COVID-19. So, it is at best misleading. At worst, intentionally subverting public health responses against the health of the populace to suggest otherwise.

Q: Thanks for answering the question, I appreciate it.

YONATAN GRAD: Yeah, no problem.

MODERATOR: Great. Next question.

Q: Thanks very much. I had a couple of immune system type questions. The first is, how do you assess the understanding, now, of the duration of antibodies after an infection with this coronavirus? Is it in line with other ones? Does it seem short lived or is it really too early to tell at this point?

YONATAN GRAD: I think it’s still too early to tell. I mean, it’s hard to imagine but this virus, it’s still only been around for a few months. So, we’re still pretty early on in trying to understand questions around the duration of immune responses and the nature of those immune responses. How protective they are, may be very different from what we can detect and what we’re able to measure. So I think there will be a lot more information on this front over the coming weeks and months.

There is, of course, a lot of concern around the possibility that infection does not confer long lasting, sterilizing immunity. So, when we think about the impact of immunity, we can think about it in a couple of ways, or along a couple of different dimensions. One of them is that even if you were to get infected, you wouldn’t develop symptoms. So there’s some protection that immunity can confer against the development of severe manifestations of disease. A second is how much shedding might happen. So, how contagious you become even if you are infected. And then it could be that you’re protected totally. So, the likelihood of getting infected is lower. So, when we think about the nature of the immune response, it’s helpful to think about the different ways in which the immune system can protect us. Those have different implications as we think about the spread of the disease and the clinical importance.

If people still get infected but don’t necessarily develop severe symptoms, well, that’s positive because they’re not going to end up in the hospital. They’re not going to end up in the ICU and deaths will go down. But, if they’re still spreading disease then as it goes to people who have not been infected before, that becomes concerning. So, there are a variety of different parameters here to consider.

The coronaviruses that cause common cold type syndromes that have been circulating in human populations, two alphacoronaviruses, two betacoronaviruses, seem to result in short-lasting immune protection from reinfection. But, there’s some evidence that they are associated with diminished symptoms. So, people might get infected a year later, but are less likely to develop symptoms or severe manifestations.

So, does this SARS-CoV-2, this new coronavirus, elicit a similar kind of immune response in dynamics of an immune response? I think we’re still learning that. How much might it depend on the severity of infection in the first go around? So, symptomatic individuals actually develop a quantitatively or qualitatively different immune response or a duration of response? There’s some suggestion there.

There was a paper in Nature Medicine by Long, where it looks like the IgG levels, this is a measure of one class antibody, seemed more sustained, at least over a period of, I think seven weeks in symptomatic individuals, on average, than in asymptomatically infected individuals. But, when they looked at the ability of antibodies to neutralize the virus, those seems to persist just as well in both symptomatic and asymptomatic individuals. So while it might mean that the particular test we’re doing to look for the antibodies might suggest those antibiotics are going down, that protective response may persist.

It’s really as we follow cohorts of individuals who have been infected over the next interval, that we’ll learn about the likelihood of reinfection, and what might be risk factors that contributed to the possibility of reinfection. That, I think is really going to be pretty critical to get to this notion of what shapes the immune response and how long lasting is it.

Q: Just sort of following that, is the mechanism in the immune system that leads some capabilities to be immune to disease like measles being long lasting versus these coronaviruses, is that understood?

YONATAN GRAD: No. Super interesting question, and one of the mysteries of the immune response. What is it about some infections that lead to long-lasting immunity? What is it about them that makes it relatively short-lasting? In some cases it might be that the pathogen itself is changing so that, for influenza, for example, we know that not only are there multiple strains that circulate, but they evolve and new strains circulate with some frequency, sometimes seasonally, sometimes every couple of seasons we see new strains. So there’s some pathogen evolution that might shape the duration of immune production. But, even for pathogens that remain somewhat constant, we see different rates of waning immune protection.

It’s an important and interesting question, but I don’t think it is well understood. And there is another factor, just to demonstrate how complex a topic this is. It may be that the duration of immunity or the nature of the immune response is influenced by other factors like how old you are when you are infected. Age may also influence the nature, the strength and the duration of the immune response. What other pathogens have you seen historically? There’s increasing understanding for influenza that the first flu strains you see, shape your lifelong responses to subsequent strains that are circulating. So, yeah, it’s a really interesting, and important field where there’s a lot yet to be understood.

Q: My last question is, do you have a view on the suggestion some people have made that the size of viral load, like the number of viral particles a person is initially exposed to, has some kind of effect on the severity of illness they suffer? My understanding was there was sort of like a number that you need to be infected and then it goes off and replicate, and if you don’t hit that number, you’re not sick. But maybe that’s wrong. How do you see this?

YONATAN GRAD: Yeah, it’s a point I can bring up, but it’s another contributor here that may well play a role. We don’t know. So, you can imagine that there is a relationship and some curve where, you know, on the x axis of this diagram, you have the viral inoculum, so how much virus are you exposed to. And then on the y axis, you could have either the probability of being infected or the probability of having symptoms if you are infected. You can think about the relationships here. And it may not be a step function, right? It may not be that, you know, below some threshold, you’re not going to get infected or you’re not going to have symptoms. And above some threshold, you are going to get infected or you are going to have symptoms. It may be a curve. So there is a likelihood. And then there’s the all there are all of these questions about what that curve might look like. And I think this is something that we’ll learn over time.

It is the case for other pathogens that there are these curves there. There are relatively few for which we have data from human challenge studies that give us a sense of what these curves look like. But they do exist for some. For cholera, bacterial pathogens, so, a little bit different. But there, we know there is a relationship where you have this curve that relates to the likelihood of infection or the likelihood of symptoms if infected to, in this case, the bacterial inoculum. That was done with human challenge studies. So, that kind of relationship, I think, is a totally reasonable one to expect, we just, as yet, don’t know what it looks like or what the factors are that shape that curve.

Q: Thanks for your patience with me.

YONATAN GRAD: Oh, please. Good questions.

MODERATOR: Next question.

Q: Can you hear me?

YONATAN GRAD: Yes.

Q: OK, perfect. So I have a couple questions about this article that was that just came out of the Center for Public Integrity, which is talking about these White House documents showing 18 states in a coronavirus red zone. Have you seen this document?

YONATAN GRAD: I haven’t.

Q: OK. So it says, you know, here I am in Florida, and this would be considered a red zone. Which, essentially means that, basically, it says that there’s one hundred new cases per one hundred thousand population. And this was made a week ago, but was never released from the White House until today. We just want to see if you’d be able to answer for us about the recommendations. They’re basically recommending, continued testing in assisted living in long-term care facilities, a mask mandate in all counties with rising positivity, decrease indoor dining and social gathering, pretty much all of the recommendations that have been there all along. And we were just wondering what you think, what difference these recommendations would make here in Florida in a red zone?

YONATAN GRAD: I haven’t reviewed the documents, so I can’t speak to the recommendations as articulated directly, because I haven’t had a chance to review them. Generally, though, given what appears to be both widespread disease and continued spread in Florida, it seems reasonable to try to look and act in mitigation efforts to try to control and slow the pandemic. So, this includes the various social distancing and masking efforts that have been proven successful in other places.

Q: And now I know our government here has really seemed to resist this. We weren’t sure if you had any idea why they might have such a resistance to this.

YONATAN GRAD: I mean, it seems political. But it’s baffling to me, you know. Obviously, there are economic and political pressures, and it seems to me those are winning out over concerns about the health of the populace.

Q: Would you have any recommendations for Florida in the sense that, you know, our cases here are growing rather rapidly?

YONATAN GRAD: Yeah, I mean, we know that the types of interventions that can slow spread, they have worked in places like northern Italy, in China, in Spain, in New York City, in Massachusetts. Again and again, we’ve seen that they can be successful in controlling spread. We’re learning more and more about what are the particularly risky environments. Bars, indoor settings without good ventilation, the absence of masking. These are factors that, it seems, could be enacted to help slow the spread. And, you know, it’s baffling why political officials would choose not try to save the health of their populations.

Q: Thank you. I appreciate it.

MODERATOR: Great. Next question.

Q: Morning. I’ve got kind of an open ended question for you, so if I catch you by surprise, I apologize. We seem on these conversations to talk about all the things we still don’t understand, which is, you know, the nature of this beast. I’m curious if there’s one thing in your mind that has been learned about the virus or the disease that we understand now, that we know, that we didn’t early on.

YONATAN GRAD: Oh, it’s interesting, the past two questions before your’s, got at two things. One. The mysteries about immunology that remain to be where we’re making inroads. But they’re still quite substantive issues that remain to be elucidated. And then, the question immediately prior was one where we we do have great knowledge, you know, how we can control the virus. And control spread. And yet, this most wealthy country in the world is letting it run rampant. So, yeah, it’s interesting how there are contrasts here.

There are absolutely things we need to learn that will be important in shaping both our ability to project what will happen in the future and help inform development of therapeutics and vaccines and so on. But, there are also tools that we have at our disposal. Even now, and we’ve had for some time, that we know work that we haven’t been able to really put into practice in some places in this country. We haven’t made a sufficient investment in testing, as we’ve talked about, as well, on this call. We don’t have enough testing capacity to really have the rapid turnaround that’s necessary to enable control measures and direct them. And, we haven’t yet invested sufficiently in these other mitigation efforts to slow the spread of the virus.

So, there are absolutely still lots of important questions to be answered. There’s still a desperate need for new therapeutics and vaccines. It’s exciting to see work on those fronts advance, and that is something that is hopeful. But, it is also hard to understand why we are not putting into practice those things we already know.

Q: Thanks for the perspective. This is a rare day where I don’t have a follow up.

MODERATOR: Next question.

Q: Good morning.

YONATAN GRAD: Hi.

Q: I would like to talk a little bit about the vaccine development. Moderna seems to be sort of leading the pack. Can you comment on whether that’s a fair characterization, but also the methodology that’s being used. You’ve referred to challenge studies before. Is that kind of a uniform thing that these different vaccine trials are doing, or are the methods varying?

YONATAN GRAD: I think I may defer those kinds of questions to Barry Bloom. I think he’s more suited to answer the details of the vaccines. The challenge studies that I was referring to earlier were actually of a different nature. Those weren’t the vaccine challenge studies. I know those have been in the news a lot as people have thought about the different ways to rapidly assess the efficacy of vaccines. Challenge studies, where you have individuals who are vaccinated, and you actually challenge them with a virus to see if they get infected, that’s a different type of challenge study than when I was describing. The one I was describing was actually studies where people were looking at what the impact is of different doses of a pathogen on the likelihood of getting infected or the likelihood of having symptoms. In the specific one I was referring to, those studies were done with the vibrio cholerae, which causes cholera. And, you know, they were done in part just to understand more about the nature of exposures and disease better. We have treatments for cholera. So, those could be done in a very different kind of context, just to make the distinction between the kinds of challenges that I was describing and vaccine challenge studies.

Back to your questions about leading the pack and and technologies and so on, I am not as up on that as I suspect Barry is, and so he’d probably be better suited. Sorry to defer the question, but he could give you a good answer.

Q: Right, that’s OK. Can you comment on the prioritization, because I’ve heard that there will not be enough supply for everyone to meet the global demand. And then I’ve heard about what I think of as rationing. And so I’m wondering if you can comment on that and when that might occur.

YONATAN GRAD: It’s a super interesting and important question. We know that by necessity, as manufacturing of any vaccine proceeds, initially, you’re going to have a limited supply, right? It’s going to take time to manufacture enough vaccine for the world’s population. So, what should guide vaccine allocation and prioritization? How do you think about it globally? Which countries do you give vaccine to or even within those countries, how do you prioritize which populations should get it? And I think this is a really important question, and one that should make us ask what our goals are.

Are we trying to reduce cases, are we trying to reduce deaths? It seems like the most reasonable thing might be to initially vaccinate the frontline workers, both health care workers and essential workers. Those are going to be people at high risk for contracting infection. You might think that you want to vaccinate the elderly, those who are at highest risk for dying from the infection. So there are a variety of different scenarios, those are just a couple, that one can imagine quite quickly off the top of my head. But, there are others you might consider, depending, again, on what your goals are.

The decision making around that I think has to be both carefully thought through and transparent. So, I think that there’s work to be done there. And then, you know, as we think about how to work through that decision making, what kinds of data do we need or what kind of assumptions do we make? So it seems, to me, unlikely that vaccines, at least initially, are really going to be tested in the elderly population in the context of these clinical trials.

Most clinical trials are done with healthy people who are not elderly. Will we get enough data, even if they are given to you, elderly individuals? Because, elderly are most likely trying to protect themselves from getting infected to begin with. We might not have sufficient power to really be able to assess the effectiveness of the vaccine in the elderly. And it may not be reasonable to extrapolate and assume from healthy young individuals the effectiveness of the vaccine. So, there are other examples where it seems like vaccines are not as effective in the elderly as they are in younger individuals. This gets to one of the comments I made earlier about factors that may shape the nature of immune responses to infection or to vaccination. So, what kind of data we need? What kind of assumptions are we making? How does that play into decision making on prioritization of vaccination when we do have only enough for one percent, five percent, 10 percent of the population. I think these are questions we’re thinking about in terms of modeling so we can just have some understanding of what the impact of these choices will be. But, I think whatever decisions are made on how to prioritize, it really, really has to be transparent.

Q: And lastly, should that be made at what level, those decisions? You know, when it comes down to policy, I mean, we’re already seeing a vacuum at the national level.

YONATAN GRAD: Yeah, it’s true. I mean, ideally, this is something that would happen at the national level. Maybe by the time we have a vaccine, there’ll be a different administrator that could actually take responsibility and not criminally abdicate its role in shaping public health response and management of a pandemic and massive public health crisis.

So, yeah, ideally it would be something at that level. And also because this is really global. It feels like there’s some consideration that must be given here to what’s happening around the world. What kinds of considerations of global equity should there be as well? So, I think there are lots of hard decisions coming.

Q: Thank you very much.

MODERATOR: Next question.

Q: Hi. Thanks so much for doing this call and taking my question. I had a question about testing criteria, which sort of seems all over the map. And I wanted to ask you, what is the optimal testing criteria at this point in the pandemic, given that there’s so much asymptomatic spread. And, you know, if one of the criteria is exposure, when you have communities spread, you don’t actually know if you’ve been exposed. So, what do you think the optimal testing criteria should be? And then in terms of testing capacity, you know, if we’re saying we need to have more testing capacity, what do you see as how many a day, per week, per million in the population? So, if you could just talk about that a little bit.

YONATAN GRAD: From the beginning, the ideal testing criteria is no criteria, for precisely the reasons you pointed out. Being able to test the broad population, because there is the possibility and the expectation that there is an extensive spread, as we’re seeing, and people can be asymptomatic. Asymptomatically infected, and can also transmit when asymptomatic. It seems like really what you want to be able to do is test everyone. So, you know, you focus on places where there are symptoms, symptomatic cases. So, where you know that there is likely spread and you might want to focus there. But that’s if you can get enough testing to confidently assess or at least get a sense of prevalence and trajectory, then on top of that, to do this contact tracing so that you can then test contacts. You can start to bring things under control. And that’s the approach that’s been demonstrated as successful in South Korea, Singapore and Germany. So, really you want to have extensive enough testing to be able to just look where there is suggestion, where there’s smoke, be able to look for where there’s fire.

From the original testing fiasco, it’s the ramifications we continue to feel. And we remain without sufficient testing. And one of the other points that was brought up earlier on the call is not only do you need testing, you need testing to be able to get you that information in a reasonable timeframe so that you can act on it and it can actually shape your decision making and actions.

So, yeah, in terms of the numbers, I’m afraid I can’t offer a kind of quantification of the number of tests that we would need to do so. But clearly, it’s not just about the the number, it’s about the speed with which we can get results back. And then, there’s also points that different types of testing may be appropriate in different contexts. Where there is a low prevalence, perhaps in those contexts doing pools testing may be one way to essentially expand capacity.

And so, you know, where the notion of pool testing is, if you expect there to just be a small number of cases in your population, you pool 10 samples and expect most of them to be negative. That way you can effectively rule infections out for a large number of people. And if one of them turns up positive and you can test each of the 10 individually. That’s one way to try to expand your testing capacity even while having the same number of tests. So, there are some times in places where that kind of strategy may be useful. It depends on how you test, and it also depends on context.

Q: And just to follow up on that, given the lag in testing turnaround and the under capacity of testing availability, should there be an assumption of positivity? And during the delay, a requirement for a quarantine? Or would that be more risk than benefit? You know, should people assume that they’re positive and be told to do the things that they would do if they were positive asymptomatically?

YONATAN GRAD: Yeah. I think it depends on exactly the context. You know, if what you’re doing is trying to reign in uncontrolled spread in a population, and people are being tested because of known exposures, then for sure they should act as if they have been exposed, and could be infected and they should quarantine. So, that is one context. If what you’re doing is trying to monitor, say, a population institution, university students returning to school, or people working in an institution, factory work, what have you, where what you’re doing is really monitoring an asymptomatic population to try to see if there are cases so that you can stem an outbreak. That’s a different kind of context where they’re right there. If there is no known exposure, you’re just really trying to observe for the entry of disease. So there are people who get tested at some regular interval every two days or something like that and continuing to go to work. So, the reason for the testing of this context, if it’s based on exposure or if it’s just doing surveillance, would warrant different types of actions.

Q: Thank you. And then, are there any places in this country where contact tracing is working? It’s clearly been ineffective, as we’ve seen in a number of places, and not even done in some places. But is there somewhere that’s got their act together?

YONATAN GRAD: I don’t think I am familiar enough with the full landscape of contact tracing to be able to answer that in a reasonable way. So, you know, I know Massachusetts has invested a fair bit and worked with Partners in Health to stand up contact tracing in the Commonwealth. And I know Partners in Health has worked with other states. So, I would direct you to them to be able to comment on where they think it’s actually been effective.

Q: Thank you.

YONATAN GRAD: You’re welcome.

MODERATOR: Next question.

Q: Thank you so much for taking our questions. I’m wondering what your best guess is for the time between when we get a vaccine or vaccines and we achieve something like 70 percent, 85 percent immunity? And what the biggest challenges you perceive are there? Is it the possibility that there is a different protective response in the elderly vs. young clinical trial volunteers? Or is it something else?

YONATAN GRAD: This is something I worry about a lot. I think people have construed the development of a vaccine as almost like a reset button that will take us back to life prior to the pandemic. I am concerned that is not a reasonable expectation. And as a consequence, people are going to be confused and disappointed if we end up with a vaccine that has modest effectiveness, and that does not generate sufficient immune response. Or if it can be manufactured quickly enough to really kind of hit that reset button.

The FDA, as I recall, has put a threshold of 50 percent effectiveness as the basis for approval. Well, 50 percent effectiveness in which population? How does that play out? You know, you get the example, I think, picking up on some of the things that I mentioned earlier about effectiveness in the elderly or the vulnerable populations, I think that’s going to be really important, the nature and the duration of immunity from natural infection. Will we need to go back and revaccinate and vaccinate people who may have been infected? Is this something we’re going to have to do every year because the duration of production is short enough that it will require multiple boosting? Is it going to be every six months?

So, you know, there are questions around implementation of vaccines that get me worried. And also that, it’s not clear that if there isn’t long lasting immune protection, will we hit, as you described, the level of herd immunity to stop spread? Or is it going to be something where we’re really going to continue to see spread, although perhaps it won’t be quite the same level. We’re gonna just end up with SARS-CoV-2 as a seasonal respiratory virus. It joins together the group of influenza, parainfluenza, respiratory syncytial virus, human immunovirus. This long list of viruses that circulate annually. That’s my guess as to what will happen. But I think it’s the notion that we’re gonna go back to pre pandemic times, I think it’s a bit concerning because I suspect it’s unlikely to happen. Now, I think at the same time, there is a potential benefit, maybe not the people in the administration, but the notion that many people have that we should not tolerate this level of death from a pandemic. It may make us revisit a number of the other infectious diseases that cause a huge amount of suffering, and redouble our efforts to try to control them. Maybe this provides a boost to research into influenza vaccination and then ultimately into making better flu vaccines so that the burden of disease from flu, which still every year kills somewhere, around twenty to sixty thousand people in United States. Maybe we can start to address that.

So, I think, from from the perspective of just the SARS-CoV-2 vaccine, I am worried that we’re not going to be able to just press a button and go from a pandemic to no pandemic. It will take a lot of time and it may not happen to quite the extent that we might imagine. So it’s, as your question is getting at, a potentially fraught situation.

Q: Something I’ve been wondering about is if, you know, immunity from infection only lasts two or three months, does that make it hard to study the effectiveness of a vaccine? Can you really tell the effectiveness of a vaccine versus a control group? You know, if a vaccine were to only confer protective response for two or three months, if that makes sense.

YONATAN GRAD: Yeah, I mean, I think you would monitor the population and see what happens over the time from when you’re vaccinated. So, you may be able to, depending on how the study is structured, see that there is an effect that’s present initially, but that it diminishes over time. So, there may be ways to assess the duration of protection. Another way to ask your question is, if natural infection elicits a protective immune response that is of short duration. Can we expect a vaccination to exceed that? Does natural infection actually place a kind of ceiling on the extent and duration of vaccine protection? And that’s another one for the vaccinologists and immunologists. I don’t know. Maybe. But I would defer to those people who really are expert immunologists to address that question. In terms of a vaccine, one of the points of the trial is really to be able to follow up the population and see the duration of protection conferred by the vaccine.

Q: Thank you so much.

MODERATOR: Next question.

Q: Thank you. Thanks for making the time, I’ll keep it quick as I know we’re running over. But, I listened to a discussion with your colleague Michael Mina a couple of days ago on this week in virology, just about this idea of testing fast, testing often and sacrificing some sensitivity with the idea that you’re still going to catch people when they’re most contagious. And I won’t ask it to kind of steal his thunder because I thought I was a brilliant idea. But, I just was curious, from your perspective, how confident you are in that we know when people are most contagious and we know enough about viral shedding, that we can kind of be comfortable with that method. And the method is, even though your sensitivity is lower, if you’re testing yourself every day by spitting on paper when you’re most contagious, it’ll pick it up. You won’t be relying on contact tracers, but you’ll be able actually just self isolate if you test positive. So, was just curious to kind of get your thoughts about it from the immunological perspective.

YONATAN GRAD: Yes. So it’s not so much an immunology question. I know, Mike, of course, and Daniel Larremore was the first author of that manuscript preprint, still undergoing peer review. But, I think the work is exceptional and again, one of the key points in the manuscript is what matters is the turnaround time, that you really need to get the information quickly so that you can act on it. And as that turnaround time gets longer and longer, the benefits are lost. So, the sensitivity isn’t critical. What is critical, is the frequency and then the turnaround time. I found it a convincing argument.

Q: Just a follow up to that. You know, one thing that we’ve been kind of nervous about here in Florida is hurricane season. And, you know, this state government has been talking about trying to get a good rapid test because, you know, everyone’s very concerned that if a hurricane rolls in and we’re still at this level, transmission, or anything really resembling this level transmission down here, the shelters are just going to be a mess. And, there needs to be a rapid test. How do you see that kind of intersecting with, maybe not even this method of testing, but just antigen testing in general? And how would you recommend our emergency management officials kind of approach that problem of possibly needing to congregate people in large open spaces?

YONATAN GRAD: Yes. So, I think it’s the large closed spaces that are most concerning. And perhaps that’s what you’re referring to. Of course, distancing, masks, and so on would be ideal where possible.

So, there are some interventions, one can imagine, trying to slow spread under challenging conditions. But, in those settings where you really want to have surveillance, to identify cases and then be able to isolate them and quarantine contacts and so on as much as possible, then this kind of large scale, rapid, frequent interval testing seems like it could be a good approach.

The platforms for doing it, I don’t think we quite have them to the extent that we would like. It would be great to have more of these rapid tests available and where they can be used in in the way that Mike outlines in that paper. So, you know, it would certainly be something that the emergency management officials, response officials, should look into.

Q: Thanks so much. And I hope you have a great weekend. Thanks for making the time.

YONATAN GRAD: You, too.

MODERATOR: And it looks like we have one last question.

Q: Thank you. I wonder if you could just talk to whether there’s any substance or evidence for multiple strains of the SARS coronavirus at this point?

YONATAN GRAD: I don’t know of any compelling evidence for there being multiple strains of clinically significant differences. There have been discussions about one particular mutation that may be important, but I don’t think we’ve seen compelling evidence about that as yet. It may emerge, but I haven’t seen it as yet.

Q: Do you think that would hinder the vaccine trials?

YONATAN GRAD: Not necessarily. I don’t think these are changes that have been in antigenic domains. So, it’s not clear to me that it would be particularly impactful. I think it gets into all sorts of contingencies that we haven’t yet seen reason to be concerned about.

Q: OK. Thank you.

YONATAN GRAD: Yes. OK, thanks, everybody.

This concludes the July 17th press conference.