You’re listening to a press conference from the Harvard School of Public Health with Marc Lipsitch, professor of epidemiology and director of the Center for Communicable Disease Dynamics, and Barry Bloom, Joan L. and Julius H. Jacobson Research Professor of Public Health. This call was recorded at 11 a.m. Eastern Time on Tuesday, January 5th.
Transcript
MARC LIPSITCH: Thanks, everyone. Welcome. I’m happy to just begin taking questions since I know there’s been a lot of questions about the new variant and about vaccine distribution and about the single versus multiple doses. So I’m happy to talk about any of those topics or to discuss others, but I think I’ll just go straight to letting people ask.
MODERATOR: Great. First question.
Q: Good morning, Dr. Lipsitch. I’m writing a story about requiring travelers to have proof of a COVID-19 vaccine as part of their passport. And at least one country has announced that they will be using that vaccine proof to replace testing requirements. But I’m wondering and I’d like to get your opinion on this, is that premature, given the uncertainty about whether the vaccine can prevent transmission, so somebody could be infected but asymptomatic?
MARC LIPSITCH: Yeah, I think that doesn’t make a lot of sense to me as a policy for the exact reason you say. I think there is modest evidence about some of the vaccines, that they have some impact on infection and transmission, but how much is unclear and it’s certainly not completely protective. So testing would be more meaningful than the vaccine at this point.
Q: OK, so they should keep the testing and also quarantine requirements? Or just the testing?
MARC LIPSITCH: Yeah, I mean, I think for the moment, the evidence is so limited about the vaccines and as it becomes more available, it will be a little about this vaccine and a little about that vaccine, and it’ll be quite hard to really standardize. So, at the moment, if I were dealing with migration into a country, you know, traveling into a country, I would treat vaccinated people like unvaccinated people for the moment.
Q: OK. And just a quick follow up to that. Do we know anything approximately about how long immunity is expected to last? I’ve heard everything from three months to a year.
MARC LIPSITCH: I think those speculations are made because really nobody knows, and it probably will depend on the product and on the individual, people who make bigger responses at the beginning may be protected for longer. But I think at the moment it would be shocking if it was less than three months for anyone. But whether it will be a year or two years, or more than two years depends on a lot of things that we just don’t know yet, including the evolution of the virus.
Q: So is it fair to say at least three months?
MARC LIPSITCH: I mean, I think the data from the trials will help to address that. If there’s another analysis of the data between the time, you know, in this sort of month or so between when the initial analyzes were done and the emergency use authorization, that’s another month of follow up that I trust, although I’m not exactly sure of the plans, but I trust the data will be analyzed on the people in the trial during that period of time. Since the median follow up was two months for the emergency use authorization purposes, it should be three months for at least half the participants if we add an extra month or so, so I think we should be able to confirm that pretty soon, I’m not sure what the companies are doing in terms of their trials, and I know they’re unblinding as we speak. But there should be data in that interim period which would confirm what everyone would expect, which is that it’s at least three months.
Q: Thank you.
MODERATOR: Next question.
Q: Hi, thanks for doing this. So according to the CDC, about 15 million doses of the various COVID vaccines have been distributed, but only about four point five million have been administered to people. What is your sense of what the problem seems to be? And do you have any idea of how the process can be improved?
MARC LIPSITCH: That is a very good question, and I don’t have much information, it’s something I’m trying to learn more about, but I don’t have much information beyond what I read. I mean, the numbers are never going to be equal because especially with a growing amount of vaccine each day, it does take a few days at least to get a vaccine from the delivery into someone’s arm. So it’s never going to be 100 percent of the doses administered. There will always be some lead. But a third of them or so is not great. And yeah, so I don’t have anything specific to add on why it’s been slow. I’m trying to learn more myself. I do think that one of the issues that it raises is, is a question of how fast we should start as a state or as a country trying to move through the priority groups. So each state has its list of ordering for who should get the vaccine and my suggestion would be to move relatively quickly through that list, not that people at the top of the list would be unable to get it, but that they would share their priority with a growing number of people over time in order to make sure that it’s not a demand problem. I think that’s not the only or maybe even the major reason for the relatively slow rollout, but I think that would be one part of a solution.
Q: And then I know you mentioned the new variant of COVID-19. Can you talk about that? And does that add any kind of new sense of urgency for getting people vaccinated?
MARC LIPSITCH: Yeah, I think that the new variant is a really big deal. I think that its rapid spread in the UK referring to that variant, not the South African variant, which seems to be less widespread. The fact that it’s now in something like three dozen countries, I haven’t seen the number from today, it was almost that as a couple of days ago. And you know, we have a very primitive system for surveillance in this country which means that it’s probably more widespread than we think. So I think it’s a very important challenge to our ability to control this virus, because if indeed it is something like 50 percent more transmissible that increases the herd immunity threshold, that means that each that as in the UK, places that were able to control spread with a certain level of interventions relatively intense in the UK, we’re not able to control the spread of the new virus. If that’s repeated, and I think there is good reason to expect it will be repeated elsewhere. That just makes this a much harder problem, and it emphasizes the need for as rapid as possible vaccination. And it also, in my view, means that we should focus our control efforts very much on that variant. I’ve talked about the limitations in the past of contact tracing and isolation of contacts and the like, which have been more successful some places and a lot less successful in most of the US. But one of the reasons it’s been a challenge to do good contact tracing is that we have so many cases and at the moment we don’t have so many cases probably of this new variant. So to the extent that we can find those and preferentially stop the spread, it won’t be perfect, it will be far from perfect, but anything we can do to delay the spread of this new variant virus will make control easier and will help us in the race to get more people vaccinated before this becomes more common.
Q: Thank you.
MODERATOR: Next question.
Q: Thank you so much, appreciate it. I did want to ask about something you mentioned earlier, which is the various dosing proposals that have been out there. The FDA did sort of weigh in on them yesterday, but in particular, the idea that one dose would be a better option and more twice as many people could be vaccinated if we only gave just one dose. Also, the idea of maybe just delaying the second dosage until, you know, more people are vaccinated up front. And lastly, the half dosing. Can you just weigh in on what we know about with any of those ideas be helpful? Do we have the data to understand? If they would, what the efficacy would be if we were to do any of those ideas? Just what your thoughts would be? And then also, I guess, your thoughts on what the FDA had to say about that yesterday?
MARC LIPSITCH: Sure. I think there are a lot of ways of describing the sort of one dose or delayed second dose or even a variant of it, I think is what I suggested of moving more quickly through the through the priority groups, because that’s a way of getting more first doses out, if very successful, might mean that some of the second doses would be delayed, they’re all variants of one approach, I think. No, I don’t know anyone who’s supporting the idea that we should have one dose and then leave it at that for good. I think everybody that I know agrees that a second dose at some point is important. So those three variants, I think, are sort of one idea. And then a second idea is half doses. I’m unaware of any data on the efficacy of half doses, and I don’t understand the interest in that, given that the logistics are just as bad, if not worse than the logistics of doing what we’re doing. And there’s really no data to support that. I think, on the other collection of ideas of somehow delaying or speeding first doses and delaying second doses collectively. There is data from both Moderna and Pfizer showing that in the weeks after the first dose and before the second dose. There is a big decline in the vaccinated people compared to the controls. Because those trials relatively tightly regulated when people got the second dose, I think in Pfizer, it was I might be getting this wrong, I think out to six weeks maximum in Pfizer and maybe even more tightly in Moderna, if I remember right. I was just talking to someone who might have misremembered. So there’s not a lot of variation in when people got their vaccines. So we don’t know a lot about how long the first dose will provide protection. But to the extent that there is data, it is suggested that the first dose does provide considerable protection. The numbers are different in the two trials. They’re both less than ninety-five percent, but also well above fifty percent.
So I think there’s a strong case to be made for, as I said, at least accelerating the move through the priority groups and trying to get more people their first vaccine with a very clear intention to get them second vaccines. I think the biggest objection or the biggest downside to that approach, because every approach has downsides, is that it will be hard to get some people back for their second dose, especially if that appointment can’t be made in four weeks. But it has to be made in, say, six or eight or twelve weeks. I think on biological grounds, there is no reason to believe that a longer interval would make the second dose worse. It might even make it better. There’s some evidence for that in the AstraZeneca trial, although that’s a different type of vaccine. But immunologically speaking, and I’ve asked a lot of biologists that because I’m not an immunologist, but I think everyone agrees that the second dose should boost just as well, if not better if given further out, so I think in the long run, it’s a perfectly acceptable strategy and it’s really a question of logistics. The other line of concern that’s been raised by a number of people and very thoughtful people is the notion that having a single dose of vaccine would be a reason, would tend to select for vaccine resistant mutants. I don’t buy that argument. I’m actually writing something about this right now with some colleagues. I just don’t see any evidence that a single dose of vaccine is the ideal environment in which to select resistant strains. I think it might be that no doses of vaccines are the ideal environment in which to select resistant strains because people are unprotected and have a lot of virus replication and then they develop an antibody response. So I think it’s an interesting theoretical possibility, but I think it’s completely speculative right now and that the opposite speculation is equally plausible. So I think to me that’s a non-argument, but it is something that a number of sensible people have raised.
Q: Thank you.
MODERATOR: Next question.
Q: Hi, thank you for doing this. I caught you earlier saying that the trials, or some of the trials, are already being unblinded. And I wondered if you could tell us what you know about that and how big a problem that is. Don’t we need all the data we can get going forward?
MARC LIPSITCH: Yeah, Pfizer sent out emails, my mother in law’s in the Pfizer trial, so I have an inside source, not very inside, and she was unblinded, I don’t know, a few days ago. And I think I’ve seen also news reports and even maybe some release from Pfizer saying that they were in the process of unblinding. I had written with two bioethics colleagues a piece in JAMA arguing that the process should be extended as much as possible, meaning that it would be unethical to deny someone who is otherwise getting the vaccine, the chance to get the vaccine. So if you’re on the trial, that shouldn’t be a disadvantage, but that the process should be that people who are in priority groups that are getting vaccinated in their own state should be unblinded or should be offered unblinding, but that those not in those priority groups should be kept in the study and that those who are unblinded, should be vaccinated within the study so that they could be followed and more data gathered. It seemed like that might be the policy that was being adopted a couple of weeks ago, and in fact, I thought it had been adopted, but then Pfizer changed its mind. And I don’t understand all the regulatory ins and outs of how they get to decide these things and who gets to tell them yes or no, but whatever that is, it turns out that they are beginning to unblind everybody, as far as I can understand.
Q: Can I ask one quick follow up, which is some people have mentioned something called phase four trials or post licensure testing. And I wondered what the companies should be doing in that regard, especially with health care workers and whether the health care workers maybe should be tested with an antibody test or a PCR test beforehand so that they can be tracked better, so we can really understand how these vaccines are working in them?
MARC LIPSITCH: Yeah. So another piece that I wrote at the beginning of all this, maybe in March or so with Rebecca Kahn and Michael Mina in Nature Medicine, argued for the value of antibody testing at the beginning of almost every kind of trial related to prophylaxis or treatment of this. Well, especially prevention of this virus. So, yes, I completely agree with that. And there’s a lot of value to knowing people’s status at the beginning. Phase four studies, mostly observational studies, will occur. It might be one of the most important things to answer is whether questions answer is whether and to what degree these vaccines prevent transmission. I think its kind of astonishing how little we know about that and a missed opportunity, although it’s hard to criticize an effort that went as quickly and as successful as the trial effort did. But one big hole in that effort is the lack of data on transmission. So there are studies being thought about and discussed, and as far as I know, none that have started on really trying to understand the impact on infection and transmission. And then there will also be the need for phase four studies on things like the duration of protection and whether that means to some extent and how fast and on some other kinds of questions. But I think to me, the infection and transmission question is arguably the most important one.
Q: Thank you.
MODERATOR: Next question.
Q: Hello. Thank you for taking my question. So the Moderna study published last week states that there were 39 asymptomatic cases in the placebo group and 15 asymptomatic cases in the mRNA-1273 group. Is this data sufficient to believe that vaccinated people will be less contagious? And is this an important factor for politicians to weigh right now as they planned mass vaccination campaigns? Thank you.
MARC LIPSITCH: I think that result is some of the very limited data that we have, and it’s good that they did that, and I believe they will be doing that again when they unblind their participants, that they will test them for asymptomatic infection. So we will get a little bit more data if they do that. It’s very hard to interpret for a number of reasons. One is that the people getting their second dose who were carrying the virus could have been infected before the first dose kicked in, because people shed for a long time, especially by PCR, which is quite sensitive, so it might underestimate the impact of the first dose moreover, the second dose probably adds to your protection compared to the first dose. So perhaps that 15 to 39 is a lower bound on the impact on contagiousness. On the flip side, we don’t know the duration of that effect, we don’t know the degree to which the vaccine changes the amount of virus you shed as opposed to yes, no shedding. So there are a lot of questions, but I think it would be safe to conclude from that very limited finding that the mRNA vaccine from Moderna has some effect on infection and therefore probably on transmission, but it’s a pretty small data set to hang your hat on and it doesn’t answer all the questions. And it also shows that I mean, apart from those two caveats that I mentioned, it shows that it’s not perfect, right? It shows that there’s a reduction, but not an abolition.
MODERATOR: Are you all set?
Q: Yes, thank you.
MODERATOR: Next question.
Q: I have a somewhat simple question, so we’re talking about the new variant. I’ve heard people say its 50 percent more transmissible. I know there’s not an exact number on that, but you had mentioned that figure, too. And I just want to be helpful and like walking through people like what that figure means. To you, when you hear a new variant is circulating, that’s 50 percent more transmissible. What do you want people to know about that? What’s the consequences of that? Is there like some kind of simple math to walk through or a kind of simple like or could you imagine like a simple visualization? I’m just basically wondering, like, how can I make that kind of figure feel a little more real?
MARC LIPSITCH: Yeah, I’m. It’s a good question. So just to put some more numbers on it. There were different estimates of the basically production number for the original SARS-CoV-2. One of the popular numbers is three. I think it’s probably quite variable across settings and the sort of consensus around two and a half or three was premature, but putting that aside, suppose it was three. And if that’s the case, what we’ve succeeded in doing in some places through a combination of social distancing and stay at home and masks and also probably some seasonal effects in the summer was to get that number down from three to one, meaning that the average person was infecting one or even fewer than one new patients. And that’s why the curve flattened out and then even went down in some places. Those same restrictions that got us to stay to one, which is about where it was in the U.K. for the old variant are going to allow it to be one and a half for the new variant. And that’s sort of how the inference was made in the U.K. that it was 50 percent more. And so that means that we need to cut our contacts down by another third compared to the already strong restrictions in order to get back to the same place where we were. So it’s a 50 percent increase, but to go back down is a 33 percent decrease. So it’s a big deal for a world that’s already stretched, trying to keep under control the old variant.
Q: Is there something also to say about how more quickly new cases can accelerate?
MARC LIPSITCH: Yeah, so I mean, the math is something like that if each case is making one and a half new cases in the serial interval of the standard number is six and a half days. So say a week. Then in less than two weeks, you get twice the number of cases and then in a month or so, you have four or five times as many cases. But there’s a lot of that’s very approximate and it seems like it might be a little bit faster than that. So if we don’t change our control measures, once it becomes common, it will accelerate transmission considerably. The two things that will push in the other direction are, and if we can delay it enough, the warmer weather and reduced indoor contacts in, say, April and May, but I think by then it’s likely to be quite common in the United States.
MODERATOR: Are you all set?
Q: If I could just do one quicker follow up on that, so, you know, people hearing that, what would you want, like an average person’s take away from, oh, there’s a new variant that’s potentially 50 percent more transmissible. Like what should any individual take away from that?
MARC LIPSITCH: If you are identified with that new variant, then your isolation and quarantine and contact tracing is considerably more important even than it was before. So you’re doing more for the world, for people you care about by isolating yourself and cooperating with contact tracers than even before. And that unfortunately, I think this just going to mean we’re in the hole for a longer time with the need for control measures because we need that much more vaccination before it’s under control.
Q: Thank you.
MODERATOR: Great. I have some questions kind of going along with the variant, whether the vaccines are as effective against this new variant, both variants, both the UK and the South African variant.
MARC LIPSITCH: I think everything I’ve seen suggests we think so. And I think there’s no evidence yet that there is any difference, but people are continuing to look at it.
MODERATOR: Great, and she said until three quarters of the Greek population gets the vaccine, what measures should be taken both from the already vaccinated people and also those who are awaiting vaccines? So more testing masks, social distancing, teleworking, that type of thing. Any particular suggestions for how the population could help this?
MARC LIPSITCH: I don’t know the situation in Greece particularly, but I think in much of the world, it’s the same situation that even without the variant, we’re having a hard time putting enough measures in place to slow the spread or to stop the spread without the vaccine, and it’s going to be a combination of all those kinds of control measures with different varieties in different localities. But I think it’s quite clear that much of the world is having a hard time, even with intense control measures keeping spread limited, and that will get worse with the new variant.
MODERATOR: Great. Thank you. Next question.
Q: So my questions are about the variant. Do you have any kind of estimates as to how widespread the UK variant is here and regarding how we should adjust our behavior in light of it? Do you have specific thoughts on what people should do to modify their behavior? Should we consider, for example, closing schools?
MARC LIPSITCH: I think it’s really hard to know exactly how widespread it is. I think in the places where people have looked, my understanding is that there have been quite low rates of the S gene drop out, that’s a signal for not only that variant, but when that variant is present, it causes an S gene dropout in a certain in the thermo fisher assay. And so far, my understanding is that it hasn’t been seen to be common really anywhere in the US. But of course, that will change if it is indeed more transmissible, as everyone believes it is. And I’ll take this opportunity to say that the U.K. has been something like, I would say, five years or so ahead of us in terms of genomic surveillance and really knowing the genetics of the pathogens circulating in their country and that’s not Trump’s fault, that’s long-term lack of investment. He didn’t fix, but he certainly didn’t start in new technologies for poor genomics that that exist in universities but just don’t exist in government on the right scale in the United States. So that’s a that’s a huge failing of our public health system. Hopefully, this will be a wakeup call, but the UK was able to find it and know what the problem was much sooner than we because of the incredible sequencing efforts that they do. In terms of what individuals should do, I mean, even now without widespread variant transmission, we’re having a hard time as a country maintaining our interventions to reduce spread. So all those, I think, are still important and we’re still not really doing them in many places to an adequate degree.
Closing schools. The one thing I will say is that if we’re not going to close other kinds of activities, we shouldn’t close schools because schools are more important than almost anything else that we do in terms of what they produce and what they allow the rest of society to do, mainly education and regular and childcare, which are their most important functions. So, you know, people who are saying, let’s close the schools and leave the restaurants open, that makes no sense to me. But whether it does become necessary to close schools is not totally clear to me, I think, the UK has decided that it needs to close schools, and I think we might find ourselves there in not too long, although a lot of schools are already closed. So it wouldn’t be that big of a difference in the United States. But I think there was some hope for getting them open and. This could potentially scuttle that.
Q: And just a follow up question in terms of how the variant affects vaccine distribution, going back to the debate about dosing, at what point do you think the more transmissible variant make a strategy like the UK is delaying a second shot look better than operation warp speed approach of reserving a second shot for people, that is to say the variant 30 percent more transmissible or 70 percent more? How do you weigh all those together?
MARC LIPSITCH: One thing it does do to vaccine distribution and we have a preprint on that which looks at this a little bit, is that as the reproduction number gets higher, so transmissibility gets higher, it becomes more advantageous to vaccinate those at high risk of complications and less advantageous instead to vaccinate those who transmit the most because essentially, the direct effect, the benefit to those vaccinated in preventing severe disease and death doesn’t really depend on how contagious it is, but the transmission benefits are most striking if you are dealing with a modestly transmissible virus to begin with and become less effective when you have a more contagious virus. So in terms of who gets priority, the elderly and comorbidities approach becomes more compelling with a more transmittable strain. I haven’t really thought through the single dose, but I would suspect that it also becomes more compelling.
MODERATOR: OK, are you all set?
Q: Yes, thank you so much.
MODERATOR: Next question.
Q: All right, thanks so much for doing this. I’m curious to hear what you think of ACIP/CDC’s decision to split the priority among older Americans into the 75 plus vs. the 65 plus population. And also, what you think of the fact that several states, most notably Florida and Texas, have decided to go their own way and not follow the CDC recommendations? And do you see any issues surrounding the fact that we’re going to have different populations eligible quicker in some states than other states?
MARC LIPSITCH: Yeah, I think that was a close call and my personal preference would have been to go with the dissenter, the one dissenting member of ACIP’s view, which was that 65 plus should have been the priority rather than 75 plus. Clearly, the risks are. Increasing exponentially with age and so seventy-five plus are indeed at higher risk overall, but 65 plus are also at very high risk. So my personal preference would have been to trace the IP to have gone with the 65 plus. I don’t know whether it’s really a problem for different states to have different policies, that’s clearly going to happen in many situations. And because of the structure of how we govern vaccine prioritization, it’s just inevitable. And, you know, I don’t agree with a lot of the policies during this pandemic from Florida and Texas, but in this particular, a good decision.
Q: Can I just follow up on why you think it would have been better to go with the 65 plus and whether there’s an issue there when it comes to availability of the vaccine? The members, some of whom even said during the meeting they wished it was 65, they were looking at it from a practical standpoint of being able to get that volume out with the extra tens of millions of people.
MARC LIPSITCH: Yeah, I think it comes down to a tradeoff between age and essential workers because the 65-75 group is a big group and so it’s a delay for the next priority group if you put 65-year old’s ahead. You know, there are different arguments for why to prioritize essential workers and who exactly that should be, and my simple view is that public health policy should, as a first pass, try to minimize the number of lives long lost and my perception, although, again, the data are sort of shockingly limited, but from my best understanding of the data is that the most lives would be saved by getting vaccine to 65 and over relative to getting it to people of who are essential workers. But I think that’s somewhat uncertain because the data are so limited, although I’m pretty sure that that’s true. Also, I think there was a view that other priorities besides the raw number of lives saved should be considered. I think Barry has also thought a lot about this. I don’t know, Barry, I don’t want to put you on the spot. But if you’re on, do you want to add anything?
BARRY BLOOM: I accept your answer. These are really tough tradeoffs that deal with who’s most likely to die and who’s at greatest risk facing COVID transmitter’s every day in the course of their work, which is required to keep governments and cities and society going. It’s a tough tradeoff. I would share personally, Marc’s view of getting down to 65 and sparing younger people in the essential workers group. Politically, I think that would be very difficult. They’re organized, they have unions. I don’t think they would like that. And I think those are the kind of difficult positions the governors are making in every state.
Q: Thank you. Just one quick follow up. We’re seeing kind of a backlog, if you will, or lagging in being able to get vaccines in arms. And I’m wondering if either one of you think that relying on the CVS’s, the Walgreens, the other chains, to do more than put them in the arms of people in nursing homes, but to open that up more to the over 65 or over 75 population would help us get these vaccines out to more people sooner?
MARC LIPSITCH: I’m not sure. This is beyond my competence.
MODERATOR: OK, great. Next question.
Q: Hi, professor Lipsitch, given this new variant and the speed with which it’s transmitting, what is your sense for the prospects for the year ahead? I think a lot of people thought that we might have this under some semblance of control by midsummer.
MARC LIPSITCH: It’s certainly not good news. I was not one of the ones who thought we would have it under control in the literal sense of decline in case numbers by midsummer, or at least I wasn’t confident in that, because I think the data on how much reduction in transmission the vaccines provide is still so limited that I don’t know that the vaccines are going to have that effect even with high coverage. There’s a blog post on that which I’ll post, and Nicole can post in the chat. So this doesn’t help, but as I mentioned earlier, one good thing about the vaccination of the most high risk people for severe outcomes is that the impact is less dependent on contagiousness. So even if this turns out to be more contagious due to the changing genetics, if someone’s protected, they’re protected, and we think, as I mentioned, that the vaccines will be protected against the new variant. And so my suspicion is that the way that we will get out of the crisis that we’re in is not by halting transmission of this virus, but by making it by defanging it effectively. In other words, by protecting enough of those highly vulnerable people so that even if there is transmission going on, it’s not causing nearly such so much destruction to human lives and to the medical system, and that, I think wouldn’t change dramatically with higher contagiousness, the ability to suppress transmission will change with higher contagiousness, but I think that was dubious or that was only part of the solution in the first place.
Q: Thank you.
MODERATOR: Next question.
Q: Hey, thank you so much for taking my question. So I’d like to bring you back to a topic you mentioned earlier in this conversation. You talked about the second dose would boost just as well if given further out than the twenty-one- or twenty-eight-day mark given by manufacturers. Can you just explain that a little more, please?
MARC LIPSITCH: Yeah. My understanding is that the choice of the three to four weeks in the trials was made because they wanted to do the trials quicker and get an answer quicker, which was a very good reason to pick that interval. But there’s nothing magical about those dates. It needs to be at least a certain length of time, because you need to make the first immune response and have the immune system sort of go back somewhere to something like baseline. So you can’t give it 10 minutes later and you can’t give it a day later as far as I’m aware, and get a proper boost. But three weeks or three months, those kinds of changes are made all the time in vaccine regimens, just for logistical reasons, for example, almost every vaccine that we give in the childhood series is given with a two month to one year interval between doses. So there’s just no reason to think that the three to four weeks is optimal. It’s optimal for getting people a second dose quickly, but it’s not optimal for getting a good immune response. And in fact, most of the dosing intervals you want to put in the childhood vaccination schedule, you put it in at the same visit as other vaccine so that people don’t have to make multiple visits and so that determines the dosing interval, so it’s not a clever calculation about the immune system. It’s just a cold decision. Again, Barry, might have something more to say on this topic.
BARRY BLOOM: I think it’s complicated as far as this, because there’s so many unknowns. There’s a difference between an RNA vaccine about which we know very little other than the companies say the RNA is not self-replicating and degrades so that the ability of the RNA to keep producing antigen, which strikes me as being very short lived and individuals compared to a measles vaccine or a mumps vaccine where you’re using a live virus that persists for quite a while until you get enough antibodies to neutralize the. I think on the issue of booster’s, boosters do a couple of things that might be relevant, particularly with mutant’s virus around the spike protein. We don’t know, but boosters both increase the amount of antibody, the half-life of ITG antibody is twenty-one days. The more you have to start with, as you every twenty-one days lose half, the longer you have persistent antibody above a threshold that would be required for neutralizing the virus. Once you get below that, your antibody not only is too low to be effective, but if you get to the threshold, that’s a good place to select for variants because you don’t have enough antibodies around to all of the potential pieces of the virus. And the second thing the booster does, it increases the number of memory cells, both T cells and B cells that sustain the memory of the response so that if you get reinfected a year from now, there are cells, even if you don’t have anybody in the blood that are sufficient to make a rapid response. So preserving the booster is not trivial. And I think Marc’s point is well taken that if you get protection for three, six or twelve months from a single shot and you put it in the right based group, you’re going to save more lives. That’s another trade off. It’s very difficult.
Q: OK, thank you so much, because I’m in Florida and we have some of that 65 and up who are getting the vaccine, but they’re really concerned they’re not going to make that window because getting appointments is difficult. So now I can tell them it’s OK if you don’t get it in that window. So thank you very much.
MODERATOR: Next question.
Q: Hi, I just want to ask how much sequencing you think we should be doing? What is the optimal amount that we should be doing especially given this higher transmissibility with the new virus? What percentage of virus, should we be testing?
MARC LIPSITCH: Yeah, it’s a good question, I mean, I think there are two issues. One is what do we do about this new variant? And the other is how do we have a system so that we don’t have a surprise like this the next time for the new variant? A colleague and I have written a piece that’s being looked at the moment at a newspaper suggesting that we actually try to refocus our contact tracing efforts on this new variant, which would mean that when someone test positive, we would use a screening tool like the thermo fisher, which doesn’t tell you if it’s a new variant, but can tell you that it might be or that it definitely isn’t. Whether the strain that person has is the new variant and if so, make extra efforts to shut down that chain of transmission. Again, imperfect, and it won’t catch everything, but slowing things down is a value in itself. And in that case, we don’t have to sequence everything, but we should be testing everything with a technique that tells us yes or no on the variant. A second thing that now is increasingly unimportant is to know whether it’s here because it’s now clearly in many places in the US, which means that it’s probably in almost every place in the US and we just haven’t seen it yet. So that gets to the question of how you set up a system. And with that, you know, the UK was sequencing thousands of isolates a month in a smaller population than ours, if you were really trying to do it on a shoestring. I think if you did a thousand isolates every two weeks or so from a representative sample around the country, perhaps oversampling places where people are coming in from outside the country, you would have a pretty sensitive early detection system if you knew what you were looking for. And you would also have a set of data telling you how the virus was evolving within the United States. That would be a sort of minimal approach. There’s no reason, given how cheap the technology is and robotics and other things, why we couldn’t do much more than that and have it for a lot of other viruses and really have a proper system. And that’s what the UK has been building over the last five years or more. And we’ve just been very, very slow. So I think, you know, when everyone has time to breathe, that should be a very high priority for setting up the public health system into the twenty twenties.
Q: And I wanted to ask you about the FDA’s statement on why we’re not doing the two doses, we’re not going to give like half a dose. And they said on the two doses, the participants who didn’t receive the two vaccine doses during the trial at either of those intervals were only followed for a short period of time. So they can’t conclude anything definitive about the depth or duration of protection from this single dose percentage as reported by the companies. Is that a function of, well, we can’t proceed because we don’t know what we don’t know or what? How would you respond to that? Barry Bloom might have sort of spoken about that as well. But how would you how do you respond to that?
MARC LIPSITCH: Yeah, I think I think that the FDA is a regulator. They’re not in the broad sense of public health agency. Their job is to make sure that the things that we inject into ourselves and take his pills and supplements and whatever are do what they are advertised as doing. And in that narrow sense, they’re right. The data are only for some weeks and they are not perfect. I mean, they’re not very many people. Well, it is a lot of people, it’s not very many cases, it’s in the tens and we don’t know how long it lasts. And so from the strictly regulatory perspective, I think they’re correct. Regulatory is one piece of the puzzle and public health is about more than sort of truth in advertising and regulation, and so I think those who take the view that we should encourage people to get first doses more rapidly and perhaps let the second dose be six weeks or twelve weeks later, are drawing on a knowledge of biology and how other vaccines work and drawing on the sense that we have a crisis here and that acting on limited information is what you have to do in a crisis and that all things considered, it’s a better public health action, and I think it’s a really interesting case where sort of science as regulators see it and science as public health in the broader sense sees it might be sort of different.
Q: Yeah, and of course, we could also do what we do with our children, which is just assume that they’re not completely protected until they have their second dose, you know, in other words, still follow the same mitigations. The only other thing I want to ask you is when you were talking about immunity, why is it that we don’t have better data on immunity, given that we can do, you know, testing for T cells and neutralizing antibodies and is the only way to get the length of immunity through real time monitoring, like, oh, it’s been six months, so you have immunity for six months or three months. Is there a way to get it through better testing or through science as opposed to just watching and waiting?
MARC LIPSITCH: Again, Barry might have thoughts on this. My simple answer is that the connection between measurements of the immune system and measurements of protection is still not well defined, so we know some things that antibodies predict a level of immunity and that you can transfer immunity to a new person or a new laboratory animal with antibodies in many cases. So we know a lot of things, but we don’t have a way of measuring a whole bunch of things in a person and saying this person is twenty-seven percent protected or eighty-four percent protected her or whatever, it’s more imperfect than that. And so, yes, we can monitor T cells and we can monitor antibodies, but we don’t have a perfect mapping from what those measurements tell us to whether the person is actually protected and then the piece about protection against infection as opposed to disease is just another level of that same problem that we don’t know what predicts that. And the trials were done in such a way that we didn’t measure that outcome very much, except like the people coming back for their second vaccine in the Moderna trial, but more or less, that question was left for later.
MODERATOR: Next question.
Q: Thanks again, Dr. Lipsitch. Someone touched on my question a little bit, but I hope you don’t mind if I press on it a bit. By spring 2020 experts yourself and others, we’re talking about what could happen come fall/winter, and I guess it’s fair to say that it did. So given that you know a lot more now about all aspects of the virus and the disease and mitigation efforts. Yet we’ve got this emerging strain. I hope you could lift your gaze and look ahead as far as you think worthwhile for the public to hear in terms of what you expect come spring, summer and perhaps fall winter.
MARC LIPSITCH: Yeah, well, I think in the next few months, we’re going to be dealing with, you know, it’s still winterish. Vaccines are rolling out slowly. Their impact on transmission is uncertain. So I think we’re in for at least the same level of impact that we’ve had. And in many parts of the of this country and the world, case numbers are continuing to go up. So that means it’s getting worse, not staying the same. And the new variant, if it behaves as we imagine it will behave, is going to make things worse. I think there’s some basis to hope that in the summer or the late spring and early summer, the level of vaccine coverage in the rich countries will get to the point where the health care system is no longer crushed because the health care workers are protected and the people most likely to need the health care system are protected by the vaccine. And that transmission may be still quite widespread, but that the impact of that will be blunted a lot and it will start to allow us, along with the impact of the seasonal changes, to have something more like a normal life. I think for the new variant, I was more hopeful of a summer that would kind of allow people to go to camp and travel and that sort of thing. I’m less sure about that now. But the vaccines assuming no surprises, no negative surprises with the vaccines and expecting that there will probably be more vaccines approved or authorized in the coming months, you know, the vaccines really are a huge change for the better, and I think that will be our way out. But I think that the new variant doesn’t help with that.
Q: Thank you for that, appreciate it.
MODERATOR: Dr. Lipsitch has about five more minutes, so we’ll try and get as many questions as we can.
Q: Hi. I heard you saying earlier that this strategy of giving just the first dose of the vaccine and spreading it to more people is acceptable. But I’m hoping to maybe put a little bit of a finer point on, you know, if you were making the call, how far would you spread that first dose before you go back and give a second dose?
MARC LIPSITCH: I don’t remember saying the word acceptable. I think I’m the more enthusiastic about that. But the short answer is I’m not sure. And we’re working on some studies to try to understand the impact of various policies, at least in modeling it. I think if I were making the call with what I know now, I would speed up the progress to the priority groups to be on a relatively rapid cadence. Each state has got its own list and subdivisions and all of that. So it’s a little hard to say what that should be, but within a few weeks of opening up to one group, I would be considering opening it to the next group, depending on how finely the groups are divided and the goal of that would be to make sure that demand is not the limiting factor for getting the vaccine out. And more than that, I can’t really say, but I think I might have more to say in a few weeks.
BARRY BLOOM: Maybe I could just make a comment. And over 50 thousand people have been tested in trials with the first two vaccines. So there’s a lot of data even as short as that period has been. Once you start saying we have data that shows that it makes sustained immune responses as high levels, ninety four percent protection, that’s what we have to work with the scientific data. Once you start speculating, if we gave it one dose and maybe we could get six months later, people back again, maybe a year, we could get them back again, although that’s unlikely and that boosters actually extend the life of immunity. That’s an area where I think many scientists and I would guess Fauci would come out on this, who has supported the current policy, that’s faith-based decision making, not evidence and data base decision making. It’s common sense. And so what has to worry about it? I would say for the integrity of the process, which is under questioned by many people, whether vaccines are safe, whether the government is corrupt, whether FDA knows what it’s doing, there’s a certain logic to saying we have good evidence, for one thing, stick with it, and hopefully it will be able to be disseminated to everybody else. I agree with Marc, I don’t think there’s anything magic about twenty-one or twenty-eight days for a booster. I don’t know how long it is appropriate to hold off the booster. And you have mentioned the recommendation of Dr. Slaoui to consider, which is also not based on a huge amount of data, but if I understand it correctly and I would urge you to check my memory, the Pfizer vaccine uses 30 micrograms of messenger RNA. The Moderna vaccine uses 100. If they both give you a 94 percent protection, is it unreasonable and when you look at the Phase two trials, the antibody titers and half the dose in the Moderna phase two are absolutely the same as they were both very high, up to one hundred micrograms. So that I would guess his thinking is you’re approaching the maximum level of protection with half the dose of radiation. That’s probably not a great extrapolation to give half a dose twice. But that’s, again, face to face decision making, not based on the data that we have in hand. And those are hard decisions that states are going to have to make. And the company.
MARC LIPSITCH: Sorry, I can’t let that one pass. I can’t accept faith-based decision making. I think there’s a really big difference between and I think this is what you mean, too, between faith based and based on our best understanding of other science and of how things work, but without precise data showing that this thing works. But faith based has a baggage that I’m not willing to accept.
MODERATOR: Dr. Lipsitch, I know you need to go. I will ask really quickly, because Dr. Bloom is already on the call and I don’t know if there are any other questions about vaccines. If there are, Dr. Bloom, would you be interested in staying on for a bit longer to answer those questions?
BARRY BLOOM: I could stay on for five minutes.
MODERATOR: Amazing. Thank you. Dr. Lipstich, do you have any final thoughts first before you go?
MARC LIPSITCH: No, thanks. As usual, it’s been a very interesting discussion. Great questions. Thank you all.
MODERATOR: It’s good seeing you again. Happy New Year and talk to you again soon, I’m sure. All right. For those of you who are left, I don’t know if you have any questions about vaccines, but if so, we’ll just try and get through those as quickly as we can.
Q: Yes. Thank you very much. Can you hear me OK?
BARRY BLOOM: Yes, great.
Q: Thank you. I appreciate your extra time. The question I wanted to ask now that vaccines are arriving, I see a lot of laypeople assuming that as soon as they and their close family or friends are vaccinated, they will be able to immediately do get-togethers and trips without having to worry about social distancing or masks. Someone just told me the other day, you know, as soon as my 10 closest friends and I are vaccinated, I’m going to go on a cabin weekend with them with no social distancing. So I want to give readers a realistic picture of what to expect. And I know if she has said social distancing and asking should continue until around 80 percent of the population is vaccinated. But what about when you’re in a group of people, all of whom have been vaccinated? There’s confusion as to whether that still applies for many people. So I hope you can address that.
BARRY BLOOM: So the first preference is no vaccine is 100 percent protective. So if everybody has been vaccinated and everybody has made a protective response, I can’t see anything wrong with having 10 or 20 people go to a restaurant. Every one of them, including the staff, are vaccinated. But the fact is, we actually, as Marc said, are not absolutely sure that everybody who receives the vaccine develops a protective response. What we know is that most people who recover from infection are not susceptible with rare instances of reinfection, which says we can get pretty high-level immunity by infection. And the question is, can we do as well with a vaccine as natural infection? And in some cases, for example, with some of the other vaccines with booster’s, can we do as well or better than natural infection? So the answer is there is absolutely for sure uncertainty that when you get a vaccine, one hundred percent of people will be protected. The second is they take time to work, and that varies from individual to individual. Two weeks is a reasonable time in the published papers, there was evidenced by 14 days, the curves bent and the people who got either of the RNA vaccines, the curves never went up, signifying that by two weeks the people in the trials had enough immunity just to become protected and stay protected for the duration that they were studied. I think the sense is that without getting full two shots, people would be very wary of assuming that everybody is going to be protected and that it makes public health sense to wear masks and do a reasonable amount of social distancing until a larger percentage of the population and in communities that people deal with. If every university student was vaccinated, it would seem to me congregation and universities would be fine, but not necessarily everybody going to the local bars at night where nobody is vaccinated, for example. So that’s the best I can do. Better to be safe than sorry.
Q: May I ask one quick follow up? I think the logic in some people’s minds right now is, you know, we hear the ninety five percent effectiveness figure and so some people say, all right, if one hundred people get a vaccine that’s ninety five percent effective at preventing symptomatic illness, then five percent of them may still develop symptomatic illness. A higher percentage of that may still get infected. But some people will say, oh, well, I don’t care if I’m going to get infected because I’ve been assured it won’t lead to symptoms or severe illness. What would you say to those people?
BARRY BLOOM: That hinges on what Marc was talking about of transmission. So one can imagine a scenario and I’ll give you a very clear cut case where you are vaccinated, you develop a protective immune response, you will not get sick, you will not die. But in fact, the virus is able to grow in your nose and transmit the other people. In public health, the effect if that vaccine is zero. You are still contributing in principle to transmission. How feasible is that? I’m quite optimistic these vaccines may not be perfect at reducing and protecting and sterilizing against all viruses, but I would bet if you’re protected against serious infection, the virus amounts that you are able to grow in the nasal pharynx is a lot lower than people who have no protective antibodies. But the classic case, for example, is Polio for children. Polio is transmitted through the gut and the feces and contaminates water supplies. People have been vaccinated 10 times with polio vaccine. They are totally immune to developing polio myelitis and they continuously shed infectious virus and contaminated their water supplies, which is one of the reasons Polio has been so difficult to get rid of. I think a respiratory infection circulating antibodies are much tougher to get into mucosal surface. They protect against systemic infection, not so well against local infection in the nose. So we just need more data on transmission to know that if you are vaccinated, not only are you protected, but you are not a threat to anyone else and the data are not there. Hopefully it will come out of the time.
Q: Thank you. Hopefully in a few weeks or a few months, we’ll have more data on them. Appreciate it.
BARRY BLOOM: I would say a couple of months unless everybody abandons the trials.
Q: A couple of months. OK, good to know. Thank you. I appreciate it.
MODERATOR: Next question.
Q: Dr. Bloom, appreciate you taking my question. I was just wondering what you make of the situation here in Florida with the vaccine rollout. We’ve had seniors camping overnight to get the shot. The appointment websites and phone lines are crashing. There’s a lot of frustration and confusion with this rollout. So my question is, do you think states are properly prepared to administer the vaccine? What needs to be done to do this in a more orderly fashion?
BARRY BLOOM: So my colleagues who are commentators in this area, and I don’t mean Marc, who write articles in the newspapers, are very good at saying what we should have done six months ago. But with now, since I served with Marc on the governor’s commission in the Commonwealth of Massachusetts, I really have learned a lot about how really complicated this process is once the state gets the vaccines. And there are challenges at every level, and one of those that I think is clear that every state is they don’t know when the vaccines are coming and you can’t line up pharmacies in remote areas when you have two days’ notice that there’s going to be vast amounts of vaccines, come and get them and deliver them to all the nursing homes in your area. So there has not been enough advance planning, not least because there hasn’t been money for the states. The CDC budget has been cut every year for the last three years. Up until this year, the amount of state budgets that have gone to public health have gone down. And this takes people it takes expertise; it takes in chromatics and databases. Everybody who gets a vaccine with these new vaccines has to fill out probably 10 to 15 minutes’ worth of records so that if anything bad happens, we will know who got which batch of which vaccine. And that’s taking more time than a flu vaccine where you just line people up in your local doctor’s office and in 15 seconds, you get the shot from the physician’s assistant. Getting a trained workforce that can give you the number of vaccines that is needed, can do the reporting, can have epinephrine present in case and able to recognize anaphylactic syndrome and an adverse effect, that’s not trivial. And there hasn’t been money to the states to line those up. Congress does not generally spend money on problems until after they happen. And public health is built on preventing problems from happening. And you can’t do that with without resources. So I think it’s going to be very difficult to get states to get themselves their information systems going and personnel trained in all of that. That’s for the first dose. What happens in twenty-one and twenty-eight days when the over 65 or the non-facing disease essential workers are coming for their first shot and people are lined up for their second shot, are states able to plan for that and come up with that? I have no idea. But this is a logistics challenge, a personal challenge. And, yes, there’s eight billion dollars in the new emergency bill that was passed. How that will get to the states, when it will be distributed and how they will get the people trained, whether its National Guard people called retired physicians, graduate students, unclear. But there’s a desperate need to have places and people trained to administer the vaccines and collect the data to be able to be certain the vaccines are provided appropriately, collect any immediate side effects and follow for any long-term side effects. This is a tremendous challenge that we’ve never had since basically smallpox in the New York City in the nineteen fifties where six million people were vaccinated in two weeks. It can be done, but this has got to be done with vast amounts of resources and new kinds of people brought in to carry it out.
Q: Thank you.
MODERATOR: Next question.
Q: I just wanted to ask if you agree that we should be moving more quickly through the ACIP’s priority groups, and I’m just curious, given all of the challenges you just laid out, why there’s been so much attention on social media and in the mainstream media on this as being kind of the source of a lot of distribution problems. And do you agree that this is the main problem with the vaccine distribution? Should we just kind of let anyone who wants access to a vaccine get access to a vaccine right away? And if not, how urgently should we move through these priority groups if the disparity between vaccines distributed in vaccine vaccines administered doesn’t begin to decrease in the next couple of weeks?
BARRY BLOOM: I don’t think it’ll be a massive decrease in the next couple of weeks because we have the second dose of vaccines for already those that have had the first dose and the need to expand would include older people and the front-line workers, the essential workers, the people over 65. It’s going to take a long time to get to people that are none of the risk groups and the younger ages with less risk and obviously not as urgent. I think the premise that all of these National Academy of Sciences, ACIP, and the state committees are working on is one of the priorities. And I could give you two extreme examples. If the priority is to prevent people from dying, when you look at who’s dying and its people over 65 represent 40 percent of all deaths. So if you want to preserve life, it tells you who you have to vaccinate and get that as quickly as possible. If you want to block transmission, which I don’t think anybody has recommended as the primary goal, you will do college students, twenty-five-year old’s, high school students, they’re the ones that are least able to be socially controlled and follow the rules of public health and stay in. They’re ones who go to places that are crowded and they’re the ones likely to be contributing a lot to transmission. So the third variable that every group is concerned that is worried about this is there to others. How do we keep civil society working? How do we have essential workers, the bus drivers, the subway drivers, the police, the firemen, the emergency workers? They’re mostly not over 65, but they’re facing an unknown threat every day. And we need them to do their jobs to keep society functioning. And that’s why essential workers after those at greatest risk for exposure in the hospitals where we need to keep the hospitals going, to keep not just COVID patients alive, but everybody with a heart attack, a stroke, automobile accident.
If they came into a Los Angeles hospital, I don’t know what’s going to happen to people who have ordinary hospitalized conditions. So that’s the rationale to keep the medical staff that is exposed to keep the hospitals functioning. I think there’s a good rationale to keep police, firemen and essential workers in every city and town to keep society functioning. And Marc would put in that category schoolteachers, if we knew we could open schools, they would be the most vulnerable group, a significant percentage are actually over 65 in the country. They would need vaccines to safely be able to teach. So there’s a set of tradeoffs that every one of these committees have made, balancing a priority for saving lives and priority for keeping society going. And I want to mention one other variable that has been in everyone’s thinking, which is which groups in society die at the greatest rates? And the answer is without question, blacks and browns, minority people are the most vulnerable to the disease, to hospitalization, to the tune of three to five times greater numbers in hospitals than age matched white individuals. How do we be sure they’re the most difficult groups to reach the most skeptical groups? There has to be an effort if the game is to preserve lives, to make it possible to get vaccines to that group as well. And that’s in everybody’s calculations. And I would just raise the question on the 75 plus versus 65 plus. In many places there are fewer blacks over the age of 75 that have survived that boom than whites, reducing the age to 65, levels the playing field for vulnerable groups where their life expectancy has been lower. Every one of those decisions is what the cities, the states and the governors are trying to do. There’s no easy black and white answer, and I would be grateful if the public realized at least what I see in Massachusetts, the seriousness with which the advisory committee of the state, the governors, the public health departments are wrestling with those value, ethical and lifesaving questions with limited doses of vaccine. I’m impressed that they really care a great deal about doing the best with what we are going to have available.
Q: Thank you.
MODERATOR: It looks like our last question.
Q: Hi, Barry. Thanks for staying on. I was listening to the answer for this in the earlier questions and I think maybe, hopefully it’s a simple math question. If the variant is one and a half times more infectious and it becomes widespread. How does that change the percentage of the population that needs to be vaccinated in order to reach herd immunity?
BARRY BLOOM: The equation for guessing at what level requires herd immunity. Is 1-1/R0. So as R0 increases the logic of the equation, assuming there are no other variables, is the more you spread it to, the more people you have to vaccinate in order to hold it at the same level. That number, of course, is essentially a theoretical number because it’s affected by everything from crowding, mask wearing, closing down schools and whatever, those numbers vary locally and over time. But the simple answer is that the higher they are zero, the more people you would take. And if you notice without saying why Tony Fauci has gone up from 70 to 80 to 70 to 85 percent coverage. And I think that’s exactly what he’s thinking about. We are likely to see the British variant. And I would just tell you to keep your eye on a new variant in South Africa that worries me a lot more than the British variant at this point. There will be new variants and we will have to track them. And the question is to what extent the vaccines continue to work on the new variants, which in their own world are trying to escape from whatever immune responses we generate.
Q: So not a precise number, but more. Is that accurate? And what about the South Africa variant worries you more than the British?
BARRY BLOOM: So, it’s brand new, but there is a concern of where the mutants are, it’s called 501.V2. There’s very little data that I can find in any publication, mostly in news reports that would suggest, in contrast to the English one, that it may be less neutralized by antibodies from convalescent patients. That’s just the early days. That would not be a good thing.
Q: Very good.
MODERATOR: I think that may be the last question for today, Dr. Bloom, to have any final thoughts for us before we go?
BARRY BLOOM: Thank you for allowing me on the call. And thank you guys for wonderful, very important questions.
This concludes the January 5th press conference.