Coronavirus (COVID-19): Press Conference with Barry Bloom and William Hanage, 02/19/21

You’re listening to a press conference from the Harvard School of Public Health with Barry Bloom, the Joan L. and Julius H. Jacobson research professor of public health and former dean of the school, and William Hanage, associate professor of epidemiology and a faculty member in the Center for Communicable Disease Dynamics. This call was recorded at 11 a.m. Eastern Time on Friday, February 19th.


MODERATOR: Dr. Bloom, do you have any opening remarks for us?

BARRY BLOOM: Well, I would say one notable bit of news that I think is important is the current Biden administration’s commitment for the first time to put four billion dollars into COVAX, the Gavi SEPI, U.N. WHO program, to distribute vaccines to one hundred and ninety developing countries. That’s a very strong international commitment that we had withdrawn from previously. And I think a good thing.

MODERATOR: Thank you, and Dr. Hanage, anything you’d like to say?

BILL HANAGE: I would agree hugely with that, because it’s a tremendously important thing to recognize and we may get to that over the next hour or so. The pandemic is in its very nature, global. And while people on this call may be focused on the United States, it really is a global issue. And I think with that we’ll get into the questions.

MODERATOR: Great. Thank you. All right, looks like we’ve got some questions already. First question. Go ahead.

Q: Yeah, hi, thanks, everybody. So there’s an epidemiologist up here who has voiced some pretty strong concerns about the variants, saying the next 14 weeks could be the worst of the pandemic, a major explosion in cases because of B.1.1.7 in particular. But I don’t get the sense that’s a universal view. And I’m just curious where the two of you come down on that. I mean, obviously, the variants could put upward pressure on cases and at the time when the vaccine would hopefully start helping. So how concerned are you about the variants? And are you expecting that the case trajectory picks up substantially in the coming weeks?

BILL HANAGE: Thanks. It’s a very good question. So just to start, this is specifically about the variant B.1.1.7, which was first detected in the UK, and which as you know, because we talked about it, is more infectious, more transmissible than the previously existing virus. It also looks like it is more dangerous in the sense that it’s somewhat more likely to lead to death given infection. When I say somewhat more likely, it’s not hugely likely, although the estimates are still enough for it to be taken really quite seriously. Now, the reason why I think epidemiologists are concerned about this and perhaps more concerned about that virus than some of the other variants which we’ve been talking about and which we’ll probably talk about more of the next hour, is that because it is certainly more transmissible, it has the capacity to infect more people more quickly before we have adequate vaccine coverage. And it also means, incidentally, we’re going to need more vaccine coverage in order to exclude the virus. Now, the question as to whether or not this means that we can expect a predictable surge in cases as a result of the introduction of that. That’s a very difficult one because I think it’s going to be quite regional. I think that, for instance, Florida, we have pretty good evidence that this lineage is locally common in Florida and that it’s increasing in roughly the same kind of way and as elsewhere, including the UK and other parts of Europe. And Florida hasn’t got a hugely active public health response against pandemic at the moment. So that’s going to be a particularly interesting situation. But at the same time, as you indicated, we’ve got this situation where the more people are being vaccinated and indeed the weather is improving. You know, regular seasonal coronaviruses, they peak in January and taken together, it may mean that the point at which this variant, B.1.1.7 is becoming locally common, is at the part of the year where it doesn’t transmit quite as well, or a high proportion of people vaccinated. So I think that the way that I am looking at this is I don’t think there’s going to be a definitive national surge, at least not in the next few months, but there may well be locally significant events, and I think that whether or not how local those are and the extent to which they spread will depend very much on what we do about the combination of the non-pharmaceutical interventions that we put in place and then the pharmaceutical ones that we now have, i.e. the vaccines. So it’s a bit of a complicated answer that I hope that helps.

Q: Very much. Just a quick follow up. Given what you mentioned about seasonality, did the UK just get really unlucky? In other words, I think part of the concern is that when you look at what happened to hospitals in London, you know, oh, boy, if that happens here. But it could be that it’s just particularly in Minnesota where we don’t have the cases that Florida is looking at, we might get lucky on the timing. I’m not sure.

BILL HANAGE: I think that that’s a very good point. I mean, the only thing I’d say in response is that there is a degree of unlikeliness there. However, the thing which is not driven by luck was the fact that there was a very high amount of transmission and hospital burden that was considered to be acceptable. And the problem of what then happened there was that on top of that, you know, running it to the limits, it actually turned out that things were going to be worse than that. So you should not play games with an exponential, you know, so when you had that and then you had that little bit more on top of it and that tipped it over. So I do think that we are going to be entering this at a better time. I want to make one other comment, though, which is I think relevant, which is that in a pandemic, seasonality doesn’t quite behave as normally or strictly as it does for other situations in other situations, usually seasonality is what kind of tisk things over the line, such as the reproductive numbers of one, given the amount of immunity that exists. And so it’s not necessarily the case that it’s going to be not transmitting everywhere. And some of the seasonality is going to be depending upon how people get together. For instance, we will remember the Sunbelt Belt surge over the summer last year, which may be related to the fact that people were getting together indoors because that’s when it gets very hot there in the summer. And I think that stuff like that is going to remain to be seen. We’re going to need to be watching it very carefully. But the overall things going into this, the moving parts are basically how much people contact each other, how many people are immune either through infection or vaccination and the overall transmissibility of the virus and with B.1.1.7, we know that one of those things is going up.

Q: Gotcha. Thank you.

MODERATOR: Next question.

Q: Thanks so much for doing these calls. We’ve been getting a lot of comments and questions from members who take other medications, maintenance medications, whether it’s heart medication, blood pressure medications, blood thinners, et cetera, concerned about whether or not they should continue to take these right before they get a vaccine, whether or not there’s any possibility that they’ll have an adverse reaction to the vaccine because they’re taking this other medication. And I know there have been all kinds of stories saying it’s OK, you can take it, but can you give us any more detailed reasons that people should not either stop their medications or should be assured that their medications are not going to affect the efficacy of the vaccine?

BARRY BLOOM: Let me take this one, Bill. Neither Bill or I are clinically trained. So one of the things on ethical grounds we refrain from is telling people how to be treated. Having said that, there were concerns, scientific concerns early on about the impact of a virus that attacks the cardiovascular system and ace receptors and people who take ace inhibitors to reduce blood pressure, hypertension, would they be at greater or lower risk? And as I understand the published data, there’s no evidence, whatever, that those drugs have any effect either on ameliorating virus infection or making things work. When you say drugs, there are all kinds of drugs. I had a call literally yesterday from someone who’s relative is taking anti-cancer drugs that might be immunosuppressive and was scheduled for a vaccination. And my advice, of course, was to consult her physician. But that’s a kind of drug that could ameliorate the effectiveness of a vaccine. So I think you have to be very specific with drugs and very specific with patients. And the best person to get advice from is probably someone who knows both.

Q: Just to follow up, other than the cancer drugs, and I’m assuming if you’ve had a transplant and have other drugs that to that would impact, too. Are there any other classes of drugs that you think people need to be concerned about? Like statins? Or the medications that people take for diabetes, things like that?

BARRY BLOOM: I don’t know of any published work that indicates there would be a contraindication, that they would make infection either more likely or more serious. And I understand the medical journals have not raised any concern in that regard. There are drugs, as I said, in anti-cancer drugs, immunosuppression where patients are in special circumstances. So one has to be very specific of what drugs and what patients.

BILL HANAGE: In particular as it relates to immunosuppression, like you say, and vaccines.

Q: OK, thank you so much.

MODERATOR: Next question.

Q: Again, thanks for doing this, I have two totally unrelated questions. The first one is there’s a Lancet letter out, I guess, yesterday from Israel that looks at one dose versus to fifteen through twenty-eight days after the first dose that is bringing up the issue again of can we delay the second dose? Wondering if you’ve seen that and whether you think that should change any hearts or minds?

BARRY BLOOM: So that’s a wonderful question. I actually did see the article, and it’s a vexed question at multiple levels. The first is, we have data provided by the companies with recommendations for approval to give a certain dose of their vaccines in a certain time interval that has been reviewed by the FDA and either approved or not approved and so far, to have been approved by the FDA. Any change in that formally would require review and approval that it’s not going to happen because we don’t govern what goes on in Israel. So the question that is raised is, when you have a vaccine like Pfizer or Moderna, that in the interval between the first and second doses provides 92 percent protection. Is there any disadvantage of delaying a booster dose? And I put that in the general context. In England, they’re discussing skipping a booster dose. So the sense I have is that the time frames were selected to get as rapid approval as possible in the middle of a pandemic for which there were then no vaccines. There are many other vaccines where you do booster shots three months or six months later where the immune response may even be better after a delay enabling booster shots to enhance and expand the immune response. Regrettably, we don’t have data on that. And we know that, for example, J&J has a two-vaccine strategy, they’re in the middle of trials extending the booster, I think, to three months, two to three months out.

The issues are what is a booster do, and this is Immunology 101. And two things happened that may be relevant. The first thing that happens is that when you stimulate an immune response for the first time, you engage a lot of different B cells in a person that to various extent see any antigen you present to them. Some bind very well, someone very poorly. But you have a mix of antibodies, very different than a monoclonal antibody that sees only one antigenic site. When you boost, you do two things, you expand the number of cells that were developed the first round and you engage some cells that see weaker sites or peripheral sites to the main neutralizing site, for example, and that does two things. It broadens the range of antibodies that you see, and it increases the absolute amount. What does that do? Well, what we know is when you get to the recent papers on the South Africa variant, 1351, that we now know is very significantly less well neutralized by serum from people who have either recovered from COVID one or have gotten one of the other vaccines. This is a mutant that is in the process of trying to escape an immune response to the target of all the vaccines. It is not a complete escape in the sense that the broad antibodies that may not be so terrific in the beginning are still able to reduce the ability of the virus in tissue culture, the antibodies are about one sixth to one ninth less effective. So it means you can’t dilute them very much or they lose their activity in a test tube. So that means two things if you have a lot of anybody, even if they’re reduced in their ability to work to one sixth or one ninth, there’s a threshold at which they will still work. And that appears to be what’s happening in South Africa, where they don’t work all that well in the test tube, but still, people are getting, for some of them, 50 percent protection. For the AstraZeneca, that went down to 10 percent. And that’s a worry. And that’s why South Africa stopped running that trial. Any vaccine that doesn’t protect better than 10 percent against the new variant, 351, it’s not going to be in a public health sense, useful. It’s going to compete out other vaccines that might be used and mislead people to believe they’d be protected. So the amount of antibody that you produce. Expands the amount of even off target antibodies that may work, so boosters increase the amount which increases the duration and even for variants, would increase to some extent the ability to bind and neutralize. So giving up a second shot, in my view, is putting people at a risk.

The question you really asked is, does it matter whether you delay that from twenty-one or twenty-eight days to three months or six months? And in general, the answer would be we have no data yet. And so on a scientific basis, there’s no evidence that we can speak to that that would support Dr. Fauci’s position that we don’t have faith based science. We have data driven science. On the other hand, knowing enough about immunology, very often boosting at a later time, actually expands then the amount of the immune response and may even broaden the specificity, increase the duration. Obviously, studies are going on in that regard, and I think it is a real tension is how many people can you protect with the first dose, which seems to have for the top two vaccines between 12 and 28 days, ninety-two percent protection. That’s pretty good. And if we could get more people with the first dose and there’s enough time for the second dose to be a booster, that would be a win for everybody. As long as there’s a threshold level that we yet do not know from in vitro studies of how low the antibody has to be in neutralizing in vitro to indicate that it’s below a level that will provide protection in patients. And I’ll add the reciprocal of that, which is more than you want to know. That’s important to know. How much antibody do you have to have to guarantee protection? We can measure that technically. But if we knew what that level was, you wouldn’t have to run trials that are forty-four thousand people for a year. You would have a surrogate endpoint, as we do for polio and hepatitis B and other viruses, that says if you have a tighter of one to 100, your guaranteed protection almost. If you have a higher tighter than one to 40, your guaranteed protection. So nailing down the threshold of antibody required for protection, even ignoring T cells and other mechanisms, could provide a surrogate endpoint that would enable other new vaccine candidates that may be cheaper and have better supply chains to be tested in compared without having to run giant trials, which are going to be increasingly difficult. Sorry for the long-winded answer, but I’m happy for follow up.

BILL HANAGE: If I can just add a little kind of what my distillation of this is. I agree with everything that you just said, Barry, and I really think that’s an extremely interesting tension between what we have data on and the fact that everything we know about immunology does not suggest that some delay is going to be a major problem. But the problem that we have is that we have a situation where there’s a tension between short term issues and longer-term issues, because in the short term, you have a situation like that currently exists in the United Kingdom, which has people just hearing from Chris has been going through an absolute hellish winter and really needs to be doing something to bring it under control. But we are going to be looking at next fall and winter as well. And so by the time we’re looking at that, we may be looking at situations by the immune landscape could be different, where we may be seeing variants like 351, which have some ability to transmit among the previously vaccinated or previously infected people. And so I think the booster is going to be important, but I think it’s important for the long game as opposed to the short term.

Oh, and one other thing. One of the things that may be interesting from South Africa is that the data from some of the vaccine trials in South Africa and how they respond to 351, may be helpful in giving us some guide as to that readout between how many neutralizing antibodies needed to provide some element of protection. But that’s a very rapidly evolving area of science.

Q: One small follow up to that, one of the things I think Tony Fauci has said is that you may be fostering the creation of more variants if you provide partial protection. Is that something you’re concerned about in the time frame of a couple of months of delayed vaccination?

BARRY BLOOM: Sure, the fact that many of these variants, particularly in the 351 and this particular variant with the EA4A7K, they are produced by selection from natural immune responses. They are the result of a person’s immune response, whether they were immune depressed or not, as unknown of a variant that managed to escape the immune response that people were making. So in any immune competent individual, you are selecting for variants that can get around that immune response. You could argue that higher titers of antibody and broader specificities reduce the probability that a variant in the major site would result in disease, if this a broad response to minor sites, if you have only a small amount of antibody and you get an escape from the major site and you don’t have a broad specificity to minor sites, then in fact you’re going to end up selecting against minor sites. Those are speculative stuff. But the fact is, the point of the question is all immune responses are selective pressure and the viruses mutate and those that survive that selective pressure have an advantage.

BILL HANAGE: Can I just jump in on this? There’s an interesting thing here, because that was all correct. And natural selection is awesome, except when it’s a virus doing it. But I think we need to remember that the opportunities to build up enough of a population within a person who was already vaccinated and where that b cell response is going to be stamping on a virus as soon as it starts trying to infect just the population size within that person is going to be really pretty small. And so people have expressed concerns about this. I will note, because it’s the sea in which I swim, though, that most of them have not been evolutionary biologists. The evolutionary biologists about this are generally comparatively relaxed. Now, the caveat to that is what Barry just said, that once you have a large amount of selection and in order to be able to survive, that will be a very powerful selection. But I want you to note that these variants that we’re looking at the moment, they arose before any vaccine was there at all. So very before any appreciable number of people were vaccinated. And we are going to need to watch it very carefully. But I don’t think that there’s any particular reason to think that a delay is going to produce more vaccine safe variants. Once a lot of people are vaccinated, we’ll be looking at this again. But I think that that’s something which is really concerned about by the evolutionary biologists.

Q: Great and sorry to be to be greedy and take a bit more time, but the other story that we’re trying to unravel is the differences, trying to understand why some states seem to be doing a great job and others not. And what sort of some of the variables are they prioritizing getting the vaccine out rather than equity is their leadership issue. Is it the technology? What do you see as the main drivers of some states doing well?

BILL HANAGE: You mean states doing well in vaccine rollout?

Q: Yes.

BILL HANAGE: I think this is a good question. Yes, this is really challenging. This is really a function of the total chaos of 50 state health systems in an uncoordinated, unresponsive underreporting system to the federal government. And there are states that seem to have done well. They tend, like West Virginia, to be small. And one of the things they’ve chosen to do is try to control as much as they can within the state. Many states, the majority, have taken the feds up on allowing major pharmacies, CVS and Walgreens to handle nursing homes and whatever. And what’s remarkable is that they’re under the control of the federal government and they essentially bypass many states’ departments of health, who have no idea what the dosage is that they’re giving, not giving, are sitting around. There is no centralized control of anything in this vaccine world across the states. The second issue is, while we do not have a single national health system and within the limitations that every state is responsible for the health of its people, crazy as that may be, that is the American way. There’s absolutely no reason why every state has to reinvent a logistics and information system for having people register, having health centers indicate who has had shot one and shot two and who can notify people and by what means they can be notified.

And the underlying tension in your question that really has certainly gotten us concerned in Massachusetts and I’m sure every other state is the issue between efficiency of vaccination and equity of vaccination. You can line people up in football stadiums and vaccinate 7000 people a day and increase your numbers. But if you’re not getting the most vulnerable populations, over 65, over 75, people with comorbidities, African Americans and Latinx, you’re not going to save that many lives. And it’s going to turn out to be an iniquitous and increased distrust of vaccines, distrust of the health care system, distrust of governments, and there’s no easy fix for that. But certainly, CDC has provided guidelines to say, look, we can only give you so many doses a week, and that’s far less than any state can use. In your considerations, do consider social vulnerability indices. Massachusetts is also considered burden of COVID cases. Where are the cases? Which towns have the most cases in order to get a 20 percent preference on where new vaccines go? I think they’re trying to balance that. But I can say the limiting factor right now is the number of doses that the states get and the short period of time the states have to know when they’re getting how many vaccines next week. How do you set up a court system where people can apply for appointments when you only know that you’ll get 20 percent less vaccines than you were promised next week? The system is not centrally controlled or even organized enough in Washington, so the states know what they’re getting, let alone what the pharmacies are getting, what gets in and out of the nursing homes and what they can distribute in community care centers versus mass vaccination sites? This is challenging, and I hope Andy Slavitt in Washington can put some at least logistics and computer order to the system, but it is not working in most states.

BILL HANAGE: My only thing to add to that is to say, yes, the fragmented nature of this is what makes it really, really, really hard. And I will echo something which I saw like about a month ago or so. Given what she achieved in Georgia. You wonder what Stacey Abrams knows about vaccine rollout. She might be very good at this kind of thing. She’s good organizing people.

MODERATOR: Dr. Hanage, is there anything you’d like to say about the link that you have?

BILL HANAGE: Yes, I put a link. We did a talk in CCDD yesterday with one of the more impressive scientists I know, Professor Colin Russell, he’s in Amsterdam and he studies flu evolution and vaccine escape. And halfway through, he gives a very, very good potted sort of question about how vaccine escape is expected to work in vaccinated communities. And I recommend it to anybody who’s gone out who wants to hear about a person living with an even more mid-Atlantic accent than mine talking about viral evolution.

MODERATOR: Mid-Atlantic, not in the U.S.. Great. Next question.

Q: Thank you. I wanted just to ask about undercounting. Testing seems to have given way a little bit to the vaccines, but there still seems to be some concerns about whether we really have a good handle on how many people right now and looking forward actually have the virus. And if we don’t have accurate numbers, what are the public health ramifications? Why does it matter?

BILL HANAGE: So undercounting has been a theme throughout this. It has been quite difficult to figure out exactly how many people have been infected and we are certainly counting fewer than actually have been infected. But that has changed quite hugely, the proportion, I think that in Massachusetts at the moment, I am kind of thinking we are missing maybe half to two thirds of actual cases and most of them are mild. People aren’t showing up. They’re going to be asymptomatic cases as well. The public health ramifications? Well, first of all, the ramifications are that we have a relatively poor understanding of the range of disease severity right now. Depending on whether or not we’re doing sequencing that is able to detect variants, we’re not going to be able to tell whether or not a variant of concern is present in a community. So we’re not going to be able to plan ahead as much. We’re also not going to have a sense of what degree of population level immunity might exist from prior infection. So what we need to do, there are fancy statistical ways of getting around that, but they do depend on having good data. And if the data are not good enough, then it becomes very, very difficult to do that. And that is relevant to understanding the expected impact of vaccination, because once you have around, I’m going to go for the higher number because there’s a variance, you expect once you’ve got 80 percent plus of the population fully immune due to even prior infection or vaccination, that the virus is not going to be able to cause outbreaks. But obviously, we’ve got a quite a long way to go before we get there.

MODERATOR: Do you have any follow ups?

Q: No, thank you, that was exactly what I wanted. Thank you. I really appreciate it.

MODERATOR: Great. Next question.

Q: Hi, thank you so much for doing this, and I’m guessing this actually might be better suited after I watched that YouTube video you mentioned about vaccine escape.

BILL HANAGE: I can summarize.

Q: But like the and measles virus is an RNA virus and there’s still a lot of rain that COVID it’s quotes unquote, just like the flu, which, as we know, is not at all accurate. So can you just speak more about compared to the flu, is COVID-19 still not as unstable as far as viruses go, or is it headed in that direction in terms of mutations and what we’re seeing with these variants? And just anything you’d like to add about that?

BILL HANAGE: Yeah, I do recommend the tool. But I mean, there are a few things we can say which will help you if you didn’t have time to watch it. One of the big problems that has been actually throughout the pandemic is that a lot of people have kind of anchored on flu. That was thought that this is like flu. And as you said, it’s not. Flu is a rapidly evolving coronavirus. SARS-CoV-2 is not a rapidly evolving RNA virus actually has error correction mechanisms. So for an RNA virus, it accumulates mutations pretty slowly. That’s not that surprising because it’s got a huge genome, way larger than most of its kind of cousins. So there’s less room, it can afford to make fewer mistakes. Having said that, one of the things which is very interesting is that if you examine quite specifically the so-called variants of concern, those which are most prominent in discussions at the moment, you do see that they have many more mutations than you would expect given when they were isolated and given that slow clock, that slow accumulation of mutations. And that was something which was quite plausible to think that similar things happen for other viruses, but it’s particularly evident in this one, we touched upon it earlier that that may be the consequence of a very long-term infection in which the virus has never been fully cleared but has been able to pick up mutations that enable persistence within the host and enable it to somewhat sidestep the immune system. And, this is important, maintain the ability to transmit, because if you’re a virus growing really well in some of these cells and just going around the body is cool if you’re trying to evolve to be very fit in the host. But it’s not necessarily the same thing which is going to be selective when it comes to getting into another host. And that’s one of the reasons why, even though we are noticing these variants now, they’re still well, maybe we will get to the point that now a lot of people seem to be reporting variants of concern, but I think that’s because we’re looking harder. While despite there having been well over one hundred million infections worldwide, we haven’t seen that many of these things arising. So I actually think it’s quite difficult to get a very large benefit from this. On the other hand, I think Angie Rasmussen came up with a great image, which was that every time you allow an infection, you’re giving the virus the opportunity to buy a lottery ticket and sometimes the lottery tickets will come back and that’ll be something which is reflected in enhanced transmissibility. So we have to not only consider that it does evolve quite slowly, but that we have had a huge number of infections and so we’ve allowed it to buy a lot of lottery tickets.

Q: Thank you so much.

MODERATOR: Thank you. Next question.

Q: Hi. I want to ask a question about the human challenge program, as I know, the US also planned to do this trial, but the effort appears to be on hold. So why is the reason and I still want to know your painting about it and how can we convince the people who have concerns about the trial? And also, experts say it’s controllable, but how is it controllable when we know not everything about the disease? Yeah, that’s my question. Thank you.

BARRY BLOOM: You know, I’m happy to talk to our very strong views on it. People may disagree. I see absolutely no justification for a human challenge situation when we have 20 companies making vaccines in phase two and three trials with thousands of people to believe that there’s anything useful that’s going to come out of challenging 90 people, that a company that’s investing a billion dollars in running trials would pay attention to. And in that context, that’s the only justification that people could give for doing something that we are told not to do in medicine, which is to do no harm, we do not have a cure for this virus. We do not know the long term and short-term consequences, even in 15-to-65-year old’s. For many other human challenge trials, for example, in cases like malaria, where we have very good drugs, we can be very certain if the vaccine doesn’t work, we can cure them. We cannot say that for this and many other viruses, and the only justification is if you could learn something essential to producing effective and safe vaccines. Since they were already made, I see no justification on either practical or ethical grounds, and I am astonished that the Brits have agreed to do that.

BILL HANAGE: I think I’d mostly agree. I agree on pretty much in particular the emphasis on the long-term chronic consequences of infection, because even though it is true that the reason why we have a pandemic of such scale and problems is not that the virus kills an enormous proportion of people it infects, but that it infects a large number of people and causes severe illness and death in a small proportion of them. But the number of people infected is so large that number of deaths becomes very large. But then there’s also that crucial chronic illness that results that people have not paid enough attention to, and which is probably going to be making a really significant impact in terms of long-term health conditions in the population as a whole over the coming decades. Now, the only wrinkle I would add to what Barry said is that if that were to be any ethical grounds, it would be the acceleration of knowledge about something, perhaps at a point when there was not a large amount of infection. But given that right now there is a huge amount of infection of naturally occurring infection in so many places around the world, it seems much more reasonable to be planning on a well-designed trial in that context. It’s not hard to find people infected with SARS-CoV-2. So I think that given that even if there were any ethical grounds for considering it at a very, very large population level, obviously strictly among volunteers, that that ship sailed quite some time ago.

BARRY BLOOM: I would just add that the people who are most at risk for dying, as you know, 80 percent of deaths in the US or people over the age of 65, they’re not involved in the trials. So one is going to learn nothing about the potential efficacy of anything in the highest risk populations. And we know that most young people don’t die from it. So challenging young people puts them at risk for some chronic effect that we don’t know without the ability to cure them. And we’re not learning anything about how to keep people that are dying from dying. So I find this really a very unfortunate step because it is isn’t necessary.

Q: Yes, thank you. So I’m still wondering what kind of people will be the volunteer because it is said that they are not forced to do the trial, but they just volunteered to do this. And they also have some in exchange. So can we say that some poor people or any other kind of people will be the volunteers?

BILL HANAGE: It’s certainly not going to be representative. It is going to be that it would be younger people who are least likely to have the most severe consequences of disease and short term. But if the volunteers are not going to be a representative sample of the population, and that’s one of the other reasons why this will provide data that it would be quite hard to extrapolate out from.

BARRY BLOOM: My understanding is there was a huge waiting list of volunteers wanting to do this early on, and their motivation was not money. It is altruism, believing that they could provide knowledge that the rest of the world couldn’t get in in any other way. My view is the world has moved past that point. So we’re getting knowledge every day on the effectiveness of vaccines, on the problems of chronic infection with the virus. I can’t see a scientific or ethical justification. I appreciate the altruism of the people who want to be helpful.

Q: Yeah, so do you think that it’s immediate need for the human challenge trials or do we have any other alternative trial designs?

BILL HANAGE: There was no immediate need for human challenge trials.

BARRY BLOOM: Right. We have randomized control trials, double blind with high reporting if there are any adverse effects at any time, short term and long term, very much more sensitive to any adverse effects than testing 90 young, healthy volunteers with an unknown amount of virus since we have no idea how much virus it takes to get someone infected. And what the real exposure is in the real world. This is a totally artificial situation.

Q: OK, so do you support the opinion that we sacrifice some people to save the world that they sing about?

BILL HANAGE: So sorry, say that again?

Q: That we sacrifice some people and so we can save the world?

BILL HANAGE: I don’t think there’s any need to do that at the moment. I think that, as I said, any acceleration to saving the world would have been in the past and the ship has sailed. So I don’t think that doing a human challenge trial at this time is really defensible.

MODERATOR: Next question.

Q: Yeah, hi, thank you. We have people, I’m sure you know, the situation is similar in other states. People drive in from Kansas to the Texas panhandle to get the vaccine because, you know, they’re seeing that different states are handling it differently in terms of who is eligible when. Meanwhile, you know, we have our meat-packing workers, thousands of meatpacking workers, they haven’t started getting the vaccine in Kansas and they only get two hours of paid time off from work to try to get the vaccine so they can’t take a day trip to another state or another county to try to get it. I guess what I’m wondering is, what are we seeing in terms of equity with like the people who work high contact, high risk jobs? Are they actually getting the vaccine versus people who can maybe work from home and such?

BILL HANAGE: This is a good question. I think I will say something quickly on that I’m sure Barry will have something longer to say. The issues of equity are incredibly important. As you say, you’re completely right that there are occasional reports of people who can work from home, you know, relatively well-off, well-informed, for example, to search the Internet, to figure out whether a vaccine is going into places, where they’re attempting to provide an equitable vaccine deployment strategy and taking the vaccines. This is obviously really bad. It is also the case that the attempts to obtain an equitable vaccine rollout have been quite variable by states and by region for the reasons that we were talking about earlier. I mean, it’s a very fragmented situation. So I mean, this is a problem. It was a foreseeable problem because these are the problems which have been with us throughout the pandemic, and it’s very regrettable that they are happening, and people should be doing more right now in order to prevent them getting worse. Unfortunately, is it is very difficult to come up with any kind of one size fits all approach because of the sheer diversity of the nation. But equity should be prioritized. And I’ll shut up on that, Barry, who I think is more knowledgeable can take this.

BARRY BLOOM: No, I absolutely agree. And look, if there are rules for anything in the United States of America, that’s a positive selection to find people who will find ways like the virus does to get around the rules or get around the antibodies. That’s a characteristic of human nature. The role of regulation is to try to assure the system is as fair as possible. So I would, for example, indicate that vaccines are allocated to states on the basis of population. So every vaccine dose that’s given to somebody from Kansas that goes into Missouri is taking a vaccine away from people in that state. And it would seem to me a little bit of news stories on that would make it less attractive for the people either to want to do that or for the vaccinators to want to give it to someone from another state. I think if we had waiting lists, as I suggested earlier, such that within 30 minutes, every vaccination site would have a list of people who promised to come in in 30 minutes or no doses are wasted. That’s a logistics, a computerized tool that could be used from community health centers or elsewhere, volunteer drivers or whatever. We could solve the problem of having any vaccines unnecessarily wasted. But people will try to get around the system. As you know, in my state, when the governor allowed people to accompany the elderly over the age of 75, Craig’s List immediately had a bunch of young taxi drivers volunteer to take 75-year-olds who were not relative to get vaccinated because they were being offered a vaccine as well. Mercifully, the government figured out that wasn’t so clever. And that will pertain only to 75-year-olds, which are now over half estimated to be vaccinated, will not be true for any of the younger groups. So keeping ahead of human ingenuity is a challenge. But really having both the governments and the press emphasized the importance of equity here, fairness, not getting the head of the line, not paying your primary care physician to say you have to comorbidities when that level is up. There is a level of honor that’s required that can’t be dealt with by law and regulation.

BILL HANAGE: And just as a small code of that, I mean, I know multiple people who are MDs well in-patient facing roles, either working in labs or they’re in a situation where they have no need to be in contact with the patient. And I know at least some of them who have been offered the vaccine and have turned it down on the basis that would be better use than somebody else right now.

BARRY BLOOM: Absolutely.

BILL HANAGE: And I’m not going to be vaccination for a long time I suspect.

BARRY BLOOM: The other thing is that I would like to say that things would be better if, for example, there are registries of people on Medicare where registries in every state, on people who are Medicaid and to the extent that the government could reach out to them rather than waiting for them who are often skeptical or worried about vaccines, we know who the people who are on Medicaid are. We know who the people in Medicare are. There must be mechanisms to reach those vulnerable people, explain to them, answer their questions, even if they don’t have a primary care physician to try to explain what we know about the safety and efficacy, why it would be a good thing for them to get vaccinated.

Q: Thank you very much.

MODERATOR: All right, next question.

Q: Thank you very much for doing this. I want to ask you about the South African variant. In Cambridge, we have the distinction of having the first case of this South African variant.

BILL HANAGE: I think that may be two now, but I think that was reported yesterday.

Q: Well, we were the first, let’s put it that way. Thank you. But anyway, what I’m wondering is, is there anything special that should be done? Should we sequence more test results from Cambridge? And it seems that we’re looking for these variants at a time at least where there’s much fewer positive cases. So, are we going to find them? We’re not even sequencing that many.

BILL HANAGE: Well. It depends on relative to what? I mean, the Broad Institute in Cambridge has actually been doing more sequencing, although not necessarily of things from Cambridge. The fact that we have in Massachusetts and in the region, multiple cases of B1351 that have no travel history means that it is circulating in the community already. Now, in the United Kingdom that was responded to with a program which was called Operation Eagle, in which the people who are there, who have already managed to make most of the rest of the world in the United States in particular, really look like tortoises when it comes to making genome sequencing work well, the government told them that they had to descend upon a region and get loads of tests from people. They were doing door to door testing where this variant was found. And then the goal was to get sequencing turned around in 48, maybe 72 hours in order to be able to say where it was because it was considered to be such a big deal. That’s one reaction to it, because they were very concerned about getting into the country partly, I think because the UK has been using a lot of the trademarks AstraZeneca vaccine, which, as we were hearing earlier, is one that this variant appears able to sidestep much of the immunity generated by that vaccine. So it’s of particular concern. That reaction is not necessarily a sensible one, because the same mutant which generates that has already emerged on the background of other variants which are circulating in that country. And that variant has, in fact, already been introduced to the United States. So it is a situation where we do need to be ideally, we should be sequencing more and we will be sequencing more and we will be looking through those results and pulling out whether or not we have a variant present fairly, hopefully pretty quickly.

Now, as you say, at the moment we have cases which are pretty low. They’ve really come down quite a lot. But, if there is a circumstance that this B1351 or B.1.1.7 present, we expect that decline to be tailing off. It may even start to increase again. It won’t happen quickly, but it is entirely possible. So I think that what that means is that we should be prepared for an anxious spring and during which we pay very, very close attention to what’s happening in our community and those around us.

Q: I guess I have just one follow. Is there anything that just on a community basis that when a case is found in a community, is there anything that needs to be done in a community that’s different from the normal precaution that they tell you to do?

BILL HANAGE: I think given the data that has come from South Africa, it would be pretty reasonable to suggest to folks, I think that some people have a feeling or belief that they have been previously infected as a result of being sort of a positive test or some serology that’s been done. I think that those individuals ought to be made aware that a variant is present, that we think is there is better able to infect folks with some previously existing immunity from infection and that they shouldn’t be thinking that they are protected. So I think that is probably the most important message to get across to a community in which we know that there’s already a community spread at that area.

BARRY BLOOM: I would simply add that once you have a community with one of these variants, people have been very cavalier about contact tracing and supplying phone numbers of people with whom they’ve been in contact and in quarantining, staying home for 7, 10 or 12 days in areas where these variants are emerging. The best way that we have right now to stop them until we have enough vaccine is to keep people locked up for two weeks so they’re not transmitting.

BILL HANAGE: Absolutely.

BARRY BLOOM: And their contacts do the same. And it would die out of its own.

BILL HANAGE: Absolutely. I could add to that some emphasis on backward contact tracing, because you want to be able to figure out where they got it from. And I mean, Barry’s right that it is depressing, but there’s been a really cavalier attitude to these things.

Q: Thank you very much.

BILL HANAGE: You’re welcome.

MODERATOR: I have a couple of things; do you have a couple more minutes either or both of you? I think I have one more question. And is that OK? The other thing is, I can also put in a link to some information on contact tracing and background contact tracing, unless you’d like to get into that?

BILL HANAGE: I can stay for a few more minutes.

MODERATOR: Are you all set?

Q: Yes, I am. Thank you.

MODERATOR: OK, I’ll see if I can find a definition for better contact tracing.

BILL HANAGE: And this when you’re trying to figure out where it came from as opposed to the transmitted to. And it’s helpful because it starts its part of a cluster busting strategy which is being at least tied to a successful pandemic management in some parts of the world.

Q: Yes, and especially since the sequencing often comes quite a bit after that test results.

BILL HANAGE: Yeah, I mean, hopefully that will be changing, but I mean, it’s not going to change overnight.

Q: Thank you very much.

MODERATOR: Next question.

Q: Sorry I’m being greedy today; I was just wondering if you could talk a little bit about why you think the cases are down so much. What do we owe this credit? And you said before about the variants, but is this good news? Can we celebrate this?

BILL HANAGE: I think it broke up a little bit, was it why things are coming down so much?

Q: Yes.

BILL HANAGE: So this is a really good question and it’s one which there is considerable discussion about. And some of the potential answers are really quite complicated. And I’m going to try an anchor and basically the big three for which I think we have at least some evidence. So the first and the most important observation is the regular coronaviruses peak in January. Something which we have seen for years, why they peak in January is it is a good question. We don’t really understand why. Very much because we also know that they exhibit less seasonality than flu does. That’s why we call those regular coronaviruses summer colds sometimes. But the cases peak in January, and that may reflect a combination of weather, which is particularly helpful for viral transmission and then also human contact patterns, you know, reflecting the different contacts which get made over the holiday season. And it’s notable that the peaks in cases in early January are pretty much where you’d expect to see them to peak up from the infection’s, which happened over New Years. Now, once that’s happened, the virus got into a whole bunch of new households, which it’s going to probably make its way through. But then human contact patterns change, and they shift back, and the weather may be changing a little bit and making a little bit more difficult for the virus. So that’s the seasonality piece.

Then in some parts of the country where there has been a lot of disease, it may be the case that infection acquired immunity is playing into that a bit, but it’s not going to be the case everywhere because we’re seeing reductions in Vermont, which is no disease to speak of, and the Dakotas, which we said this before, you know, over one in five, three, five hundred people there has died. And almost all of that happened since October. So just over the last few months. And so those are very, very different experiences and yet they’re both coming down. So the final possibility, which I think does make some difference, is that when you people alter their behavior, when they see something, when they get a signal like that’s a very large number of people who are infected. There’s a very large number of deaths and they change their behavior, and they make different contact patterns. But that doesn’t actually immediately happen. Instead, stuff that happens, say, at the start of January, is not going to be making it self-felt in the case numbers until a few weeks later because of the time it takes for those changes to start having their effect and as a result of that, I think some combination of those taken together can explain the sustained decrease. Whether or not there’s something else going on is not at all clear, but I think that it is quite crucial to the comment I made to Chris earlier at the start of this, that while it’s there is every reason to be intensely concerned about the variants. We don’t necessarily think that they’re going to take off in a deterministic fashion everywhere at the same time for much the same reason, by the way, as the pandemic didn’t take off everywhere at the same time. There are these random things that happened early on. So that was a long answer and Barry may have something to add, but I hope it helps.

MODERATOR: Barry, do you have anything you’d like to add?

BARRY BLOOM: I’m in full agreement.

MODERATOR: OK, I’m sorry. One more quick question. And Dr. Hanage, if you need to go, fully understand. CDC’s MMWR report today on the data is collected on COVID-19 vaccine safety that says both the Pfizer by BioNTech and mRNA safety profiles are reassuring. How can health care providers and the government use this data to reassure people about the vaccine’s?

BILL HANAGE: I think this sounds like Barry’s.

BARRY BLOOM: I’m not sure I fully understand the question. CDC puts out information and relatively few primary care physicians see it. Very few primary care physicians have vaccines. So the issue of how to get information out at the present time, which may change once the categories of people open up and vaccines become available to primary care providers would be a very different story. One thing that I think is worth mentioning quite brand new is that Pfizer believes that they can maintain their vaccine as a stable vaccine at minus 20 degrees, which is the same temperature as Moderna. And they have applied to the FDA for EUA approval of that condition. And if that’s the case, it will make it a lot easier to get the Pfizer biotech vaccine to many, many more places that at least have a freezer compartment in a refrigerator, as opposed to the complex shipping and high-tech minus safety degree freezers. So if that’s the case, we will have a great deal greater flexibility in where that vaccine can be applied. But on the public information and, you know, one of the things that I really don’t have an answer and you people probably do, where do people go for information in inner cities in Chelsea, in Roxbury and Dorchester, in Brookline, in Lawrence, in Berkshires? Where do they go for information on vaccines? Where do they learn where they’re available? Where do they learn whether they have adverse effects or not? That’s a kind of information that would be enormously helpful to answering your question of how we tailor a vaccine to very different communities who have very different sources and expectations on the reliability of information.

BILL HANAGE: Yeah, vaccine hesitancy is not something that I have ever worked on, but I do think it’s important to listen to people and understand why they are they have attitudes that they have. And part of that is, like we just said, it’s like figuring out where they get their information from.

MODERATOR: Do either of you have any comments for us of before we go?

BILL HANAGE: I think my comment is that maybe just the world in which I’ve been living, that I was expecting a lot of questions about variants. So I’m going to very briefly make the comment here, which may be helpful for people going forward. We’re going to hear a lot about particular mutations and whether or not they constitute variants and what they mean. And I get two or three questions about this a day, sometimes more than those of us in the US. I think we need to remember that people are now doing a lot more sequencing. And so what you’re often finding when you’re sequencing is you’re finding something which is locally spreading and that makes people suddenly become very excited. But it may not mean anything very much, because at the moment we’re looking at a lot more closely than we were. Even the variants that you’ve heard of and that are famous, like Eek, for those of you who aren’t familiar with the some of these mutations have been given names. And then there’s Nellie as well. Nellie and Eek and a number of these mutations have actually arisen many times and many of the times have arisen, most of them have gone extinct. So when you hear about that being something circulating with a worrisome mutation, try not to become terribly anxious about it. Note that it’s not only having a worrisome mutation, but also a combination of mutations and it’s what that lineage seems to be doing over time as a growing is it has arisen recently and is growing more than it is expected. And so that will all be helped by better understanding and better sampling and more genomes. But if you’re getting a lot of local stuff about saying, oh, we’ve got this amazing, terrifying variant here, please, I would urge a little bit of skepticism and calm in the face of that.

BARRY BLOOM: I would only thank everybody for their questions and say that as this epidemic has gone on, I am more and more appreciative of the important role of the press in providing relevant and cogent and honest information to people that they can begin to trust. Given the chaos that’s out there in the health care system, getting true information in any place can only be helpful. And so I thank you for what you do.

This concludes the February 19th press conference.

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