Coronavirus (COVID-19) Press Conference: Barry Bloom and Bill Hanage, 04/29/20

You’re listening to a press conference from the Harvard T.H. Chan School of Public Health with Barry Bloom, professor of immunology and infectious diseases and former dean of the school, and Bill Hanage, associate professor of epidemiology. This call was recorded at 11:30 AM Eastern Time on Wednesday, April 29.

Previous press conferences are linked at the bottom of this transcript.

Transcript

BILL HANAGE: Good morning, everybody. Good to be with you. Hi to those of you I know and nice to meet you to those of you I don’t. So, April 29. In the United States, we have more than 1 million cases here and we’re nearing 60,000 fatalities, which is likely an underestimate because there are some which are not being counted and it varies very much state by state. But I’m sure you’ve seen the recording which is indicating that the CDC is showing an excess of deaths over and above those which have been attributed pandemic.

Now I also would point you to the fact that, despite that we have in this country – and I’m sorry to be emphasizing the United States, in this case, it’s where I know best – we have fewer than 150,000 recovered. So, what that means is that are very large number of active cases ongoing. And of course, they are continuing to grow with the pandemic being in a different state in different states as a result of when it was introduced, and the degrees of distancing which have been implemented.

I think that there’s been a lot of interesting things which have been becoming evident over the last week, and some of them are the serology data which I mentioned earlier, but also, I’m beginning to see more evidence of potential roles of things like secondary infections over and above those which either the COVID virus or the SARS-CoV-2 virus itself. And so, and with that I’m very happy to take any questions that you have.

MODERATOR: Great, thank you. First question.

Q: Thanks so much. So, I wanted to get your take on what we’re looking at kind of in terms of a long-term prognosis for COVID-19. Obviously, there’s a lot that comes down to when a vaccine is available. Is it realistic to think that we could be rid of this when a vaccine is available in a year or so, or is this really something that we expect to stick around in some form, like the seasonal flu, which kind of ebbs and flows but is always there?

BILL HANAGE: Okay, so your voice was a little up and down there, so I’m going to repeat the question just to make sure that I got it right. The question as I heard it was what is the long-term prognosis for the pandemic, given that we are about a year out from getting a vaccine and what would it become like potentially like seasonal flu. Is that roughly correct?
Q: Yes.

BILL HANAGE: Okay. So, in the absence of a vaccine that produces long-term immunity, then indeed we would, I think, expect to see sort of a range of possible outcomes. The first thing, which is most important to note, is that, given what we know about the transmissibility of the virus, the only point at which we will expect it to start slowing down in terms of transmission, unless we do – you know, absent a vaccine, is when about 60% of the population has become infected and has immunity. So, that’s quite a lot of people, and it might take quite a long time to get there.

Now, the rate with which that happens depends a great deal upon factors, including the amount of contacts that people are making locally, the degree to which those contacts might change with the seasons, the degree to which there might be some slowing of transmission due to better weather in the summer. I don’t think it will go away. But I think it might slow down. And then the extent to which we get more things happening in the fall and the winter. Now, I think that it is – absent a vaccine, I think it would quite likely become like seasonal flu or perhaps like some of the other coronavirus that we are familiar with.

Now, there are lots of things in this that we do not know. And some of the things we do not know all the role of long-term immunity, which results from the kind of infections, we’re seeing now; how much immunity results from the relatively mild infections, which have been documented; and if that immunity is not, you know, very long lasting. And we have good reason from other kind of viruses, including the original SARS, to think that it won’t be. What type of infections will people have when they’re immunity starts to wane. Will they be as severe as this, will they be as transmissible as this. And I think the first thing that says we don’t know, but I think it’s also plausible to suggest that they might be milder. So really looking long term, other than the kind of very, I want to say this very clearly, we don’t really know the moment, it is entirely plausible that this could become part of our regular landscape of respiratory viral infections, absent a vaccine. And I think that Dr. Bloom was going to talk about the vaccine but he’s unfortunately not here.

MODERATOR: Next question.

Q: Thank you, Nicole. Doctor, thanks for doing this. I’m curious about – we’ve talked in the State of Massachusetts about, you know, the latest tentative reopening date is May 18. Is it inevitable when we reopen, no matter what, whenever that is and no matter what restrictions we put in place that there will be a surge, simply because people will be out and about again?

BILL HANAGE: Thanks for the question. It’s a good one. It’s not inevitable that there will be a surge. It is inevitable that there will be more transmission because people are going to be out and about. The degree to which it will increase transmission is not clear. This is why one of the most important things to do with anybody, anywhere that is thinking of opening up, or as I would rather put it – I would rather put it as refining the way that we are responding to the pandemic – if you have a surge, then you need to put some pretty strict things in place in order to preserve your health care system.

But then if you get to the point where you feel you have capacity to deal with an increased risk on health care and you are comfortable with, you know, more people potentially becoming infected, especially in low risk groups, then it is reasonable to think you can refine what we’re doing in order to enable more in economic activity, while at the same time trying to decrease the rate of infections such that you’re not going to damage healthcare.

So, it’s not inevitable that there will be a surge. However, it is inevitable that you will see more new infections and you’re seeing right now. And in order to be prepared for that, that’s one of the reasons why we need such good testing and we need to have a I would also say, I think that it’s a good idea to have a pretty clear plan for how you’re going to move forward. So, in other words, there’s going to be a need for continued monitoring and if you see an exponential coming your way in the form of a surge then you should be prepared to take pretty decisive action pretty early on.

Q: Can I follow up with: we’ve seen what’s happened in nursing homes, in VA hospitals here in Massachusetts and really across the country. Could we see or would it make sense to see, for example, that those places, stay under more strict restrictions, even as the rest of the world opens up?

BILL HANAGE: Absolutely. Brian. You’re absolutely correct. The situation with the early stages of the pandemic has been in many places that a surge was allowed to build before sort of appropriate action could be taken to shield vulnerable members of the of the community. So, I think that going forward, those individuals who are most likely to be under severe risk of, you know, of death or severe disease, those people should be protected, and we should be continuing to put in place measures which will which will help places like nursing homes be able to deal with the pressure of the pandemic. You know plenty of personal protective equipment, plenty of testing, lots of, you know, good standard public health things which are going on in there and that’s will have to continue for quite some time.

Q: Thank you, Doctor.

BILL HANAGE: Thank you.

MODERATOR: Okay, next question.

Q: Hi, thanks so much for doing this. I was wondering if you could talk a little bit about what’s going on in Sweden and their approach to this virus. There’s been talk about herd immunity. But then, I’ve heard that they’re not using that term and just, I don’t understand how they could possibly get to herd immunity with 19,000 infections and 10 million people, but, um, yeah. If you could talk about that.

BILL HANAGE: Thanks, Karen. It’s actually a very good question. So, Sweden is one of these countries, which has been attempting to handle the pandemic in a somewhat different way. I cannot speak for what the political aim is, but I do know that there has been talk about herd immunity. Note that you will only get herd immunity, like we said, if 60% of the population has been infected and as immune, which is quite long way to get to.

There are claims that Sweden is not in lockdown, but that’s not actually true. There has been substantial encouragement of people, for instance, you can work from home to work from home and I forget exactly how many it is, but some relatively large proportion of the population is not doing that. So, there is social distancing. And there’s a ban on gatherings larger than 50 people. So, the goal appears to have been to allow immunity to build in a sort of natural fashion, but at a slower rate in the low risk population, but there has not been steps taken to protect the higher risk population. It seems to be that this is advice from the government rather than an injunction – you know, 70-year olds plus should stay at home, and we will provide you with food and stuff so you don’t have to go out.

Now it’s very instructive to compare what has happened in Sweden with the other Nordic countries. I forget exactly what it is, but its mortality rate at the moment, per capita is, I think, at least three times that of Denmark, which is the closest comparison and much, much more than Finland. So, in other words, whatever they have done has been leading to more deaths. This has mostly been in nursing homes as a result of the fact that, just going for what I was just saying to Brian, it does not seem as if there were appropriate steps taken to ensure the safety of people in those nursing homes. That does not appear to be the case. So, if you’re going to have a strategy like that you really need to be thinking about a vulnerable population.

And the last thing I’ll say, which is, you know, something which I’m sure a lot of you appreciate: everything that I’m saying about this, it means right now at this point in time, because we are quite early on in the pandemic, it’s going to take a very long time to either get to a vaccine or herd immunity, whichever one you pick, and as such the strategy that Sweden is following at the moment may look quite different in a year or so, because the total epidemic size in different places may be quite similar, it would be just stretched out over a longer period. So, Sweden is a pretty complicated case – it’s not in lockdown, but it’s also not completely without restrictions. That appears have had the consequences that it’s had a worse earlier pandemic than its neighbors. But as I said, it’s early on in the day and we’re going to have to look back at this and a few months to see what happens next.

Oh, actually, one more thing that I should add, and this relates to some of what we were saying earlier, the number of cases that are being reported may be an underestimate of the true number of cases which are occurring in the community. But as I’m sure you can appreciate, the number of cases which are not being counted are not going to be of any sort of scale that you would expect to be gaining 60% of the population, having any immunity.

MODERATOR: Did you have a follow up?

Q: I think that you brought up in your intro something about more evidence of the role of secondary infections. Do you mean repeat infections with the same virus or secondary – what did you mean by that?

BILL HANAGE: I’m sorry. I actually wr0te down secondary infections. I think I was being a bit – I misspoke. I think I was saying secondary about something else, because I was thinking about onward transmission and household transmission. No, I was thinking more there about co-infections because I think there’s emerging evidence and sort of bacterial infections, especially in severe cases.

In the case of in case of Sweden and, indeed, generally, I will point out that at present, we do not know the extent to which immunity is going to protect people from secondary infections or future infections, when they are exposed at a later date. It’s – as I say, the science is not solid at the moment, but there do appear to be quite a range of antibody responses which amounted.

Q: Great. Thank you.

MODERATOR: Next question.

Q: Thanks for taking the question, appreciate you doing call. I had a question about as states and, you know, counties across the country are beginning plans to reopen in some way, you know, obviously, there’s been a call for more testing across the board, but I’ve been curious, what’s your level of testing you would hope to be seeing in in states and counties if they are making plans to reopen in some capacity.

BILL HANAGE: So, I mean, this is a question that I get a lot. So, the official sort of WHO sort of standard is that you want to have 10% of the tests you do coming back positive. And that if it ends up being more than that, then basically it means you don’t really have a very good idea of the scale of the iceberg, what you might not be testing. But I think the 10% is a pretty good, even if it’s an arbitrary sort of rule of thumb for you should be doing if it’s lower than that, great.

The other thing that’s important is that the tests are good. They need to be sensitive and they need to be specific so right, good diagnostic testing, but you also want it to be sort of ideally in a sort of within the community because of the fact that this is where the community is why the transmission is going to happen, which will lead to any future surge. And so, you need to be having a pretty good plan for what you’re going to be, you know, what you’re looking for in order to take any steps that will lead to alternative sort of distancing measures in future thinking back by the way to Sweden and present it does not appear that Sweden’s health care system has been hugely under strain. But again, that could be due to these milder distancing things that have been put in place at an earlier stage of the pandemic.

So again, I would appeal to states throughout the nation to be thinking what is going to be the trigger for taking stronger action, what is the thing which is going to lead to me thinking, okay, I might not want to do this, but I have to do this.

Q: Great.

MODERATOR: Did you have a follow up?

Q: Yeah, sort of a quick follow up. So, your thinking is entirely in sort of the rate of positives, not in terms of any sort, per capita measure of tests? And related to that, any difference between rural areas of improvement?

BILL HANAGE: Yeah, that’s very interesting. So, in general, the differences between rural areas and urban areas are important and they’re beginning to emerge now. I have concerns about rural areas – I know I’ve spoken about them on the call before – because we are now beginning to see them in some of these like smaller towns, which have, you know, have industries, whether assembly line conditions, but once the virus gets in there, it can quite rapidly spread. And some of the smaller towns are being hit really hard.

So, in terms of the – so, this is a question which I haven’t given as much thought to as I should, so I’m going to think about it and mention it on a future call, but I think that you not only want to have a portion of tests coming back positive that suggests you’re doing good surveillance. You also should reflect upon whether or not you are doing adequate surveillance across the area that you’re worried about because you don’t want to have these kind of areas where you’re just not really looking where you can be having you could be having problems because, you know, a pandemic is so called because it has the capacity to infect everywhere, not only the areas which are of incidence.

I love the sound of typing.

MODERATOR: I just want to also quickly welcome Dr. Barry Bloom to the call. Dr. Bloom, did you have anything you’d like to say as a brief introduction?

BARRY BLOOM: I’m very pleased to be here. Sorry I joined late.

MODERATOR: Not a problem at all. We’re very glad you’re here. Alright, next question.

Q: Great, thank you so much for taking the time and doing the call. My question is, kind of at the beginning of the pandemic, we heard a lot about the need to slow the spread, to flatten the curve, to spread infections out over a longer period of time, avoid overloading hospital systems. You know, in some states, hospital systems are operating at half capacity right now, things like that. Does that remain kind of the overarching goal, do you think, of the measures that we’re taking right now or have we developed a more comprehensive approach or view of kind of the deadliness of the virus and that means that we need to work rather to flatten the curve and spread it out more to minimize the total number of new infections?

BILL HANAGE: I think that having talked enough, I will leave this to my esteemed colleague.

BARRY BLOOM: Thank you very much. Thanks for the question. Two points. The first is I am not dismayed by the fact that there are empty beds, in fact I’m encouraged by that because if there are outbreaks and spikes and even a second wave, we can’t start all over again preparing hospitals to be overwhelmed. So, it’s a good investment to have that time to prepare the hospital systems, the PPE, the diagnostic procedures and all of that. So, we could respond a great deal more quickly.

The second, as you well know, is that we are embarking on a relaxation of the constraints that have been put on in most parts, but not all of the country and to learn, since no one really knows the optimum ways of opening up society, there are experiments going on everywhere of how to do that best. Am I worried that we’re not collecting centralized data, let’s say, at CDC or elsewhere to find out what things are working effectively and what are not. For the short term, the expectation is we’re focused on American workers, going back to essential jobs and then easing up on nonessential jobs.

Big debate is not being had because we have no data on whether it’s a good or a bad idea to open schools. We know that kids are relatively resistant to the severe effects of this coronavirus, and so the temptation would be to say the risk of killing too many kids is not too great. But we learned from pneumococcal vaccines that what happened when we vaccinated kids, grandma and grandpa had a markedly diminished rate of mortality from pneumonia. And that is kids are direct transmitters of infectious diseases to grandma and grandpa, who were at the most high risk and vulnerable in the country and I don’t know of any good data on a surveillance of school age children to know whether they can be transmitters and spreaders or that’s not likely to be a significant problem. In places like New Zealand that have now started to come out of complete lockdown, it’s interesting. School kids are allowed now to go to school, but junior high and high school students are still not and that will be a set of phases that goes in there.

I don’t think we have a national priority of, who are the most vulnerable that need protection. And I know you were talking about Sweden before. A third of all the deaths in Sweden or in nursing homes, and so clearly the lack of restrictions in Sweden has taken a vulnerable population and really been pretty devastating to them. And that’s true with the US and Massachusetts as well. A very high percentage of deaths are nursing home deaths. So, I think we have to focus on two things: who to let out and who to provide high levels of protection to, and I would say the elderly, those with medical conditions and institutions like nursing homes. Before we ease up on them, do they have some specific plans in place to protect the most vulnerable.

MODERATOR: Dr. Hanage, did you have anything you’d like to add? billhanage: I’m not sure I have anything to add other than that I fully agree, in particular regarding the importance of protecting vulnerable. As we’re moving into the next stage of this, we are all learning more and like Barry was saying, I mean it would be absolutely wonderful to have a coherent centralized collection of data on what has been done where and we can then link that to the potential impact of that on the progress of the pandemic in that region. As regards children, yes, I would. I would love to be able to send my kids safe school but moment there is very little data. There was a paper that was published in the Lancet Infectious Diseases I think yesterday, which was looking at transmission in Shenzhen within households. And it founded the transmission to children happened at a similar rate as that to as the adults. It’s very difficult to understand exactly what that means for the role of children in transmission. I’m hoping that there is going to be a little bit more definitive data coming out on that within the next few weeks.

MODERATOR: Okay, did you have a follow up or are you all set?

Q: Yeah, just one more. Kind of as you’re talking about the most vulnerable populations and that we have to protect those. It seems like we’re learning so much more about the impact of the virus, kind of, as we go. There’s been a lot of new research on blood clotting and things like that. Do we know yet who the most vulnerable populations are or is that something that we need a little bit more time under these kind of extreme lockdown measures to figure out who can most safely reenter society until there’s vaccine?

BARRY BLOOM: Well, I think in terms of mortality, the data are pretty striking that people over the age of 60 have much higher mortality when they’re coronavirus infected than younger people, but in a sense. And what makes the worry about releasing of the constraints. Everybody is vulnerable. There are kids that are dying in infancy from this virus in China and in the US and we have no idea. And it’s a tremendously interesting research question, how general it will be, is why are kids not dying at the same rate. If you were to look at influenza, it’s young children and old people who died from flu. This is very different than that in that young children seem to get infected, and as Bill said they get infected as easily as anyone else in the household. What we don’t know is how good are they transmitting to grandma and grandpa within the household and there shouldn’t be data from China on that I would hope. But I don’t know.

BILL HANAGE: Yeah. Yes, exactly. I completely agree. The only thing I would, the thing I would add to that, but it’s actually pretty much what

Barry was saying, the risk is not zero for any cohort. And there is always a risk, it is just lower. But if a very large number become infected as we are seeing, you may discover interesting things. I’ve been seeing reports coming out of the UK yesterday, which has been very hard hit, that there appears to be a suggestion of a syndrome similar to Kawasaki disease or something, which suggests some kind of [INAUDIBLE] regulation, which may be linked to COVID infection which has been identified and children.

It’s very early days. What it is and whether it’s linked to the pandemic is not remotely clear. However, I just bring it up in order to note that sometimes you can, if a very large number of people become infected with something, you can discover rare sort of consequences that that you would not detect if things were somewhat better controlled.

Q: Great. Thank you so much.

MODERATOR: Next question. There’s some evidence of the virus strains studied by the Cambridge group that the virus. A, B, and C spread in Japan, the US, especially New York, and they’re from Europe, not China. What does this mean? What can we learn next from the virus strains?

BILL HANAGE: Okay, I think I’ll take this one. I think the first thing I will say about strains, is that I personally think it is a little bit premature to be nailing down notions of strains. This is still a very genetically quite uniform virus, which has got all the variation that’s in it has descended from common ancestor probably sometime in November last year. So, there’s not very much genetic information to distinguish between, you know, different strains and certainly not enough data to strongly say, whereas, we’re not any of them are associated with particular clinical presentations.

Having said that, your question is – you’re quite correct in that, if we look at these deep branching things within what we call phylogeny, or the tree of the virus, you can see that, in general, the West Coast of the United States has been infected probably by a virus which was circulating around China, whereas the East Coast has been infected predominantly by viruses which were introduced from Europe. That is pretty clear. It’s also not 100% because a study out of Yale that was published I think a couple weeks ago showed that there were cases in Connecticut of disease that was quite similar of disease caused by viruses that were genetically similar to those which were found in Washington State. So, this already indicates that by mid-March essentially, your chance of getting infected

with COVID-2 was more likely – you were more likely to be infected from within the United States than you were by somebody who is traveling from overseas.

I think that we are going to hopefully understand a lot more from the genetics of the virus and from looking at these phylogenetic trees. However, I think that we have to be very careful in interpreting those sorts of data when there’s not very much variation, really, to go on.

I mean, there’s more than a handful of mutations which are present in the population now which we can use but there’s still not very many in comparison with other things like say influenza.

MODERATOR: Dr. Bloom, did you have anything you would like to add?

BARRY BLOOM: No, I think that’s true. And it’s lucky that we have small mutation markers that tell us where the virus is likely to have come from. That suggests that there was an awful lot of travel of the virus before we had our first case and knew where they came from. So, it shouldn’t be a great surprise given the number of flights that came out of China between December and March.

MODERATOR: Next question.

Q: Hi, thank you so much for doing this. I have a question about Germany, which I know started this week to take some tentative steps that easing some of their measures. But then reports to come out with the reproduction rate had ticked up and I was curious how effective of a measure that is to look at the reproduction rate when evaluating these kinds of lockdown measures. And also, basically, Germany’s done a better job of kind of controlling the virus compared to some other European countries and what lessons can sort of the US learn from their experiment do you think as we kind of evaluate our own stay at home measures.

BARRY BLOOM: Why don’t you take R0 and I’ll take the time frame?

BILL HANAGE: That’s exactly what I was about to suggest. So, as you say, Germany has done very well and is now in the process of refining the instructions to stay at home. This has an impact upon the reproductive number. Now what we’re thinking about here specifically would be the effective reproductive number. If you want to come up with a very rough estimate of that for yourself. It’s really easy. You just take the number of cases that have happened over the last two serial intervals, which is about six days, so last six days and then you compare that with the six days before that and you see wherever it’s going up or if it’s going down, and that gives you an indication of whether or not the epidemic is growing or not.

Now obviously there’s much more to the statistics and that because your ability to accurately count the number of, sort of, incident cases [INAUDBIBLE}. And as a result of this, I think the changes that we’re seeing in the reproductive number can be considered to be real and to be the consequence of this. And you can reasonably infer that they could be the consequence of the relaxations which will be put in place. This doesn’t mean necessarily that refining or relaxing some restrictions is not a possible thing to do, but it does indicate very clearly that these actions have consequences. And so, we should be similarly prepared as we start doing things on United States to be watching very carefully and to be trying to look at those changes in the effective reproductive number and then gaining them out into the future to ensure that we don’t find ourselves writing another exponential.

BARRY BLOOM: I’ll just chip in that within two weeks of the publication in January of the RNA or cDNA sequence of the virus, the Germans had produced a diagnostic kit which was then tested and found to be valid at WHO and was widely being used in Germany and sent elsewhere, while we were struggling for weeks and weeks and weeks to get started, to be able to know what the state of the epidemic was here. So, in a sense, the reason their numbers are down is that in the case of an infectious disease speed is of the essence. If things are doubling exponentially, every day you lose, if it’s a one day or two-day exponential, you’re getting behind the curve. And Germany in that context, I was in a way remarkably surprised, was the country that actually got there first outside of China with an effective diagnostic testing strategy to use it.

BILL HANAGE: Yeah, Germany’s been really impressive so far.

MODERATOR: Okay, great. Thank you. Next question.

Q: Hi, thanks for doing the call. I just want to know if you can give an overview of the race for a vaccine. Can you just talk about who the major players are? I know there’s J&J, Pfizer, Oxford University. And what’s your best guess for a timeline in terms of having something in hand for emergency use and then some scale for widespread use? Thank you.

BILL HANAGE: I think that’s for you, Barry.

BARRY BLOOM: This is an exploding field, so perhaps I would go back a bit and say, what makes this different than any other set of vaccines that has been developed in the past is that preparations were made starting a number of years ago, maybe a decade ago, before SARS, but after bad flus to realize that we’re going to get infectious outbreaks and epidemics on a continuing basis and catch up with vaccines, which is the only thing if they really work is a way to get rid of infectious diseases.

And we have a lot of experience from polio, and smallpox to know that can be done at a global level. But in the past, no one invested in making a vaccine for an infection that didn’t exist. And I would say certainly here after 9/11 there was a tremendous concern about terrorism in the United States, both the standard kind of terrorism and the nonstandard kinds, which would include biological and chemical and radiological warfare. And so, I had been on a National Academy committee in 2001 that recognized that we were extremely vulnerable for both terrorism and epidemics and, as a result of lots of people’s concerns, the government created an organization called BARDA, the Biological Advanced Research and Development Agency whose job was to be able to anticipate biological and radiological and chemical threats, including pandemic influenza. At a talk given at the Kennedy School here are a couple of years ago, the director said the mission of BARDA was to be able to make a vaccine against a new agent in 60 days. And if you could think about where we were on January 1, had we had a vaccine available in 60 days we wouldn’t be on this phone call.

Ordinarily, vaccines take years and years to develop. And so what BARDA did initially was to say we’re not going to plan for additional vaccine, we’re going to create platforms. We’re going to create entities that once we know what a new agent is we can put the genes in for the particular antigens that will be protected. And we will have a backbone that is safe and effective that has flexibility to have genes added and proteins added that can rapidly take advantage of the platform and get this stuff in people.

And that’s exactly what BARDA did. it has three platforms. One is RNA, which is what encodes for protein and what is being put in there by a company called Moderna is an RNA with lots of genetic tricks to keep it a stable and effective, that when they stick it into you, your muscle cells actually make the antigen and produce the vaccine. And that can be done, just like in 62 days that vaccine was from the time of a sequence into the first volunteer’s arm prepared and given in a phase one safety test. J&J had perfected for other infections for influenza for Ebola, lots of people made vaccines for Ebola. They couldn’t be tested because Ebola died out before you could run real trials, which is one of the worries about investing billions in vaccines. If the epidemic goes away because social distancing works so well and people get herd immunity, you’ve lost a complete investment. In any case, that’s a platform with an adenovirus have a harmless respiratory virus, for which you switch the antigens for the coronavirus spike protein and you put it into this vaccine that has been tested in people before, and that’s on the way. And the Oxford group has another backbone and Pfizer has another platform. And these are being put forward. And so there will be, I think there are 70 companies that are preparing creative vaccines against this coronavirus

What will be limiting is not the imagination or the ability of genetic engineering, it’s who has the capacity to produce at a global scale level billions of doses if in the initial studies is shown to be safe and effective. And I think there’s a caution no vaccine is really 100% effective. And there is no vaccine that has zero level of adverse effects. For the common vaccines we use in kids, adverse effects that target is one in a million because humans are so variable that there is some kid somewhere or adult somewhere that’s going to have an oddball reaction when everybody else minus one in a million will have an adverse effect.

So, J&J is preparing to produce at scale, Pfizer is able to produce it scale. Oxford is working with probably the world’s largest vaccine producer, I would guess, which is a first-rate place in India called the Serum Institute of India, and they are racing for market dominance if their vaccines are shown to be safe and effective.

Two points: to build a vaccine, you need to invest huge amounts of money to build a factory and if the vaccine is unsafe or ineffective, all the money is invested upfront and it’s a huge gamble. So, we should be very grateful for the companies that are now committed themselves to move forward with this vaccine which on a global level strikes me as not likely to be a big money winner. And the little companies I think are going to have a great deal of difficulty getting into the market if any or all of the big initial vaccines are safe and effective.

Q: Any sense of timeline when you’ll be able to, you know, walk into doctor’s office possibly get a vaccine. I know it’s a guessing game, but any sense?

BARRY BLOOM: The current race is suggesting they can prepare vaccines that have been shown in a small number of people to be safe enough that they might get the FDA to give them emergency use clearance to expand the immunization and run trials while they are protecting people, for example, healthcare workers or people in nursing homes.

That remains to be seen. But I think that’s the strategy, not doing traditional studies, as we’ve always done phase one, phase two, phase three, but getting them out, maybe even in the late autumn, but collecting data on them in the most rigorous way, using them to protect vulnerable populations and begin to collect data on safety and efficacy. So, we might see stuff in people before Tony Fauci’s famous 18 months. Whether we’ll have real information on their effectiveness and comparative effectiveness, I don’t think we’re going to have that easily before 18 months or two years.

MODERATOR: Great, thank you. Next question. He would like to ask first with the shutdown orders in Massachusetts extended until May 18 what sort of easing of restrictions, do you think would be appropriate at that date, if any, and second, what do you think of the face covering orders in cities like Cambridge and Somerville that require people to wear some sort of mask at all times and in public? And quick addendum to that second question, do you think these orders are effective or necessary given that the outdoor transmission appears to be very low?

BILL HANAGE: Barry, do you want to start with this?

BARRY BLOOM: No, I’ll start. And I have to say that I’m a big believer in facemasks, and I think we all know their limitations but if there are asymptomatic people to the tune of possibly even 25% or more who have virus and can transmit virus, it would be good for everybody’s health if they wore a facemask that isn’t necessarily perfect but reduces the chances that they will spread their virus that anyone else.

For those of us who believe we are not carrying coronavirus again even though they are imperfect, wearing a facemask if we have an encounter in a shop or a store, even if imperfect, can reduce what we would call in my business of infectious diseases, the force of infection. There are very few infectious agents that do not show in animals and most likely people a dose response curve. The more you get the higher, the chance you’ll get sick. The less you get, the more chance that you will get a subclinical infection or by innate immune mechanisms, just get rid of it.

So, reducing the spread at both ends from those who aren’t able to spread, but I’m aware of it, or a symptomatic and from those that might be on the receiving end, reducing whatever the exposure is strikes me as a terrific idea, and we should have done it a long time ago. It is aesthetically not pleasing, unless as in China, Korea and Asia, it becomes part of the culture. As we can see from the leadership in Washington, it is not part of the culture of politicians to walk around with masks. So, we will have an uphill battle maintaining that I think it’s a good idea. As far as the shutdown in Boston, I’ll turn it over to Bill.

BILL HANAGE: Thanks, Barry. So, I think you’re right to say that there is – I’m going to start off by saying that I agree on the topic of the importance of facemasks as a way of preventing transmission from unwitting transmission from people who do not know they’re infected, in particular the large what the potentially large fraction of people who are at the time asymptomatic or pre-symptomatic.

Now having said that, you are correct that there are these orders which have been put into place in both Somerville and Cambridge. I will be honest, I have had some discussion about some of these things in particular because I am on the expert advisory panel for the city of Cambridge but I have not had the chance to read what has been going on within the city council, so I cannot claim to be fully briefed on that.

So, I will comment on the science. The science is that if you are outside and you are not very close to anybody, for instance, wearing a face mask when you cannot see anybody, it is not really likely to be preventing transmission. However, if you do say that facemasks should be one under all circumstances, then you potentially then you have the potential to

urge people to be wearing them at all times and perhaps you cut down on the number of folks, you might be walking into a grocery store not wearing one. So, it’s a public health measure, which I think is intended to maximize the interruption of transmission. I think that it will need to be followed up with like public consultation in order to make sure that it’s communicated well to the people, you know, who live in those cities and to make the importance of it absolutely clear to them.

MODERATOR: Okay. And the first part of the question was with shutdown orders in Massachusetts extended until May 18, what sort of easing restrictions, do you think would be appropriate at that date if any.

BILL HANAGE: Barry, do you want to take this? I know you have views on easing restrictions.

BARRY BLOOM: I would say that I would work backwards and define who the most vulnerable people are, which is elderly and people with illnesses and I would be quite clear that they would have to plan on living under some sort of restrictions as best possible. I would ask for office businesses, for example, to be able to start as they have in New Zealand with smaller workforces, alternate days, disinfectant, temperature taking potential to get everybody who needs to be tested, opportunity for testing. And as you know, that is not true in Boston at the moment. I believe Somerville has now enabled anyone who wants to test to go register to be able to get that I would like to see major businesses have testing facilities within business that can test people on the spot if there’s a concern, but certainly checking temperatures and reducing distances within companies would be a smart thing.

For me, a big issue by fall is what to do with schools and it would be really important to get some data on that which has huge implications both for transmission, but also for freeing up the households, freeing up the families to go back to a more normal life. So, this is an essential thing for which we have essentially no data. And I’m not sure anybody is looking at a card at the moment. And then service business in many places in Sweden was, you know, in New Zealand and Australia, they opened up restaurants, which are really suffering enormously in this epidemic crisis, and again, there are ways to open them up with distancing between tables, people wearing facemask, testing people coming in for lack of fever. I’m not a big fan of the fever tests. If you get a positive it’s terrific. If you don’t, it doesn’t mean very much.

But at least it suggests that people are trying to be as careful as possible, which is terribly important in that context. So, I would start opening up those things where the public can go back to. And the last thing I would open up are places where people get crowded place to place, sitting next to each other would be Fenway Park and baseball games, I hate to say this because I know what stopped popular, houses of worship. That’s what created the epidemic in Korea. I think there have to be creative ways to allow worship to go on either with appropriate distancing and testing for fevers, like every other business should do, or doing it remotely, but getting people shoulder to shoulder under any circumstance should be really restricted until we see how things ease up and that we can have occasional flares of a few cases here and there, but not a major exponential impact.

BILL HANAGE: I have very little to add to that other than to point out that for some people Fenway Park is a place of worship. I would also say that – I think that you mentioned this, but the importance of being able to have enough testing that you would be able to detect some changes in the effect of regressive number, meaning that you’ve got something that’s building. So, you’ve always got a point where you’re like, we’re this far away from things going bad. And we have a plan for what we’re going to do if we have that kind of, if we see that happening. I also agree with everything that Barry said. I hope that those things are implemented. I

MODERATOR: Great, thank you. Next question.

Q: Thanks. Hopefully I can come in through a little more clearly. Now, just wanted to follow up on my question from earlier you had said basically that, you know, absent a vaccine, that this is going to be around, perhaps in a milder form long term. So really, kind of, what does this look like in the future hinges on the nature of the vaccine, if I’m understanding correctly. Will this be something that can provide a true and complete immunity to some degree, or is it just something that’s going to so less than it is that kind of, I understand that correctly.

BILL HANAGE: Yeah, just to summarize, I’ll say this again and then Barry can leap in with whatever else he would like to add. In the absence of a vaccine, it depends on how many people gain immunity, how quickly, and what that immunity looks like in terms of protecting people from subsequent infections and then what those infections then look like when they happen. And at the moment, really all, everything is on the table.

There could be milder, less transmissible or, indeed, there is the theoretical possibility at least of antibody dependent enhancement. So, at the moment, it’s very, very unclear. In the presence of a vaccine that was 100% effective and gave lifelong immunity, then you’d be able to exclude the virus of the population, which would be wonderful. However, vaccines may not be quite that effective, in which case the impact upon disease will be to reduce it and we may then have to look to see what happens when people who’ve been vaccinated sort of get boosted by exposure to the natural coronavirus which is then circulating. So, Barry, anything you want to add to that?

BARRY BLOOM: No, I think that that’s right. Vaccines are almost never perfect. And I would say there is a countervailing force that we’ve seen emerge that to those of us in sciences is very worrisome. The first anti-vaccine organization occurred I think in this country in the 1880s. So, there’s a great tradition in this country of attacking vaccines which, in our view, has protected kids against 14 lethal diseases.

And if there were a credible vaccine that isn’t perfect, would people volunteer to take it early on and, if it were shown to be safe and effective, would they take it later on? We know there is enormous misinformation in the social media that is continuously fed upon by skeptics and doubters that actually in this context would threaten our ability to control the outbreak, the epidemic. So, the vaccine is a tool only if it’s used.

BILL HANAGE: I think the one other thing I’d add to that is just a reflection that people who don’t like vaccines, who don’t like herd immunity generated by a vaccine should reflect on what herd immunity generated by an actual infection looks like.

Q: Thank you.

MODERATOR: Next question. In the Caribbean region, reopening or refining is largely twofold effort. For example, in the British Virgin Islands, the territory ended its month-long continuous lockdown on Monday, allowing for limited movement within the territory. However, a bigger question is when we will look at reopening the orders to tourism. What are some key considerations to take into account as the Caribbean countries plan for the long term?

BARRY BLOOM: I could just start by saying that I have found the circumstances in Australia and New Zealand fascinating. They have done a marvelous job if – for example, on December 31 when the Chinese announced they had an epidemic going on in Wuhan and they announced there were a total of 27 cases. So, for any country to respond to report of an epidemic in a remote part of China with 27 countries as New Zealand did in shutting down all flights from China, that was an extraordinary bold move by their extraordinary Prime Minister, and that has helped to keep the total number of cases in that island down to something like – don’t hold me to the exact number, last time I looked, it was 1400 in the entire accumulated number of cases in this island.

And so, the thought would be, what WHO and many epidemiologists have always been skeptical of that stopping air flights and travel is not going to have much of an impact. In an island like New Zealand and to a similar extent in Australia, it worked, but only if it happened very early in the beginning. So, I would ask you to imagine Manhattan Island trying to do what New Zealand and Australia and you would realize the futility of that as an effective strategy of keeping the virus out of a country. Having said that, then you have to look at places like Hong Kong and Singapore where they did relax travel restraints and the epidemic burst up in both places, one from migrants, which is an unexpected source of infection living in very close housing and that’s accounted for Singapore and for China. And now for Hong Kong, it’s people flying in from Europe and the United States. And what they’ve done is they are working to be able to take samples at the airport and insist that you stay in a hotel for two weeks until it’s shown that you are negative, and able to go out.

So, I think we really have to think about if we did things down here, the big worry will be as it was in China, Hong Kong, and Singapore, reintroduction from those parts of the world, possibly in the sense Southern Hemisphere, which are coming into the time their winter time where you would expect respiratory infections to rise. And I think we have to think very seriously about how to control visitors from overseas in a way that protects our population and ensures that they are well taken care of before they can enter into a constant flow within the American population. That’s going to be expensive.

BILL HANAGE: Yeah, I would echo all of that. I will comment that if you look at places which seem to be doing really well, certainly early on in the pandemic, what they have in common in almost all cases is that that they are islands and islands are able to control who comes in and out, especially small islands in a way that is much more heart of the places like Barry was saying, Manhattan.

Moving forward for a place like the Virgin Islands, for which tourism is such an important part of the economy, you have to reflect that, you know, these while these travel bans are, as we were saying, typically they’re only really helpful at the end in terms of sort of controlling stuff. However, if you at the moment, have no pandemic on your island, and that’s a state you want to maintain, then it is something you very seriously have to look at travel restrictions. Perhaps travel from places with relatively low COVID activity. Perhaps you can think of all these temperature checks and the likes were talking about that, as we were saying, if the temperature check comes back and they got a fever, okay, maybe that is COVID, maybe it’s something else. If it comes back to regular, no temperature, it doesn’t mean that you don’t have the, you know, you’re not potentially infectious. So, the safest thing to recommend would be a sort of quarantining process, but that’s probably not something which is going to be possible within the context of a vacation. And so, it’s going to be very difficult, moving forward, and I wish I had something which was, I wish I could have more positive prescriptions, but a pandemic is a pandemic.

BARRY BLOOM: What could be is in the grand scheme of the plans for from the government from people who were in government who made very thoughtful plans of how to stage open up the country. I haven’t seen anything serious about how to handle the necessity of people traveling from one part of the country that has one set of regulations in one state coming into another state, let alone what we do in airports and mostly travel from foreign countries that would come by air. I think that’s an area that really need some serious thinking.

MODERATOR: Thank you. Next question.

Q: Hi, thanks for doing this. My question is about vaccines. Given the number that are currently in development, are there any objective milestones that would allow reporters to assess which vaccine is actually furthest along in development?

BARRY BLOOM: Yeah, I mean the ones that can get into people’s arms the quickest are the most advanced and some of that is the technical preparation that was put in over the last five years, developing platforms that could be adapted to any new viral agent that comes around. And the second piece of it is companies that have the money to be able to move it forward at a level producing it under appropriate safety conditions that little biotech company simply cannot do.

And so, the issue of scale becomes a major variable, perhaps even more than the science with one caveat: we won’t know how those vaccines work until they’re put into people and we get some real data on how protective they are. And I have to mention that there is a potential adverse effect for vaccines against certain viruses that can actually enhance the infection and make things worse. And the companies are all acutely aware of that. It has dampened any interest or ability to think of vaccines against respiratory syncytial virus where that turned out to be a very big practical problem in a small number of children.

So, the safety stuff cannot be taken for granted just because someone puts it into the arm first. There’s lots of careful follow up at study

and then the questions are, how long does the immunity last. Let’s say they’re all good but one lasts a year and the other one lasts five years. Don’t forget measles vaccines largely lasts, at least measles infection lasts a lifetime. We thought the vaccines lasted a lifetime. They don’t last the lifetime. And now we give a second shot to adolescents so they can maintain it. So, there’s just an enormous amount to be learned, but those that are already moving quickly, have been in the works for a while, have tested related viruses before – this is not their first shot. They were in Ebola. They were in MERS. They were in influenza. So, there’s a community of experience that gives me hope that most of them will have some degree of efficacy and that most will be shown to be quite safe.

And then the question is, how good are the immune responses they produce. Do we only need antibodies or do we need T cells? Nobody knows. And how long would they last over time. Since 1796 when Edward Jenner tested the first smallpox vaccine, there’s essentially no vaccine that has ever worked the first time perfectly. So, vaccines are an iterative process. And if Pfizer or J&J find a biotech vaccine that does what they do better, they will certainly acquire it and get it into the field, but to get it into the field, we’re talking about vaccines that have to be available globally. It would be inconceivable practically, morally, and politically to have a vaccine that is only given to Americans and let the rest of the world not have a vaccine. The hope is that the vaccines can be made in different countries and we will not be responsible for every bit of saving the world against this disease. But at this point, the scale has to be global.

Q: Thank you.
MODERATOR: Dr. Hanage, do you have anything you’d like to add?

BILL HANAGE: I’d echo what Barry was saying that the availability of a vaccine will enter into all kinds of logistical issues. And also, you know, important moral ones about making it available to the world. Because, you know, as we’ve seen from the testing, it’s not enough to just have the tests. It also got to have the stuff that I said, the RNA and you’ve got to have the swabs, so you’re not only going to need a vaccine, you’re going to need to be able to get out there quickly.

Q: Thank you.

MODERATOR: Next question. Go ahead.

BILL HANAGE: I can see you.

Q: It sounds to me as if there are three horses in this race: the vaccines, the herd immunity and perhaps some sort of pharmacological treatment. Is my count right? Are there three horses, and if so, which one do you think will win?

BARRY BLOOM: There are four horses of the apocalypse, I’m afraid. The one that we haven’t talked about is drugs and I would just say that there are a slew of drugs underway for testing where the object is to keep people from dying, and I am modestly optimistic that the science behind those many of those drugs. Much of it is empirical, but a lot of it is careful design of drugs that would prevent this virus from really going whole hog in any individual.

Having said that, that will not have a huge effect on the susceptibility of the vast majority of the uninfected people, which is to the tune of 80 to 90% in most parts of this country. So, drugs will have a big effect on reducing the mortality and we really are then stuck with finding ways to postpone the serious consequences of the disease, both on people and on the economy of people until vaccines can get out and provide some degree of protection. I’m often criticized when I support vaccines. When people say, ‘but the flu vaccine is only 50% important.’ 60,000 people got influenza and that’s with a 50% of people getting vaccine. So, 60,000 is better than 120,000. Even if the vaccines aren’t perfect, they can have a great deal to contribute. Without vaccines, we are left at how do we get herd immunity without having so many people killed.

BILL HANAGE: I agree with all of that. I would say that in terms of the number of horses on to add maybe one very small horse, maybe like a pony or something, which is we’re learning different ways on how to manage this. So, for instance, the need for ventilators has been – initially, there’s been a great incentive on ventilators, but it’s also been found that there are alternative ways of managing some patients which do not require ventilators, which is great because you don’t want to, you know, you don’t want to mechanically ventilate somebody if you don’t have to.

Similarly, we may find other smart ways of talking about or thinking about this. I mentioned co-infections earlier, roughly, there’s I’ve seen two k series now, [Inaudible]. So, it’s possible that effective ways of being able to identify them earlier and manage them effectively might help with that. So, it’s not going to solve things, but if we can learn more about it and if we can manage to do so in such a way that we’re not straining to avoid our healthcare systems being overwhelmed, then I’m optimistic that we can do better. Even if you know this pony isn’t going to take us to the finish line, but it might, it might help us some of the way there.

MODERATOR: Did you have any other follow up questions?

Q: Yes, yes, just briefly, and so I had been until today, imagining the vaccine as a date in history that we’d see Dr. Fauci coming to the podium at the White House or someone else saying we have it. But it doesn’t sound like it’s going to be a precise point in time, it sounds like you’re going to be competing vaccines, that they will go through various trials, some will be effective, some will be not, that through won’t the vaccine development won’t be a point in time, but along stretched out period where it’s introduced tested and then may be taken back. Is that right?

BARRY BLOOM: At the same time that the number of cases is dropping so that the ability to know whether multiple vaccines are working is going to become more and more constraint. That’s why the Ebola vaccines were dropped. There weren’t any more cases.

BILL HANAGE: Yeah, if it’s going down, it’s been hard to actually test to see whether it’s stopping more people getting infected.

BARRY BLOOM: So, to go back to your earlier question, the quicker they get out safely, the more likely we will know how effective they are.

BILL HANAGE: But I think also, I think that you’re right that there’s not going to be a point when there’s a sudden announcement, ‘ooh, the vaccine is here’ and it would be more likely to be negotiated with whichever company has got something has some positive data which they think is going to be helpful. And then there are people who are trying to think about more sort of different study designs. So, I know that my colleague Marc Lipsitch has been thinking about how to do like more rapid ethical vaccine trials because obviously when you’ve got a pandemic going on, you want to be able to get this done as quickly as possible.

MODERATOR: Okay. I have one last question. She said she understands that the data show that older people are at greater risk of dying from this virus, but what do you know about the ages of people who are sick enough that they need to be hospitalized?

BILL HANAGE: I have not looked at any of those data recently. I can only – I’m only faintly remembering some of which come from Italy and Wuhan and as a very good study from California, the first author for which is Joe Lunard, but I’m blanking on what it found so I’ll leave this one for Barry.

BARRY BLOOM: I don’t have the expertise to answer that.

MODERATOR: Okay. I guess that’s our last question. Dr. Bloom, did you have any final words you’d like to say before we end the call?

BARRY BLOOM: No, I appreciated the questions very much.

MODERATOR: Okay. Dr. Hanage, you have anything else to add?

BILL HANAGE: I would say the same thing. Thanks everybody for tuning in. And thanks for doing the work of telling people about this.

This concludes the April 29 press conference.

Michael Mina, assistant professor of epidemiology (April 28, 2020)

Michael Mina, assistant professor of epidemiology (April 27, 2020)

Michael Mina, assistant professor of epidemiology (April 24, 2020)