Coronavirus (COVID-19): Press Conference with Barry Bloom and Bill Hanage, 08/25/20

You’re listening to a press conference from the Harvard T.H. Chan School of Public Health with Barry Bloom, the Joan L. and Julius H. Jacobson Research Professor of Public Health, and William Hanage, associate professor of epidemiology and a faculty member in the Center for Communicable Disease Dynamics. This call was recorded at 11:30 a.m. Eastern Time on Tuesday, August 25th. 


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

BARRY BLOOM: I would say one thing that is very much on my mind is the issues related to what I would categorize as the absolutely critical need for trust in science. It is critical that the press keep the scientific community as well as the leadership within the country as honest and transparent as possible. On the other hand, being critical can also compromise trust in the leadership and trust in the science. So I have enormous respect for the responsibilities of good journalists and I think this is a really tough time to carry out that role in as fair and unbiased way as possible. 

MODERATOR: Great. Looks like Dr. Hanage still isn’t on the call yet; he’s still having some technical difficulties, I think. He was unable to hear anything. So I guess we will go ahead and start taking questions. Looks like first question. 

Q: Thank you for taking the question. Dr. Bloom, this actually gets to your opening remarks. We were speaking to a principal investigator here at our research university who’s actually trying to launch a convalescent plasma trial, a randomized clinical trial, this week with other hospitals in other parts of the country. And he describes himself as being in an awkward position because, you know, you have this treatment that they don’t really know how it works or how to best use it. And it’s been hailed as a breakthrough. And now they have to convince people to enroll in a clinical trial based on their altruism, which he said is not typically how it works. So I just wondered if we could get your comments on that and that kind of position that clinical trial researchers have found themselves in. 

BARRY BLOOM: So it’s been known since the 1890s in the case of diphtheria, that you could take serum containing antibodies or plasma containing antibodies from children or adults who recovered. And if given early in the course of diphtheria, you could save lives. And that’s been used on and for a number of infectious diseases. So there’s nothing new or mysterious, particularly about plasma therapy. When you have nothing else to provide, it makes a lot of sense to give it a try. The way in modern times give it a try is done is to run a meaningful clinical trial to see whether it works, in whom it works, how long it works, and whether there are any adverse effects. In this circumstance of COVID with not a lot of spectacular treatments available for people. One of the things that I think has been missed in the press is the use of plasma has not been limited by anything in the FDA. It is available for expanded access program. Not the same as emergency use authorization. Separate them. The expanded access program is what used to be called compassionate use. When a patient is in a condition where they’re on ideal or well recognized treatments and threatening death, you can get extended access to new potential treatments. And that has been not really limited in the case of COVID. For the Mayo study, which had multiple institutions, about two thousand institutions recording their experiences with giving convalescent plasma. There were thirty two thousand people who received convalescent plasma. There was essentially then no necessity for people to have an emergency use authorization to be able to have access to a potentially lifesaving procedure. 

What is missing is the data from randomized control trials to know answers to all the questions I raised. Does it work? When does it work? How effective is it? And is it, given the complexity and variation in plasmas? Is it really worth pursuing at a major level? And fourthly, with the randomized control trials under way, does this make it, as the questioner asked, as bad? Is there any reason for anyone to volunteer for a trial and have a risk of getting placebo when they can simply ask for extended access use to the plasma without knowing when it works? So that’s a real problem for us. And at least for me, because this isn’t a circumstance where that approval had to be given in order to provide access. The other issue also raised is once it’s available, why should volunteers continue in the randomized control trials to find out if it works and and how it works? This is important for a couple reasons. The first is in the Mayo trial, using a, I must say, so-called semi qualitative assay, which is not quantitative. After the plasma is taken, may send it to a laboratory to find out how much gamaglobulin it has, how much antibodies it has. And they broke it into a low, medium and high based on no absolute figures. And the answer was this, in that paper, worked a little bit for people under 60 in the first three days of infection and only essentially useful in those plasmas that had the highest level of igg antibodies. That’s a pretty narrow group, given all the people who end up in a hospital with COVID. And what we’d really like to know is how effective is that. Now, what are the alternatives? And they’re not available yet in any large amount, but this is how I would see this playing out a lot better if it were tested in time. First, you have the potential of what was used in many other circumstances of what’s called hyper immune immunoglobulin, where you screen plasma donors for those that have the highest level of antibodies and you only make a gamaglobulin fraction from those donors. And that doesn’t have to be given as this convalescent plasma by going to a hospital and getting an intravenous injection over a matter of hours. That can be given in the muscle because it’s concentrated high level antibodies and they last for perhaps a month or two. And so you could keep people protected in that circumstances in a much more secure way. There are trials proposed to do that. But as I’m not aware, hyper immune, anti COVID gamaglobulin reagents are available for intramuscular use at this point. The second alternative, as I’m sure you know, is monoclonal antibodies that were selected from hundreds of donors that have recovered to get B cells making very high affinity antibodies. So there are two things that count when you want to neutralize a virus. One is how much antibody, and the second is, how firmly does it bind the receptor binding domain of the virus? How effective is it at blocking infection? And it turns out with really high affinity antibodies, you don’t need a whole lot to get protection. So that simply measuring high g.g levels may not be the absolute best way to know whether a serum or an antibody or hyper immunoglobulin is likely to be the most protected. And again, that requires producing hyper immune globulin or testing these monoclonal antibodies. The monoclonals have been designed to be high affinity and I have a problem with monoclonal antibodies is they are expensive to produce and they’re hard to produce in huge amounts because they’re made in bioreactors with mammalian cells. So that’s where we are at the moment. We have plasma available without any good understanding of when and how effective it is and a lot of hoopla around it that may be inhibiting. Which is my fear, the development of better reagents that are more likely to be predictably effective. 

MODERATOR: Do you have a follow up question? 

Q: Yes, I think just real quick. You were kind of getting at this before. The physicians and local hospitals we spoke to about this said that they the physicians oftentimes don’t know and sometimes they don’t think the blood bank itself knows what level of antibody feeders are in the plasma. I’m just wondering how unusual that is. It kind of seems unusual to me, but I’m not familiar with how these things typically work. 

BARRY BLOOM: No, that’s normal for a plasma transfusion. What they what they do is they bank plasma from convalescent patients. And then when there’s a patient who needs plasma, as in the Mayo study, they give the plasma, each donor pint of blood and each donor lot of about 200 milliliters of plasma, in the case for the Mayo study, was sent to a laboratory and only measured for antibody after the fact. Does that matter? Well, we can infer from the study, if the plasma didn’t have good antibodies, it didn’t do very much. That was helpful. And so the ideal would be to have plasmas screened by the blood banks for a test for measuring antibodies. So patients got the high antibody plasmas, which they did not and do not in this case. That’s not the wisest thing. It seems to me for the benefit of the patients. 

Q: Thank you very much. 

BARRY BLOOM: Can I just say one more thing? There is a remote possibility, but not to be dismissed, that not only would low antibody or low affinity antibody plasmas not be protective, there are circumstances, for example, with places like respiratory synthetical virus or in the old days, in measles, where low affinity antibodies can actually enhance infection. It’s a little different than antibody dependent enhancement that we’ve been worrying about. But lousy antibodies not only cannot be helpful, they can sometimes bias the response. So it is important that they get data on your question, ideally before it is given to people. And we don’t have a system to do that that I’m aware of. 

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

BILL HANAGE: Other than to say, hi, everybody, sorry I was delayed. I have had a Zoom crisis and I’m having to talk to an external microphone with headphones, as you can see, it’s all very weird. I did not hear the initial question. Could you ask it quickly again? 

Q: Sure. Yeah. So I was just asking about this position. We spoke to a clinical research trial leader here in Miami who said that he’s been put in this awkward position of trying to enroll people in a clinical trial after it’s already been celebrated. Yeah. So that was the start of the question. 

BILL HANAGE: I think the only thing I have to add on this, Barry mentioned this, is that the results that we’re talking about are being pushed as a sort of 35 percent improvement, but that’s actually a 35 percent change in small numbers. So it’s like going from eight percent of people showing improvement to 11 percent of people showing improvement. So the actual benefit per patient is not as high as it may be to be immediately apparent. And that’s sort of statistical work in the way that you interpret the outcomes of these things. If that wasn’t mentioned. I just want to emphasize that. 

BILL HANAGE: That’s great context, thank you. 

MODERATOR: Next question. 

Q: Thanks so much for doing this. I was hoping you could speak about this in the context of vaccine development. Does it concern you that the FDA approved this, as you say, unnecessarily at a time when we’re very worried about their credibility in terms of vaccine development? 

BARRY BLOOM: So I think the answer is for almost everybody that I know in the scientific community is very concerned. And it was a concern that we’ve really never had before. I’ve tried to make the point that through compassionate use or extended access, plasmas have been available and accessible to patients. There was no significant restriction on their use. When the vaccines become available, the limit will be the availability, the number of doses. Once a vaccine is approved, it can be applied to the population. And the high priority groups to get it early on. So they’ll be even enormously greater pressure when the availability of vaccines is limited. For every group, every pressure group, every organized group and lots of influential individuals to try to get access to that vaccine. And we have always held at the FDA, a very large agency, we know has technically competent, long term, experienced people dealing with safety, safety issues mostly gets it right and works really hard to protect the public. 

I would point out, for example, that people have to sign off on a new drug, have personal liability so their names are associated with the sign off. And in this emergency use, it is a worry to me that someone who was involved in the procedure did not allow his name or her name to be used. Which I’ve never heard of before. So I have a lot of faith that the FBI, technical people who sit through one government after another doing their job are going to do their job. What is disturbing here, after a history of hydroxychloroquine of antibody assays, that we’re just all allowed can be used without any standardization. And now an overnight revelation that a plasma treatment that was available to people on Thursday without an emergency use authorization got authorized in some way with, as far as we can tell, data that don’t answer the critical questions of how effective is it, how safe it is and for whom is it effective and who is it not. That is worrisome because in the case of vaccines, the pressure will be far greater. And I would hope the leadership of the FDA would stand firm on the scientific basis. Otherwise, the trust in the whole scientific enterprise becomes compromised. And there are a lot of people in the anti vaccine world that are looking forward to precisely that. 

MODERATOR: Dr. Hanage, do you have anything you would like to add?

BILL HANAGE: I thought that was an absolutely brilliant answer. I agree wholeheartedly with all of it. Sorry, Barry. Sorry to be giving you too much. I would only add, as I’ve said before, that even if a vaccine is for true, emergency use authorization. And I would be very anxious about the circumstances under which that would happen. I think they need to be considered very, very seriously for all the reasons that we just said. I would add that getting a vaccine is only the first step. And we’ve said this before. Getting the vaccine is the first time. Getting it out to people is the important thing. And that is going to be an absolutely crucial thing moving forward. But the most important thing is that it’s a vaccine which actually does what we wanted to do and that it doesn’t have damaging, rare side effects and things like that, because there are a lot of people who are opposed to vaccination who will jump on it immediately, with any excuse they got. 

MODERATOR: Do you have a follow up question? 

Q: One tiny one on that and then a separate one. So I want to be a hog, but tiny one on that was Dr. Bloom, you mentioned that nobody signed their name on this one and just wondered if you could expand on that. I wasn’t aware of that. 

BARRY BLOOM: I only read it in The New York Times that it was no name given, and that’s a very unusual procedure. I would be keen for the press to pursue that where I mentioned it. 

Q:  And then on a totally different topic. Wondering if you guys could talk to the Biogen report that came out this morning or yesterday maybe, about Biogen and the spread of that infection and the implications of our understanding of that, if you’re aware of it. 

BILL HANAGE: Is this the preprint on genomics? I’m on the paper, or I’m on the preprint. So, yes, I think I can talk about it. I think if it’s what I’m thinking of and it’s familiar, if it’s what I’m thinking about, it does certainly appear that this isn’t surprising. We shouldn’t be pointing fingers. It does appear that a substantial fraction of the genomes within that sample, which is not a perfect sample, but it’s one of the better ones that we have from Massachusetts. A substantial fraction of them were descended from that super spreading event. And I would say this illustrates a number of important things. The first of them is the role of these large spreading events and introducing the virus to a community. And the other thing I’ll comment about it is that we see very rapidly within a short period of time that you find a genetically identical virus which has a mutation, which is pretty indicative that it came from that meeting in very, very different settings. So once again, this illustrates the fact that this is a transmissible virus that is able to move very rapidly and among different parts of our society. And the difficulty in keeping a lid on it and some virus which transmits by the respiratory route. And those are very difficult to contain. 

MODERATOR: Dr. Bloom, do you have any comments? 

BARRY BLOOM: Oh, absolutely spot on the answer. Wonderful to have Bill on the paper, and know the real data. This virus spreads in communities and spreads up and down the socio economic status in ways that we really don’t understand. And that’s been true of super spreader events in Korea. One person came to visit and went to five bars and one night and created a major outbreak. So control of this virus, community spread of this virus is absolutely essential. 

MODERATOR: All right. Do you have a follow up to that or are you all set? 

Q: Just wondering if this super spreading changed at all our understanding of the contagion of how it passes, it seemed obviously people were shaking hands, but it seems sort of stunning that that many people would have gotten, I guess 96 people would have gotten it that quickly in one large room. 

BILL HANAGE: Indeed, we don’t. There is a large amount about these kind of very clustered events that we do not understand well enough at the moment. The absolute details of it remains to be seen. And I know it does illustrate that these super spreading events are not likely to be in the same kind of thing that we see in run of the mill transmission events. And that means they deserve a lot further study. Now, obviously, that means we have to look at others as they occur. And hopefully, I have to say super spreading events are going to remain rare because we are hopefully not going to give the virus so many opportunities to spread via that. However, we are going to have to continue watching this openness in coming months. 

Q: Thanks. 

BARRY BLOOM: Would point out that they were in a room at least two days, all day, in a closed room. 

BILL HANAGE: With unknown amounts of ventilation. 


MODERATOR:  All right. Next question. 

Q: Thank you guys for taking my call. Can you hear me? 


Q: Fantastic. OK, so the first thing I want to say is that, you know, we’re getting the reports today that Oxford and AstraZeneca’s coronavirus vaccine could be in front of regulators this year. So with the word ‘could’ being included one, how likely is it that vaccine will go before regulators? Two, what does that actually mean for the vaccine? And three, how does that impact the timeline, getting the vaccine out? 

BILL HANAGE: These sound like Barry questions. 

BARRY BLOOM: The answer for, at least in my understanding, is not clear in the following sense. It is possible, but unlikely that the Phase three trial of individual volunteers in the US, thirty thousand people, will be completed by mid to end October. On the other hand, that vaccine is being tested in Europe, in Brazil, and there will almost certainly be accumulated data on that number of people, possibly by mid-October or early November. 

It is traditional that the FDA requires data on American or United States individuals and doesn’t take the word of other vaccine authorities in general to substitute for data from U.S. people. It is not impossible that the FDA, with or without pressure from above, could go on. The accumulated data from Brazil and Europe added up to get thirty thousand people. And if the data are then allowed to be opened by the Data Safety and Monitoring Board, the DSMB, if those data show very significant protection, they could issue an emergency use authorization. So that’s a possibility that I have read. Appears to be a technically real. And the estimates that I have also received is if you’re waiting for data solely from the NIH organized randomized control or placebo controlled trials within the U.S., it’s not likely that you’ll have that number by mid-October. So that’s something. It seems to me, to keep one’s eye on and hopefully, the data will be monitored very carefully by the data monitoring boards and Bill mentioned the emergency use authorization. 

If that trial, let’s say they did get the data from the U.S., and it was overwhelmingly protected, clear cut, 80 percent protection when they had the appropriate number of endpoints. Data Safety Monitoring Board has the prerogative of recommending that the trial be stopped. It can be stopped for two reasons. One is, if the trial worked unambiguously and clearly, or that the trial was unsafe, unambiguously and clearly. And in either case, they can recommend that the trial be stopped. It is highly effective. It is not impossible that the Data Safety and Monitoring Board would recommend that further enrollment and further follow up not be done. And it is appropriate to issue an emergency use authorization. Not an uncommon procedure on a final ideological license is granted. So once a product is known to work really well, paperwork, a lot of checking, a lot of independent stuff that is done subsequently to get the biological license done and the products authorized within emergency use, while they finish the final paperwork. This case is just absolutely unclear how they will get the numbers. The recommendations will be of the Data Safety and Monitoring Board. 

MODERATOR: Did you have a follow up? 

Q: Yes, please. And this was somewhat asked and answered already, but I’m asking it just a little differently, so my apologies if you feel like you’re repeating yourself. But based on everything that’s swirling around the vaccine’s development, so government pressure to get it out, but also all of the rules, regulations and agencies involved that you’ve mentioned. How confident are you that when a vaccine does come out, it’ll be safe for people? 

BARRY BLOOM: So that’s an easy answer and that is the following. So we concentrate on phase three trials, which are trials with large numbers of people that pick a vaccine that has been apparently a safe and effective in animal models in general, safe in a small number of people in phase one at different doses. You pick a dose, it doesn’t cause too much fever, but does produce an antibody. You measure it in a couple thousand people that it actually seems to produce an immune response that might be protective. Belgica, a phase three trial, the phase three trial is designed to get a critical number of so-called endpoints that as people in the trial that will give a statistically significant result on what the effectiveness is of the product. In this case a vaccine. It’s a statistical answer. The bigger the trial, the shorter the trial can be. All you need is the statistical number of people with cases. You vaccinate a lot of people in a part of the country or the world where there’s as high a rate of transmission as you can find so that you have the fewest number of people that you need to test to get the number of cases that will tell you whether the vaccine is 50 percent or better. And that is what would allow emergency use authorization or even forwarding to biological licensing. 

That is not the answer to your question. That’s the answer to the results in thirty thousand people or fifteen thousand people, you would know that there were no significant or only a small number of significant adverse effects. If there were, it would be stopped at that point. If it’s only muscle pain, they have fevers. Nothing very serious. In fifteen or twenty thousand people, it would be allowed to proceed. And what I want to emphasize, and that’s the part that is least defined in the FDA guidelines to the companies, is we have something called phase four in vaccine trials, which is post licensure surveillance, and this should ideally be done for two years. Everybody who got the vaccine should be followed to see if there are any long term adverse effects, low incidence adverse effects that would simply not be predictable in fifteen thousand people. And that is part of every trial. So to give a full answer to your question, we won’t have a real degree of certainty of what the adverse effects are, how minor they are, and whether there are any serious ones, probably a long time after the vaccine is authorized for use. But that’s as good as it can be done. And I think what’s important is that every batch of child vaccines, every batch is recorded such that if there is a child with a potential adverse effect, not only do they know what vaccine they got, they know what batch of that vaccine. And if they’re three or four kids in any batch that show an adverse effect that batch is killed. So there’s a mechanism to pursue any long term rare adverse events. And I would assume and must assume that will be continued after this vaccine goes through the initial safety and efficacy phase three trial. 

Q: Thank you very much. 

MODERATOR: Next question. 

Q: Hi. Thank you for taking my question, Dr. Hanage and Dr. Bloom. I wanted to ask something about here in Florida, because we’re starting to come down from a pretty big surge of cases that we had in July and early August. We’re also seeing fewer cases, but testing has also dropped significantly, and it seems that fewer and fewer people are even interested in getting tested. And in addition to contact tracing program in Miami-Dade County, reports that there is a high level of people refusing to even cooperate with case investigators. Now, I’m wondering, like, do you sense fatigue setting in and what are the dangers of that and what can our health department do if they can’t compel people to get tested or cooperate with contractors? 

BARRY BLOOM: Bill, do you want to take that? 

BILL HANAGE: The first thing to say is that yeah, I mean, there are some positive things which we’ve been seeing in the across the Sunbelt and Florida. I mean, we did always think that there was going to be this kind of horrible, long, slow burn over the summer with cases carrying on it, you know, and deaths happening at a high rate, but slowly declining and coming down around now. And that’s exactly what we’re seeing. The amount of continuing transmission within a community is always going to be important because it determines the quantity of risk to the population as a whole, even if the majority of transmission is among younger people who are very unlikely to suffer the worst consequences of infection, they still present a transmission risk. And they raise the fulsome infection for those individuals were more who are more at risk of severe disease and death. That said, there is fatigue. The difficulty in maintaining these things, a difficulty in contact tracing and social distancing, but contact tracing becomes very difficult when you have a certain amount of people who you’re trying to follow. So it’s particularly unfortunate now because as cases come down, that’s the point of which contact tracing may be able to be most effective at reducing the onward transmission and bring things down more quickly. Now, looking forward for Florida, it’s going to be very interesting to see what happens in the coming months, because in contrast with a lot of the country, Florida is going to be pretty nice to be able to gather outside in the fall, in the winter, whereas around where I live, it’s going to be much less pleasant. So that may have some impact on getting transmission. But I would say, please, I urge public health authorities to not take their eye off the ball and continue surveillance in such a way that you can monitor the amount of transmission which is going on locally. 

BARRY BLOOM: Well, if I could just add a thought to that. I agree. I think the questioner is right and Bill is right. . There is a fatigue. And when the numbers of cases are high, contact tracing simply can’t come to grips with it. They have to be low enough so that you have a reasonable chance of getting many of the contacts within 24 hours. When the tests take five to seven days and the public knows the answer is useless. It’s hard to generate confidence. The only thing that I would mention is there is real enthusiasm or interest in a set of new tests that are rapid tests that can be done within 24 hours, whether they’re testing for antigen or whether they’re testing for viral RNA. Not available yet because they’re almost certainly not as sensitive ability to detect low levels as the commercial PCR tests. But it would seem to me an awful lot more confidence could be generated, if not very sensitive tests could be done on every schoolchild three times a week. And if it’s positive, you know it’s not a sensitive test. So it means that it’s picking up something that is not trivial. How the FDA, which generally bases its standard on the best available tests, if you want a new test, you have to show it’s equivalent or better. That’s another dilemma the FDA has to face. I think there are ways of redefining the tests. There’s not a diagnostic test, but some sort of public health indicator that might give them a way out of the standard comparison with PCR. But I think the way to engage the public is actually to engage the public in doing or at least having ready access to rapid tests. 

BILL HANAGE: Yeah, I would agree with that, making the point that surveillance is somewhat different from screening and these kinds of tests are a way of doing very rapid screening, which people would in some cases be able to do at home. And even if they’re only 50 percent sensitive, meaning they miss half of the true cases, finding half of the true cases and telling them immediately you are a true case would still be a lot better than anything we’re doing at the moment. 

Q: All right. If I could just add a quick follow up. It seems that at the same time that this fatigue is setting in, we’re hearing from our hospital systems that you’re preparing for a potential resurgence in the fall and they’re discouraging people from gathering and large crowds on Labor Day, which is just coming up in two weeks. And yesterday, our governor came out and said that spectators will be allowed to return to the Hard Rock Stadium for football games in September. And I don’t know, it just seems like the message that’s going out is that, hey, everything is going back to normal. And I’m wondering if that’s also contributing to people’s lack of interest in getting tested. If you have any thoughts on that?

BILL HANAGE: I think that would be speculation because, you know, I don’t know what is going through people’s minds at this time, but I think that it is certainly true that people take their cues from those kinds of places. And I think that what we want to be very careful about is as we move into the fall in the winter, maintaining situational awareness. Meaning that we know what is happening within our communities. This is why surveillance matters. Because we have seen what happens if you see things going wrong and you don’t do anything. So I think that maintaining situational awareness is going to be absolutely crucial. 

Q: Thank you. 

BARRY BLOOM: Let me just add that the control of the epidemic is really not in the hands of the public health authorities. It’s in the hands of the public. Either you have people not wearing masks or people congregating in very close quarters. And if that’s the case, the epidemic will take its natural course, which is to transmit. It’s seeking its own survival. And what we have learned in the down curves in Arizona and Texas and Georgia, and I think the interesting curve to me is Louisiana, when you put in social distancing, the numbers fall. And when Louisiana got complacent and decided they could open up, they saw that the only state in the country that has had a second peak and they had to reimpose restrictions. So empowering the public to take responsibility for their own safety is the way these curves are going to get better. 

MODERATOR: Are you all set? 

Q: Yes, I am. Thank you so much. 

MODERATOR: OK. And this is about the Hong Kong report that demonstrates the coronavirus reinfection in a 33 year old man. Given the possibility of reinfection, is it important to include people that recover from COVID-19 in ongoing vaccine trials? To what extent is this being done? Some scientists have claimed the Hong Kong report raises questions about the durability of immune protection, while others say it suggests a vaccine may be needed to develop stronger immunity. Is there enough evidence to support such claims, given that some important correlates of immunity have been left unmeasured T and B cell responses? 

BARRY BLOOM: What a wonderful question. Absolutely perceptive question. And the answer is, of course, I don’t know the answer to the question. At this point, that unique case is puzzling. But the perspective is it’s a very unusual finding and what one would like to know, and I don’t think is available is serial’s blood samples that were collected to understand whether there was antibody developed after the first conversion, whether it disappeared, whether it was low levels, whether it was low affinity. And clearly, what they didn’t do is the genetics of the virus and it was a different virus. So there’s no question this was a reinfection. No immune response is perfect. But we are used to things like vaccines and recovery from infections for the most part, to import some degree for some duration of protection against reinfection. 

MODERATOR: OK. Otherwise Dr. Hanage, do you have anything you’d like to add to that? 

BILL HANAGE:  No, I was going to echo what Barry said about this being the first case, which I think we have definitively seen, which I was saying is definitely reinfection. It’s not only the fact that it’s genetically distinct, but it’s genetically typical of what’s currently circulating in Spain, which is where this person had been on vacation. So it simulates like reinfection. Now, whether or not this is a rare thing, very rare thing indeed or not is not clear at the moment. So we know it can happen, but we don’t know how important it is or how it’s going to contribute to dynamics. These CT value in which is a way of measuring value, load, viral load was 26, which is not highest, but it’s also not the lowest either. So it suggests that there was a reasonable amount of virus being shed. What we do not know is of the utmost importance for this is whether this person was as able to transmit the virus during the second bout of infection as they were during the first. So that’s something which is currently unknown. But I would point out the fact that something can happen does not necessarily tell us how important it is overall for dynamics. I’m fond of pointing out, you know, my soccer club Arsenal can beat Liverpool, but they have to keep beating Liverpool in order to make a difference to the end of league season. 

MODERATOR: Very good to know. And how do we interpret serial dilution findings? 

BARRY BLOOM: This was the qualitative measurement of the levels of antibody in the Mayo study? 

MODERATOR: I am not sure. 

BARRY BLOOM: It’s arbitrary. It’s qualitative, and it is what we would really like, which is quantitative measurements of neutralizing antibodies. But in a study that was done in two thousand different places with plasma that was given and only measured for antibody thereafter, it is the best that they could do to get an estimate. So it’s a very qualitative estimate. We can do better if they were randomized controlled trials where plasma would be tested before it’s given. I think we would have a more definitive answer, which is one of the reasons we want randomized controlled trials to proceed. 

MODERATOR: Next question. 

Q: Thanks, everyone, for doing this again. I think this question is probably for Dr. Hanage. I was just hoping you could speak about the hybrid school model that we’ve seen many school districts in Massachusetts choose and how safe that model truly is compared to sort of what other districts we’re talking about with a full return and remote. Obviously remote, they’re not in school. But if you had to choose between a full return and hybrid, is the hybrid all that much safer?

BILL HANAGE: Yeah, I’ve been somewhat vocal about this in various places. So the first thing I want to point out is I want to ask people what they mean exactly when they say hybrid, because there are many potential hybrid models that would mix in person learning with remote learning. But what people usually mean when they say this is some situation in which you have half of the kids in for some days, maybe a week, and then you alternate them coming in and out, in and out. Now, that does solve the problem with child care. While children are in school, but it doesn’t help very much when they are out of school, and they may be having remote learning then, but they’re still going to need to be supervised. And the problem or the potential challenge with a such a hybrid model is that who looks after the kids in that time? All the kids sort of being looked after by a family member while the parent works is that maybe an older adult who’s at risk of severe consequences of infection, or is it some kind of ad hoc childcare solution which is being bought by a bunch of parents who are maybe alternating supervising the kids. 

The issue that there is with such hybrid school models is that they can increase the number of contacts outside the school, meaning that the risks of introduction to the school if community transmission is high, become higher. So instead of actually keeping the virus out of the schools, it just produces a whole bunch of new links by which it would be able to get to them. So that is something which I think needs to be considered quite carefully. I will also point out that I’ve said this on schools several times, ideally in an ideal world, schools would be the last thing to close and the first thing to open. Because while I think it’s reasonable to suggest you cannot open schools without there being some increase in transmission, it’s also true that you cannot close schools without that being large negative impacts on education and all the other things that schools do in our communities. However, the reality is, of course, that we are trying to open schools within a context where other things are open and there is more community transmission going on than there was even a few weeks ago. It’s still at very low levels in Massachusetts at least, but it is still somewhat higher and we can expect schools to add some more to it. How much? We don’t know. But it’s going to be something which we’re going to be watching extremely carefully over the next few months. 

MODERATOR: Do you have a follow up?

Q: Yeah, just quickly, to clarify, in terms of a full return, would you say that it’s safer than a hybrid because there is fewer networks by which the virus can spread or it’s sort of, you know, districts out there evaluate their individual sort of community transmission and determine there’s no clearcut, like a full return is safer than a hybrid. 

BILL HANAGE: If your goal is to prevent introductions to the school, there are circumstances in which a full return could be better. Now, the reason why people are doing the hybrid method is for the very reasonable kind of approach they want to do densify and they want to enable schools to be able to do social distancing. I think that’s a good thing. However, I would point out that there are other ways of achieving this. For instance, in Denmark, people have been, you know, for some kids being educated in public parks between the hours and think of three and four, eight and three thirty. So that’s outdoors. That really limits risk of transmission. There are also vacant indoor spaces that could be repurposed to be used in schooling, you know, around different places. So there are lots of different options. The thing is that once you produce a hybrid model, you produce more links outside. And they’re also, you know, you can’t test them. It’s much more challenging to test those people. As Barry was saying, you can do an antigen test on people in morning, and, you know, you can do an antigen test on kids three days a week all three times a week. And you’ll be able to get an idea of exactly how much transmission was going on in schools very readily. But you’re not gonna be able to do that if they’re outside in these kinds of learning pods or ad hoc things or with a babysitter or nanny that people are paid for. That’s just outside the school system you have the control over. 

Q: Thank you. 

BARRY BLOOM: My favorite case is New Zealand, where, as you know, they really close down the country early on and really wiped out endemic or local transmission. They kept the lower school grades open, but they closed down high schools. So my worry on the schooling is everybody talks about schools like they’re all the same. I think it’s probably easier to deal with young kids in some senses than it is to deal with social connotation of adolescence. And that’s not been a major part of the school discussions that I’m aware of. 

BILL HANAGE: Yes, I would completely echo that. It’s really interesting. I mean, it’s really interesting to compare New Zealand and Sweden because New Zealand kept the younger schools open, but because it had stamped on the virus and managed to keep them, you know, have no endemic transmission, that’s had no consequence. Whereas in Sweden, there’s pretty good evidence that there were outbreaks in schools and there has definitely been a much, much higher per capita mortality rate. And even in Sweden, they closed high schools and universities. So all age groups are not alike. I would add to what Barry said, that if you were to have in-person instruction, it’s probably more valuable to younger kids. And if there’s to be a situation where someone remote and some are in person, it would be better done on the basis of need. Whether that be because you’re the children of essential workers or whether that be because are going to be disproportionately educationally damaged by remote learning. 

MODERATOR: Are you all set? 

Q: Yes. Thank you. 

MODERATOR: Great. Looks like we’re about out of time. And that’s our last question. Dr. Bloom, do you have any comments you’d like to share before you go? 

BARRY BLOOM: No, I thank you for a really sharp questions as always. Great fun to have these discussions. Thank you all very much. 

MODERATOR: And Dr. Hanage, do you have any closing thoughts? 

BILL HANAGE: Only to say thanks for bearing with my weird audio setup. Always a pleasure to see you all and hang out with Barry. 

This concludes the August 25th press conference. 

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