Coronavirus (COVID-19): Press Conference with Bill Hanage, 05/29/20


You’re listening to a press conference from the Harvard T.H. Chan School of Public Health with Bill Hanage, associate professor of epidemiology. This call was recorded at 11:30 am Eastern Time on Friday, May 29.

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

Transcript

BILL HANAGE: So good morning, everybody. Especially those we have not actually had the opportunity to speak to before. As you all know, as of now, we’ve passed the milestone of 100,000 reported COVID deaths in the United States, among more than 360,000 worldwide. And as you all know, these are likely undercounts. So since I last spoke with you, all serology data, antibody tests have started to come in from New York, Spain, France and the United Kingdom, which have indicated that in these places despite really significant mortality from the initial surge, those populations are very far from the levels of immunity that would be required to impede significantly its spread.

Now, despite this, lockdowns are lifting and the immediate consequences are hard to predict beyond new opportunities for transmission. And the effective reproductive number is around about one in a lot of places in the US, so we can expect that to be an effect. But the doubling time will be quite slow unless there’s a big change and we might see more isolated spikes as a result of stochastic effects. Now, in terms of when we will know what this looks like, it will likely be a few weeks because that’s how long it takes for new infections to present themselves and get tested. Finally, I made the comment that those antibody results are beginning to suggest an infection fatality rate, which is distinct from a case fatality rate on the higher side of between one in 200 infections and one in 100 infections. And of course, it’s much, much higher than that in some age groups and people would come morbidities. And with that, I’m happy just not taking questions.

MODERATOR: Great. Thank you, Dr. Hanage. Well, it looks like our first question.

Q:  Thank you, Bill, for doing this. I’m facing this very challenging task of trying to write something relatively upbeat about our pandemic response. And it stems from the fact that everyone I know is extremely depressed by our pandemic response. I’m somewhat less depressed because I cover health care and really the hospitals and the doctors and their health care staffers have been doing some really wonderful things. But I wanted to ask you, from the epidemiological standpoint, I’m not asking you to be optimistic, but could you just say what you have found most heartening about the pandemic response, whether at a national level or just at the Massachusetts level? Well, you know, what do you see as having gone just relatively right, if you could?

BILL HANAGE: So that’s a challenge. I completely understand where you’re coming from, also in particular from what you’re in terms of health reporting. I mean, I have been really astonished at the ability of people to orient themselves to threats locally around here in Massachusetts, especially the health care providers and so on. I think we’ve had – it’s been truly impressive what we’ve seen. It’s come at a certain cost because, you know, if you’re dealing with as many infections as you see during the surge, then it’s difficult for health care to proceed remotely as normal. But in terms of what has happened in response to the surge, it’s been extraordinary. And I pay tribute to my colleagues. I’ve seen a few thousand yard stares I’ve got to say on Zoom over the last few weeks, even more so than you got just talking on Zoom. But they’ve been truly, truly impressive.

But beyond that, I’m also amazed and humbled by the people in our community, the public health authorities around where I live and the way that they’ve reached out to help people in communities have been really hard hit like Chelsea. And, you know, this is a time more than almost any other when we really ought to look out for each other. And I have been moved by the number of people who have been doing that.

Q: Thank you. Can I ask one follow up, even though it’s unrelated?

MODERATOR: Oh, sure. Yeah.

Q: OK. So there’s the CDC is putting out something at 1:00p that we’re probably not allowed to talk about yet. But my takeaway from it was that we really couldn’t have caught the at 19 earlier because it was not triggering surveillance in emergency departments. And it raises the question –  you know, it didn’t rise to the level that it would have sent a signal in emergency departments. It raises the question of when the next wave comes, if it does, how will we catch that earlier?

BILL HANAGE: Excellent question. I’m not sure – I think I know what you’re talking about. But I mean, what I’m going to make the comment about in the first place is that essentially, if you know you have a, if you really you have an infectious disease which is deadly in a small number of people, small fraction of people, but which can transmit asymptomatically, you have to be doing active surveillance. You have to be doing that in order to catch it earlier. So, this is one of the things I’ve been trying to say very clearly to people who are preparing to reopen. You want to know what’s the signal that would be causing you to take action to shut down again.

And that means a lot of, that means testing. And, you know, the worst signal you can get is if you test people who died already because it means – and they died positive – because it means they were infected a while ago and you’ve now got a lot of transmission in the community. Next worse is people who are severely ill and in hospital because, again, it means that’s a fraction of people and they were infecting the community sometime in the past. And then, you know, beyond that, it’s people who are showing up to primary care. And if you’ve really got a really good handle on it, you might be doing asymptomatic testing, just for active surveillance in the community.

But that’s not really helping very many places. There is the possibility that we could test wastewater because the virus is shed by people who are infected via the, through stool. So you can detect viral RNA in wastewater. Now, relating that to exactly how many people are infected in the community is much more difficult. But that kind of environmental surveillance has a history of being used in other diseases. For instance, it’s being used to detect polio outbreaks. And so it’s the sort of thing which might be one of the, might be a helpful way to look at this moving forward.

Q: OK. Thank you.

MODERATOR: Next question.

Q: Hi. I’m writing about the Olympics and the impact from the ongoing pandemic, and I wanted to ask you, the Tokyo Olympics were postponed too late July and early August of next year. Where do you think we will be in the second wave at that point? And I’ve also heard from non-epidemiologists and they’ve all said that in their research or in their fields, they believe the Olympics is the worst possible scenario for the pandemic. And I’m curious if you share that outlook?

BILL HANAGE: By worst possible scenario, do you mean like a really bad thing to happen?

Q: Yeah, just the density of the athletes housing of closeness, of spectators, of the global transportation. Just everything it seems everybody is very has a very dismal outlook for the Olympics.

BILL HANAGE: Absolutely. So now predicting what’s going to happen in August  or the summer of, you know, this August is challenging. I think I can offer you roughly two possible scenarios. And I can give you what I think, based on my understanding from other infections, is likely to be the case, and then hopefully that’ll be something for you to be able go with and you can maybe have follow up. Everything depends, really, on how much transmission starts happening over the summer in various different places around the world in the next few months. Because these coronaviruses are more transmissible in the summer months than some of the things we might be used to, like flu.

So there will be opportunities for it to build up to a so-called second wave that could be taking place over the summer. Now, it wouldn’t necessarily be very large. What we expect to be worse, and it would be proportionately even worse if there isn’t much happening on in the summer, is something in the fall. And there are a lot of reasons for that, because we know that’s the most effective ways of transmitting this thing are droplet spread, people indoors talking to each other for an extended period of time. We’ve seen the outbreaks in like the Korean call center where a lot of people who were quite closely connected to each other obviously sat nearby each other, talking to each other or talking on the phone all the time. A large proportion of them became infected. And in the fall, we are more likely to be in situations like that, so there’s going to be more transmission happening. So we expect the next wave to be probably happening around about the fall of next year. But it could quite easily start before then.

Now, what that means for the Olympics really depends on the extent to which we have either got some measure of control over it, which would be, which I think is unlikely to be present at a sufficiently global level. The Olympics would be able to go ahead without significant risk. Or possibly, just possibly, there has been a large amount of population level immunity built up by that stage, which will be at the cost, I should say, of, you know, a considerable amount of illness and death. But if that were the case, then as a result of the second wave, then the Olympics could be a relatively safe, comparatively speaking, safe place.

Now, as for the question of whether or not the Olympics is the worst possible thing to happen like this, there’s a whole science of mass gatherings and stuff like that, which is one of the reasons why pilgrims to the Haj, for instance, are required to have vaccinations, because we know that they can have things like this, have the potential to spread diseases of all kinds from one geographic region to the other. And what that means is the – I mean, the Olympics, the housing of the athletes, as you say, to say nothing of the crowds, would be a tremendous opportunity for spread and for reintroduction of the virus to places that might have managed to literally eliminate it. About the only good thing I could say about that is that a lot of the events happen outside. Not all of them, but a lot of them happen outside. And we know that transmission is less likely outside than inside.

Q: Thank you.

MODERATOR: Next question.

Q: Good morning. Thank you. I actually have a couple. I want to start with just one and you the floor. If no vaccine is developed, the math suggests if we need to get to, say, 70 percent herd immunity in a natural way, that that would involve anywhere from a little over a million to maybe 1.8 million U.S. deaths. That’s just my back of the envelope calculation. So I wanted to get your view on that. You know, both the numbers and the prospect of that playing out if no vaccine is developed and over what timeframe that might play out.

BILL HANAGE: So, again, those are very good questions. When it comes to back of the envelope calculations, I like them more than you might think. But the way that I tend to think about that when it comes to complicated ideas in epidemiology is once you get above a certain number of deaths, the exact numbers are not what you should be worrying about. It’s more that you should be recognizing the scale of the threat.

And I think the scale of the threat is quite large. Now, as for that, I think that it is large. It is potentially within that kind of framework. Now, whether or not that’s actually realized depends on a number of things, including our ability to protect individuals who are at risk. So I’ve noticed that in Massachusetts, if you look at the number of – a very high proportion getting close to 10 percent of the population in care homes and nursing homes in Massachusetts, which is around 39,000, more than 3600 of them are, I believe, dead already. So, I mean, we might be able to do a lot of good by coming up with better ways of protecting the most at risk populations. Now, that will have an impact.

The other thing will be whether or not we come up with better ways to treat. I mean, remdesivir doesn’t seem to be the kind of miracle that we might have wanted it to be, but we’ll learn how to use it better if it has any effects. A lot of antiviral medications work better if they’re given earlier on in infection. And we could discover that there might be some better ways of using the medicines that we already have at our disposal, the drugs in our disposal, in order to prevent some of those deaths. So the timescale over which that will happen, it’s very hard to predict because, again, of the unknown things that are going to happen around human contact patterns, because, you know, you can even hardly have failed to notice that among places which are coming out of their lockdowns, there is a range of different kinds of responses. Some places are the bars are full and probably transmitting in those bars. Other places people are being really wary and that packs a lot with whether or not you’ve had an experience locally of a search.

Now, that means that I would expect that we’re going to see this kind of stuttering outbreak, which happens for over the next few months, and then it’s going to be – the big question is what’s going to happen in the over the fall and the winter. Because that’s when we anticipate there being another wave. Now, how we’re going to deal with that wave, this is one of the reasons why I really wish we can be learning from what we have just been through, because the lessons that we can learn from what we’re going through at the moment and how to make things sustainable and how to stop everybody going crazy with endless Zoom calls, for instance, is something that is going to be really useful to us if, and I would say when, we need to face up to the possibility that we need to do something similar in the future. So it going by the experience of other outbreaks and other pandemics of this kind, I would expect it to be playing out over the next few years with the most important period being the fall and the winter of this year, but potentially starting somewhat before then. I’m sorry I can’t be more precise because of the fact that, unfortunately, there are remarkably so many unknowns about this and there are even more unknowns about the way the human beings are going to respond in response to it.

Q: Yeah, no, that’s helpful. Quick follow. I just kind of clarify, make sure I understand what you’ve said, that the exact figure for herd immunity, which is often put at 70 percent or 60 to 80, it’s not just that number that’s important, but the extent to which we develop herd immunity among younger adults and children and people who move around a lot and do a better job protecting the older, more vulnerable population. Is that fair to say?

BILL HANAGE: Yeah, I think that is fair to say. I mean, one of the things which is frustrating when non-epi people sometimes ask questions about herd immunity, is that they all sort of say that, they will point to it as a thing which needs to happen. And that’s, there’s an element of truth to that. But the point is, the infections among the vulnerable population are kind of wasted when it comes to herd immunity. I mean, a dead person is unable to be infected, so they present no kind of firebreak in order to the virus in the community. And we don’t want to be in the position of, you know, justifying deaths rather than saving lives. Now, I will also point out that in the younger age groups, those too have risks, as we’ve seen from the Kawasaki-like syndrome, which has been developing among some of the younger, some children who have been infected with it, which are only beginning to be understood. And that’s a very rare outcome. However, if you’re going to infect perhaps a large fraction of children, then you’re going to see more of that. We need to be upfront about the potential public health risks.

Q: Thank you very much.

MODERATOR: Next question.

Q: Hi. Thanks again for for doing this. Really appreciate it. This is a little bit redundant, but a not on a story looking at cell phone records of people over Memorial Day weekend. And it turned out that I think it was 400 zip codes nationwide where cell phone data showed a doubling or more of device movement into retail businesses and other locales. And just wondering kind of what your concerns are about that. What that burst of activity could mean, what we should be watching for, that sort of thing. 

BILL HANAGE: So, again, it’s a good question with sort of, with an opportunity for a somewhat subtle answer. I mean, the first thing is to say, like I say, you give the virus a highway along which to transmit and, you know, chances are it will take it. It’s certainly going to take an opportunity if the highway is there, rather than if the highway is not there. But the issue with cell phone data, which is a bit hard to work with, is that it’s not clear exactly how the kind of data that’s recorded by a cell phone relates to an opportunity for transmission.

And you can kind of see this. I mean, if you think about it, you know, if you imagine you’re living in an apartment building and you put your phone to charge by your bed every night, if your phone is trying to sort of, you know, take the argument that you’re using Bluetooth to detect connections. Your cell phone is going to be shown being very close to that of your neighbor who lives the other side of the wall. But it has no way of managing to pick up that kind of information because it doesn’t have that resolution.

So all of these mobility statistics correlate with each other and they will reflect opportunities for transmission. But it’s hard to say, it’s hard to figure out a simple way in which they do that. I think that the bigger concern would be likely to be movements from places where we know there’s a high population prevalence to places where I know that there’s a low population prevalence at the moment because there’d the opportunity to introduce it to places where it’s currently not particularly common. And every time you introduce somewhere new, then there’s the opportunity for local outbreaks.

MODERATOR:  Did you have a follow up?

Q: Yes, thanks. Sorry, I was muted. So your point is that cell phone data isn’t that reliable. But then also we could be going to the beach and staying six feet apart. What should we as journalists, I guess, be looking for to see whether this is a dangerous zone or is is cell phone data just not good?

BILL HANAGE: Well, I think cell phone data is good as a kind of – cell phone data is good as a way of sort of taking the temperature about how much people are moving and how much people are – looking at the way it changes within itself over time is a metric of human activity. But how that human activity relates to opportunities for transmission isn’t clear. Now what, you know, what will become clear in due course is there will be, I predict that there will be local spikes of infection. Probably not everywhere. And unless you have a relatively high reproductive number, I mean, even if it starts growing, if the reproductive number is sufficiently above one that the epidemic starts to grow, but not so high that it grows very quickly, it could be as much as a month before you really get a reliable signal.

So what you need to be doing is sort of, the way that I would say as a pro, watch the hospitalizations. If you don’t have good population surveillance going on, keep an eye on the hospitalizations and see if and when they start to increase. Look to see whether or not there’s a long term trend in terms of increasing. And also, as reporters, go and check to see whether or not local authorities are doing funny things about what they class as hospitalizations or not.

Q: Can you think of a specific example there?

BILL HANAGE: I can think of too many specific examples. Because sometimes you’ll find that, you know, in some places they will say that if somebody moves from a nursing home to a hospital, it doesn’t count as a hospitalization. Or in some places they will count, hey, you know, it’s hard to tell the difference between a person who has been hospitalized with COVID versus a patient who has been infected with COVID while in the hospital. So I would just recommend that people think carefully because data streams are not always comparable from different places.

Q: Thank you.

MODERATOR: Next question.

Q: Hi. Thanks so much for letting me in on this. It’s very interesting. So I don’t know of these on the call. I mean, I’m in Minnesota, and so we tend to be really focused on Minnesota to the exclusion of too many other things. And so my sense, though, is that the numbers here in Minnesota, particularly the Twin Cities, are sort of at variance, I think, from sort of the national trend, which is to say I get the idea that sort of case counts and fatalities seem to be trending down across a lot of the country, but not not in Minneapolis, not Chicago, and not the mid-Atlantic. Do you think that’s right? And if that’s right, I wondered if you had any thoughts about sort of what explains the outliers.

BILL HANAGE: So that’s a good question. And give my love to Minnesota. The first thing to say is that the trend down over the entirety of the country is a little misleading. Don’t forget that you’re still if you’re looking at the overall counts, you’re looking at stuff which is overwhelmingly driven by the Northeast, where there have been very many more cases like Massachusetts, New York, New Jersey. And those, if you’re looking overall, that’s what’s making that happen.

Now, if you look at different states individually, it looks as if there are, and again, with the difficulty of reporting maybe not comparable between all of those states, numbers of them do seem to be ticking up. And among them are Chicago and Minneapolis seems to be, although Nicole actually forwarded me the email that you sent, and it’s quite noticeable to see that the numbers of deaths per week have been staying roughly constant. So that suggests to me that you actually have an outbreak which is ticking along and which you may be seeing sudden flare ups. And this is one of the important things.

We know that the urban areas such as Minneapolis are more relatively vulnerable to this because of the fact that there’s something, it is more deterministic how many people they kind of sample. So if you got a small town, it depends on whether or not somebody who’s infected happens to come there and happens to infect some people to kick off an outbreak. You know, if they stop off in the Dairy Queen and just get something, don’t infect anybody and drive on through, they may not have done anything. Whereas in Minneapolis or in other large cities, you’re more likely to go there and have sustained contact with the kind of interaction which is likely to kick off an outbreak. And I think that that’s probably true in a number of these places. I also think it’s hard to separate out the possibility that we are only seeing things now because we are testing.

So I’m sorry if this isn’t a more definitive answer than you might like, but the evidence from the death rate, which has been around 20 a day for the last four weeks or so, and some apparently up ticking in hospitalizations, it’s a little hard to know exactly what that means. It reflects activity in the past, remember, rather than activity happening right now. But I would say that as a metropolitan, you know, as an urban area, I would be paying attention to places like Minneapolis, Chicago right now, because those are the places where I would expect to see the first signs of activity from a reopening.

Q: That’s really helpful. Just real quick. The follow up to a comment you made to someone earlier and you just touched on it briefly, that hospitalizations. So is there a state that you would say is is sort of doing the best job at reporting out of full information on hospitalized cases with this?

BILL HANAGE: Good question. I haven’t compared them all enough recently. Sorry. So I can’t give you a more definitive answer on that. And I was more able to sort of say – I’m more able to point the finger at places where I mean, I don’t know, California changed, but I remember California wasn’t counting hospitalizations for quite some time. So it’s more likely to see people who are, you know, the states which as an epidemiologist I would put on the naughty scale. So I will come up  with a league table of the states which I think are doing the best job and prepare it for the next time I do this call. I should say Minnesota has a great department of public health as well. So, you know, kudos to them.

Q: Gotcha. Thank you so much.

MODERATOR: Next question.

Q: Thank you for doing this. I’m interested in finding out what how can we know how much is enough testing and what kind of local area are we talking about? How local do we want to be looking? That’s number one. And number two, what kind of testing? Some of your colleagues think that antibody testing is a lot better than PCR testing. You have any opinion about those those issues?

BILL HANAGE: So, OK. The first thing I will say is that testing is really hard. And the science of testing is really hard. But it depends on what you want to know. At the moment, in most places, what we want to know is a question of does this person who we suspect have COVID, do they actually have COVID? And if they do, that’s important because it determines how we treat them and it determines the effort that we then go to to do contact tracing in order to try and limit the spread beyond that individual and whoever they might, they infected. Now, what we would like to be able to do would be a kind of, sort of population-wide passive surveillance, which is perhaps people who have shown up and who just sort of said that they want to get tested or, even better, going like house to house in order to determine who is, in fact, at any one time. We’re nowhere near that, even though, as you probably know, any resident in Cambridge can get tested. Now, I’m not sure how much that’s being taken up.

Now, the other thing I want to point out is that the PCR test is very, very different from the antibody test. Because the antibody test tells you if it’s right and they’re not all very good tests, I should point out, so let’s assume that it’s a great antibody test. If it works really well, it will tell you if you have been infected at some point, up to three weeks in the past. Now, if it’s less than three weeks in the past, antibodies may not have had time to develop, so you don’t know. So that’s telling you something happened in the past, whereas the PCR tests are telling you whether or not somebody is infected and potentially infectious right now.

So combining the two of them, as you know, the CDC had apparently been doing and that was in the news last week, is not very sensible because of the fact that if you think about it like if you’re the superintendent of schools to figure out whether or not call a snow day tomorrow, what you’re going to be doing there is you’re going to be looking at the forecast of the blizzard, which is coming in overnight and not the snowfall totals for the year up to three weeks ago. That’s just not a helpful thing to have. So the type of testing that you would really like to have would be something which is able to give you an accurate sense of the state of the pandemic in a community.

And I would say at a relatively local scale, because within Cambridge, as you must know, there are some areas which are much more impacted than others. The port, which is just like a few streets in that direction, has got more disease in it than areas up and around sort of the Harvard campus. And, you know, tracking those things is extremely important for public health purposes.

Q: Could I ask a follow up?

BILL HANAGE: Go for it.

Q: So the PCR test. Yes. It tells you whether you have it or whether people have it at that time. But it doesn’t tell you over a period of time. That is, it’s good for that particular moment, but it doesn’t tell you anything about the next two weeks or on a continuing basis if you want to do some kind of surveillance to know whether, say, opening up this particular activity is OK or not okay. I mean, how do you do that?

BILL HANAGE: It’s not a one time thing. A PCR test cannot be a one time thing. It’s even – and by the way, I’ve got to tell you, it’s even worse than that, because if you look at the sensitivity of these tests, they’re often very good early on in infection, but then they fade pretty quickly. So you can have a situation in which, you know, there have been many cases where people who now apparently have serology or reportedly have positive serology tested negative when they were tested. They were probably tested too late on in the course of infection. But you’re right, it’s not a one time thing. We need to be doing a continuous monitoring.

This is the important thing because people need to know what’s going on right now in order to make smart decisions for the future, which are going to protect lives, which are going to stop unnecessary infections from occurring and prevent those transmission trees growing until such a point when you have to take more intense action to stop a building surge that is actually [INAUDIBLE]. So you’re completely right. We need to be doing – you need to be having continuous testing. Now, that’s one of the reasons why the kind of environmental surveillance I was mentioning earlier might be helpful.

Q: Thank you.

BILL HANAGE: You’re welcome.

MODERATOR: Next question.

Q: Hi. Thanks, Dr. Hanage, for doing this call. I actually have a testing question that follows up on the one that was just asked. But I wonder if, you mentioned sensitivity for the diagnostic tests in particular. Is there a threshold or a minimum that you think diagnostic tests for COVID-19 should have as far as a percentage? And I’m wondering if you think there’s any difference between tests that say are done in a laboratory setting versus ones that are deployed out in nursing homes or homeless shelters or any other kind of like mobile testing site?

BILL HANAGE: Those are good questions. I mean, I think that the sensitivity question depends on what your goal is, because there are some situations where you can see – I think that there is a – you want to have sort of gold standard tests that are done under laboratory conditions in which you can sort of, you know, always fall back on if there’s any uncertainty. But then rapid testing in the field is likely important in a large number of situations.

And what you want to have there is I mean, again, it depends on the specific circumstance. You do want the tests to be highly specific, because if you were in, say, a homeless shelter and a person ends up becoming wrongly identified as infected, then that’s a you know, that’s something which is potentially quite worrisome in terms of consequences that could have that individual. So then when it comes to sensitivity, there are you know, ideally you would like to have a test that was perfect and sensitive and perfect and specific, but in practice as a tradeoff between those two things.

And it could be that for field deployments, something that could be done very quickly in order to test people on a very frequent basis to see whether or not they had evidence of infection could be very helpful. I mean, you can easily imagine a test with low sensitivity which was, if somebody was able to use it every day, then if it was that cheap, then you could get information about people who were actually infected very early on and take action to prevent transmission from them. And that would be a really helpful thing to do. But at present,  there’s a very different sort of set of questions from the type of testing which you want to be doing within the clinical setting versus the type of testing you want to be doing out in the community.

MODERATOR: Did you have a follow up?

Q: I think I’ve got it. I mean, basically, are you saying essentially that, you know, if you are able to do testing very frequently, perhaps we can afford to have something that’s a little less sensitive.

BILL HANAGE: Yeah.

Q: But I mean, is that really realistic given our current situation? I mean, I’m not sure if I hear of many people other than, you know, perhaps employees in the White House who are getting tested very regularly. You know, if I wonder if you could speak about the practicalities.

BILL HANAGE: I think you’re right that that does demand a different sort of test. I mean, there is a – in my opinion, the ability to do an inexpensive test in the community, even if it was comparatively less sensitive than the ideal within a clinical setting would be helpful, but inexpensive is a key thing. And so far as I’m aware at the moment, no such really exists.

MODERATOR: Next question.

Q: So sticking with tradition here, I’ve got a question that I know doesn’t have an answer, but I might ask it anyway. To what extent do you think extensive do you think that super spreaders are contributing to the spread versus less dramatic, you know, person to person spread where somebody infects one or two? And I’m speaking specifically where one person infects dozens or hundreds of people at a time.

BILL HANAGE: That’s an excellent question. And I think that we can go a little bit further than just saying there isn’t an answer because I think there is an answer emerging. So super spreading events arise from what is technically called an over-dispersed R0. Now, you all know by now that the reproductive number is the average number of people who are infected by a single case. But it can be over-dispersed, which means that some people infect way, way, way more. So rather than being sort of a bell curve, you end up with one side of it which is skewed and that fraction of people end up doing a lot more of the onward infections. And the classic figure that people come up with, and it’s similar, there’s some evidence that this is the kind of thing that we might be seeing with this, is that 20 percent of the infected people are responsible for 80 percent of onward infections.

And in this, it may even be a smaller number than that. I’ve seen 10 to 15 percent of evidence for that. Now, this is really important. I mean, there’s a biological backdrop to this, which is that we know that such an over-dispersed RO is present in other beta coronaviruses. It known in the original SARS. It’s been known in MERS, Middle East Respiratory Syndrome. And it’s got an important role in health care as a result of, you know, sometimes you can see super spreading events happening as a result of invasive intubations and self generating aerosols and stuff like that.

Now, the impact for the community with the transmission of this is that it leads to some of what I was saying about those random effects in local communities, because if the majority or a large fraction of transmission chains are likely to go extinct, but a minority of them end up infecting between 10 or 80 people, then the thing that we really want to be looking for is not only infections, but transmission, because once you see one transmission, there’s more likely to be more of them. And we are collecting data on the sizes of these clusters. It’s quite difficult sometimes to know if they will descend from one individual. I mean, we certainly see things like this kind of happening when the virus enters nursing homes where very rapidly a large fraction of the staff and the residents can be infected.

And we’ve certainly seen it in, for instance, South Korea, the South Korean nightclub outbreak, which was in the news a couple weeks ago, I think. It’s believed the one person infected 90 people at a nightclub and then those 90 people went on to infect, the last count, I believe it was 63 more before they were caught, because it was a very rapid testing – more than 40000 tests were put in place in order to stay on top of this. But that shows you how rapidly the virus can enter a population. There’s one more thing I want to say about super spreading at an over-dispersed reproductive number. There’s a theoretical prediction which is quite interesting, which is that the majority of introductions for community go extinct. But the ones that don’t can initiate explosive outbreaks. And that is one of the things which is really important if you start looking at the progress of the pandemic across the heartland of the United States, where small communities where you’re seeing large bursts of transmission associated with churches, meatpacking plants or any of the other situations in which folks get together and are in close contact that they can transmit.

Q: Thank you for that. Quick follow, and this might just be a yes answer. You’ve already spoken to the things that need to be done to prevent second waves and outbreaks and further transmission. Is there anything is that – all those same things apply to super spreaders or is there something unique that needs to be done to deal with this particular problem?

BILL HANAGE: So, you know, you’re right in the sense that there are two ways to deal with the super spreader. If you know what the super spreader is or you know what the risks of super spreading are, you can do something careful about it. You can take precautions. It’s one of the reasons why intubations are done by expert staff in order to prevent, you know, super spreading events within health care settings. The other thing you can do is that you just don’t give them the opportunity. Even if an individual infection has the potential to infect 90 other people if given the exposure to them, if that person during that period of time is practicing social distancing, then the opportunity for transmission just isn’t going to happen. And you’re going to be able to avoid these very large surges, local surges of infections.

So it’s pretty much the same kind of playbook. But the thing about it, which I think is something that can be very exciting if we can only figure it out, would be what are the risk factors for super spreading? One of the things that we can do which might be able to intervene. And at the moment it’s not even clear if it’s driven by factors of the virus. You know, this person happens to shed more. Or just a contact network, so that this person makes more contacts, this person shakes hands with a lot of people every day. So we’re not even clear on those two things. But as we are able to figure out more detail about that kind of thing, it could be very important in how we approach the next wave.

Q: Thanks, very helpful.

BILL HANAGE: You’re welcome.

MODERATOR: Next question.

Q: Hello. Hi. Thank you for taking my questions. So as you can understand by my name and my accent, I’m not from the U.S. I am based in Brussels and I’m Italian. So in Italy, the de-confinement has just started. I wish you were a scientific adviser to my government. So I will try to summarize. So, basically, the ideal setting of measures that basically you are suggesting the government should take and attach them to the de-confinement. So all this combination of different assessments of transmission, infection, combining different kinds of tests like high or low sensitivity, all this combination of things that the government doesn’t seem to be able to do or they don’t seem willing to do so. Is it feasible financially, is it financially sustainable, socially acceptable, at what kind of scale these tests should be done, at the constituency level, building level or businesses level. So what actually is the recipe for government to do that, do all the things that you said in a realistic way or is that impossible actually for government to do that?

BILL HANAGE: OK. Thanks for the question. Stefano, you might not be able to tell but I also don’t have an American accent. I’m originally British, but I now pronounce my Ts like D. So I say Brid-ish. So, Europe is actually very interesting because you see a range of different sort of responses to it from Italy to Germany. And indeed, in fact, Belgium, which has got some excellent reporting but has got some fairly sobering statistics.

I think that in situations such as this, possibly the best model that you can have is to examine the models of governmental responses which have been effective at different stages. And it’s unquestionable that the most effective and sustainable of these so far appears to be Germany. And if you can manage to obtain a situation where you are able to have a force of infection, which is comparatively controllable, as you see in Germany, then moving forward on that basis is a wise thing to do. They’ve got a very good – I mean, the federal system in Germany, the Lander, they were able to put in extremely impressive and, you know, local testing structures which were part of the good response.

Now, the other thing which is somewhat different, I believe, from Europe writ large and the United States and the U.K. is that in Europe, what we are seeing as a sort of cautious refinement of lockdown, recognizing that the consequences of getting it wrong could be pretty great. Whereas in other places, there appears to be a sort of like let’s throw the doors open and it’s over. It’s, you know, it’s fine, which is, as we understand it, not the case. And human beings will probably not respond as is expected.

Now, I believe based on Germany, that it is feasible for governments to be able to mount an effective pandemic response. The only caveat that I will place on that, and by the way, apologies if there’s any ambient noise but the bins are being collected outside and so there’s a big truck there. So the caveat that I will place upon that, which is a caveat which really should be placed on everything that anybody tells you about the pandemic, is that we’re still very early on in it. So you can see, for instance, that Britain, France, Spain, northern Italy had really, really bad first waves. Same with Massachusetts. The problem is going to be what happens as we move forward and what that means for the future course of the pandemic, because it’s not actually obvious. And, you know, you should reflect the people we’re going to be arguing over exactly how many people were killed, at which stage and which place and what the best strategy was probably for decades to come.

Q: OK. So just a follow up. So, I mean, for sure, the Italian government is not doing all the things you said. It doesn’t plan to do serological test and PCR test at the really high level scale. So what I wonder is if it is not doing it because it doesn’t consider that it’s necessary or because it lacks the resources that Germany has.

BILL HANAGE: So I do not know enough about what resources are available, but it is worth saying that if the resources are not available, then you’d have hard choices in what test you’re going to be doing. When it comes to serology, it’s actually quite important because it determines your vulnerability to future waves of infection. Now, the reason why you could make the case for governments having not done that is that we are now increasingly able to look at the number of cases that were seen during that first wave and kind of back-calculate from that to what we think the likely exposure might have been. And so the only benefit of serology would end a sort of individual benefit. And the individual benefits is a different kettle of fish from the population benefit.

Q: And the geographical scale that you mean when you say local level, you mean the entire district, or even buildings or shopping centers? What is the scale?

BILL HANAGE: What I mean is that – I mean, it’s something that is – so for instance, if you wanted to take this suburb of Boston, which is known as Chelsea, Chelsea has been hit very hard. And it’s not clear how many people have any immunity there. But it could be as high as 30 percent. That means you’re sort of halfway on the route to a significant amount of herd immunity and it would reduce the maximum possible transmission rate within that community. And that’s the important thing to note. But for most places, it’s not going to get that high.

And so the results of serological testing would really be an advantage for that individual to know rather than for that community to know because they might – and by the way, I’m not necessarily advocating people go out and get serological testing because they are quite variable in terms of their reliability, and you need to remember that if it tells you you’re immune, you may not be immune because we don’t actually know necessarily what antibody titers correlate with immunity. And so we have here something which would be useful for that person, but it’s not necessarily useful for the population as a whole. There’s a paper in Science which explains it very eloquently, which I’m doing a worse job with it here. But I’d be very happy to send it to you if you send me an email.

Q: OK. Thank you. Thank you.

MODERATOR: Next question.

Q: Thanks. Just one quick thing. At the outset, you mentioned antibody results suggesting an infection fatality rate of one in two hundred and one in one hundred, somewhere in that ballpark. And I guess I wondered two things about that real quick. How new or emerging would you say that sense of things is? And then secondly, most of us have a sense of cases in our community and can do, you know, a division on deaths over cases for what would be kind of a rough case fatality rate. Is there any way to think about the relationship between an infection fatality rate and a case fatality rate? In other words, if that’s the emerging sense of what the infection fatality rate is, can you therefore look at cases in a community and say, you know, here’s what what volume of of deaths we might expect? I’m not sure.

BILL HANAGE: Up to a point, but I would emphasize up to a point. I mean, as you understand, the distinction between the two is that the case fatality rate, or sometimes known as the crude fatality rate, is just the number of, you know, the rate with which people just having the infection die, the proportion of the dying. But if for whatever reason, the people who are identified as cases are not all of the people who are infected, which may well be the case if you have a subset of individuals who are minimally symptomatic or have different sets of symptoms, who never present to health care, never get the test, who you never know anything about, then the infection fatality rate, which is what’s really going on, can be quite different from what you see in the case fatality rate.

Now, the infection fatality rate, as I was saying earlier, is, as I say, based upon the observed numbers of deaths from COVID infection in places like New York, Spain, France, the United Kingdom, and then relating that to the numbers of people who we know have been exposed because of the fact that they have antibodies. And there is a bit of a caveat that the essence may be a bit off, because, as I said, it takes time for antibodies to develop, but it’s beginning to zero in on that kind of proportion I was talking about ,one in 100 or one in 200. Now, if you’re looking at a local level, it’s more difficult because local dynamics are often driven by sort of very local effects. In particular, if this happens to be one of those diseases which can suddenly transmit to a very large number of people as a result of getting into a sporting event or a church or a music gig or something.

And foremost of those are when you look at nursing homes because you can quite rapidly get a local spike in the apparent, sort of, in the apparent mortality rate as a result of these kind of events. But that doesn’t necessarily reflect the actual risks of community transmission. In order to do that, you need to be going out. You need to be looking for a little bit more.

Q: Thank you very much.

MODERATOR: Dr. Hanage, I received an e-mail question, would you have just a couple of minutes for that?

BILL HANAGE: Go for it.

MODERATOR: Okay. From a public health standpoint, what would you like to see the media emphasize in its reporting on reopenings?

BILL HANAGE: Phew. That’s an excellent question.

MODERATOR: And good for this audience too.

BILL HANAGE: And good for this audience. I wish I had a bit more time to think about it. I think that what I would like the media to emphasize is the fact that we writ large, meaning the public health crowd, are not, you know, we are quite grim about the long term prospects. But that’s not the same as being grim about the short term prospects or making strong predictions that if you do this in this community, you will have a wave of infections in this amount of time. That’s not the way this works. I’ve emphasized to various people on this call the inherent uncertainty in dealing with a disease, which has this sort of over-distributed R0 and which transmits quite differently in different communities and quite differently in crowded urban settings in comparison with more sort of isolated rural ones. And then going on top of that to figure out kind of behavior that human beings are going to engage in.

The only thing we can be sure of is that given opportunities to transmit, more opportunities to transmit, the virus will transmit more. Now, that will, we would say, in due course, translate into more infections, more transmission chains can potentially surge. But exactly when that happens and where is something that’s very difficult to predict. I would urge reporters who are covering this to make it clear that the epidemiologists and the modelers are capable of predicting the future in the most general sense, and that perhaps specifically locally, you can see some things with the effect of reproductive number on your local forecasts and stuff. But exactly what happens where and when is beyond us. However, if we keep making contacts and we let the virus transmit, the outlook is grim. And if not now, then, well, as a famous author once said, winter is coming. So think about that.

MODERATOR: OK, thank you, Dr. Hanage. Do you have any final thoughts for today?

BILL HANAGE: I don’t think so, other than the fact that it’s been really nice talking to all of you.

This concludes the May 29 press conference.

Leonard Marcus, founding co-director of the National Preparedness Leadership Initiative (May 27, 2020)

Paul Biddinger, vice chair for emergency preparedness in the Department of Emergency Medicine at Massachusetts General Hospital and medical director for Emergency Preparedness at the Hospital and Partners Health Care (May 26, 2020)

Michael Mina, assistant professor of epidemiology (May 22, 2020)