You’re listening to a press conference from the Harvard T.H. Chan School of Public Health with Caroline Buckee, associate professor of epidemiology and associate director of the Center for Communicable Disease Dynamics. This call was recorded at 11:30 AM Eastern Time on Wednesday, April 15.
Previous press conferences are linked at the bottom of this transcript.
Transcript
CAROLINE BUCKEE: I’m happy to talk about the recent work that came out of the center about the longevity of physical-distancing interventions and future scenarios for relaxing them. So, I’ll just open it up to questions.
MODERATOR: All right, looks like the first question.
Q: Hi, Caroline. Thank you very much for taking this question. I wondered how you infer the reproductive number of the virus given all the changing parameters and the inability to – I mean, that is both to say the social-distancing measures changes, perhaps, immunity that wanes over time. How do you do that?
CAROLINE BUCKEE: Well, so you can estimate the reproduction number from the epi curve itself even if there is social distancing going on. The issue is that right now we don’t have accurate case numbers because testing continues to be a problem. So, it’s quite difficult to make those estimations from the epi curve.
We’re starting to see enough deaths in some cities around the US, for example, unfortunately, that we’re going to be able to use the deaths as a delayed way to look at the trajectory of the epidemic overall. And we can estimate the effective reproduction number from that. In terms – what was the rest of the question about? How t o – oh, I know, about immunity.
Q: Yeah.
CAROLINE BUCKEE: So, because we’re still at the early phase of the epidemic, most people are still susceptible. So, the estimates won’t be massively affected by what we assume about immunity, largely because we think there’s probably at least some short-term protection. Although that’s still unclear.
I think the data on immunity is going to become critical as we start to try to model out the relaxation of physical-distancing interventions for scenarios moving forward and thinking through possibilities of resurgence and how we relax physical distancing in the future. That’s when the questions about immunity become critical.
But we can still estimate the reproduction number. Right now, probably the best way to do that is using deaths and kind of extrapolating back from there to try and understand how cases are changing over time. Does that answer the question?
Q: It does. The only other aspect of that that I wondered about is this question of seasonality.
CAROLINE BUCKEE: Mhm.
Q: When does that start to interfere with your estimates of the reproductive number?
CAROLINE BUCKEE: So again, the reproduction number can be evaluated just from the change of cases over time. Now, understanding what’s driving changes in the reproduction number is a separate issue. So, whether that’s being able to understand how much of the reproduction number changes are due to physical-distancing interventions which reduce the contact rate or whether it’s due to seasonal changes in the overall transmissibility of the virus, that becomes more difficult to disentangle.
But the reproduction number itself is something that we can calculate. And then we want to kind of back-estimate the causes driving changes and incidents. And that’s much harder.
So, I think as we move into summer, there’s some suggestion that perhaps there will be reduction of transmission and because we know that respiratory viruses are impacted by things like humidity. But we still don’t know that yet.
And we’ve seen efficient transmission of the virus in warm places and warmer countries. So, we don’t think that there’s likely to be very strong seasonal forcing from a climate perspective. Again, that remains to be seen.
Q: Thank you.
MODERATOR: Next question.
Q: Thank you so much. Thank you for taking my question. Dr. Buckee, as you may be aware, the CDC, in its last flu report for the season, indicated that there may be some confusion in the numbers because of the COVID-19 pandemic. I’m just wondering if that confusion does indeed exist and what implications it has in terms of our understanding of the scope of the pandemic and how to address it.
CAROLINE BUCKEE: I think this relates to whether we’re not attributing mortality and other epidemiological parameters correctly to COVID-19 as opposed to other causes. So, for example, some colleagues at Yale, like Dan Weinberger, have been looking at variations in pneumonia and influenza-related deaths. And if you compare that to what’s happening with COVID-19 deaths, you can get some indication of the uncertainty because it’s likely that some people that are dying of COVID-19 have been misclassified or it hasn’t been recognized as being the causal factor.
Of course, there are a lot of comorbidities. So, for any infectious disease, you may have more than one pathogen because you’ll have coinfections. And so, attributing a death or a case to one of the pathogens that you have is sometimes challenging. And I think that’s a source of confusion.
So, there are coinfections. There are deaths that are potentially not attributed to COVID-19 even though they are COVID-19. And then how do we make sense of that in relation to the pneumonia and influenza deaths-reporting, which the CDC does regularly?
So, there are multiple sources of uncertainty in the data, even around deaths, to get a really definitive number. And that’s some of the reasons for that.
Q: Does it affect the response to the outbreak at all?
CAROLINE BUCKEE: Does it affect the response to the outbreak? I think it affects our overall sense for things like the case fatality rate and how urgently we need to put particular interventions into place.
But I don’t think it’s going to change the numbers wildly. There is uncertainty. But I’m not sure the extent to which it will affect the response. That’s probably going to depend on the local data.
Q: Thank you very much.
MODERATOR: Next question.
Q: Hi, Dr. Buckee. Thank you for taking the time. Circling back on seasonality of the virus, I am wondering if there are any indications that there is a certain climate or specific temperature that might be more favorable when it comes to COVID-19 spread.
CAROLINE BUCKEE: Well, we still don’t know a lot about the virus. It is spreading efficiently in countries with higher temperatures. So, we don’t think that it’s unable to transmit in those conditions.
In general, I think we know in terms of fomites – so that’s viral particles that exist on surfaces. UV light, the virus doesn’t like UV light. And so, it could reduce some kinds of transmission if there’s more sunshine around.
And then we know from other respiratory viruses that humidity plays an important role for some of them. Again, a lot of the transmission mechanisms are still being worked out.
So, I think the general feeling is that, while there are likely to be some impacts of climatic variability over the seasons, we know that the virus is able to transmit in multiple different environments, including in hot countries. So, we don’t anticipate a dramatic reduction in transmission over the summer, even if there may be some.
Q: And is what we’re seeing unique to COVID-19? Or is this just because we don’t know much about the virus and it’s in the early stages? Does this kind of un-clarity about the seasonal variability, does it pose particular challenges when it comes to tackling COVID-19 in comparison to other viruses that we’ve seen before?
CAROLINE BUCKEE: So, I think it’s really important to remember that we had never heard of this virus until a couple of months ago. So, for any emerging infectious disease that’s new in a human population, there’s going to be a ton of unknowns. And that makes it quite hard to project scenarios for intervention planning with any certainty.
And I think we’re seeing that with a lot of the model projections that have huge uncertainty around them. It’s partly just because it’s a new virus.
And so far, a lot of the models have been leveraging information from other coronaviruses and assuming that there’s going to be a similar parameter with this one. But we still don’t know that. So, we’re learning as we go and trying to fill in some of the gaps there.
I think the big question for seasonality here is that if we go into the summer and continue to do strong physical-distancing interventions through the summer and then we start to reopen in the fall, then we risk a resurgence in the fall and winter months. And for a variety of reasons, including co-circulating respiratory viruses of other kinds, the potential that there is some climatic variation that’s going to enhance or at least facilitate transmission, the concern is that a winter second wave is going to be very problematic.
So, I think for thinking through scenarios for control in the future, that seasonal question is important. And some of these unknowns are really critical because we don’t know yet how to think through planning for the relaxation of physical distancing in that context.
The other thing I would say is a major unknown right now that’s going to be key is how many people have no symptoms at all for the whole duration of their infection and whether those people are immune, because if they are and if there are many more asymptomatic people than we had realized, that’s good news because it means we’re further along in the epidemic than we thought we were.
So, there are a number of, sort of, epidemiological unknowns here that we need to race to find out so that we can really make sense of what to expect for the coming months and this possibility of resurgence in the fall and the winter.
MODERATOR: OK, next question.
Q: Hi, yeah, thanks for doing this. I’m wondering if you can discuss the role of contact tracing in replacing the more, sort of, blunt social-distancing measures that we have in place now and, given what we know about the scope of the epidemic and how the virus spreads, what needs to happen in order to make contact tracing a realistic alternative to social distancing and whether or not technological interventions or tools like apps are necessary.
CAROLINE BUCKEE: I would say that contact tracing is not going to be an alternative for physical distancing but rather an additional tool that we have to use sensibly in combination with other interventions. So, we’re not going to go back to normal in terms of physical distancing and just do contact tracing instead. I don’t think that’s going to happen.
What we could try to anticipate is integrating contact tracing as we release some aspects of physical-distancing interventions in a very measured and strategic way. So I don’t think it’s a case of replacement. I think it’s a case of combined interventions, with contact tracing being effective potentially on top of physical distancing to control the outbreak.
Certainly, if we bring transmission down to zero, then contact tracing is one of the first things we want to do aggressively in a containment sense if there’s a resurgence from that point onwards. But right now, with where we are in the epidemic, I see contact tracing as an additional layer that we need to think about on top of physical-distancing interventions.
And as we try to reopen parts of the economy and parts of our society, contact tracing can be a tool by which we contain and control limited outbreaks in that context and try to really make sure that we’re tuning our physical-distancing interventions effectively to protect people who are vulnerable.
As far as apps go, I think there are a number of apps that are being developed right now. And they have promise to help contact tracing in a way that’s going to reduce the need for personnel to do the contact tracing and automate some of it.
I still think that a lot needs to be worked out in terms of interoperability between different apps. And of course, we need to make sure that these are all done with privacy and the protection of personal data at the forefront of the decision on how to roll those out.
So, I think that there are a number of promising contact-tracing apps that could be useful, especially in particular contexts. So not all countries are in a position to be able to roll out contact-tracing apps and follow up on them, right?
So, you don’t just have to do contact tracing. Then you have to actually do something with that data and make sure that you’re isolating people, quarantining people, making sure people have access to information they need about access to health care and so on. So, I guess, yeah. So, the short answer is contact tracing is a very important tool on top of other interventions at this point.
Q: Thanks.
MODERATOR: Next question.
Q: Thank you so much for taking our calls. We greatly appreciate for all of the resources that you guys have provided for us and enabled us to share. Quick question for you about the testing and just the social distancing and all of that.
So, we’re in a state that’s tested less than 30,000 right now. It’s less than 1% of our population statewide. We do not have a shelter in place that’s inclusive of everyone right now. And we have about 110 deaths so far and about 2,100 cases as of yesterday. So –
CAROLINE BUCKEE: Which state are you in? Sorry.
Q: Oklahoma.
CAROLINE BUCKEE: Oklahoma, okay.
Q: Uh-huh. Yeah, so about 2,100 positive cases, about 26,000 negative, and 108 deaths so far. The testing has been an ongoing issue, as you know, nationwide – not just here but nationwide – with supplies and the reagent and now swabs and all of that.
So, what would be some of the important things – you know, state leaders and local leaders are saying they will listen to health experts about when would be the time to reopen right now. You know, some of the individual cities have the mandatory shelter in place for everybody.
But we know that obviously every health official I’ve heard, from Dr. Fauci and all around the country, people saying that it wouldn’t be advised until there’s widespread testing and contact tracing or both. So, I just want to get your thoughts about that and what would need to happen, not just here but anywhere that’s considering that.
CAROLINE BUCKEE: Yeah, I think that’s absolutely critical. You can’t just relax physical-distancing interventions in the absence of knowing where you are in the epidemic because you’d lead to enormous resurgence and a lot of deaths. So, I think testing is absolutely critical. And that needs to be the first priority.
And by testing, I mean diagnostic and virilogical testing to see who has the virus right now. That’s important not only just to get a sense of where we are with the epidemic, but also for hospitals and so on.
There’s another kind of testing that I think is going to be absolutely critical before we start reopening broadly. And that’s serological testing. So, these are tests that look for an immune response to the virus, not the virus itself.
And a serological test can tell you if a person has been infected in the past. So, the reason that that’s really important is that, assuming that there is some immune protection once you’ve got an immune response to the virus, if we can provide evidence that you’ve already been infected, then those people can go back to work, theoretically, whether it’s health workers that need to go back to work or other kinds of essential services.
So I think those serological tests – they’re called – they’re coming online now. And we need to implement them in two ways. The first way is to test people who we need to return to work, who are essential for the functioning of the economy, including health workers.
And the second way to use those tests is to do a random survey of the population that will tell you the proportion of people who have already been infected and have an immune response to the virus. That is one of the only ways that we’ll know how far along we are in this epidemic and when we can even consider opening up the economy again.
Because the other kinds of test, the virilogical tests, have been so patchy, we’ve missed a lot of people partly because testing capacity hasn’t ramped up fast enough but also because many people just have mild symptoms or no symptoms at all. And they’re not being seen in the health system. And they’re not being counted.
So really, until we start looking for evidence of past infection through the immune response, we won’t know how far along we are. And if we don’t know how far along we are, we won’t be able to say when it’s safe to reopen.
So, I think that that’s a priority. And certainly, in the absence of clear evidence that we’re far along in this epidemic and that there are communities that are safe to reopen, I don’t think we should be considering that without strong testing capacity and other types of interventions that we can act upon quickly when relaxation starts to happen.
Q: OK, I understand. Dr. Buckee, thank you for explaining that. Just a follow-up question. You know, I can remember when we were first starting to report about this here in the United States in February and the end of January. And obviously we were just reporting the overseas things at first.
But initially we were reporting that the concern was heavily for the elderly. And we know that that’s still the case, obviously. However, what has proven to be true, what we’ve seen in France and what we’ve seen in Spain and then obviously certainly here in the United States, is that it’s impacting people of all ages.
And specifically in our state, we see numbers within a hundred of each other among the 18 to 35, 36 to 49, 50 to 64. And 65-plus, just a few hundred more. But we are seeing hundreds and hundreds of cases in each category of those. Could you speak to that a little bit about just how we have seen it? And we have several in the 5 to 17 and 0 to 4, as well.
CAROLINE BUCKEE: Yeah, so this virus certainly affects everybody. And I think the numbers that we’re seeing of younger people – of course, comorbidities aside. So, if you have underlying health conditions, we know that you’re at higher risk.
And that’s going to be a lot of the young people that are coming in. They’re people that are already at higher risk for various reasons. And of course, the elderly are also at much higher risk of hospitalization and death.
I think it’s really important to consider how many people are in each of those age categories. So, what is your denominator in these calculations?
You know, if you compare hospitalized patients, I’ve seen statistics like x percentage of people in the ICU beds are between the ages of 18 and 65. And while that’s very worrying and certainly a big issue, the number of people in that age category is enormous.
So as a fraction of people who are getting infected, it’s still a very low fraction. However, it certainly is still affecting those populations at a low level.
And I think really the answer to why we’re seeing young people affected, short of underlying conditions, is that this is just a very transmissible virus and it’s affecting huge numbers of people. And so inevitably we’re going to see some people across all age categories who are symptomatic and some of whom unfortunately require hospitalization.
So, I think that the overall risk in the younger age groups is still low. It’s just that because the virus affects so many people, we’re going to see some of them coming into hospital and being quite sick.
Q: OK, that makes sense. Thank you very much. We so appreciate that. Thank you.
MODERATOR: Next question.
Q: Hi. Yeah, thank you for helping us make sense of this. So, you seem to agree that testing is going to be sort of paramount as the pandemic progresses past its peak and begins to wind down.
There’s no shortage of news reports about the issues we’ve experienced with testing so far in terms of supply, technology, processing times, all of those issues. Are you concerned about more hang-ups and more issues as we move into this next phase of the pandemic?
CAROLINE BUCKEE: Well, I think we’re ramping up testing. I guess the issue that I see is that there’s a lot of geographic heterogeneity in testing capacity.
So, in some areas, the testing capacity is now up and running pretty well. And in other areas, it’s not. And so, I think we need to think about scaling in all of the communities that are currently affected to keep up with the realities that this epidemic is affecting the whole country.
As far as serological testing, there are a number of different countries who are developing serological tests right now with plans to scale. Each of them have different sensitivity and specificities and profiles. And we’ll need to do some work to validate and compare across those tests before we can really implement seroprevalence surveys at scale.
I don’t think I’m qualified to speak on the manufacturing of serological tests and what the [INAUDIBLE] might be. But I think, in terms of just testing capacity right now, the biggest issue is coverage and geographic heterogeneity.
Q: OK, thank you. And can you elaborate at all on some of the big unanswered questions we have right now when it comes to serological testing?
CAROLINE BUCKEE: I think the big unanswered question is, how many people have no symptoms? How many people have only mild symptoms?
We really don’t know where we are in terms of the epidemic curve and whether we’re even close to the peak of transmission in any particular area. So until we really know how many cases there are – and as I said before, we won’t know that until we start to do serological testing – until we understand that, we won’t really have a sensible plan for when we can relax physical distancing and what the future’s going to look like.
Of course, we also need to know about immunity and what these antibody levels that we’re measuring with the serological tests actually mean for protection. That’s a huge unanswered question, as well. We hope, we hope, that there will be at least some immune protection if you have antibodies. But we still don’t know that.
So, there are two things. The first is, are antibodies protective? And how much antibody do you need to be protected against reinfection? And then the second one is, how many people have been infected? How many people have no symptoms or only mild symptoms? So those are the two big unknowns, I think, in terms of the epidemiology right now.
Q: OK, great. Thank you very much.
MODERATOR: Next question.
Q: Thank you so much for having me. I’m calling from Spain. We’ve seen recurrences in Italy and Korea of people who have previously had the disease and subsequently tested negative emerging again and testing positive.
We’ve seen in Northern Italy, for example, the isolation period’s been extended from 14 days to 28. What do you make of all of this? What are the sort of conundrums here? And what are the possible reasons?
CAROLINE BUCKEE: Reports like this have actually come out for some time from China and elsewhere. And I think that while it’s possible, formally, that there’s some interesting within-host dynamics of the virus that’s causing this kind of changing patterns of infection, I think many of us suspect that it’s just a testing issue.
So, for lots of pathogens, you can test positive or negative due to a combination of your pathogen load in the body and the test sensitivity and specificity. So over time, you might test negative and then positive and then negative again, even though it’s one infection. And I think that is one possibility that this is just these are people that continue to shed virus.
They’re testing variably positive and negative over time. But it’s not necessarily the case that they’re getting re-infected or there’s something else going on. So, I think the answer is we don’t know yet. But I think there’s a strong possibility that it’s just a test-sensitivity issue.
Q: Just a follow-up. In the cases in China, which I imagine are the ones that we have the most data on, does this represent an anomaly? Or is it a statistically significant sample of people? What are the implications in terms of having to test and retest?
CAROLINE BUCKEE: I don’t know about the statistical significance. I can’t answer that. I think that there are a small number of cases where it’s been observed. But you know, even, I think, in many situations people test negative or positive and there’s test-sensitivity issues. So my sense is that it’s probably a kind of testing issue.
I mean, I normally work on malaria. And you can test positive and negative one day to the next. And it doesn’t necessarily mean anything epidemiologically. It just reflects the within-host dynamics of the pathogen and the tests that you have.
Q: Thank you very much.
MODERATOR: Next question.
Q: Hi. Thanks, again. I’ve noticed some variations in death rates by country. What do you think is the reason for that? And does that mean that you have to calculate a reproduction number by nation?
CAROLINE BUCKEE: Well, so there are two parts to that. I’ll answer the latter one first. So yes, you absolutely have to calculate a reproduction number based on a setting that’s specific because the reproduction number is composed of – the way you calculate it incorporates the – I can just tell you the parameters.
There is the probability of transmission given a contact, the duration of infectiousness, and the contact rate. And because the contact rate itself is very dependent on the place, the setting that you are in, so whether you’re in a city, whether you’re in the countryside, we know that that’s country-specific.
So even the parameters that we put into models, we use setting-specific contact rates to the extent that we can. And they’re very different. So yes, the reproduction numbers are going to be very much dependent on the population in question.
Again, the way you calculate the reproduction number is the same. But we’ll see different R0 values in different settings. What was the first part of the question? Oh, the –
Q: Variations in death rates.
CAROLINE BUCKEE: Yeah, OK. So the death rate is something that we still – because of all the things I’ve been talking about, because we still don’t actually know what the denominator is, which is how many people have been infected, how many people have very mild symptoms, no symptoms at all, because of that, it’s very hard to measure what we call the infection fatality rate, which is of everybody infected, how many people die, because we don’t know how many people have been infected.
What we can calculate is, for example, the symptomatic case fatality rate or the hospitalized fatality rate. So, if you’re hospitalized, we know the probability that you die. And we have some guess at, if you have symptoms, what is the probability that you die.
So just to make a distinction, those are very different things. And that’s why there’s been uncertainty around how deadly this disease is. It’s because we don’t know how many people have been infected. So, the denominator is still uncertain.
As far as the death rate in different places, I think that’s going to reflect a combination of things. It’s often going to reflect the demography of the place in question. So, if you look at the age structure, for example, given how important age is in determining your probability of dying, the age distribution of your population is really important for determining the impact of this outbreak.
You know, in Sub-Saharan African countries, a huge fraction of people are very young, under the age of 20. So, we expect a very different mortality impact of the outbreak compared to somewhere like Italy, where a large fraction of people are over the age of 70. So, there are demographic features of the population that make it more or less likely to kill people based on their ages and underlying conditions.
And then the contact rate itself is also going to vary. So, if you compare Italy and Germany, for example, we know that the patterns of contacts between different age groups look very different because household structures are different. Children live with elderly parents, and so on.
So, all of these things are going to play an important role in determining how the disease spreads and also who’s going to die from it. So that’s why we’re seeing quite different patterns of mortality in different places.
Q: Thank you.
This concludes the April 15 press conference.
Yonatan Grad, the Melvin J. And Geraldine L. Glimcher Assistant Professor of Immunology and Infectious Diseases (April 8, 2020)