COVID-19: Immunity and contact tracing

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RICK WEISS: I’m Rick Weiss, the director of SciLine. Quick introduction to SciLine for those of you who may not be familiar with us – we are a philanthropically funded, editorially independent, free service for reporters. Our goal is to help you get the best science and contact with scientists for use as you put together your stories. We offer a variety of free services that I encourage you to check out on our website, sciline.org. But among them are these media briefings, at which we feature a number of experts who can get you up to speed on different areas with short presentations followed by live Q&A. Today’s two speakers have full bios listed on our landing page on the website, so I won’t go into all that detail now. I will just tell you that we will hear first from Dr. Nahid Bhadelia. She is an infectious diseases physician and medical director of the special pathogens unit – sounds scary – at Boston University’s School of Medicine. She also oversees the medical response program at BU’s maximum containment biosafety level 4 program – part of a national network of secure facilities that study infectious diseases that pose a major public health risk. She is going to focus on what we know about the immune response to the virus that causes COVID-19 and how that informs strategies for recovery on both the personal health level and on public health levels.

And then, second, we will hear from Dr. Crystal Watson, senior scholar at the Johns Hopkins Center for Health Security and an assistant professor in the Department of Environmental Health and Engineering at Johns Hopkins Bloomberg School of Public Health. Dr. Watson is the co-author on several recent comprehensive reports outlining what it’s going to take to skillfully initiate a phased reopening of the country, including a national plan for COVID-19 case identification and contact tracing – which is a topic we all know is very much in the news right now, and which she will focus on in part today. So with that, why don’t we get started with Dr. Bhadelia?

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NAHID BHADELIA: Thanks so much, Rick. I’m just going to share my slides. Thank you for everyone listening in. I wanted to not scare everybody with that introduction and just give you a 30-second introduction of what I do and what I don’t do, just to clarify my background. So I’m an infectious diseases physician – that was mentioned. So we have a laboratory that’s a maximum containment laboratory that works on biosafety level 4 pathogens – so these are viral hemorrhagic fevers – and many of these are emerging infections that we don’t know much about. And so my job is to run a medical backup program, basically making sensible medical and public health policies about pathogens that we are still – we still have sort of an evolving scientific understanding about. And so I run a three-bed medical unit at the hospital that’s similar to Emory’s and the one at NIH that provides that backup. And it’s what’s drawn me into a lot of work in the field for a lot of outbreaks, including the West African outbreak of Ebola in 2013 to 2016. And then, again, currently with the DRC outbreak that’s thankfully coming to an end and at the border of Uganda. And so the work that – so I’m – what I’m not is a virologist or an immunologist.

And so my sort of explanation to this – which I think might be a bit more – might be where your questions are oriented or are going to be oriented – around the clinical manifestations of this, on the public health manifestations of immunity, but also to give you a little bit of a background of what terminology is to help you interpret what it means. So just to start off, why is it important for us to measure immunity; is it important for us to measure immunity to COVID-19? And I think these are things that you can probably guess yourselves. You know, I think the biggest part of this is that we’re getting signals from our current understanding of this pandemic – is that we’re off in terms of the number of people that we think may be infected. When infection started to appear – infection started appearing here in the United States – almost three days ago – or two days ago, there was a report of deaths in California that occurred two weeks prior to the death in Washington, which was thought to be the first death in the United States of COVID-19. And what that does is it basically tells us that these two deaths, which were individuals who had no travel, no known contact – it means that, basically, the transmission of this disease started at some point in multiple cities in the United States some point in January.

And so the part of measuring this immunity – the other part of this – is that we now have science that says a lot of – there might be a significant portion of the population – between 25 to 50%, depending on the series that you look at – that may get this disease and actually never have any symptoms at all. And if that’s the case, there might be a large group of people who’ve had it, may be immune to it, and we just don’t know. And so measuring immunity – and I’ll talk about how we do that – it gives us an idea of the current baseline. Where are we with this pandemic? How many people has it affected, you know? And that tells us a bit more about how many people are left that are not affected – that haven’t gained immunity – and those are what we consider vulnerable populations. And so that gives us a strategy as we move forward to potentially opening of society. And this portion of time between now and when we have the vaccine – how many people do we see potentially getting sick in this period of time? – which affects my part of the equation, which is, you know, how many people do I have space to take care of within medical facilities? The other part that it tells us is it gives us the idea of the denominator, right?

Once we know how many people actually got the infection, we can adjust our numbers in terms of the mortality or what we call case fatality, which is this idea – it’s different than mortality because it measures from the time you got infected and takes into account the fact that there’s a lag time to when people pass away from that disease or recover from that disease. It gives us an idea of how deadly this disease is, in short. And then last bit that I’ll talk about – it’s important because what we’re trying to attain, whether it – and, ideally, it does this through a vaccine – we’re trying to obtain something called herd immunity – the concept that there are enough people in a group of people that are immune to a disease. Those who haven’t yet had the disease could keep themselves from getting infected because everybody around them has already had it and are no longer going to be infectious. And so there’s calculations around how this is measured that has to do with the transmission of the disease itself. But just to make it simple, I’ll quote Michael Osterholm, who’s talked about the fact that, generally, for this disease – for COVID-19 – we’d probably want to see between 60 to 70% of the population being immune before we can say we’re comfortable. I think others may give you other numbers, but that’s sort of the general sense.

So what is our current understanding of the immunity from SARS – after SARS – infection with SARS-CoV-2? Just to give you an idea, we hear a lot about something called the antibody test. So antibodies are the proteins in your body that are markers of the fact that your immune system has encountered a pathogen – that it has then built soldiers against – proteins against – which are fitted to the structure of the actual virus or the bacteria that it’s attacking. And so the antibodies are this immune memory. And so in reality, what happens is when a person encounters an infection, they build the antibodies – some of which are directly targeted to the action of the virus itself, some that may not be at the target of the virus itself, but they help in other ways – the antibodies that may block sites where, you know, viruses may go but not directly. And then there was this whole other part of the immune system, which is the T cells, or the cellular immunity – not to get into too much complex part of this, but just to tell you that antibodies, in themselves, are a marker. And, sometimes, they’re useful in saying if someone’s immune. But immunity, itself, is a very complex picture. And so for most infectious diseases – viral infectious diseases – we do end up looking at what we call – what we would call – are the levels of these antibodies in people. So measles, for example – clinically, when we deal with patients who’ve had this disease, we look at their immune cell – we look at their blood, and we look for the levels of antibodies that are in this blood.

For measles, we have a sense of what that level needs to be for that person to say that if that person encounters measles again, they will not get infected. That number – so those titers – that level of antibody level in the body is – we don’t know what that is yet for SARS-CoV-2. What we do know is that survivors of this current disease, COVID-19, do develop antibodies that seem to be directly targeted, effectively, at blocking the virus. Is that enough? How high does that level need to be? We also know that when we looked at other novel coronaviruses, like SARS and MERS, those survivors also had similar antibodies – so-called neutralizing antibodies – that are antibodies that are directly blocking the impact of the virus or the action of the virus. But they declined. It’s not a lifetime immunity in those diseases. And so most closely, this disease resembles SARS – the original SARS – it’s a virus unto itself. And SARS – the data that we have from SARS is that people develop these antibodies, but they fade away over time, over two to three – one to two years it sort of declines in the level. What we know from other coronaviruses is that, you know, if you get a run-of-the-mill cold or type of coronavirus, if you get it again down the road with a slightly different coronavirus in the same season or a year down the road, you might get the disease.

But the severity of that disease with the new strain may not be as severe. And then lastly, for this particular virus, we note that SARS-CoV-2 – the biggest question is, if you have these antibodies, if I give you the virus again, will you get infected? You know, if I give it to you now, will you get infected? If I give it to you six months from now, will you get infected? A year from now, will you get infected? And that is the basis, the question then drives everything else. And you can’t do that study in humans because, clearly, what you don’t want to do is try to infect people again. And so the data that we currently have is actually data from animal studies, a small study that was done in four animals that showed – nonhuman primates that showed that when you took these survivors, these animals who would survive the disease, and you gave them the virus again, they did not get sick. Again, a very small number, but it does give us hope that if they have these levels of antibodies that, potentially, we may see immunity. The last bit – that’s not on this on the slide. And just to give you a caveat – if you need reference for any of these studies, I’m happy to provide that. The last thing that we’ve noticed is that there was a study out of China about two and a half, three weeks ago that said that when they looked at all the survivors of this disease of COVID-19, a portion of them, 30% of them, had lower titers than one would have expected.

Again, what is high enough? So keep that in mind. We don’t know. But there is a portion that have a lower titer than others or antibody levels than others. So the – let me make sure I had – yeah, the current testing out there for COVID-19 – there are two types of tests you may be hearing about. One are these diagnostic tests that are looking for the actual genetic material of the virus. They do that using a technology called nucleic acid detection, and they’re looking for – what they’re doing is they’re looking directly for the virus, for the active infection. It’s useful to use this test. And generally, the tests are performed on – more accurately on saliva or fluid that comes from the nose or from the respiratory tract in general. And so this is what hospitals are using when patients come in when they’re symptomatic. The trouble is, you know, they’re getting use also in asymptomatic patients, which means patients who have no symptoms, because we know that a portion of the population may have this disease, as they said earlier, and may not have any symptoms. The trouble is we don’t know how accurate these disease – these tests are when testing them in patients who do not have any symptoms.

That’s still being worked out. The validation for some of these tests for that indication aren’t there yet. The other issue with these diagnostic tests – when you hear about issues, it’s supplies and other elements. You’re hearing about these tests because they require personal protective equipment. They require, you know, a bunch of different things, such as a nasal swab that you can use to get the fluid, a tube that contains material that keeps the virus alive. All of those things are what’s lacking right now, as well as everything else that it requires to run them in the laboratory. In fact, the kits are there. It’s everything else that sort of, you know, we have issues with. The other type of test, the ones that they’re being used right now for antibody testing, are actually the ones that – there’s a whole slew of them the FDA has provided emergency use authorization for. Same thing with a diagnostic test. So what that means is that they showed a capacity to detect the virus or capacity to detect the antibody in the laboratory. And so a lot of them still require a fair amount of what we call clinical validation. You got to take it for a test drive in a real population to see how it plays out because the accuracy of the test is, you know, determined by many other points rather than just the – what you see in the laboratory.

And the concern has been with these antibody tests that are out there is that many of them test positive when they should be negative. So they’re false positive. And vice versa – many of them test negative when they should actually test positive. And these are generally drawn because – through a pinprick. There’s a couple of tests of antibody tests done by pinprick and others that are done by blood draws. And the pinprick ones are the ones that, really, people are looking at for – potentially for home use and other elements, as well. So are the current immunity tests useful for individuals? So we’re facing this problem, right? So we can now have antibody tests right now in our hospital. And we’re considering using these in all our health care workers and saying, OK, who has positive test? The trouble is, as I said, for – depending on the test, there’s a whole range. We haven’t even determined how high the levels of false positivity or false negativity are. I apologize for the typo on the slide there. And so we don’t know what to tell people when we test them. If it turns out to be positive, we have to say, well, it could also be false positive. Or and if they turn out to be negative, we have to say, well, it could still be false negative. And so we don’t know what to say in terms of people’s immunities.

The other part is even if they are positive, we don’t yet know what immunity means, as I mentioned in the first slide. So we can’t guarantee, given our current science, that when we give them a positive test, that actually means the test is actually positive and that they’re actually immune. And so even if they’re positive, you know, we have this caveat. But the other thing that we need to do is we generally need to figure out if these are tests that just give you plus/minus. Do you have it? Do you not have it? Or do they actually test the levels? You know, as I mentioned, the levels of antibodies are important. So those are qualitative antibody tests – the ones that just check to see plus/minus – versus quantitative antibody tests that give you an idea of what the levels are. And so the latter ones are a bit more useful to tell you one way or the other. So there – all that to say that, at the current time, they don’t remain super helpful for the individual. As science gets better, if the tests’ accuracies get better, you know, I think, in certain populations with higher prevalence of the disease, they might be a bit more useful. But then for the public health part – so why are they being used – right? – at the population levels? You keep hearing about all these studies, including the ones that were done in New York City about the antibody tests that showed about 14% overall prevalence all across the state, 21% prevalence in New York City. Similar ones that were done in Santa Clara and California – why are we doing this test if given all these caveats?

So as – even though we don’t know what it means for the population because you don’t know if you’re the – that one individual that gets the false positive or false negative, over a population? It matters a little bit less when you have small portions of either one of those tests that are inaccurate because it gives us a comparative sense of burden for the entire population. It tells you, for example, that New York City has higher rates than Queens did or whatever – you know, I’m trying remember the lesser prevalence in that study. But it tells you comparatively that there are certain geographical areas that have it, and others don’t. It might also be used, for example, to detect hotspots – that certain populations, you know, are – as we open up, you know, you might find that certain populations already – you’re noticing – have higher rates of antibody positivity. That means that disease is transmitting much, much higher rates in those populations versus not.

And that gives you targets for public health intervention, for education, for, you know, improved sort of detection in the future because you’re noticing that the disease is spreading, you know, with that realization. And then it tells us – these tests over time – if you do the same antibody tests on the same population over time, it gives you a sense of, how is this changing? Let’s say you eased up – I don’t know – restrictions a little bit in society, and you tested the same population again two months from now – would be the same tests – it would tell you, you know, how many more people have been infected that maybe you didn’t detect through some of your active testing for people who might have had symptoms because, you know, there’s a whole portion that may have never had symptoms. So I’ll end there and just will take more of these questions during the Q&A part.

RICK WEISS: Fantastic. So interesting. Thank you. And we’ll go now to Dr. Crystal Watson.

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CRYSTAL WATSON: Thanks very much. Let me share my screen here. OK. So I’m going to talk to you today about kind of those next steps that you just heard about – reopening safely in the next months and weeks. So what is our roadmap for reopening? Lifting population-wide social distancing measures which we have in place across the country, like stay-at-home orders, will only be possible if we do a number of critical things. First, the reason that we have these measures in place is to reduce transmission. We also want to shore up our hospital systems. We want to make sure that they’re not overburdened and not overwhelmed by the cases that they’re receiving, and they can provide the care that’s needed. And we need to build some core public health capacities before we can open things up. So just as an introduction, here are the four phases of response that we see right now. We’re in phase one, which is slowing the spread. This is the broad-based, population-level social distancing measures. Phase two is really state-by-state and gradual reopening. We can begin to lift some of these measures. Phase three is establishing immune protection in our populations and lifting these measures more fully. And finally, phase four is rebuilding readiness for the next pandemic.

So I’ll skip over phase one because we’re in that phase now. We all know what’s happening. We have these social distancing measures in place. But where we all want to move to is easing these social distancing measures at a state or city or other local level. But before we can gradually start lifting these measures, we have to have four things happen. First, we need a sustained reduction in daily case numbers. We need to be sure that infections are coming down to a manageable level in cities and other localities around the country. We need to treat this, as I said, more at a local level. This is not one national epidemic. This is many epidemics across our country, and they’re going to look slightly different in different places. So we need to see that sustained reduction in each location. We need to see that hospitals are not under stress – that they are not operating in a crisis mode, that they can handle the patients they have, and they have room to surge up if they receive additional patients if we lift the measures, and we have a surge in cases. We also need to make sure that there are plentiful supplies of personal protective equipment, essential medicines to treat people and ventilators in our hospitals before we reopen.

So those are two kind of metrics that we need to meet. There are also capacities and capabilities that we need to build. So first is much more widespread testing for infection, so that first type of testing that was just discussed. We need to be able to test anyone with symptoms and, ideally, test their contacts, although testing people who have symptoms is more important right now. Up to this point, we have not been testing people who are mildly or moderately ill for the most part. We’re mostly testing people who present at a hospital and are sick enough to warrant care or at least having a look at them at the hospital. They will get the tests first. So we need to widen that. And lastly, we need to scale up our public health workforce to identify cases where they’re occurring and to trace the contacts of each case, and I’ll talk more about that step next. So what is this scaling up of contact tracing? Contact tracing is a core public health tool. This is not new. Public health agencies have been doing contact tracing for decades, possibly longer. We do contact tracing for lots of different types of infectious diseases. Routinely, we trace contacts of people with sexually transmitted infections. Measles is a good example where we would use contact tracing, and the outbreak in New York state last year was brought under control with good case identification and contact tracing and other measures, including vaccination. So we know how to do this; we just don’t have enough.

So what does contact tracing actually look like? Contact tracing means – that once someone presents, they have the symptoms of COVID, they’re either diagnosed presumptively because they have the symptoms or they receive a test that says that they are positive, the next step is for a health official to reach out to that patient and, first, ask them to isolate at home or isolate them in a health care facility if that’s needed, but then ask them who their contacts have been during the course of their illness. And the timing of this is a little bit different for this virus because we know that it can transmit presymptomatically. So they would ask for contacts – close contacts of that person even before symptoms started showing up, so maybe two days before that. And the idea is to identify anyone who might have had some kind of this qualitative close contact. It’s kind of a judgment call how close is close enough. It’s a combination of that proximity and kind of the length of time that that person was in contact. So once you identify those close contacts, you would get in touch with them and ask them to quarantine at home for 14 days. For some people, this may not be feasible, so another thing that public health will do in that case is maybe provide another place for someone to quarantine safely.

For example, if they – if they’re homeless, they don’t have a home to quarantine in, or if they live with people who might be susceptible to the disease and don’t want to infect them. So the purpose of this is – of contacting these people, asking them to quarantine at home is to really break chains of transmission. So hopefully, if they quarantine for those 14 days, then they’re not passing this along to someone else. So this capacity is really needed to break those chains of transmission, but more importantly, at a population level, it’s to manage this epidemic on an ongoing low level in different places around the country. This is helpful because it will help us identify every case or nearly every case and stop them from transmitting to more people, and it will help us prevent future waves or surges of cases. We’ve probably all heard recently discussion about a fall wave of the pandemic, which we’ve seen in history that has happened before that there are multiple waves. But I think if we have this capacity built around the country, we can, in large part, prevent that because there won’t be this large pool of unrecognized people that are transmitting the virus in our community. So the purpose of this overall is to prevent illness and death, but also to enable us to get back to work in a much safer way if we’re able to manage this virus.

You’ve also probably heard about technologies and apps for contact tracing. The way I look at technologies for this purpose is that they’re a workforce multiplier. So technologies themselves are not going to do the job. They won’t be able to perform this service that public health does for us. But if a public health worker has access to, say, Bluetooth information about who – where – who a person was in contact with when they went out to the grocery store, for example – because that person who has the illness may not be able to tell you all those people, and so it helps public health track those people down and notify them, which is a really good thing. It’s a little bit tricky in terms of the timing. These apps need to provide detailed information about people’s whereabouts and about the people who they’ve been in contact with as well as be timely. Right now, even testing is a bit of an issue with this because if we wait for someone to have a positive test, often, that’s taking three, four, five days to get a test result back. So with contact tracing now, until we have testing up, running more quickly and more ubiquitously, we need to be able to presumptively diagnose those people, ask them to stay at home in isolation and then ask them for their contacts so we can notify them right away. If we wait, those contacts, if they were infected, will go on to be infectious themselves and spread it to others if we’re waiting for a test result.

So how do we accomplish this? We need a massive workforce upgrade for public health. As I said, public health knows how to do this. We just don’t have enough people. We think that it may take as many as 100,000 new workers to accomplish this across the country at a cost of about 3.6 billion. Fortunately, in the bill that was passed yesterday, there was funding for state and local health departments to do some of this work. It did call out contact tracing. It didn’t provide a specific funding amount for contact tracing in and of itself, but there is – I believe it was $11 billion was included in that for contact tracing, testing, other workforce and EPI efforts that public health is doing. So that is positive. We also need coordination and guidance and support from state levels, who are going to have to run some of these programs, and at the national level. CDC has been putting more guidance about this on their website, but I think kind of more – additional national guidance for states and locals about how they can scale up this workforce, how they can manage them, what are best practices, and possibly some technical assistance as well would be appropriate. And this can be done in many different ways. So some states may want to receive money and hire people themselves.

Other states, like Massachusetts, which is the community tracing collaborative here, may partner with a nongovernmental organization like Partners In Health to hire contact tracers and put them to work. In that initiative, they’ve already begun hiring a thousand contact tracers. And there are other similar initiatives, like with the state of New York and Bloomberg Philanthropies, that are in the works now. So that brings us to phase three. So if we can build this capacity to do case-based intervention and do contact tracing, we can manage this at a relatively low level over time and react appropriately if we do have surges of cases. So that brings us to when we can provide greater immune protection for our population, and that means a safe and effective vaccine that’s widely available. Hopefully, that will come to pass in – the estimated time has been 12 to 18 months since the start of those efforts. Once we have that and we’re able to vaccinate our population, or even when we have some therapeutics that could provide some protection or reduce the severity of illness if people do become infected, that might allow us to relax social distancing further and get back to a more normal life or economy.

Up until that point, even though we may start to go back to work, it will be a modified work environment. We’ll still be using social distancing to a great extent. And finally, phase four – I don’t want to belabor this but I do think it’s an important point to bring up. We need to rebuild our readiness for the next pandemic. This is not the worst-case scenario that me, as a public health preparedness expert, have envisioned, and so we need to make sure that we take lessons from this and we build our systems so that we can respond better the next time. And this last slide – which the slides will be shared with you – this is just a number of resources from our Center for Health Security. The website has a great deal of resources for COVID-19, as well as these are some of the reports that we’ve put out over the last few weeks, actually. So thank you very much. Can’t hear you.

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RICK WEISS: Dangerous when I had noise outside. Thank you very much. And a reminder to the reporters that these slides will be available after the briefing on our website, so you can refer to them later. And now, if reporters have questions, please go ahead and click on the chat symbol at the bottom of your screen and submit them.

RICK WEISS: I’ll start right off the bat with one from Doug Fraser at the Cape Cod Times. The first part I think has been answered – whether contact tracing can be effective in the municipal, regional state levels, or does it have to be deployed nationally? We’ve heard it makes sense to do this piece by piece. But the second part of the question is, what percentage of a given population needs to be tested in order for contact tracing to be effective?

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CRYSTAL WATSON: Yeah. So it’s hard to put a percentage on that. And as I said, we can do contact tracing even when we don’t have a positive test. It makes it much easier if we know for sure or at least with reasonable certainty that someone does have the virus, but it really is focusing on that case-by-case level. If we can find a large majority of cases and quarantine their contacts, that’s when we can manage this at a much more effective level.

NAHID BHADELIA: Just to add on to that, one thing that I was going to mention is that, you know, I can tell you there is not enough testing now. So I’ll give you an example. So if we say that 25% of the people could be out there who have this infection who are asymptomatic and never develop any symptoms, that means when people come to the hospital, 25% of the people who come to the hospital who are not there for COVID-19 could potentially have this infection. Wouldn’t it be great to know, for the hospitals, which patients that are on general wards have COVID-19, right? So we can sort of treat them. We can separate them. As it is, we separate everybody and we put most health care workers in some level of personal protective equipment for this reason. Right now, if I wanted to do a whole week of testing in Boston of all the emergency rooms just to get a sense, the – to sort of get – see how big of a problem it is in terms of how many people are coming to the hospital, we don’t have enough swabs to run those tests.

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RICK WEISS: Great. I have a question here for Dr. Bhadelia from Christine Herman from Illinois Public Media. Do you worry, as antibody testing becomes more widespread with marketing from so many commercial labs, that people who test positive will have false assurance that they’re protected from infection when that may not be the case?

NAHID BHADELIA: Yes. I think that is the concern that we’re sort of expressing because if we don’t have clinical validation and more data about these rates of positivity and negative – negativity – false positivity and false negativity, that if these are marketed straight to consumers, that it will lead to, exactly as you mentioned, either false assurance if they haven’t had it or, you know – and that’s actually the bigger concern, right? If somebody had it and tested negative, they would continue, hopefully, not to change their behaviors. The concern is if they’ve had it, would a portion of people change their behavior and, you know, and potentially put themselves into risks that they shouldn’t. So it is of concern that we get these tests to be as accurate as possible before they’re sent to consumers.

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RICK WEISS: Got it. A question here maybe for Dr. Watson from Andrew Joseph at STAT News. If some states – sorry. If some states start to open up and it’s premature, presumably, cases will rise there. But from there, cases could be imported to states that are still on lockdown and reseed transmission. How likely is that scenario, and what can those other states do to try to be on the lookout for that?

CRYSTAL WATSON: Yeah. Yeah, I think that is a big concern. Without these broad-based social distancing measures and without the capacity to do case finding and contact tracing, I do believe we are going to see additional surges of cases in – from this epidemic. So – and that will not be contained within a state. So neighboring states and perhaps states across the country and countries across the world are going to have cases imported from those outbreaks. So what neighboring states can do is really to build this capacity to find every case and trace their contacts because that will suppress any other surges, but it will also find those cases that are imported from other outbreaks as well. So it really is about building this capacity. And I think, unfortunately, for the states that are opening up right now, what it may mean is when they have additional surges of cases, they may need to go back under these population-level social distancing measures. So we may have stay-at-home orders reinstated in those places, which, for me, at least my impression is that that is going to be a lot more detrimental to morale – to health, certainly, but also morale, and also our economy to have this yo-yo of up and down, stay at home, go back out. I think it’s better if we can manage it on an ongoing basis on a low level. So building these capacities is really critical.

[0:37:50]

RICK WEISS: A question about, basically, immunity here. Maybe this is more for you, Dr. Bhadelia, but this is from Mike Sherry, Kansas City PBS. Can either one of the speakers speak to the effectiveness or promise of convalescent plasma treatment?

NAHID BHADELIA: Sure. So convalescent plasma – not a new concept. Actually, we’ve looked at it for a lot of other diseases. So it was actually thought of in Ebola as well. And, you know, when we – actually, in small studies that had no controls, convalescent plasma showed promise. And when it was actually tried out as a randomized controlled trial, it wasn’t effective. And so there is a small randomized controlled trial – I think it was almost 10 to 12 patients – that did show that there was a drop in the amount of virus in very sick patients who got donated plasma from survivors of convalescent plasma. And there are currently randomized – large randomized controlled trials, including, actually, one in Boston led by Brigham that we are here at Boston Medical Center also a site for that’s looking at the effectiveness in a larger group of people to see that it’s useful or not. So there are two limitations to convalescent plasma. One is – so what it’s basically doing is it’s taking this blanket of immunity – right? – from a person who’s recovered and passing it on to somebody else, and so it’s overlying all the fight against the virus in that person’s body with these tools that have already been developed from the survivor. So it’s a blood product, so the first limitation is it requires somebody to donate that. And it’s almost like, you know, one-to-one or, you know, one-to-two, so you need a lot of donations to meet the amount of need.

The second is because it’s a blood product, there’s always a concern that you might have transfusion-related acute lung injury or other sort of adverse effects from giving a blood product to somebody else. We see that in a small people – group of people who get blood donations as well. The more effective answer probably in the long term – so I don’t know yet about the convalescent plasma. I think the trials – promising. The bigger trials will answer it. The more promising thing, you know, is what we saw in Ebola. What happens with virus disease – viral diseases is there are two attacks. There is the direct attack initially of the virus itself as it attacks different lung tissues and – or different tissues around the body, ones that it actually glues (ph) into because of how it gets into the cells – human cells themselves and where it finds those entrances. Then there is the damage that comes from your immune response itself. And so your body revs up. And with this disease, it just runs amok. You know, it creates a lot of something called cytokines, which are just alarm – you know, it’s – they’re, again, more proteins of the immune system that awaken different parts of your immune system and increase the inflammatory response. And then that itself then damages your body.

And so in a lot of viral diseases, what we find is that drugs that control the virus itself, so antivirals – so the kind of drugs that have been looked at currently for that are things like hydroxychloroquine, which, you know, doesn’t look like it might be effective from earlier signals from the randomized control trials that are potentially coming out and smaller ones that have come out already, and remdesivir, which is another antiviral. So that’s – favipiravir has been looked at. There’s HIV drugs that have been looked at about this. All this to say that in many other viral diseases – not this one – the data has been that if you give antivirals too late, they’re probably not that effective ’cause what’s causing the damage later on is your own immune system. And so there are a whole other class of drugs, such as antibodies – there’s a great paper that came out in Nature yesterday where they looked at the antibodies of survivors and they found – actually detected the very specific ones which, with high affinity, blocked the site of entrance on the virus that it uses to enter human cells, the receptor-binding domain.

I don’t want to go into too much details about this, but they identified two antibodies. And what they were able to do is then clone them. They created something called monoclonal antibodies. And so in Ebola, once we did the randomized controlled trials, what we found was that drugs that were in all comers (ph) for later on in disease were actually three of these monoclonal antibodies that were identified from other survivors that were useful. And that work is actually currently undergoing some – there’s going to be a lot of steps between now and then, but that’s another promising strategy to address this disease.

[0:42:19]

RICK WEISS: Great. A question that I think I’ll direct to you first, Dr. Watson – do you anticipate that contract – contact-tracing smartphone apps will be part of the solution? If so, what challenges do you anticipate? For example, what about buy-in from citizens worried about privacy?

CRYSTAL WATSON: Yeah. So I do think there’s potential there for using smartphone apps, and specifically Bluetooth technologies I think are kind of the thing that we’re zeroing in on as might – that – the technology that might be the most useful in the context of the U.S. There are privacy concerns around this. I think Bluetooth is fairly privacy-preserving in that it doesn’t identify – there are not personal identifiers that are attached with that data. But there are also challenges with putting privacy first, and I think we need to both preserve privacy and identify how we can get useful information to public health officials and contact tracers. So there’s this balance between protecting privacy and collecting the information that’s needed, and public health needs pretty granular information in order to identify the contacts to get in touch with them.

And the reason they need to get in touch with them is not just to identify them and tell them to quarantine. That potentially could be done by an app. But when you ask somebody to stay home for 14 days, they may need support to do that. I don’t advocate using technologies to help enforce quarantine. We don’t want to force people to stay at home. We want this to be voluntary. And so what public health can do is provide support for those people – make sure they have the food they need, other necessities like medicine, that they have care for the – their loved ones if that’s needed as well. So there are a lot of issues that public health needs to attend to here. So the combination of the application and the workforce is what’s really necessary. And so we need to make sure that that balance of information availability and privacy is a good one. And so we’re still figuring out what that balance is.

[0:44:36]

RICK WEISS: I should’ve mentioned that was a question from Susan D’Agostino, freelance reporter based in New Hampshire. The next question is from Barbara Moran from WBUR in Boston. At some point, if we determine that a certain percentage of people with antibodies are immune and can move freely and go back to work, is there a risk that people will start infecting themselves on purpose? Have you heard about this happening yet? Either of you want to take that?

NAHID BHADELIA: Crystal, do you want to start?

CRYSTAL WATSON: I think there are some cases where I’ve heard of COVID parties. So we’ve heard of chickenpox parties, which I also don’t think are a good idea. But this is an especially bad idea because – and Dr. Bhadelia can talk more about who is especially susceptible to severe disease. Sometimes we don’t know. Sometimes it is a younger person who becomes severely ill. And so you can’t predict that if you have a – have an intentional infection, trying to expose yourself so you can have immunity, that could mean severe illness or even death. So the risk of doing that is pretty high here. And I would not recommend that at all.

[0:45:50]

NAHID BHADELIA: Yeah. I’m just going to go ahead and say ditto on that. I think that we’re still understanding what things make people vulnerable to this disease, right? And this is one of the challenges with emerging infectious diseases. So I’m just going to take this second because I saw a question in chat that I wanted to make sure I clarified. The question of my – early on, I said in my presentation that I think our understanding has been off. I wasn’t talking about immunity. I was talking about the epidemiology of this disease. I just wanted to clarify that. We just don’t know enough about immunity for us to be off about anything. I’m sure we will be, but we don’t know enough about it yet. But it’s the epidemiology and how early we think this pandemic started.

[0:46:34]

RICK WEISS: So just a little clarification requested on that point, actually, from Kerry Fehr-Snyder at KJZZ in Arizona. Researchers now say the first cases appeared in individuals, as you mentioned, without travel or contact with this virus. So how did they get it? What do we think about how this started in this country?

NAHID BHADELIA: I’m sure Dr. Watson can actually also reflect on this. But if you think back to the fact that these were very sick patients, that means they got it at least a week or two maybe beforehand, right? And then they don’t know who they got it from, which means the person who they got it from probably didn’t know they had it either. And so that means that if you move that backwards, if you say they got infected at the beginning of February, that means that in California, in addition to what Trevor Bedford’s lab has already shown in Washington, there was already community transmission of this virus in California and in Washington. And there was a Northeastern model – Northeastern University model that looked at the numbers, which, you know, people are sort of saying is the magnitude, right or not.

But what they said was that in at least five states, including Boston, there were probably already community transmission without us realizing that it was here. And when we think back to this – right? – to this moment, hindsight is always 20/20. I can tell you a lot of us doctors at the beginning of March and end of February were going, we should test everybody. You know, if there were tests, we should’ve tested everybody. And at that point, this is going to sound – it sounds so ridiculous when you say it – up until beginning of March, we were still only testing people with travel to China and symptoms. And when you look at it in line with, like, the data that we’re seeing now, we were really off. I mean, not we as in we knew that there was something going on, but we had – as a community, as a country, we did not test as many people as we should have upfront to detect this.

[0:48:31]

CRYSTAL WATSON: Right. And I think we delayed in developing testing. There were lots of problems with testing and rolling out testing on a wide scale. And we’re still seeing the ramifications of that. But, yeah, I agree with you. Even in early February, I think people in my office were kind of clamoring for – we need to test much more widely because we were seeing spread to other parts of the world already at that point. So we knew it was – there was probably a high probability that we were having cases start in the U.S.

[0:49:03]

RICK WEISS: Along similar lines, a question from Vincent Gabrielle at the Knoxville News Sentinel. Locally, we’ve had product test shortages, not just in terms of capacity to run tests, but swabs and other collection kits. The local public health department says they can expand contact tracing capacity, but it seems unlikely under the current testing regime. We’re going to open up next week. It seems like a major risk to open up in these conditions. Could you speak to those concerns?

CRYSTAL WATSON: Yeah, I agree with that. I think it is a major risk, and it is not worth the risk. It’s worth waiting a few more weeks to have testing capacity in place, to have the workforce for contact tracing and the approach to contact tracing figured out in each state. Without that, we’re really just opening up our community to transmission again. There’s nothing there to stop it at that point. And we’re going to see hospitals become overwhelmed. And we’re going to see more people die as a result. So I am really concerned about some of these actions. And I think it would be much better to wait a few more weeks to have these capacities in place.

[0:50:17]

NAHID BHADELIA: And just on the hospital point, I mean, think about what hospitals across the country are doing. You may have heard about the fact that there’s this new technology where we’re actually decontaminating respirators or one-use respirators to use them again, and that’s effective. It is effective technology. You know, that’s why we’re all doing it. But we had to get to a point where we had to reuse respirators after getting them decontaminated. So clearly, there isn’t enough personal protective equipment. And, you know, when we are looking at our supply chains over the summer and moving ahead, there’s no guarantee. You know, I think we have enough for now, but as we project out, depending on if there are big peaks that are coming up, we might, you know – everybody across the country, and particularly cities that have had big outbreaks, might see future ones and are going to be in dire straits if we have another big peak like this.

[0:51:07]

RICK WEISS: Going to try to get a few more questions in our last five minutes or so here. This is from Don Paul from Buffalo News in New York for Dr. Bhadelia. Is there anything new on the FDA-approved Rutgers saliva test? Might that type of test lower the ratio of false negatives through a more uniform protocol?

NAHID BHADELIA: So I think, you know, the concept is a great one because if you’re using saliva, there’s a couple of benefits to that because you don’t have to use the same swab. And the other thing is there’s actually a risk to health care workers when they do the nasal swab, and which doesn’t get talked about anyway. But we use personal protective equipment partly because when we stick that nasal swab up someone’s nose, what’s the natural reaction? They’re going to cough or sneeze because it’s really uncomfortable. And so when they do that, they generate aerosols. And that’s why people wear personal protective equipment when they do that testing.

And so if you have a saliva test that somebody potentially could do at home or could do at a health care setting, it carries a little bit less a chance as a sort of transmission or need for more advanced personal protective equipment, including respirators. So – but that test in itself not – I have not – again, I always caveat this. Never have I ever faced in an emerging infectious diseases outbreak where 24 hours can mean the difference about knowing, like, truth and false about something. I have not seen anything else new. It will probably require the same kind of clinical validation that I was talking about about every other test we have to take for a test drive in a large population to see how it actually plays out in terms of accuracy.

[0:52:45]

RICK WEISS: Question from Hal Dardick from the Chicago Tribune for Dr. Watson – can contact tracing be fully effective in the absence of widespread testing or does testing need to be widespread before contact tracing will truly work?

CRYSTAL WATSON: You know, I think testing is really important, and so we shouldn’t take our eye off the ball. As Dr. Bhadelia said, there are other reasons that we need to test widely. Specifically, we need to have more tests in health care facilities to help test health care workers. So we shouldn’t take our eye off the ball for that. But we also shouldn’t delay in conducting contact tracing until we have a perfect testing system. We can presumptively diagnose someone and ask them to isolate and identify their contacts and ask them to quarantine. We can do that without a test. It’s better if we have a test because we can be more sure about that diagnosis and we won’t be quarantining people who don’t need to be. But we shouldn’t delay because this is the way we’re going to control the spread of this virus. And so if we can do it without a test, we should until we have enough tests to help out.

[0:53:53]

RICK WEISS: That’s helpful. And from Mindy Wood, reporter at The Norman Transcript in Oklahoma – with the uncertainty of antibody testing that you mentioned or that Dr. Bhadelia mentioned, can you comment on the reliability of PCR testing for genetic virus materials? Do they have the same false positive and false negative issues?

NAHID BHADELIA: Yeah, there are a couple of things that are inherent to antibodies that are not as big of a problem for nucleic acid tests. So antibodies are imperfect – right? – because what your body is doing is this – initially is just a scattershot of throwing out a bunch of targets at a new pathogen, and then it looks to see what sticks. It literally looks to see what sticks, and then it produces more of the antibodies are effective. And so then the response becomes more specific, and then, you know, you sort of aim for that particular disease. And it’s every individual is making different antibodies. And so the trouble is, you know, when someone creates an antibody, which is what you’re trying to detect with your antibody test, sometimes the targets of what the body has produced can be imperfect. So it could be similar to a couple of different viruses – the response that you’ve produced to a couple of different viruses, particularly maybe other coronaviruses and things like that.

And so we see those in many, many different diseases where if an antibody is positive for one viral – hemorrhagic fever, for example – we’re always concerned, well, is it positive for this one or is it positive to this other species? Could this person have been exposed to Ebola – you know, Zaire Ebola, like, Bundibugyo? Like, we don’t know because there are similarities in the antibodies themselves. So the antibodies have to be very specific. You have to find an antibody – testing for an antibody that’s very specific to the disease that you’re actually looking for. And so there is that inherent problem because there’s a lot of noise in the background. You might have other antibodies that, you know, test positive. And so that’s one inherent problem with it. And so that leads to some of the issues that I talked about. But the nucleic acid actually tests for the genetic material itself. And so in the laboratories, you know, once you get a cassette that logs on to, you know, to the genetic material of the virus, the primer or probe that logged on to the genetic material of the virus, it’s detecting something very specific, so as long as you’ve got your science right to begin with – and that way, they’re accurate. The trouble with nucleic acid tests is that it then depends on when you deploy it in a person. It depends on where’s the virus in their body. You know, this is a virus that moves from your nose down to your lower tract. And so depending on where you collect, what time and when you collect the sample and how well the sample is collected, that might also affect the accuracy of whether or not the test is positive or not. It’s a yield issue, you know? And was the person – did the person have enough virus in their body?

And that’s a detection issue. There’s a limit at which nucleic acid tests can – they have it in their brochure. There’s a limit of the virus that they can detect. When the patient’s below that, they won’t detect it. And the other problem with the nucleic acid test is, you know, less of an issue here, but this was a concern in other outbreaks that if you collect a whole lot of these tests and they’re just hanging out and you can’t run them, that over time, the viability of the virus itself on a swab – the virus may die, right? You don’t have enough media. It’s not in the right conditions. And so by the time the test gets to the lab, there’s not enough there. It’s less of an issue. I mean, I don’t know. It was more of an issue for some of the outbreaks that we saw in resource-limited settings.

[0:57:26]

RICK WEISS: Interesting. Great. I’m going to squeeze in a quick last question for Dr. Watson. Then I’m going to ask each of you to take a half-minute to give a last take-home point that you really want reporters to keep in mind going forward. But a quick question for you, Dr. Watson, from Ashley Luthern at the Milwaukee Journal Sentinel. When scaling up the workforce for contact tracing, how important is it for tracers to have a public health background? How long does it take to train non-public-health folks in contact tracing?

CRYSTAL WATSON: Yeah, that’s a great question. So I think we can take people who are in public health and might not be involved in this response yet. I think that’s a good idea. We can take people with a medical background. But while this is a very resource-intensive process to do contact tracing, it is not something that takes a long time to train. So I think we could do very quick trainings within a matter of a few days and bring even laypeople on board to do some of this work. And I think given that, it’s a good opportunity, possibly, to put people to work not only to help with the response, but also possibly people who have lost their jobs from this pandemic. It’ll give us a sense of efficacy in the response itself and maybe give us some work to do. So I do think we can have lots of types of people, but including laypeople.

[0:58:51]

RICK WEISS: Great. So I want to ask each of you just to take a half-minute or a minute to hammer home any take-home that you’d like reporters to carry with them as they leave this briefing today. Dr. Bhadelia, I’ll start with you.

NAHID BHADELIA: Sure. So I’ll say one functional thing. I saw a question in the Q&A about the references. So the version of the slide that SciLine will post, I’ll just put the last slide as references. The take-home, I think, is just, you know, this is maybe – what? – third or fourth outbreak that I’ve been on the front lines for for emerging infectious diseases. And then the trouble is always the same, which is that you’re learning about the science as you’re responding. And the issue is to always take everything you hear about new studies as they’re coming out, particularly now, you know, as you see them in this preprint versions – I think most of you already do this – to take it with a grain of salt because science ends up being this body of consensus. It’s not one big, striking – it’s usually not this one big, striking finding. It’s over time confirming the same finding to make sure that something is accurate.

RICK WEISS: Thank you. And, Dr. Watson, take-home message from you?

CRYSTAL WATSON: Yeah, my take-home message, really, is we don’t have that many tools to respond to this pandemic. But the tool that we have – the two tools that we have that I’ve talked about, testing and contact tracing, they can be very effective. We have seen this implemented in other countries to great effect, managing the pandemic there in South Korea, for example, in Singapore. They’re able to manage surges of cases and bring that back down to a low level. And this has to be sustained. So these are the tools we need to develop. We need to put resources towards this. And we need to prioritize this at a national level because this is how we get back to work and do it safely.

RICK WEISS: Great. I want to thank Dr. Bhadelia, Dr. Watson for some excellent information shared today. Thank you so much. To our reporters, thanks for attending. Please check out our website. We have a COVID-19 resource page you can get to from our main homepage at sciline.org. Follow us at @RealSciLine. And I do want to mention when you sign off, you will get a prompt for a very short three-question survey. I know everyone has immune systems against surveys, but it really helps us if you would just take the one minute it will take to answer those three questions so that we can keep providing you services like this that take care of exactly what you want to have help with. So thanks again to everyone for attending. And we’ll see you at the next SciLine media briefing.