"The Response to COVID-19: A Global Health Perspective" SwatTalk
with David Kaufman ’94, head of Translational Development at the Bill & Melinda Gates Medical Research Institute
Recorded on Thursday, April 16, 2020
TRANSCRIPT
Ayanna Johnson:
Hey. Good evening everyone. And welcome to tonight's SwatTalks, The Response to COVID-19: A Global Health Perspective featuring Dr. David Kaufman, class of 1994. My name is Ayanna Johnson and I am a member of the Swarthmore Alumni Council and a Swarthmore graduate class of 2009. As a public health professional, I'm really excited today to moderate our session. I hope that wherever you are tuning into the session from that you are well. I wanted to first let folks know that this session is being recorded and will be made available online. After David's presentation, we will have ample time for Q&A, and you can use the chat feature in the Zoom platform. And when you do ask a question, please be sure to include your name and class year if you're an alumni.
Ayanna Johnson:
SwatTalks is an Alumni Council initiative to engage the broader Swarthmore community in free virtual seminars featuring professors, students and alumni excelling in their field and sharing their knowledge and experience. Tonight's webinar is the second part of a special series on the pandemic caused by the novel coronavirus. Our previous talk focused on biomedical research at the NIH in the age of COVID-19. And this coming Sunday will be our third webinar on disaster economics getting through the coronavirus pandemic. You can register for upcoming webinars and find recordings of previous SwatTalks on the alumni page of the Swarthmore website. And so now we'll get started with our talk.
Ayanna Johnson:
As of today, around 4:30 p.m. I did a check there were approximately 2.1 million cases worldwide of Coronavirus. Of course, we know that here in the US, we are leading that number with over 600 confirmed cases. But other countries like Spain and Italy also have a high case. Conversely, when you look at countries like Thailand and South Africa, they're only reporting a couple thousand and yet others like Taiwan, Kenya and Guatemala are reporting only 100 or so cases. We also know that in good news that 540,000 people at this point have recovered from Coronavirus.
Ayanna Johnson:
And while we were hearing stories of devastation, we are also hearing stories of resilience, innovation and compassion across the world, really highlighting the best of humankind. Today's talk is ever important as we learn about how collaboration and scientific endeavors on a global scale could help address this global pandemic. I would like to introduce tonight's speaker, Dr. David Kaufman.
Ayanna Johnson:
David Kaufman is the Head of Translational Development at the Bill and Melinda Gates Medical Research Institute. David joined the Institute at its founding in 2018, and has served as Chief Medical Officer and Head of Translational Development. He helped establish the Gates MRI as a nonprofit biotech, developing novel drugs and vaccines for tuberculosis, malaria and enteric disease, neonatal health and other global health challenges. Previously, he led translational oncology at Merck research laboratories, where he oversaw immuno-oncology, translational medicine, biomarker development and global translational research.
Ayanna Johnson:
He trained in internal medicine at the University of California, San Francisco and Infectious Diseases at the Mass General Hospital and Brigham and Women's Hospital. And of course, he's a Swarthmore alum, class of 1994. We're thrilled that David was able to be here today in this what I can imagine is a very busy schedule. So with that, I will turn today's session over to David.
Dr. David Kaufman:
Ayanna, thank you so much for the kind introduction. Let me share a few slides. I promise that there are only a few of them. Okay. All right. So Ayanna I mentioned, after many years of additional schooling following Swarthmore, I now have a real job. Just to situate myself for you guys in terms of how I'm looking at the COVID-19 epidemic, I'll just tell you a little bit about where I work.
Dr. David Kaufman:
So the Gates Medical Research Institute is a subsidiary of the Gates Foundation that was launched in 2018 to essentially serve as a nonprofit biotech in the global health community. So in many ways, we function like a for profit R&D organization, a small pharma or a large biotech. But our focus is on developing vaccines and drugs for diseases like tuberculosis and malaria, enteric and diarrheal diseases and major causes of infant mortality.
Dr. David Kaufman:
I want to start by just giving a real shout out and a moment of appreciation for all of our friends and colleagues who are actually out there working on the front line, risking their safety to take care of the patients in this epidemic. I'm not doing that, I'm sitting at my desk at home trying to hopefully make an impact on this epidemic through scientific collaboration and working on some of the drug and vaccine efforts in this space.
Dr. David Kaufman:
So to get started, I think it'd be helpful to talk about maybe some things that are positive that are going on behind the scenes right now. I use this cartoon just because it came out last week that, while cats are susceptible to COVID-19, dogs actually or not. And so I think it's apropos that the dogs are working in the lab right now. But what we're seeing is just an unprecedented amount of collaboration in the scientific community. And we're seeing barriers being broken down.
Dr. David Kaufman:
You hear a lot of nationalism coming out in the politics around the epidemic. But in the scientific community, you're seeing a lot of those barriers not restricting the free sharing of information. You're seeing data being published at record speed. And the breakdown of barriers both within academia, but also even within industry. While I don't want to overstate the degree of collaboration, even for example, earlier this week, two major pharma companies announced putting their vaccine related products together to make a novel COVID vaccine, which is something that really hasn't happened in the vaccine space previously.
Dr. David Kaufman:
We are also seeing regulatory bodies just working overtime to create emergency authorizations for diagnostics, to really speed applications for registration of clinical trials for novel drugs. And we're also seeing funders come together with nonprofits and companies to launch global clinical trials that can actually get us answers about what works and what doesn't work.
Dr. David Kaufman:
Collaboration is not the same thing as coordination. And maybe later we can touch on that because I think one of the lessons learned from this pandemic is that we were completely unprepared from a coordination standpoint to mount an integrated response, coordinated response from an organizational standpoint, even though the will is clearly there to work together. So before us really turning to the topic of the global health aspects of the epidemic, I just wanted to go over at a high level what's the same regardless of setting in terms of what we need to control COVID-19. They're really just some very basic tenets that everyone I think has heard about, but I'll just sort of reiterate.
Dr. David Kaufman:
First of all, we need to test, we need to trace because we need to understand the contours of the epidemic, we need to see where the fires are burning and where they've been put out, and be able to moderate our social distancing policies accordingly. And this is the kind of effort that needs to be community-based. It's going to take boots on the ground, and in some places, including in low income settings, technology may be very enabling for that. But ultimately, it's going to require mobilization of a lot of health workers, wherever we are.
Dr. David Kaufman:
A second really important aspect of that testing and tracing is being able to use data. We need to be both to aggregate data and it needs to be shared freely with the public and with people who are responsible for making decisions so we can make those decisions in real time. Another really critical component is supporting health care systems. And I kind of break this into two components. One is, which is so critical is protection of health care providers, right? It's around access to personal protective equipment. It's around early access to testing. And as soon as we start to have the first effective treatments and prophylaxis and even vaccines, healthcare workers need to be on the front lines in terms of accessing those things.
Dr. David Kaufman:
Flattening the curve is the other main part of supporting health care systems, preventing them from being overwhelmed. If we can't do this, then it's not just the deaths that we're coming from COVID that matter, it's also the degradation and loss of health services for everybody else with every other kind of disease. And ultimately, I think we will have an accounting of that, but it's going to be just as significant, I think, particularly in places where healthcare systems aren't strong.
Dr. David Kaufman:
Prophylaxis is really important. Vaccines, of course, are sort of the end all be all of prophylaxis. But we actually can use things like hyperimmune serum from people who have recovered, really as an initial treatment. There's actually a major collaboration right now going on, for example, between four or five of the major producers have immune serum, which is normally used for other diseases. They're basically working together on a single manufacturing process that can be registered around the globe so they can start getting immune globulin out to people. And then many of the drugs that we're talking about in a treatment setting can also potentially be used for prevention of infection as well in high risk populations. And so we really want to get prophylaxis out.
Dr. David Kaufman:
Treatment is important because we can change outcomes. If people don't get sick, then we can treat this epidemic differently and they can behave differently. And then the final critical component is understanding immunity. Because right now, we don't really know what it means when you've recovered. What level of antibody response or immune response actually means that you're protected? How long does that last? Is there any point where you actually might be even hyper-susceptible to infection if your immunity wanes? That's important for whether you can go back to work and what you can do. It's also really important to understand this because it directly informs how we develop vaccines. It provides basically milestones for understanding whether our vaccines are likely to be protective or not.
Dr. David Kaufman:
So I also wanted to really emphasize that COVID-19 is a global disease. It's obviously as we're hearing here, but also around the globe, it's really the impulse of global leaders to externalize blame, to nationalize response, to compete for limited resources and hoard resources, drive up prices. These things are devastating for low income countries that have to compete in the same market for this limited resources. And that's true right now for things like swabs for tests and for personal protective equipment, but that kind of competition is going to be a problem as soon as we have effective treatments or vaccines, and low income countries are going to suffer from that.
Dr. David Kaufman:
And as I already said, science is collaborating in ways that the politicians are not. But this slide, I think illustrates the problem if we just tried to fight this disease locally, which is that we can't prevent reintroduction unless we have a global solution. And so this is a photo of Singapore. What you can see here, Singapore was one of the places that was an early success story. Very, very aggressive central government measures to restrict movement, to quarantine people who came into the country, to screen everybody. Best technology being used for tracing even relatively intrusive to personal privacy. And that worked for a couple of months.
Dr. David Kaufman:
But what you're seeing now in Singapore, as well as places like Hong Kong or Taiwan, is the epidemic curve is now climbing. And this disease is very insidious. It has long incubation period and it can just get past even the best screening measures. So if we can't prevent reintroduction, we're never going to create control. And so it's critical to have a global response, which really, very critically includes low income countries as well as high income countries.
Dr. David Kaufman:
So as we talk about low and middle income countries settings, what's actually different there? A critical factor, of course, is the inability to socially distance, right? When you have to earn money to eat that day, you can't stop working, you can't house yourself away from other people. And aside from the factors of poverty, there are other components, right? I was just talking to a current Swarthmore student who is from Pakistan and is in Lahore right now.
Dr. David Kaufman:
He was basically saying social distancing is very much different at different class levels. People who are wealthy and educated are following those precepts, whereas people who are poor are really not only incapable, but also just not really listening to that message from political leaders. He said that the big shift actually came when religious leaders actually got on board and started giving the message that coming to Friday prayers was not a good idea. So the way that you message in different settings also has to be very, very different.
Dr. David Kaufman:
Aside from the lack of social distancing for multiple reasons, healthcare systems are much more fragile, of course. There's many fewer hospital beds, fewer ICU beds and fewer ventilators, and health care providers are even more vulnerable as a result of lack of protections. So healthcare systems are more vulnerable to collapse and collapse will worsen the outcomes for many other diseases. This is on top of limited testing capability, less capability around data aggregation and tracking. And then a lot of comorbidities like HIV, tuberculosis, malnutrition. We also environmental factors like air pollution portend poor prognosis and make the disease worse. These are all pretty bad ... This is a setup for a lot of bad outcomes for COVID in low income settings.
Dr. David Kaufman:
That being said, there are things that sort of go against that negative tide. For one thing, demographically, many countries that are on the lower end of the income spectrum, have a much younger population demographically. And because this disease is so much worse than the elderly, there may be a very different population distribution of disease. Populations are less mobile, there's less international travel importing the disease. Also, these are countries that have a lot of experience dealing with infectious disease burden. And so at least in some places, there's real infrastructure for treatment for research and things like that, but it can be limited.
Dr. David Kaufman:
One of the most interesting things, I think, that's going on right now in terms of that kind of expertise, is that we're actually now seeing it re-imported back into the US. And this was one of the most interesting things in Massachusetts, where I am, is that Partners In Health, which is an organization that was founded to do community health promotion based care in some of the poorest regions of the world, is absolutely now being asked to partner with Massachusetts State to build a boots on the ground screening army, essentially, for the state of Massachusetts.
Dr. David Kaufman:
And it's kind of a sad commentary on our own public health infrastructure that we need to learn from these settings what to do. It's an amazing opportunity that we have to learn from an organization like Partners In Health. Hearing about their training, they're focusing not just on training people to go and test, but to be empathetic, to actually provide some support to people and some hope to people as they go around. Which I also think is is going to be a really critical component as the public health effort ramps up.
Dr. David Kaufman:
So I don't think we can say yet, I think it's too early in most low income settings to know exactly what the contours of this epidemic are going to look like. As Ayanna mentioned, we're hearing relatively small numbers out of a lot of these places, that's really because we probably don't have very good information. One of my classmates, Kathy Sturm-Ramirez is in Senegal right now, and she's a respiratory disease epidemiologist who works for the CDC.
Dr. David Kaufman:
She's been doing modeling of disease transmission in some Senegal for COVID. Her perception from sort of preliminary work was that the curves may not necessarily look super steep there, just because of some of the factors that I mentioned that fly in the face of some of the risk factors for worsening outcomes and worse transmission. So I think there's a lot that we need to see, but I think we do really need to plan for the worst in the settings.
Dr. David Kaufman:
So how is the Gates Foundation and by extension my medical research institute working in this space? Really, the three pillars from the Gates Foundation perspective is around testing, treatment and prevention with an idea for optimizing how we're ultimately going to get to the endgame of delivery of each of these in low income country settings. And so I'll just take a little time to go through each of these three areas in brief.
Dr. David Kaufman:
So what are some of the considerations from a diagnostic standpoint, just generally? First of all, there are basically two types of diagnostics. There are those that track the virus, and there are those that track your immune response to the virus, and both are really important. All the PCR testing and these nasal swabs and things like that are actually to look for the virus. And that really can tell us very early on if somebody is sick or not sick from the disease. That's the blue curve in this graph.
Dr. David Kaufman:
The green curve represents a very early form of antibody response by IgM, and then the red curve is what's called IgG antibody responses. And those are what usually provide durable protection. And so measuring IgG antibody responses is what we think is going to be important for figuring out whether you can go back to work, et cetera. If we can get the IgM test sensitive enough they may actually help in diagnosis as well. But there's tons that we don't even understand here about what the threshold of protection is. And as you've heard, there are lots of problems with these tests in terms of sensitivity, specificity, and obviously, just the logistics of getting them moving forward.
Dr. David Kaufman:
In low income settings [inaudible 00:20:33] important to have simple tests that can be used in a community setting. And for the antibody test, that's actually quite feasible. We basically use the same technology that's used in a home pregnancy test, but can be done with a drop of blood and basically showing the same kind of readout. So we do have a technology to sort of put these into very sort of low tech settings once we can get enough of these tests moving. But again, we need to produce them at a scale where we can get them into low income settings, and it's going to require boots on the ground, and it's going to require just a pretty large effort to make this happen in some places with such limited infrastructure.
Dr. David Kaufman:
So moving on to therapeutics, what are some of the major considerations, particularly in low income settings? Well, first of all, we really want to focus on earlier stage disease, just because the healthcare infrastructure for treating patients related disease is still limited. So the Gates Foundation is very much focused on preventative treatment, for post-exposure prophylaxis, so treating the contacts, the household contacts of somebody who's sick, and then treating folks with mild disease. We in the foundation are focused on oral therapies.
Dr. David Kaufman:
And as opposed to sort of maybe some of the coolest experimental treatments, were really focused on repurposing existing drugs or using drugs that are in late stage development. Because those are the ones where we're going to actually be able to manufacture quickly at scale, and get them to the places where we need to get them. There's been a lot of clinical trials already launched around treating in different settings. And a lot of these trials are too small, they've been launched too quickly. They're going to be inconclusive. Hopefully, next time around, we will have the infrastructure already built to rapidly run very high quality trials.
Dr. David Kaufman:
But finally, some of those are getting off the ground. One of them, for example, is a Solidarity Trial run by the World Health Organization. And a couple of the key features that we think are important in these global clinical trials are one, A, they are global. When you have an epidemic that's as fascinating as this one, by the time you get a trial site up and running somewhere that's a hotspot, the hotspot may have moved on somewhere else. So having a global network that can run trials allows you to shift your patient enrollment to where the patients actually are.
Dr. David Kaufman:
And then there are a lot of different design elements to consider. But one of the sort of key types of trials that we want to see more of are what are called platform trials. This is a kind of trial where instead of sort of starting everybody at the same time with whatever you decide at the beginning of the trial you want to treat people with, you create sort of a continuously open trial where as you get new ideas, you can bring new drugs into the treatment paradigm. And then different drugs can either graduate for success or be taken out of the trial for futility, based on sort of continuous statistical analysis.
Dr. David Kaufman:
So there are several trials like this underway in different settings. And these are really probably the studies that are going to give us the most definitive early signals about what treatments work, and what treatments don't work at this point. Finally, I'll just mention that there are basically two main categories of drugs that are being used right now. There are antivirals that directly target the virus. But then there are also what we call post-directed therapies.
Dr. David Kaufman:
And in this disease basically people are suffering both from the effects of the virus directly, but also from the effects to host immune response, and they're happening at the same time. And so we need probably to actually both tamp down the bad aspects of the immune response that are causing damage at the same time that we try to lower viral load and eliminate the virus.
Dr. David Kaufman:
Finally, I will touch on where we are in terms of vaccine development. For me, the big picture here is that there are really two waves of vaccine development. And I've called them the fast wave and the scalable wave. The fast technology are mainly those that are based on the gene sequence of the COVID virus and using that for the vaccine. So those are RNA based vaccines. Or you may have heard of something called viral vectors, which means taking a harmless cold virus, for example, and putting in the genes where the COVID spike protein. Those are the kinds of things that can get into the clinic very quickly once you have the published sequence the virus. So these are the places where trials have either started or about to start.
Dr. David Kaufman:
The flip side there, though, is that these are not tried and true platforms from a global vaccine development perspective. We don't have the manufacturing capabilities for making these at scale, and there's fewer things that are known about the safety of these technologies. And so one can envision that these will probably get approved by maybe an emergency use authorization with less robust data. So maybe phase two rather than phase three trial data. And that will be an appropriate risk benefit for the highest risk folks like healthcare workers and maybe elderly patients. But to really get to sort of a global scale, we're going to need a second wave.
Dr. David Kaufman:
And from low income country setting in terms of price, in terms of safety, in terms of many factors, that's going to be really important. And so that's what we're focused on is sort of using tried and true technologies like synthesizing proteins, and we already are pretty good at making proteins at scale in big factories. We focus on something called adjuvants which can be dose sparing for the protein. Those are kind of like immune boosters that you mix into to the vaccine. And so that's where we really think what's going to be needed ultimately to get to the scale where we can have mass vaccination campaigns in low income settings.
Dr. David Kaufman:
I'll mention here as I should have also mentioned with drug trials, that we also think it's important to be enrolling patients in low income settings. And that's because there are many factors that can lead to different outcomes with both drugs and vaccines, including comorbidities and the kinds of concomitant medications that people are taking for things like HIV and TB, and other factors that just influence the outcome from either vaccination or from treatment. And so while I don't think that necessarily would exclusively want to test in low income settings, we think it's very important that trial sites in low income settings be part of where we're going.
Dr. David Kaufman:
Once we have vaccines, there are significant issues in terms of how we pay for them, and then how we deliver them. There's an organization for example called GAVI, the Global Alliance for Vaccines and Immunizations, which is really going to be strengthened and have to be funded, because its role globally is to help essentially buy vaccines and give them to the public systems in many low income settings. And delivery is a huge challenge, right? It's about distribution. It's about countering misinformation about vaccines. It's about reaching displaced people. So there's just going to be many layers of challenge before, not only we have the first eureka with the vaccine, but until we actually get it to everybody who needs it.
Dr. David Kaufman:
So finally, I'll just close with saying, how can we prepare for future pandemics? I think there's a lot of answers to this question. I'll just leave you with a few. One of the critical answers here, which is probably relevant here as well as in low income settings is that we need to strengthen primary health systems. Primary health systems, particularly in low income countries are so critical for surveillance, for example, as well as for vaccination and for treatment. We also need just to maintain much more capacity for pandemic response in between epidemics. And that has to do with manufacturing capacity, because that's going to be one of the biggest challenges, is scaling up any of these interventions. And it also really refers to the clinical trial and research infrastructure.
Dr. David Kaufman:
We have spent precious months just getting organized to run the right trials and to set up the right collaborations. And with forethought, we can maintain that infrastructure in between epidemics. And finally, I'll just say that I hope that the level of collaboration scientifically between companies and academics and regulators, et cetera, that we're seeing right now, really persists after this pandemic is over. Because I think that there's so much more we can do as scientists when we work together in these modes. So there's many things to be skeptical of or pessimistic about, but I want to leave with that note of optimism. And with that, I will stop and try to get out of slideshow mode here. And I'm happy to take any questions from Ayanna or questions that Ayanna receives through the chat.
Ayanna Johnson:
Great. Thank you, David. That was such a wonderful presentation. I really learned a lot, I was taking notes, even as you were speaking. So, let's open it up for questions. I think a few have already come in. But maybe we can start with sort of your last slide just talking about how do we prepare for pandemics like this or other outbreaks in the future and do a better job at surveillance, identifying cases and really stopping case spread both here in the US and also abroad. What can you do better next time around?
Dr. David Kaufman:
Well, I think there's different things that take different levels of political will to maintain when we're not in the midst of something like this. I think we could argue that pretty much every aspect of the health system if strengthened and made equitable would be really important for having a response to the next epidemic. And on top of that, there are many layers of social safety net that likewise should be strengthened and maintained. And we're seeing countries that have more equitable access to health care and stronger public health systems doing better. So that's important.
Dr. David Kaufman:
But when it comes to the R&D infrastructure, which is the place that I'm most familiar with, I touched on a couple of points. But I think it works really well in this day and age is just sharing information. We have such good tools for that now that information just moves around really freely. What we have to really counter though, is sort of the abundance of sort of bad information that swamps the really critical data. And that's something every single person who works in a healthcare setting is so eager to make a contribution that we're awash in stuff that's just very, very hard to sort through.
Dr. David Kaufman:
That's why preparing for how we're going to respond to the next time from a scientific perspective is so critical. I mean, we can maintain the laboratory capacity to do sort of broad scale screening for antivirals. We can invest in the clinical trials infrastructure so that we can run those trials within a few weeks of actually seeing a new pathogen, et cetera.
Ayanna Johnson:
Great. Thank you. so we're getting a lot of questions are coming in fast and furious, of course. So let's talk about vaccine development. We've gotten a few questions asking about, I guess, essentially intellectual property and what is the private role, the private company role? So I have a question from Lisa Juliet from class of '02. And she would like you to speak more about the role of the private sector in vaccine development. Particularly she's concerned about the lack of it appears of private sector investment in coronavirus, problems like Ebola or SARS as well.
Ayanna Johnson:
And maybe you can speak a little bit to Fauci earlier comment, I think, last week about the fact that there was no major pharma company willing to manufacture the vaccine [inaudible 00:32:25]. And relatedly, it'd be interesting to actually talk about how does the work that your group is doing, how does it interface with vaccine research development here in the federal government?
Dr. David Kaufman:
Yeah. So that's a very complex topic, and I'm not sure that I necessarily have all the answers there. What I think is really true is that companies haven't necessarily prepared themselves to just launch out of the gate for epidemic preparedness. With that being said, I think that most major vaccine companies are shifting very quickly to try to be major players in this space. And to be very clear, there is no nonprofit or governmental organization that can actually make these vaccines at scale. We absolutely need the private sector, whether it is purely major pharma players, or whether it's contract manufacturing organizations working in conjunction with an organization like Gates.
Dr. David Kaufman:
There's a number of different ways that this kind of vaccine development can be structured. But in no way can we do this without drawing on the private sector. We've actually seen a large number of private sector players make major commitments in the space, those would tend to be public private partnerships. So you heard that Johnson & Johnson announced a very, very large collaboration with BARDA to advance the platform that they actually have now ... They previously used it for Ebola, actually, and they're also working on it for HIV. [inaudible 00:34:06] virus vector platform and BARDA and J&J will be jointly building a large manufacturing plant planning for success of these vaccines.
Dr. David Kaufman:
You heard earlier that GSK and Sanofi who are normally major competitors are working together so that GSK is getting their Agilent and Sanofi is giving their protein to put together in a vaccine. And so these things are actually moving forward very quickly. I don't entirely know the economics of COVID-19 vaccine development because I think there's so many factors that could make it either profitable or less profitable for companies. I think a lot of companies are considering this, at least, in part a philanthropic endeavor.
Dr. David Kaufman:
What I'll say about the large number of vaccines where Gates is or one of Gates's fundies, CEPI, is involved, is that the funding from Gates or from our partners comes with global access provisions, so that there's a requirement that the technologies are made available for low income settings. And so I think that ... That represents a large swap of the vaccines that are being funded. So I think that ultimately, I don't think that intellectual property barriers will necessarily keep these vaccines from low income settings.
Dr. David Kaufman:
That being said, when these vaccines are in short supply, there's going to be competition. And I think there's going to be have to be a lot of pushback from the global health community and a lot of political will to say no, it's not that low income countries have to lie up behind the richest countries to get access to these vaccines early. That's not a given unless we really push for it.
Ayanna Johnson:
We have a question from Peter [Jakay 00:35:48]. What is your best guess for timeline for vaccine development and appointment and deployment? And also another related question. I didn't catch who it's from but another related question about how effective do we think a likely vaccine candidate will be as compared to other vaccines we have.
Dr. David Kaufman:
Yeah. So for the first question and the second question, there's just so much that we don't know about immunity to this coronavirus that I think that I can ... I can give you my opinion, but it really is just a best guess. We know that with other coronaviruses from common cold coronaviruses to SARS and MERS, that there's a varying degree of post-infectious immunity that can be a few months to a year or can be much longer. And we really don't know where that's going to fall naturally for people who recover from this particular epidemic, this particular disease or whether it's going to be the same from mild or severe cases.
Dr. David Kaufman:
We have a lot to learn from how those patients recovered and protected in terms of understanding what we need to do to get a good vaccine working. But I think that one of the things is that we did do some vaccine development, particularly for SARS and a little bit more from MERS. The funding for those efforts dried up when the disease's became less worrisome to the globe. But we still learned enough that we think we understand how to get neutralizing antibodies against the major ... With the spike protein that's responsible for viral entry into cells.
Dr. David Kaufman:
So I think that there's a pretty high likelihood given that we understand the spike protein, what part we need to get antibodies to bind to, and some of the early preclinical data that we've seen for the earliest candidates, that these early candidates have a reasonable chance of being at least partially successful. So I think that given the speed at which we're running, I think we'll have solid phase two data on the lead candidates by the end of the year. And then I think regulators will have to decide on whether to make an emergency use authorization based on that limited data.
Dr. David Kaufman:
The big problem there is that if there are rare side effects caused by this vaccines, we won't see them. There's also been something called enhancement where vaccine paradoxically can make an infection worse. And that's been seen with vaccines for other respiratory diseases. That's always a worry for something like this. We think we understand that phenomenon well enough to avoid it, and the FDA and other regulators are going to require tests for that. But we use an emergency use authorization, we may not be 100% sure that we're avoiding these kinds of side effects.
Dr. David Kaufman:
So if we get an emergency authorization, we could get a vaccine to very high risk populations in a year. But that's very different than actually running careful phase three studies to prove that a vaccine is safe to roll out to billions of people. To do that is going to take longer to actually get it to people at the scale could very easily take two years. So that's kind of my very high level prognostication about this.
Ayanna Johnson:
That's great. We have so many questions and they're really all over the board. I'm trying to figure out where do we want to go next? I think we've talked a lot about vaccine development and gotten really detailed into the science. But maybe we can do a shift into thinking about what happens when we're actually sort of just trying to identify the cases. So we have a question. I lost it. There's so many. Really just a question about how do we identify cases? What should we be doing? How do we deal with false positives and how that changes social distancing?
Dr. David Kaufman:
Yeah. Well, I think that when we're thinking about ... Maybe I'll just start with sort of the tests and how well they work. One of the big problems with the testing right now is actually false negatives. So 10, maybe even 20% of people who are infected and getting nasal swab actually don't test positive. We think we can improve that but some of it is probably limited just by the fact that the virus doesn't replicate very well in the nasopharynx. And so actually getting virus on the swab isn't always an easy proposition.
Dr. David Kaufman:
So at the level of basically saying, I swab you, you're negative, okay, you're safe to be with other people, that's very difficult to do. But even with the test, it's imperfect, if it's widely administered enough, we can actually understand at a very granular level what's happening in the community. So at the community scale, and this assumes that we've actually gotten things under control, that allows us essentially to see where the brush fires are. And if we're very sophisticated doing that, then we may not have to perfect testing at an individual level in order to be able to relax social distancing.
Dr. David Kaufman:
The other thing is that once people recover, we need to understand what that means. So we need antibody tests and we need to understand what they mean, who's protected? Who's not? For how long? Who can go back to work? Of course, we've had conversations about people having cards that say, I'm COVID immune. That's really scary because if people can't work unless they have this cards, you can imagine the incentive, a perverse incentive for people to actually get sick, so that they can recover, so they can go back to work. I mean, that's only one level of social complexity to this whole testing situation.
Ayanna Johnson:
Thank you. We have another question kind of related from John Connor, class of '94. He says this virus appears to be transmitted when people are pre-symptomatic or rather asymptomatic. Is the Gates Foundation supporting work on how to identify these individuals?
Dr. David Kaufman:
Yeah. Well, I think that really from a technical standpoint, that revolves around making more sensitive diagnostics. But really, the technical challenges is secondary in that situation to doing community based screening. If there's a lot of asymptomatic people and they're responsible for transmission, then we need to be doing random screening in the community, not just contact tracing in order to find that asymptomatic transmission where it started to happen.
Dr. David Kaufman:
If we can do that we may be able to identify places where there's recrudescence earlier, and then reinstate social distancing and do aggressive contact racing in a more effective way. This is really hard, though. I mean, I think it's hard to think that this alone will get us to the end game. I think we really need a vaccine or we need very effective treatments that can be broadly distributed before we can really feel like we've moved out of this very strange era that we're living through right now.
Ayanna Johnson:
Agreed. We have a question about from Ted Abel, classes of '85. Hi, David. Thanks for a great talk. He had a question about the role of telemedicine and standard of care in this pandemic. Said, "We found here at Iowa that telemedicine has helped us treat patients at early stages of the disease remotely. And one thing that stands out is the importance of staying hydrated in the fire of the high fevers. Are developments in telemedicine something that we might be able to enable in clinical care going forward?"
Dr. David Kaufman:
Yeah. That is not necessarily my area of expertise. But I certainly think that we're accelerating a trend that already existed even before this epidemic. And I think American physicians have been slow to sort of realize the potential of telemedicine, particularly in areas that are underserved by physicians. So I think that's actually a potential silver lining is that we can accelerate the use of telemedicine broadly in our health system, and that will help overall strengthen our healthcare infrastructure.
Dr. David Kaufman:
I don't know very much about sort of using telemedicine specifically for COVID. But I think one of the things you allude to is that there's a lot of things about just the clinical presentation of this disease, and what makes it better or worse that we're just starting to learn. There's an article this week, for example, about positioning patients who come in with low oxygen saturation, and lying them prone on their bellies as opposed to supine can actually, in many cases, get oxygenation up and avoid the need for intubation.
Dr. David Kaufman:
An intubation is not associated with good outcomes for COVID. So there's a lot of mystery, medical mystery surrounding this disease. And I think the most important thing is to have a way to rapidly share those learnings and to disseminate them to the broader medical community.
Ayanna Johnson:
So we have another question from Anne Zhang, class of '17. She's wondering what is the current situation with the Solidarity Trial? We've heard about that they've been able to sequence the virus. So do you have a sense of what they're working on right now?
Dr. David Kaufman:
Well, the Solidarity Trial very specifically is a treatment trial for ... At this point, I think it's focused on hospitalized patients with COVID-19. Although, I think they want to add more of a community component. There's an initial list of four to six compounds that they're putting into that study. As I mentioned, it is what I call the platform design, so they can be able to bring in more patients or more drugs, as new drugs perhaps come to the top of the list as potential treatments.
Dr. David Kaufman:
The NIH is trying to launch a similar study. There are a couple of other trial networks that are also moving forward with similar designs. So like I said, I think ... I don't know actually the exact status of the Solidarity Trial at this point, because I think it's still in the launch phase. What I'll just say is that this is the kind of thing that we want to have already set up before an epidemic hits. It takes real investment to maintain that kind of infrastructure, absent of pandemic. And so then you have to think about is there a multi-use clinical trials infrastructure that can be used for other types of trials when we don't have a pandemic and can be rapidly repurposed in this setting?
Dr. David Kaufman:
There's actually an example of that right now, there's a trial called REMAP-CAP, which is a study of community acquired pneumonia. That's a platform trial that's been run by this critical care network, globally, but they've always planned for the setting where there might be a pandemic, and they might have to switch to include that pandemic use case in the trial. They've actually done that for COVID. So they've pivoted very, very rapidly. And they're one of the first platform trials, it's really starting to evaluate therapies and supportive care interventions for critically ill patients with COVID.
Ayanna Johnson:
So we have a question from Meg Mass, class of '95. And we'll do a bit of a shift. So talking about sort of the social issues around vaccination various countries comfort level with mass vaccination campaigns. So her question is, "I'm hearing a lot of skepticism and distress from contacts across Africa about vaccination programs in general, specifically about using vaccines for testing in a profit motive. Can you speak to how Gates or other groups you are familiar with are addressing this historical distrust, and what information can we share to allay those fears?
Dr. David Kaufman:
Yeah. I think that's such a critical issue. You'll allude to this. There's such a long history of failed vaccine trials in low income settings or vaccine trials where there wasn't adequate community engagement and education. And we have a lot to counteract there. And on top of that, there's just a lot of misinformation about vaccines. I think that one of the precepts of how we do clinical research in low income settings in general, is that we can't do it without partnership in the community, and without the appropriate relationships.
Dr. David Kaufman:
So it can't be just folks swooping in from the outside and doing this kind of trial without making sure that there's real partnership on the ground. Overall, I think that if we can't include patients in low income settings in our trials, we may not understand differences in how therapeutics or vaccines work in these settings. And so it's really critical to have inclusiveness from a global standpoint. But that being said, that can't be accomplished purely by scientists trying to do science. It has to be accomplished by boots on the ground and community engagement.
Dr. David Kaufman:
I will say that there is a lot of clinical trials infrastructure now in lower income settings, where there's been a huge amount of effort made to create community between investigators who have been in these communities for a long time and the communities that they serve. And so I think there's a lot of knowledge about how to do this well from a trial standpoint. There's a whole other layer around this when we actually want to roll out an actual delivery program, and the misinformation and the disparities that surround that kind of an effort.
Dr. David Kaufman:
We have major setbacks sometimes. Like, for example, in the vaccine against the viral disease called dengue, there was a vaccine that was tried in the Philippines not too long ago, that actually or at least one of the viral strains caused the disease to get worse rather than better. And that really set the entire dengue field back because of the distrust that it created. So these are really, really important issues. I don't have all the answers but I just agree with you that these are critical to address.
Ayanna Johnson:
I think that sort of ties in nicely to a number of questions that we've just gotten about what can we learn from how we've dealt with other pandemics like Ebola or SARS or MERS? And also, what can we learn from some of the treatments that we have used from those outbreaks to deal with COVID in a much more holistic way?
Dr. David Kaufman:
Sure. Now, I think that the two examples people point to when we try to learn about what to do or not do like [inaudible 00:50:38] settings are the Ebola epidemic, which is in parts of the world where there's so much distrust of the government, of healthcare professionals, et cetera. And so much complexity to actually delivering even a single vaccine intervention. And then the other one is the polio eradication effort where likewise people have had to work in some of the most difficult areas in order to really get the vaccine everywhere it needs to go.
Dr. David Kaufman:
I think that these efforts reveal that there are really significant challenges and it's very easy to make missteps in trying to reach some of the most alienated and displaced populations. So to have a really equitable and global distribution of vaccine, once we have one available, is certainly just as big a challenge as the science. In terms of repurposing, I think there's a huge amount of effort to repurpose compounds that are out there, and may have been effective in other settings for this virus.
Dr. David Kaufman:
So for example, one of the antivirals that's been touted, most prominently the media has called them Desivir, which is a Gilead a drug, that they were initially actually testing for Ebola. It didn't really work for Ebola, but it actually seemed to have in the test to a pretty good activity against this virus. And so it's been repurposed and it's been put out there. There's also these just efforts to take basically every known approved drug and screen them in what we call high-throughput screens to see if they have any ability to inhibit viral replication in cells.
Dr. David Kaufman:
And so based on hits from those screens, we're basically going about repurposing other drugs to target the virus. A similar effort is going on with drugs that basically have some sort of anti inflammatory property, because a lot of the damage that's done to the lungs is from inflammatory processes. And so there are many, many different ideas about what to do in that setting. And what we need are very efficient clinical trials to be able to test those drugs in a repurposing settings as well.
Ayanna Johnson:
That was interesting as well. I think we have a number of questions. You and I talked about this before the webinar. But really just understanding really how this pandemic has underscored a number of the sort of fact fissures in our society and health care, and public health prevention. And so we've gotten a couple of questions, just sort of, what do we do? How do we balance sort of bringing people back to work? And not really fully understanding how this virus is working?
Ayanna Johnson:
Who's susceptible? Who's not? Who's contagious or not? And then how do we sort of balance that with the care that's needed, the economic loss? What should we be on the lookout for when you sort of resume business as normal? How do we sort of phase in if we should do a phase in?
Dr. David Kaufman:
Those are such complex questions. I mean, I think the good news for Swarthmore social science majors is that there are decades of PhDs that are going to be based on what's happening right now. And so there's amazing job security for those folks. I mean, these are such complex questions. I think we're seeing already how much economic damage in which real pain people are suffering from this. Donald Trump said very belittlely, when is the cure worst than the disease? And he said that in the wrong context, and he's the wrong person to be saying it, maybe.
Dr. David Kaufman:
But this is a real reckoning here in the United States about what kind of trade-offs we make as this goes on. I think you've seen that even more so in some settings globally, where it's not just economic pain, but it's people losing their rights. It's the press being restricted, it's violence erupting in places, and it's dictators and strong men consolidating power. These are not areas of expertise that I can release. For me, I can't really speak to these issues except to just note that it's we can never just look at this purely from a public health perspective.
Dr. David Kaufman:
I think what you've heard in terms of getting cosy normal again, is just the importance of that widespread testing, understanding what it means and being able to aggregate and rapidly react in real time to the data. But we're nowhere near having that capacity. We continue to have huge problems in our supply chain for swabs and reagents. And even if we have laboratories with the capacity to run these tests, we don't have the boots on the ground going out and making this testing happen.
Dr. David Kaufman:
There is technology that can enable tracking, and we've heard about Apple and Google collaborating to make tools. But then there becomes a question about how much privacy we're willing to give up to have our movements tracked and our contacts traced and things like that. So there's some very profound questions that we'll have to answer as a society as we think about trade-offs and as we think about how to deploy all the tools that we could potentially deploy to get back to work.
Ayanna Johnson:
We're almost nearing the end of our webinar today, but I thought we'd maybe do a quick switch before you can give final remarks. We had a question from Bryn Lindblad, class of '09. And this is kind of a recap but could you please outline the main milestones that will be needed to achieve a widespread and safe vaccine? And related we rather not you attach it to like a specific date or month. But we also had a question about, has anyone looked at using IgA looking at the lungs being mucosal tissue and whether or not that sort of antibody work or treatment could be investigated?
Dr. David Kaufman:
Yeah. Very quickly, sort of the main things we need for a vaccine is we need ... We have now established animal models of the disease. They don't mimic severe disease, but we can basically see whether a vaccine gives you immune responses in animals. And now we can actually look at protection, which may or may not be really exactly the same as protecting humans. First, we run early phase clinical trials in healthy volunteers to show that the vaccine is safe at a small scale and induces good immune responses, then we take sort of the most immunogenic dose into phase two studies.
Dr. David Kaufman:
What we can do is target high risk populations like healthcare workers, and do relatively small studies, hopefully to show protection. As I mentioned before, once we show protection in that kind of a setting, we have to decide whether there should be some emergency use authorization for the vaccines at that point, or whether larger phase three studies are really needed to really demonstrate a higher level of safety and durability of protection before we really roll vaccines out. And after that, then we need to manufacture hundreds of millions of doses and deliver them. So that's the quick version of product development.
Ayanna Johnson:
That's the easy part.
Dr. David Kaufman:
And then in terms of antibody therapeutics, they are some of the most promising and potentially rapidly deployable therapeutics. I've talked about hyperimmune serum, and there are ... Like I said, this actually can repurpose machinery that's already present at companies that make a product called IVIG. That's a product that's used to treat a couple of different conditions. But basically they can just make IVIG but for people who have coronavirus. So it's a very quick way to get antibody product to people. People are working on very, very high potency, monoclonal antibodies, single antibodies that can bind the virus with picomolar affinity. And those are going really well.
Dr. David Kaufman:
But again, making antibodies is a little complex and so it's going to take a little bit of time. I haven't heard about anyone trying to make an IgA product. Generally, IgG antibodies get to mucosal surfaces really well when you deliver them as products. And so from a vaccines type one, it may be important to enlist IgA immunity. It's something that we might want to think about. But in terms of antibody products, I think IgG therapies are going to be going to be adequate.
Ayanna Johnson:
Well, David seems like we have rapidly, quickly approach the end of our session. And I know this was so informative for me and as you can see on the questions that we've gotten, we've just gotten so much. I don't know if you had any last words, and then we can quickly conclude.
Dr. David Kaufman:
Well, I just want to say it's been a real pleasure and a privilege to talk to the Swarthmore community about this. And I hope that everyone stays healthy and stay sane through this crazy time.
Ayanna Johnson:
I agree. And thank you so much, everyone for your robust discussion and thoughtful questions. And of course, thank you, David, for joining us tonight, and sharing your great work that you want to colleagues that MRI are doing. And really opening our eyes to the complexities of actually tackling this pandemic in building a viable vaccine that can protect our health. I wanted to just let everyone know that this webinar is being recorded and will be made available online on the Swarthmore website under SwatTalks. You can find it there.
Ayanna Johnson:
On behalf of the Alumni Council, I'd like to thank everyone but also really acknowledge those who've just been so deeply impacted by this pandemic. Our thoughts are with you and we really want to express our gratitude to the multitude of alums in our greater Swarthmore community who are on the front lines of really saving lives, developing treatment and vaccines and/or maintaining essential services or increasing how we can [inaudible 01:00:25]. Thank you everyone, because you have really risen to the challenge.
Ayanna Johnson:
So with that, I'll conclude our session. I know there are a couple of questions that have come in. So, David, if you wanted to offer to stay a little bit and answer some before we close it, but I know that I think we've really gotten to the bulk of this. So thank you, everyone and have a good-
Dr. David Kaufman:
Thank you, guys.
