Dr. Jonna Mazet is a very high profile member of our community who uses her expertise in veterinary medicine and wildlife epidemiology to protect us from the next emerging infectious disease threat, or can tell us why we're having a pandemic right now, and can answer your questions about that. She has been recognized in a number of ways, including by Research America. This is an advocacy group for federally funded research at researchamerica.org where Dr. Mazet's been named a public health hero, and she did an interview with them. She is a professor of epidemiology in School of Veterinary Medicine here at UC Davis and is the director of the UC Davis based One Health Institute, which includes the PREDICT program that she'll tell us about today. She's a Doctor of Veterinary Medicine. She also has a PhD in Wildlife Epidemiology, and a master's in Preventative Veterinary Medicine. At the end of the interview (from Research America), there's a quote from her saying, "We are one global society now, even though we haven't organized into one political system, and don't have one health threat warning system. We can't just hold up here in the US and think that we're protected, we're not. We're all together in this and the more that we can come together across regions and political boundaries, the healthier we are gonna be." So with her words put out in front of her, I'd like to introduce Dr. Jonna Mazet.
*Introduction of Dr. Mazet above was done by Dr. Mark Winey, the Dean of UC Davis College of Biological Sciences.
Prof. Jonna Mazet Town Hall video with English and Spanish subtitles can be found here.
Transcript of Dr. Jonna Mazet's talk
I don't know, so I look forward to sharing with you why I think science is so needed and building the respect for science and for all of you being the future for a healthy planet and healthy people on the planet. We really need you and I hope that some of you, maybe all of you will find this tragedy a call to action to help contribute throughout your career. So thrilled to be with you all.
Just share a few slides with you now and put these into, there we go. Yeah, so I know that you've been going and having great speakers and topics throughout this town hall. And I'd like to add some of my background and expertise but also look forward to a rich discussion with you all. Certainly, one of the areas that I work in immensely is thinking about the host and the spillover risk transmission factors, the drivers for us being exposed to these potentially pandemic viruses and in the current situation, of course, as we know, a truly pandemic virus.
Coronaviruses are super interesting and important and something that we've been looking at for over a decade, and I know that you have some of the papers that you looked at for your background. But when we started this endeavor called the PREDICT project that I'll get to a bit in a minute, there were just a handful of viruses really that we were looking at in the coronavirus family, about seven known, now seven, six before known to infect humans and cause disease, but many veterinary important coronaviruses that we were also looking at and even throughout the project and throughout this last decade, we were identifying new spillovers that were causing animal disease that also raised our concern and awareness about coronaviruses. And really, I think about what we like to think of now WHO is calling disease x. And I'd like us to think about that for a healthy future for human populations and the planet. We really need to be planning for and strengthening our public health and global health systems to be ready for disease x, not just this coronavirus, or right before this, thinking about Ebola viruses, or SARS or Zika virus.
So we spend a lot of time chasing the last important viruses, and that's a bit important because we need to understand them well so that they don't cause big problems again, but we also need to really be thinking about what might come next and be prepared, have resilient, nimble systems to respond to whatever might come. Right now, we're certainly all facing a lot of obstacles and for those of you who are sheltering alone, I hope that you are getting what you need, and by way, of human contact. I know, video contact isn't as good as a hug and connecting with people personally, and so I do think that we need to be careful and thoughtful about what's happening and our recommendations to the world, in reference, not only to coronavirus, but the other unintended consequences of sheltering and our social distancing and mitigation measures. That said, we absolutely need to be careful and to be able to keep the curve as flat as we can. And California has done quite a good job. I'm happy to talk to you about some of that as we go into the question period. But as you know, we still are not testing to the level that would give us the data to really be able to understand what's happening with COVID disease, especially in our country now.
We don't have a vaccine, but we do have many candidate vaccines. I think we have over 50 candidate vaccines, at least four of those are in human trials now. So I'm hopeful that we'll be close to a vaccine soon, but then it still remains to be seen how long that will take for manufacturing to be able to cover the globe's human population. And then what other measures are we implementing, including, I show the mask here.
I serve on a standing committee for the National Academies of Science, Engineering, and Medicine that did recommend to, all of us here to go to wearing the masks. And that has consequences, hopefully beneficial ones, as intended but also other consequences it does distance us. Then again, just mentoring the sheltering and the toll that that takes especially the inequitable toll. So some of us who have bigger homes and people that can and do shelter in our families with us, compared to people who are in tight quarters, perhaps we're already in violent homes or homes with other major issues and then putting the stress of being always together and not able to get apart is very significant. So, the pending challenges include what we're calling the next at least epidemic but pandemic that is in the mental health realm and we can talk a bit about that.
As I mentioned, I am a veterinarian as my first doctoral degree, but I am also an epidemiologist and at UC Davis, we trained in epidemiology together, the veterinary backgrounds, human, public health backgrounds as well as math and statistics, because we have a very analytical program and I feel I benefited from decades and of sort of progress that went before me at UC Davis that allowed me to have that training that was really integrated. What are we are missing in the One Health arena or have been is really bringing the social scientist to bear and while we've always had the environmental concepts, I think we have less representation of the environmental scientists. And those are critical realms to really understand the drivers and the consequences and the mitigation. So I hope some of you will pursue careers in those realms and contribute to collaborative work by bringing your disciplines and expertise. Economics being one of the social sciences that we desperately need and I can speak to some of the economic analyses that we've done around zoonotic disease and disease emergence prevention of pandemics as we move forward.
The PREDICT project was mentioned. I am honored to have been able to lead the PREDICT project for a decade and it's a $200 million project funded by the US Agencies for International Development, where we worked in more than 30 countries around the world, trained almost 7,000 individuals in the One Health approach, including bio safety and security, safe PPE use, field sampling for safety for humans, but also safety for the animals that we were sampling, we're sampling humans and animals in the field, looking for the viruses that could cause epidemics and pandemics as well as the risk transmission around all of those viruses that we identified. We sampled more than 160,000 individual animals and people and strengthened capacities in more than 60 laboratories, animal and human health laboratories. As a proof of concept, we identified more than 1,200 viruses. Some of those, and this is not quite up-to-date with our final numbers, but some of those known viruses and with those known viruses as we were identifying them, we were identifying new geographic locations and new hosts for those viruses, which is critically important to understanding transmission and then novel viruses like more than 100 coronaviruses that we identified in the project. And I call that a proof of concept because it helped us and allowed us in the PREDICT project to be able to understand the curves of how many viruses, different species and different locations, probably harbor that are in zoonotic families or families of taxonomic families that are known to cause disease in people and be available for spillover, and show us how much it would take to find all the rest of them, and we'll talk a little bit more about that.
During this COVID response, your UC Davis community and our team specifically has been really active in helping around the world. Just our team, there's much going on and I know you're hearing about that from a lot of different people so I'll speak to our team and maybe we can answer some questions about the broader UC Davis community. But we've been, as I mentioned, working in all those labs and building the network of linkages, and what we saw at the beginning of this COVID tragedy was that our laboratories jumped into action. Actually, the project for the country activities had come to an end and they were no longer funded, but they did jump in and assist their countries in testing the initial introductions into their countries. So cases of sick people, especially those coming with travel history from China were tested in countries and PREDICT-supported labs all around China as well. And anybody following social media will know I'm spending a lot of time defending science and scientists, including our partners in the Wuhan Institute of Virology, and I'm happy to talk to the pros and cons of putting yourself out there to do things like that when you believe that it's important. But those labs identified, even before we had a full sequence of the SARS-2 coronavirus, we're able to identify using the PREDICT platforms whether or not those people were sick with this coronavirus or whether they needed to keep looking for the regular kinds of diseases. So we really helped with early identification and those folks are continuing and we are continuing to support them for diagnostic testing in labs around the world. Now more in Africa, where they are starting to see introducing cases as well as community spread.
Finally, I just like to mention that we do use the PREDICT project as a proof of concept for another global call to action. And that is to identify and understand viruses the way that we understand some other things like bacteria. We're calling that the Global Virome Project. And it's really a request to countries all over the world, scientists all over the world to participate, share their data, come up with a minimum data standard and shared fields so that we can understand viruses and amplify, do this relatively quickly. We do know that we can identify almost all the viruses that are available to spill over to people right now a snapshot in time. For about 10% of what, for example, the first SARS epidemic costs, it would be much, much infinitesimal amount of money compared to what we're spending on this outbreak. And again, even before we put the huge numbers of this outbreak into the mathematical equations, we only would need to see about a .3% return decrease impact from new epidemics and outbreaks to pay for the whole Global Virome Project around the world, but that is a project that's in the low billions, so it's a large number to consider for a research or academic-type project.
I'm now the director, co-director with professor about Woutrina Smith, also in the veterinary school of the One Health Workforce-Next Generation project which is also funded by USAID and is supporting curricular developments in over 100 faculties in Southeast Asia and Africa to do just this kind of work, basically training the next generation like you all around the world to be great contributors to this One Health sort of coalition, to be strong scientists, to have what they need, and also to collaborate with the faculty members around the world to be ready and willing to work in this realm, and to help us prevent pandemics, be ready for them and support nimble and flexible public health systems as well as conservation all around the world.
When I mentioned conservation, I want to make sure to share with you that I do think it's critically important that we not vilify any species that might be a host, that includes humans, but also specifically bats, and I can speak to you about why we think bats are an important piece of this puzzle, but bats are so important for biodiversity and ecosystem strength. Many species are insectivorous, many are pollinators, others are seed dispersers, and they connect fragmented landscapes as humans continue to disrupt landscapes. These seed dispersers that can fly long distances and connect those landscapes to keep plants from going extinct are incredibly important. Also, when we reduce bat populations, they've shown us throughout the years that we're not very good at it. Killing bats puts us at risk of being exposed to their viruses, and it encourages recruitment or increased birth rates of the bat populations, which does increase transmission potential and we've done several studies that show that shedding a virus or probability of increasing transmission is increased during the reproductive season especially when the pups are being weaned from the mother.
Transcript of the questions from students and highlights
Q: I don't know if I'm gonna get the terminology right, but about viral ecologies that are expanding, or maybe contracting due to climate change. Has your team been able to map those kinds of changes? I mean, people talk about that, but I don't know what the data is.
Yeah, certainly, it's easiest to look at the sort of real time driver of climate variability from the perspective of vector-borne diseases, those that are carried primarily by mosquitoes and other arthropods. So that would be the easiest ones to look at from a climate variability perspective, because we can see the host moving quite easily depending on climate change. That said, we did do a study, my colleague and I, Dr. Tracey Goldstein, have done several studies with collaborators in the marine mammal world and we were able to identify the movement of distemper virus, Phocine distemper from Europe into the Pacific Ocean through changing migratory patterns of large mammals, so marine mammals, and that was correlated with shrunken sea ice, and able to see animals changing their migratory patterns and mixing with species and populations that they normally didn't mix with. So really more from the host perspective we're seeing that, but certainly, the rapid evolution, especially of RNA viruses that I work with more are likely to be driven specifically at the virus stage as well but I haven't done that work myself.
Q: With your experience in epidemiology, what do you think the next year will look like for us with or without pharmaceutical interventions and what are our chances for seeing a second surge of infections this winter?
So this has been a big week, so I'm sure most of you are following and absorbing all of this information, though I will say, back to my mental health perspective, I also hope you're taking breaks and not constantly watching all the news and social media because it's important to go outside safely and take a break from the noise that can be anxiety-inducing. But this has been a really big week epidemiologically. I think some of the suspicions that many of us had about the virus and disease being present here in California and elsewhere earlier than was already generally thought has come to be proven to be correct. So we do know that we had early deaths, early February, we had deaths in California. Now, we also know that those deaths are at the same time as what was being seen up in Seattle where some hypotheses were that what was happening in California was introduced through Washington. Think that probably isn't correct. I think we probably had multiple introductions of similar strains of this virus. So what that means is that, that there's been a lot of circulation, there's more virus and more opportunity for exposure and cases than we thought before and longer circulating. We're not going to really get a handle on how widespread until we have more widespread testing. And I'd love to speak to that a bit more about the gaps there and how that can help, also the two different kinds of testing and I don't know, I don't wanna go into and cover things you've already covered, and I'm not totally aware of what you've already covered. So, ask me to continue or rein me back but we could talk about the PCR-based testing or the diagnostic testing as well as the antibody testing and the challenges with both of those. Both of those have really big impacts on understanding where we're going and how we'll get through this.
Right now, our best defense is what we're doing and that is sheltering. But as I said, especially at about this five or six week mark, depending on where you live, and when your counties went into sheltering, some earlier than the state. Where I live, I actually went in earlier than the state in quite a few days. This is about the mark where people sheltering alone really have huge issues with depression and anxiety. Humans are mammals, and we need to interact with other mammals, we're social mammals, and this is where we really get into issues. That said, we need to figure out how to continue to keep the curve flat, and I think most of you know that we're on a whole order of magnitude, less cases than many other big metropolitan states like New York. Now we're testing maybe still a little bit less so we can talk about that. So the problem is vaccines are unlikely to be available to all of us for many months to come. So we're going to have to look at how we maintain as flat a curve as possible while also getting things going again, and allowing some things to proceed. So what it's looking like right now is that there will be a slow release of certain populations, demographic groups, occupations out of sheltering. And so they'll probably be staged. It's almost like a social experiment as we start to get back to work and come out without a vaccine. If we had a vaccine, we would feel much more comfortable if it was efficacious, that we can all get back out at once. So what I am anticipating and this is a bit conjecture, but more from working with consulting with governments and everything is that we will be getting back out to work. There will be increased number of cases as we do that, and then we will have to be adaptive and flexible to be able to continue to have a health system that can respond and take care of the cases as we go back out, and we really need good serology, or those antibody tests to be able to identify a bit more about where these major flows of virus have already gone through versus areas that need a lot more protection, probably because they've had less exposure so far. So it's not that great of an answer, but it's a truthful answer. And I think we're all gonna need to be flexible about going out and possibly coming back in just to manage this until we have a vaccine.
Q: Do you think in terms of the serological testing, is that going to be a way that people determine which populations are gonna go back to work? In other words, you could imagine a situation where there were people who were seropositive for antibodies who could work and others who couldn't work? Which I imagine would be not a great thing for social reasons, but I'm curious.
There's a lot of social things here and equity issues that I'd also like to speak about when we think about who's getting exposed and who's getting sick and how people are sheltering and sort of what kind of density people are living in and what that means for exposure. Certainly, there are multiple, so we have no perfect serologic or antibody tests out there. So if we have perfect tests, we would be able to say who's been exposed, who's not. Now another piece of information that's missing is whether or not when we have antibody, if that antibody's actually protective and keeps us from being re exposed and sick again. And it doesn't mean just because we might be recovered and well and have antibody that we're not still contagious. So some individuals, it appears, can shed virus for longer periods of time than others and possibly, even intermittently shed virus. So there are a lot of questions yet to be answered, but without perfect test, we have tests that some have better sensitivity than specificity or better at being specifically telling you that a case is a case, so less false negatives, and other tests have less false positives. So the specificity, depending on the prevalence, these things change. We would use different test characteristics or different types of tests for different reasons. So one reason that's been proposed is getting back to work. So saying you can go back to work if you've already been exposed and you have antibody. Now only if that antibody's protective, right? So that's one piece that some people are very concerned about, like sort of social engineering and whether or not there would potentially be people gaming the system there, those who wanna go back to work and some who don't. There all sorts of pros and cons to that. Other, I think, more reasonable ways to use the antibody testing is to look not at the individual level and who goes back to work and who does it but more at whole cities and communities and how much exposure has already been there, which would kind of affect what larger groups go back to work. Another piece of going back to work is really that, the people that are suffering economically, hugely are those that often are working hourly or working with tips and things and those tend to be more at risk demographics for also living in higher densities and being underserved by our health community. So, we're likely to see great disparities and who gets sick if we're not careful about how we really address health care and who goes back to work.
Q: A student asked that they learned in class about pangolin coronavirus and how they're more strongly related to human coronaviruses than that of bats. Has your organization learned any more information about the origins of this virus, in general?
Well, one of the things that we're doing right now, thankfully, with some support to continue the PREDICT project, is look at many more hosts than we were able to look at before. So we were sampling in markets in China, but more around China and Southeast Asia because we were really asked to work in Southeast Asia. We are just working along the southern border of China as sort of support across border trafficking of wildlife and things. So we will be and are just now starting with some additional funding that just is coming through right now, looking at more hosts. I wanna be careful about the pangolin story. The whole genome is actually most closely related to the whole bat sequence, so viruses found in bats. And we do believe that evolutionary host of the majority of coronavirus, and I think you had this paper, our global viral diversity paper as part of the homework, the whole sequence looking at the whole genome is most closely related to a bat virus, a bat origin virus, but none of these viruses are very closely related. So they are quite different viruses, all of the ones that have been found so far. So the most closely whole genome-wise is a bat virus but the ones that I think people are talking, referring to as being very interesting from pangolins is because that spike protein, that is kind of the key that fits into the lock of the ACE-2 receptor and allows invasion into cells, the spike protein that was found in the pangolins is more closely related to this SARS-CoV-2 than what we have found in the bat virus that is the most closely related across the whole genome sequence. Hopefully that's clear, but I can talk about that more if you like.
Q: I think we have a related question and this is one that speaks out to pet owners in general. So obviously, there's been a lot in the news about cats being infected by this COVID-19 virus. The question is, what makes the virus species specific? I know you were sort of getting to that, and I guess the follow-up is, why can't dogs contract the coronavirus? At least, that's what this person heard.
Well, dogs can contract the coronavirus and in fact, the first species, domestic pet species known to contract the virus were dogs. So in Hong Kong, people were testing dogs that were living with coronavirus positive patients. And they were identifying and reporting that coronavirus was detected out of those dogs and even when the dog and the patient were separated, the dogs were showing to be positive for at least RNA, whether it was viable or not, but at least RNA for SARS-2 coronavirus for at least two weeks after being exposed to their infected owners, so dogs can get coronavirus. The question of the difference between dogs and cats is whether or not dogs can transmit live virus to another dog or another person in the household. So there was a good scientific study done, I think, the one that this question is referring to that did do laboratory studies to look at dogs, cats, ferrets, and many other domestic animals, food animals. And the species that appeared to be able to be infected and then infect others without contact, so separated but in the same room were cats and ferrets. So cats and ferrets are the ones that seemed to be of interest and that study was particularly looking at what might be good laboratory animal models for doing future work. So cats and ferrets were of interest there. Cats, especially of interest because they also we're getting sick, and so we were seeing illness in the cats where we have not seen illness in dogs. And now obviously, most people know about the tiger and illness in the tiger as well. So yes, dogs can get infected, and what we've been saying from the beginning back to the Hong Kong data which preceded the experimental data was that people should be careful. This is a virus that is able to jump species, and when we think about, especially this spike protein, that again is kind of allows it to bind to at least one human receptor that is found in many mammals, the ACE-2 receptor, that ability to bind is one thing but the affinity and how well it binds and enters the cell is really important and we can look at both the receptors. And there's a nice paper also from Harris Lewin and our UC Davis colleagues that is in the pre-print stage that talks about looking at the host side of the receptors, but we still have a lot of gaps of information about how the host and the virus interact. So it's not just on the virus side, it's not just on the host side, and there are also environmental factors that we need to think about for that interaction.
Q: Since you mentioned the wet markets, what are risky human behaviors that we should try to curtail? And the student question was maybe at the far end from a wet market, should people consider having the equivalent of this disease, just get it and become immune?
Okay, I missed part of that. I think my internet connection might be a little bit interrupted, but I think I got the gist and I know it's a joke. I'm sheltering with my adult millennial children and there's a joke here around, "Just give me a shot of COVID, please." And I do understand that mentality. And though I wanna be super careful to say, you all aren't protected and young people can get very sick and even die, but certainly, we don't die even at my age as much as people that are older or have other debilitating diseases, but you are at risk. Please, please don't intentionally infect yourself and the other reason for that is that you can transmit, even if you don't think you are sick. So if you get exposed, we have this, the big problem with control for this disease is that when it infects us, we are contagious before we have symptoms and the majority of us probably won't get any symptoms or the symptoms will be so mild, we won't be able to tell them from allergies in Davis, for example. So you could put people at mortal risk with that. So I kind of got on a soapbox there and probably missed the beginning part. We don't wanna intentionally infect ourselves.
Moderator- Great, thanks. The first part was about other human behaviors like wet markets. Leering wild areas that we might want to think about curtailing.
Before January, that was my whole career, so I should be able to speak to that, instead of some of the rest of this, right? So certainly, we know a lot about what puts us at risk for exposure to these viruses that go between animals and people. And one of them, the live animal market or the human, we call it a human food value chain. So the whole thing from hunting and collecting animals, either dead or alive, bringing them into farming situations, or directly into market situations, that's very high risk behavior. Actually, we just did a study in Vietnam that shows the highest risk is actually at the end of that food value chain, for coronaviruses anyway, at the restaurants. So live wildlife restaurants actually amplified the risk as it goes through that value chain. So we expect those who collect the animals in the field and butcher them especially or farm them and put them into intense circumstances as well as at the other end where there is this sort of live selection and butchery. Those are really extremely high risk things to be doing. It's also got huge conservation implications and so we're seeing a lot of conservation organizations taking this opportunity to remind people that it's not just about biodiversity, that we wanna protect wildlife, but also our own health. That said, if I could step back scientifically and be a bit more general, the risk factors that we've identified over actually the last two decades have to do with where these factors come together, and they are primarily biodiversity, so where you have more virus, because you have more hosts, so bio diverse areas where those overlap with large human populations, especially growing populations and dense populations. So just like putting a whole bunch of animals in a cage when we hold on to people in a city or an apartment building, it increases our stress and our contact with each other. So where those two things come together, with habitat change or land use change, that's where we see the highest risks for viral spillover. And we, in the PREDICT project, took those factors and met with the country's governments and brought together the ministries of health, environment, and agriculture to say, "Where are these coming together? "And where does that overlay geographically "with high numbers of fevers of unknown origin?" So where are people getting sick and those illnesses are going undiagnosed and that's where we focused. And one of the things that we found specifically around the human value, wildlife food value chain was that people working in that value chain were much more likely to have SARS-related antibodies, and this was before the COVID tragedy. But we were seeing that people working in those occupations were much higher, more likely to have antibody evidence of having been exposed and infected with a SARS-related virus, and in communities, small communities in general, we saw some communities up to 3% of the population being exposed to these things, even though they weren't researchers or working with virus or anything else, so there was a lot of opportunity for exposure.
Q: In that population, was there a decrease in respiratory illnesses from those viruses?
A decrease, if they have protective antibodies, provide any protection?
I don't know, that was in Southern China, and I think if you're following, China was very restrictive on movement pretty quickly especially around cities. They protected their big cities because those are areas where people are living densely and transmission can happen. So it's hard to know had they not had those protective measures, if you would see decrease or it or whether or not there's immunity, so I actually don't know.
Q: A student had asked about whether there were specific kinds of animals or hosts that were more likely to transmit viruses to humans? but I guess you could expand that a little bit, even that host viruses in general? So are there particular species?
In broad strokes, when we think about animals that evolve with viruses, we used to call them reservoir hosts, but there's lots of problems with that. I think, when we talk about the evolutionary host of a virus, they generally have developed and co-evolved with the viruses that might be pathogenic to other species, but in them, it's just part of their microbiome, so they've evolved to not get sick. So unless stressed or otherwise, immunocompromised, they generally don't get sick from the viruses that have evolved with them. So you could see that they actually would have a spike protein receptor. In this case, we talk a lot about the ACE-2 receptor, but they might be using a different receptor that is very much adapted to letting the virus in, but they'll have other cellular and whole body systems that keep the virus from making them sick. So it's not just understanding how the virus gets in that determines whether or not that host will be sick and be a good transmitter of virus. So it goes beyond sort of what's mostly talked about now in general terms of being able to enter the cells. So these viruses can enter different species at different affinities or different efficiencies, but then they also have completely different levels of immunity and control once they get into the cells. So there are a lot of predictors for that. They have to do with many things like interferon and other pathways and we're definitely studying that and we were studying that before this all happened because we're very interested in coronaviruses. So some things predict what species might be able to get it but we're not quite sure yet who will be effective transmitters and who will get sick.
Q: There was a question about immunity passports, which, I guess, is a little bit, maybe what we were talking about before. So a student is wondering if you could talk about the issues with this approach.
Dr. Mazet- I think, so forgive me, but I just wanna be clear when you say immunity passport, like having a card that says, "I'm immune so I can go back to work?"
Dr. Mazet- Yeah, I mean, I think there's some interesting applications in that and some big social problems with that, in that it also sets up questions about testing and opportunities for corruption around testing as well as sort of social engineering of who gets to work and who doesn't. The only actual real talk that I've heard around using this antibody testing for who's going to work and out and about and who's not is around the health care workers and trying to understand if certain people are, that their own personal safety is enhanced by having been exposed already and being protected more than transmitting it back and forth. So I think the healthcare worker question is still under consideration. But again, I think primarily, and really because the tests are not very good yet, I think the conversations are much more realistic and reasonable around looking at how much virus has already gone through populations, and what cities and towns have more immunity versus where we might need to be ramping up the healthcare system and be ready or even put in more stringent controls in areas where there's less immunity. So sort of trying to get in front of the waves, if you will, by using this kind of testing on a population basis.
Q: There have been a lot of reports about people who have recovered being reinfected or coming down with symptoms again, is it clear yet? What's going on? I think a lot of the earlier reports were false, maybe false negatives, but it wasn't 100% clear. Do you have any insights?
Yeah, and this goes back in that, there's some of us in the, especially in the emerging infectious disease community that have worked a lot with coronaviruses that, actually, I got on the phone and called the California Department of Public Health and said, "CDC's recommendations are wrong, what can we do about it?" When it says you can go back out of quarantine after seven days of no fever. That was just pulled out of the sky as far as I'm concerned. It didn't even match any of the studies for SARS or MERS, and it didn't match what was happening, even with culturing live virus out of patients who were at least eight days. I think that there are multiple possibilities. One is that the negatives weren't negative, right? So false negatives as you bring up, and that can happen for multiple reasons, and physicians, clinicians were quite defensive around that argument because they say, "Well, I'm taking a high quality swab," and I wanna be sure to say that that's not, I mean, certainly if you take a poor quality swab, that can cause false negatives, but even with high quality swabs, you can have false negatives because you might not have, there might have only been a bit of virus in one side of the oropharynx versus the other side and you missed it, or as you go from step-to-step, and I'm sure some of your students work in labs, and understand the different steps in PCR testing, but you go through dilutions, and you go through, you aliquot, if you just, you aliquot tiny bits of material from one tube to the next in each step, and when you do that, you might not catch the virus, right? You might move from step to step without catching the virus.
Now, once we have the sequence, we were doing much better testing that was increasing sensitivity, and so allowing there to be less likelihood for missing virus in that testing. But still, a negative PCR doesn't mean that you are negative. A negative PCR just means none got into that last step. And so the recommendations from a lot of us from the beginning was that you needed at least two negative tests by PCR, and they should be at a distance at least a day apart, but preferably more to be able to feel a lot more confident. And there's a lot of folks talking about if, yes, but you could pick up non-viable virus for quite some time, and I have a lot of problems with that idea as well. We know that the viral RNA can be infectious. So if it's the whole genome, it can still be infectious, even if it's very difficult to culture. So anyway, that's on that side. The other, so false negatives are quite possible, that people get reinfected is possible. I actually, and this is just my educated suspicion, I put that people are getting reinfected much lower on the probability list based on virology and immunology, and it sounds like you'll have a great person to talk to about that. If this virus is really, really different than other viruses, including coronaviruses, then maybe there's no immunity. But for most viruses, there is some period of protection. It's not lifelong, and we don't know how long it is, but there is some period of protection and it should be longer than we know this virus has been around, so we shouldn't be seeing people already having waning immunity. That said, individuals have different immunological responses than other people in their communities, and some individuals are likely not able to be protected, so that there is the possibility of reinfection that way. And then finally, I think, in my mind, the logical, highest probability of what's going on is intermittent shedding, that we don't shed the same thing from day to day. So one day, I might be negative. I'm not having a bad day, I'm not coughing, I'm not, you know, and the next day I am. And so people feel better, they go home, and they don't realize that they still have the virus and they are too active and they get sick again, and they start shedding again. It's not that they got reinfected, they just weren't all the way better because our tests are all imperfect, and our bodies don't cooperate. So I think that's much more likely and we used to say even with things like Ebola, that you are lifelong protected and you're immune once you are out and that you weren't shedding, and we know people that have antibodies can now still shed in semen for six months. So once we get huge numbers, which we will, of cases, we can understand that much better. But in the early days, it's very difficult to know.
Q: What struck me was you were talking about the CDC initial recommendation, which seemed just so off to you. I don't know what happened at the CDC, but obviously, there's a need for expertise in virology. And so what would you say to our students as they're thinking about careers?
I think the CDC is a great place to work. So I mean, as far as aspirationally, wanting to do something, you can make a big impact working for the CDC. I don't think that what happened was a reflection of the lack of expertise or quality of scientists at the CDC. So I wanna go on the record with that. I have some wonderful colleagues, brilliant scientists that work at the CDC, and I don't think they were utilized, frankly, very much in this epidemic and pandemic, at least in early days. So where I do see a big problem in our US response and what happened here has to do with the siloing of systems. So one thing that I have and my CDC friends get sick of hearing from me about this is that CDC is very much organized over time, and it makes sense when you have very old institutions, and I don't mean that that means that they're not good just they have a long history. They develop in response to things. So they develop in response to influenza, in response to smallpox, in response to measles, and they end up having departments, and this is how CDC is organized, departments that are siloed by disease. So when a new disease comes, who responds? Because there isn't a department for that new disease. Now, they do have a special pathogens branch. Those are the people I work with the most that tend to deal with things like filoviruses, Ebolas, and terribly dangerous diseases, and they're brilliant people. I don't think they were really called upon enough in this specific situation. I also think that our political system was such that people were not encouraged to hurry up and get ready, and that was a big problem. And another problem is that we have multiple agencies in our government that have to look at it and approve things like testing. So in this case, both the CDC and FDA have very specific roles, and they need to interact with each other and implement their different activities and that took a toll on our ability to quickly respond, I guess that's how I'll say it and you can read the New York Times article, they did a good review of that. But basically, it was very difficult for laboratories that did have expertise to jump in and help early and there are a lot of reasons for that, that I think will get fixed, unfortunately too late for this one, but hopefully to prevent this kind of tragedy from happening in the future.
Moderator- So the activity of scientists are not gonna go to waste here. We're gonna be able to marshal our forces hopefully and political wills notwithstanding, we'll be able to make some progress.
Dr. Mazet- Yeah, but there's only so much we can do. So I've spent a lot of my career working on emerging infectious diseases and Dean Winey, read the quotes. I mean, there's many, for many of us that have been working in this saying, "Hey, look out, be careful, here we go, let's get ready." And it does take political will to make those changes. So some agencies I mentioned my main funder, but also NIH as a funder of work we do have been proactive and forward thinking, maybe from a self-serving perspective because they were spending a lot of money on vaccines after the fact. So USAID is how we do a lot of global diplomacy, health diplomacy around the world, and they would be asked to come in and respond to these huge epidemics around the world and bring vaccines. So they were spending millions to billions on vaccines, often after an event or at the very tail end when the vaccine is not that helpful. And they wanted to say, "Can we invest in something upstream?" So I think it was quite visionary and economically beneficial. But others were saying, "Hey, that disease x thing”, "that thing that we don't know is coming isn't my top priority 'cause I don't have enough money to deal with what's right in front of me”. And so that's normal, but I hope that this is a real call to action that we need to be ready and that we can rethink systems to be more nimble so that we can respond to whatever comes our way.
Q: Is the emergence of this novel coronavirus, was it a surprise or could you predict it? And I guess that's looking to the future? Can we predict the next one?
It depends what you mean by predict. I can predict very reasonably that we will have more of these. Yes, it's predictable that this will happen, it has been, which is why we are on record that something was coming. Can I predict right now where and when and what the next one will be? Absolutely not, and that's why I believe, we need the Global Virome Project that I mentioned, because by working together around the world and gathering the information on the viruses, the host, the geographic distribution, and the transmission risk potential for the different activities that put people in contact with the virus, we can get to a place where we are starting to identify all those risk factors and put the information into the hands of communities so that they can reduce their risk. Will that predict and prevent every single spillover? Absolutely not, but will it do what I kind of call create a global immune system? I think we can, because we cannot have laboratories that are ready and able to detect and diagnose new viruses. That was what I said was true that our PREDICT labs in many countries were the main ones that people went to. They're also the ones under fire for having caused this thing, and I spend a lot of time on that. And then also, it means that people understand where and how these things might start and can, hopefully, catch and prevent most of them, but also catch new ones at the source, control them right at the source, instead of the whole globe having to go into sheltering.
Q: So I'm gonna interpret that to our students as a call to action. I mean, not everyone's gonna wanna do that. But yeah, there's work to be done, and it's incredibly interesting as a biologist.
You had mentioned that viruses co-evolved with their reservoir hosts and those hosts can be immune to the viral effects. Is that a place for us to gain insights into developing treatments for COVID-19?
Absolutely, and again, I don't wanna sound like I'm on this advocacy soapbox. But I do believe with a thing like the Global Virome Project, we could find the viruses. So for example, let's stick with coronaviruses here. If we go out and find the thousands of coronaviruses that we believe are out there, and all the mammalian hosts and water bird hosts that might have them and we can start to understand which ones are pathogenic when they spillover into other species, even not humans, but other animal species, we can start to understand which ones have markers for pathogenesis, and which ones don't and develop targets better, specifically at those, I guess, target, I don't wanna use target twice here, but we can better target our development of diagnostics, therapeutics, and preventives. If we only look at the last one that made us sick, this one, we have a very limited data set to understand where to target, you know? And then what we do is we develop a vaccine just to that one. I think the whole community wants us to get to a place where we have more panviral family or even just panspecies in the case of influenza vaccines, so that we are, as we do with influenza vaccine, sometimes missing that next strain that's going to come around. But I truly believe that part of what's hampered our ability to do a great job with viruses, is that we only have been studying the very few that have caused us big problems in the past.
Q: As a cell biologist, I think the biology of viral infection and what's limiting virus production is incredibly interesting. So there are lots of ways to think about the problem. Somebody asked about, I guess, I think the question is about antibody pools in the reservoir host and its effect in battling the virus there. So in other words, I think maybe you sort of addressed this a little bit, but are the host, the reservoir host, amounting to an immune response to these viruses that's protecting them?
So there's a couple pieces. So certainly, looking at the immune response and the antibody production is one, but even if you go upstream from that, it's whether or not the virus actually elicits an immune response in the host. So at times we can have the virus enter the cells, but the cells have the mechanisms to either kill the virus or allow the virus to live if you wanna use live stuff, we don't talk about viruses so much as living entities, but anyway, that inactivate the virus without causing any cellular damage or be able to harbor the virus without a reaction. And it's a bit more complicated than simply whether or not they produce antibody as to whether or not it causes disease. So I'll leave it to the immunologist to talk more about that and we are working on that and studying that now. So I hope to be able to come back to you with better answers, but I don't have great ones right now.
Q: How do we trust each other to be transparent and report? And I think it would help to hear your perspective on scientists that were reporting out of Wuhan? I think we get a lot of mixed messages in the media. But from what I understand, there's been a lot of really good scientific reports coming out of China on the virus that's been helpful. So can you shed some light on that issue?
Yeah. And I've had a lot of media inquiries and taken some of those and frankly, taken a lot of personal attacks over having collaborated with the Wuhan Institute of Virology because people are, you know, wanting to point fingers that this came from a lab. There's great data and information out in the sector that shows that this virus was not created in a laboratory, that it was a naturally evolved virus, and so then the fingers were pointing at yes, but the labs released it. And certainly accidents can happen but I've been on record this weekend, last week about why we think that, while accidents can happen, they're unlikely to be the source of this particular virus. It's not very impossible, but unlikely, and people have attacked me and said, "That's because you work with them." Well, the reason that I think it's unlikely is because I work with them and I understand the safety procedures that they use. So you can't say don't ask me because I work with them. But then don't ask anyone who knows how they worked, and then just use conjecture to blame the scientists. And I think a big problem here is the lack of trust in science and scientists in our current political environment. And then the nationalizing of this crisis that nationalism stuff was really preceding this crisis, and then has just been inflated. And my first, to the first part about safety and what's happening in China, I don't know all of the Chinese researchers or all of the research projects that were going on in and around all of the different research institutes in China. I do know that my colleague received samples from sick, dead people actually, the first deaths, and did identify this virus and it was a virus that neither she nor our project had identified ever before, and that she was the logical person to receive the sample because she had spent her career working on these kinds of emerging infectious diseases and happened to be in the city where there was a lot of virus and illness. Where that virus originated, whether it was in a market, I think probably it wasn't in the market that was originally sort of targeted, I think it's more likely that that market was where, it could have started there, I have no idea, but it's more likely that that's a market is where people interact a lot, and there was exposure in that market. The timelines don't necessarily line up perfectly for it to be the primary source unless there are a lot of sick people working in that market for some time before it was identified, so it's possible, and it was a live animal market. And we do know the live animal markets are high risk for these kinds of spillovers, but we also aren't sure that the right species were in that market, because we don't know the species. We don't know the species that transmitted this into people. I haven't said this publicly, so this will be the first time to say this, but it's even quite possible that this disease didn't start in Wuhan. So it's possible that it got diagnosed in Wuhan because there were experts in Wuhan, but it actually started somewhere else. And the evidence that I offer for that is that we thought in the Western United States that this first illnesses were in Seattle where we saw the first cluster of deaths that were enough to be detected, but actually we had people dying in Santa Clara at the same time or before that, so it was in California, earlier potentially then even Seattle or at the same time as Seattle. We don't have the data because we aren't doing the retrospective testing. Once we do the retrospective testing and China does the retrospective testing on sample archives, we have influenza samples from all the counties, we can start to go back and just as Santa Clara County did, we can go back to autopsy samples as well. We have the ability to find out and trace this back but everyone is, rightfully so, spending their time now trying to stop the problem that is going forward, but we do need to go back, but until we do, this is all conjecture and finger pointing. Obviously, you're not going to detect an outbreak until you have a cluster of deaths or you go back in time and you look for it. So clusters of deaths are generally only noticed when there's enough cases that come to one physician or one hospital. And that generally happens in cities, frankly. So if there was an exposure in a cave or wherever, in Hubei province or far distance and that person came and started cases in Wuhan, that's quite a viable hypothesis as well. So, again, we don't know when, where, and how, and from what host this thing started yet. And I wanna know, I think everybody wants to know, but until then, there's a lot of circumstantial evidence and there are things that increase and decrease the probability of a lot of these hypotheses.
Moderator- Yeah, that's very helpful. That's a great reminder to be patient and follow the facts and not just finger pointing.
Q: A student was wondering how you detect viruses that are co-evolving with a host probably before the spillover? And they assumed it's sequencing efforts. So how do you go about finding those viruses, categorizing them, and perhaps trying to predict whether they're likely to become something that can jump?
Well, thanks for the question, again, more back to my real job, than all of the stuff around the response. I mentioned getting together with one health group from governments first and asking them, "Do you have the worry, the concern about these emerging infections? And if so, we'd like to work with you”. And then overlaying those risk factors for spillover with where they are having fevers of unknown origin, and then diving down into areas that we identified with that sort of government group, going to the communities, and working with communities to identify where those risky behaviors are most likely. So for example, going into caves for guano mining or using attractants to farm basically guano to get bats to come and give you their poop, so that you could put it on crops are two of the ones for coronaviruses that we worry about. And once you're there in those systems, there are a couple different ways you can go about identifying the virus. One is you capture the animals and again, we use huge safety precautions, including getting lots of ethical permissions, and then handling the animals safely and we didn't kill animals at all in PREDICT. We released animals back. I'm getting, again on social media, "Well, you should have killed all the animals”. Like, okay, well, we're about conservation as well. And so when we capture the animals, again, depending on each species really and what it needs to be safely handled, we handle them in that way. Sometimes that means anesthesia. In many other cases, because we weren't targeting bats and rodents as well as non-human primates. For the bats, the rodents, many of the species are quite small, they could most safely be manually restrained with heavy gloves and swabs. So we swab the oropharynx as well as the rectum, collected urine if they chose to give us some and then took some blood, so that's sort of the most common way, but in large bat roosts, we would use huge tarps to put under the roosts and also sample directly as the bats were giving those samples, again, in Tyvek suits to protect the people from exposure. In non-human primates, we did sample some directly but we also worked on non-invasive procedures. We have some great papers on working out all of the ways to noninvasively sample primates because they're hard to capture, they're tricky, and in many places, they're revered or even worshiped in some instances, and it wouldn't have been appropriate or ethical to capture them. So we worked with zoos and the primate center to come up with methods when we anesthetize the animals and swab them that we got the exact same viruses than if we use certain kinds of ropes. We optimized the rope material, we optimized the attractant, so bananas versus strawberry jam versus peanut butter, what has less PCR inhibition and gives us the same viruses if we swab the exact same animal. So we did a lot of hard work to come up with optimized sampling. Then you have to get into the lab and figure out how to do low cost viral detection and discovery and if you want me to go into that, I can, but I don't wanna keep going on and on. But you do just to sort of close the loop, once you identify the viruses, we felt we had the responsibility to bring those findings to those ministries that I mentioned, all of the ministries, and let them go through their process and help them with risk communication so that they can get that information back to the communities but also give us permission to release the information to the public and actually, April 30th, the final pieces of our data will be completely released to the public. We've been releasing all the data as we go through the HealthMap site and GenBank, but we'll be releasing the metadata as we’ll on April 30th for the whole 10 years of the project.
Q: Just to clarify then, so what triggers to go warn the government or the population? Is it just the presence of a novel coronavirus sequence or other? So how do you make that determination?
We had a team that would do an initial interpretation of risk, and that initial interpretation of risk was based mostly on virological characteristics, and we communicate that to the governments but we've now developed, because there was no real risk paradigm for emerging viruses or novel viruses, we've actually worked to develop one, and that's in review and I hope that will come out quite soon. But we identified through the literature and our own work on PREDICT, we identified 40 factors, so that we can go beyond just the viral characteristics and bring in the ecological and epidemiological characteristics. And we took those 40 factors that we identified, again, through literature searches and our own work. And we asked all of the experts in emerging infectious diseases, heads of labs all over the world that were willing to give their expertise to help us rank how important those different factors were for coming up with the risk for the viruses, and so we were able to rank the importance of those. And then we actually have a web-based tool that we'll be putting out that people can upload new sequence of their viruses, if they're willing to share it. They can also just do it on their desktop if they're not yet ready to go full public release, and in our system helps to pull all of the different information from public datasets from just about seven questions that people can answer. It allows us to rank all of those 40 factors, which include how many species is this virus found in so far? How easy, that tells us something about its jumping potential or host plasticity. It includes the activities at the geographic location where they found the virus, so is there land use change? Is there intense agriculture? How many continents or WHO regions is the virus found? And how widely distributed is it? So, as well as, is it an RNA versus a DNA virus? And all of those different factors. So it's about 40 factors and we'll be happy to get that out in the public domain really soon.
Q: With this pandemic, and then maybe with MERS and SARS previously, what have we learned? Why did this one get away from us? What would be the big takeaway and planning for the next one?
I think one of the things that, well, shame on us, frankly, is that we didn't, we didn't let ourselves have the community memory that we should have. Now that's human nature. I kind of, I use the metaphor with smoking. So if you lost someone in your family recently to lung cancer, their kids and grandkids are less likely to smoke than the household next door who maybe hasn't had a loss for several generations. And we've seen that and please, all of you stop smoking, and don't vape until this is over if, and I don't just mean tobacco, all of it, stop it. There are other ways to deal with what's going on. I'm worried about you, I tweeted about this as well. We don't know all the risk factors, but we wanna know what's making young people really have adverse consequences, especially strokes, and we need you to reduce your risks, okay? So that's one. But anyway, that basically, we get complacent. And so we see right at the time of outbreaks, things like reductions and moratoria on wildlife trafficking, on wildlife markets, on wildlife restaurants, and then not too long after, those restrictions, get loosened up and people go back to their behavior. So that's the kind of shame on us part, like we should learn lessons and not just go back to our old ways. Did we know that coronaviruses, specifically SARS-related coronaviruses were dangerous? Yes, we did. Should we have been more careful and ready for them? Yes, we should, but again, I think this one really shows us that it is worth investing in contingency plans to be able to respond to whatever it is, a new paramyxovirus or filovirus or coronavirus next time. The other part that I think is, frankly, more concerning to me is that we let our nationalistic and anti-science political environment keep us from responding really quickly, and I hope that we find a way and maybe even as scientists, we choose to not wait for our governments to respond when we know something is happening. So we certainly knew things were happening back to the beginning of January. And it was months before, we really worked hard on our control plans.