[, Music, ] hello and welcome to this author interview, sorry for being a few minutes late, but we had some technical problems. This is Howard Bachner, editor-in-chief of JAMA. This is conversations with Dr. Bach nur and I’m joined today by Gregory Pollan hi Greg, hey Howard, good to be here so for our listeners, who don’t know who Greg is he’s one of the world’s experts in vaccines, he’s at the Mayo Clinic and he’s the Mary Loli Reap refer in in medicine and Greg’s been at this for well over three decades, but before we start, and we start the conversation, I just wanted our listeners and our Watchers to understand what we’re trying to accomplish with JAMA through the kovat 19 pandemic. The first is our research papers, which are the basis of the journal, but around that we build numerous opinion, pieces viewpoints, editorials and then, of course, our clinical review and education section. But more importantly, over the last couple weeks we’ve tried to bring these live streams to people as well as podcasts and and that’s a mix of live streams and podcasts. I think people are aware that I’ve done quite a few with Tony Fauci and and some other people and Greg have agreed to join us today. So thanks Greg, you’ve got. This is important that we get information out to people who need it most. So I wanted a focus on two issues. This is a bit more looking around the corner of. What’S coming as we move through the acute phases of the pandemic, which I have tremendous faith about, the capacity of the of US health care system and our committed physicians and workforce to respond. But I want to. I want to look a bit into the future, but Greg every time I have done these in the past. One question that keeps coming up with with people from folks who are listening is: why will it take so long to develop a vaccine? Are there any shortcuts or there is there anything new that would potentially bring us a vaccine on this side of January yeah, it’s hard for me to see that we’d have it on this side of January and – and I should sort frame this Howard by saying that The process is in many ways designed to be slow, reflective, peer-reviewed, evidence-based because almost as opposed to any other therapy that we do we’re taking healthy people giving them a vaccine to prevent an infection they might encounter and might have symptoms from so what takes so long Is not so much the science part of building the vaccine, it’s the safety testing in enough people across enough time. So, your sense like doctor, foul cheese and other people. It’S it’s a year away! Oh, easily. I mean, if you take as another example, a major public health emergency, Ebola vaccine that took six years to get to licensure now that that epidemic also kind of stopped and started where, as I suspect, our attention will be a little more sustained here. But a couple of things are happening that I think get to the root of. Can you move things along? I? I know my institution and other institutions are doing everything they can for expedited IRB review so that we can. We can get approval to do these studies as quickly as possible. I know with the FDA, they’re banking, reviewers, right and left so that applications can be reviewed quickly. Almost unprecedented is that the FDA is allowing non-human primate studies and human studies to happen simultaneously. It has always been the case that it was small animal non-human primate pause then allow first in manned trials and they’re they’re moving toward letting those latter. Two things happen together, but nonetheless, just the effort involved in enrolling thousands to tens of thousands of people into a trial and looking for safety as well as efficacy, is a tough row. Yeah, – and I do want to remind our listeners before we move off this topic – is once we develop the vaccine. Thats no guarantee of efficacy, correct, correct, so Greg! You know. Theres about 50,000 people in the US have now been a infected with Kobe 19. Do we know much about their immunological? What form does it take and will it be sustained yeah? Those are really critical questions and – and I like to answer it this way, while it is a beta human coronavirus – and we have known about those since the 1960s, with this specific strain of corona virus nobody’s knowledge is greater than 12 weeks old that that’s it. So we don’t have a lot of pixels on the canvas yet to really see the picture. Clearly. We know, for example, that with SARS that immunity waned very quickly in those individuals with MERS, it did not why the difference. Its not really clear, with the seat before seasonal beta human coronaviruses, that circulate cause all the upper respiratory infections that you’ve seen in your practice. Those people lose immunity in months to a year or two. Why is that? Well, it’s because it’s primarily a th too focused immune response and not so much a a cellular driven immune response where memory is included. Now that impacts our knowledge, not only on are these folks going to be protected, but also when you have had these many infections have you started to develop any herd immunity for the years following and it informs vaccine development now is science advanced enough? I mean people are now clearly being infected, they’re surviving, thankfully, and so we will be able to access some of their immune system after they have survived how science advanced enough, so that we’ll know what their immunologic response looks like. Where is it going to take more months to understand that it’ll still take? You know more weeks at least to understand that, because what you really end up, doing or whatever, what my lab and a number of other labs do call systems biology, type studies. So we really want to know our t follicular helper cells involved. Do we see involvement of memory, plasma cells, things that would help us to better understand? Are we likely to see long-lasting immunity, or is this going to be short-term humoral immunity? Now, as I said, you know, I no one knows the time period but say two months in the future: it’s quiet in the u.s

Around new infections similar to what’s happened in China, Korea and we get to the fall, and we don’t really quite know. What’S going to happen, will it’s safe to bring it? Will it be safe to bring people back to college campuses or to have large meetings again? Yeah, these are the kinds of questions that make me sympathetic to the weatherman there they’re very hard to predict, but there’s a key concept, two key concepts, really one that will be familiar to our listeners. What we have seen in the last 11 weeks is the very tip of the pyramid. We don’t know that great base of the pyramid yet and we will once testing gets accelerated and that is happening. The second is a lag period in the dynamics and kinetics of an infection like this. What I mean is what we’re seeing now in terms of cases which I don’t believe have come anywhere near peaking yet so that’s an important point. What we see right now is a reflection of transmission to plus even out to four weeks ago. So what has to happen when we talk about flattening or bending the curve is that you’ve got to get down to a small enough number of cases and wait two or four more weeks before you really sound me all clear and I think that’s going to be A very tough decision in the fall time, as you say, with all the college, kids and and the resumption of the kind of normal business. How do we make that decision and I think, we’re literally kind of building the airplane while we fly it here and we’re gon na have to watch and yes pay attention to what some of the modelers are saying, but equally is important. What are we actually seeing and then add two weeks to that, can you see a future that would involve forms of passive immunization or convalescent serum? I mean convalescent. Serum is a century old, yeah you’re, not a lot, not a lot of good clinical trials, but on the other hand, it’s been used in almost every other pandemic and I’m just wondering it as you peer into the future into August or September or October, and we’re Trying to get large groups of people back or you’re you’re bringing students to a college campus. Can you see convalescent, serum or passive immunization being part of that process? Yeah? So, probably not okay. I don’t think that we would have enough, but I do think that what we need to do right now is: we need polyclonal, even monoclonal antibody development. We need that now simultaneously, you see antivirals trying to be repurposed or redirected and studied for this and then of necessity lagging behind that will be vaccine development. The the the issues with, for example, plasma-derived therapy polyclonal antibodies immune globulin, is that maybe you get a dose or two out of each person, you plasmapheresis, so the idea of getting a very large number. You know, when you and I were college students. If you went overseas, you got immune globulin to protect yourself against hepatitis, A right. There was plenty of it. I don’t think we’re gon na have quite that kind of supply. Now monoclonal antibodies would be a possibility because you can synthesize those in mass quantities, but they’ve got to go through. You know the usual clinical trial, a kind of time frame. The thing that’s really gon na protect us over the mid to long term is getting a vaccine, and – and I have some reservations about the some of the approaches being taken now. This is an RNA virus. It’S it’s not something. I know that much about. Does that affect vaccine development? It does in a way, I mean you’re right. This is a positive strand, positive-sense single-stranded RNA virus. In this case, I think it actually makes vaccine development a little easier. We know the structural and non-structural proteins. We have some indicators of immunity developing from the S protein or the so-called spike protein. My concerns about current vaccine development is that they’re focused almost entirely on a protein, which is a very th2 directed immune driver, as opposed to including the one and the functional consequence of that can be what was seen in spike protein SARS vaccine trials and animals. Where you actually got disease enhancement in some cases and th2, pulmonary pathology and hepatitis like pictures, the other thing is that provides a mutational force on that protein. So what we would generally like to do is to say: well, let’s include the protein, the N protein, maybe the e or M protein, so that a virus can’t mutate around the vaccine, design and as you and I were talking about earlier. Hopefully, the development of more broadly neutralizing antibodies would be a would be a better immune picture if you will try to prevent not only mutation around it, but also antibody enhanced disease, which we’ve seen with lots of vaccine candidates. You’Ve been at this a long time. You have an enormous amount of experience. You know China is reporting, essentially no cases. You know, I don’t know how active their detection is at the moment, but clearly there’s less cases and that’s been true in almost every other country I mean Taiwan. Singapore to me are more difficult because they’re so small, they never had many cases, but Korea had quite a few cases and they’re really much less. Now. Are your instincts suggest that it’s like influenza, and that we will see more in the fall or it’s not like influenza? Sometimes we want it to be like influenza, which usually wane in the in the spring and summer, and then I go. People are hopeful. Its like influenza, but there’s a problem. If it’s like influenza, do you have any instincts about that? Gregg? No, not really! You know, we sort of have three points on a curve. We can’t quite see yet what point one was that the seasonal Bay, the human coronaviruses, do recur every fall point to the the SARS virus or SARS Co v1, as it’s actually known as now started in November of o2, disappeared by July of 3. Now now a fundamental difference is there really was not asymptomatic transmission? The way there has been with SARS Coby 2/3 point on the curve is MERS, which has still circulating in very low levels on the Arabian Peninsula, but still small clusters of cases here and there so which one will this be like we’re hoping because of genetic similarity. Dis ours, that it will be more like that and as we get to warmer weather will see a dampening of cases. Now, that’s not a good sign for the southern hemisphere, sort of like what you’re suggesting and then would it recirculate for those of us that didn’t get infected in the following fall and we’re just going to have to stay tuned, but it makes a critical point. You mentioned, which is the need for ongoing surveillance. We’re gon na have to be very careful about that. What was interesting was about a week or ten days ago. I’M sure you read about it. The UK was debating whether or not they could somehow create herd immunity by keeping their pups open and letting quite a few people get infected that that was suggested. It didn’t, I think, go over very well with some leading health scientists and it’s very interesting because they really dramatically changed just in the last two or three days to really accept the guidance that w-h-o has offered about social distancing. It was really quite a reversal, so I don’t think they’re there pursuing this kind of herd, immunity, yeah, probably thankfully Greg have you seen enough data comes up every time. I do I do these live streams and Michael’s sending me questions. People really want to know if individuals can get reinfected. Do you have a sense of that yet or you know, there’s not enough data, or it’s really not likely. Can you answer that question yeah, not enough data again with the seasonal coronaviruses? Absolutely they can so that suggests that there is a mechanism with SARS that didn’t happen with MERS. It hasn’t happened that we know of so I suspect what happens is that the the protein is so elegantly and efficiently adapted, particularly in this case to the ACE 2 receptor that you’re not getting low-level infection you’re getting pretty hefty infection, and I think that drives A more balanced immune response that I’m hoping is more likely to lead to longer-lasting, durable immunity, but this is a problem. We are beginning to notice this with some of the standard childhood vaccines that we get where we know, for example, with closer study that, when you’re not having concomitant circulating subclinical challenges that mumps vaccine antibody induced durability wanes really pretty quickly same with pertussis. So will this, be, you know, measles, like immunity or mumps, like immunity, don’t know yet well. One of the questions that came in is particularly in the child population and our viewers and listeners know I am a pediatrician by training. I am quite sure what will come up quickly, as should children still receive their immunizations? Well, can you comment on that? I haven’t seen an opinion from the American Academy of Pediatrics, but generally have been very strongly committed to immunizations yeah, your you’re exactly right, Howard and they still are aap, did release a statement. They did that basically said this. You know immunizations are important to get and but the one caution is what we don’t want. If you know a hundred kids, and maybe I’m exaggerating here, but a hundred and fifty kids in the waiting room, all mixing waiting to get their immunization. So, let’s do this by appointment: let’s do this carefully, so we don’t actually in induce risk now the other big point about this and I think a lot of clinicians forget about it, especially with sort of the drive-through testing their thinking, binary, kovat. Yes, coke did know, but depending on where you are in the United States, you’ve got influenza A influenza B, parainfluenza human metapneumovirus, RSV, all kinds of viruses, mumps, measles, pertussis, you’ve got all kinds of viruses and bacteria espera, torie pathogens circulating, and so what you don’t know In a given case, if you don’t do a respiratory pathogen panel is and the one that would be the the most likely statistically is Coinfection with influenza and Tsarskoe v2 well, one we have a definitive treatment for and the other we don’t so you’d want To know that and reduce the burden of disease, particularly from a pulmonary point of view. Well, I you know I, in months to come years to come, we’ll rehash the testing fiasco in the United States. My spout, I spoke to Michelle gone from Montefiore earlier, oh yeah. I saw that yeah. Michelle said you know. As soon as we got to test it totally changed everything you know they could organizationally and logistically sort out what to do in their institution. They brought it in-house, it’s a few hours versus sending it out for a few days. I mean you can quarantine someone at home and say you know in a few days, we’ll know if you’re a disease, but if you’re trying to trying to run a hospital a healthcare system a few days doesn’t really help you it’s it’s critical yeah. So I’m sure. Well, we’ll come back to that now an astute, astute, listen said well Howard, you asked you asked Gregg about children, but children are pretty protected in the sense of day. They have not gotten much disease or, if they’ve gotten disease, they fared pretty. Well. What about adults and immunizations yeah? Would you change the recommendations for adults over the next three four five six months yeah, so you know no clear guidance, one way or another has come out. We know that vaccine-preventable diseases and adults are the majority of cases. When you look at deaths due to vaccine-preventable diseases, over 90 percent of those are in adults, of course, not kids, and so they are important in the midst of a pandemic in a city, let’s say light like New York, I would probably say I don’t want A lot of patients in my waiting room. I want you to get flu vaccine because that’s circulating right now. Those symptoms overlap so so carefully that I want to be able to take a bunch of that off the off the system. I probably want you to get your pneumococcal vaccines, but the rest of the vaccines, I’m perfectly willing to say you know what there’s a little more risk by you travel to my office to waiting in my waiting room. Let’S delay those for a few weeks. I don’t think that’s likely to do any harm. I feel a little differently with the respiratory born pathogens. For the reason I mentioned, and that’s co-infection, so a crystal ball, it’s you know when we chatted by email. You said Howard, there’s so much unknown yeah, but do you have a sense of what the next month, two months three months, are going to look like yeah, yeah III think we have not come anywhere near the peak of this. Yet I think what we’re going to see is what has historically been seen in every pandemic, where we have data, and that is people start to flee cities, particularly where there’s going to be any kind of containment or cordon sanitaire type restrictions that just broadens out. One person is called these rings of fire, that’ll, they’ll, spread out and eventually coalesce. I think we’re gon na see a lot more infections. I think the health care system is going to be under increasing stress. I think we’re in this for months – plural, not weeks. I don’t think this is gon na be two or three weeks and then boy, the the all clear flag, goes up. I just don’t. I don’t see it happening that way. I’Ve was impressed when I’ve spoken to people around the country. Obviously it’s a tremendous struggle in New York City and to our listeners who were there or have friends there. I wish everyone to be well, but particularly the health care workers. As I’ve said, you can double the number of ICU beds, but if you either don’t have equipment or healthcare workers, it will make no difference, but we seem to have bought some time from China, which we didn’t do very well, which was squandered around testing. But we bought some more time in different areas around the country and in talking to people I really do think health systems have had really re-engineered themselves incredibly quickly, just within the last ten days to two weeks, you know telehealth telemedicine. I think the ICUs are really ready to expand if they have sufficient supplies and health care workers. Hopefully, testing on in hospital testing. Rapid exchanges will be available everywhere in the country, so I feel like we’ve bought another week or two at least outside of New York, and I hope we really use that time wisely. I don’t know what your impressions are of that scenario: yeah yeah, you know, as I talked to my colleagues around the nation, I feel very similar Howard to how you feel is that you know there’s a few if we will call them up centers right where the System has been very strained, but you know what I think after SARS, after MERS after pandemic influenza, a couple of aborted potential pandemic influenza. I think the health care system got the message. There was concern remember about bioterrorism after 9/11 and I think Paradis is at an all-time high. I think people are more prepared for this. You know, Mayo Clinic, for example, we’ve got a bright young guy who actually trained in this kind of preparedness and that’s been a big boon to our very large system being prepared. And yet, when something really Wallops you like New York City, you know you’re hearing things like they’ve got 7,000 ventilators and they need 30,000 more. I think the other thing that has helped is that the strategic national stockpile initiative has been a benefit. Now they need to really open those gates up. They can, they can replace them at another time, but they need to get those mass PPE out to our fellow healthcare workers. So I personally think that in probably every arena other than testing and other than vaccine development, we have been as prepared as I think you can ever be for this, and I’m only putting the finger on vaccine development because you know SARS MERS and now SARS Kobe, To three times in 18 years you know us we coulda shoulda had a vaccine, but they occurred just beyond the human attention span and once it kind of dampens down and or disappears. You know we turn the research spicket off and and that’s not a good way to do science, it’s an it’s an ongoing endeavor. You know, one of the really nice things to see over the last few years is a dramatic increase in the NIH budget. Yes, now it’s gone from 30 billion to 43 or 44 billion. Some of it’s been earmarked for the brain initiative, some for cancer, obviously the heal initiative around the opioid epidemic, but it’s been a dramatic increase and I’m pleased to see that Congress has been able to invest. Once again, you know we, the US has been kind of the leader and biotechnology and science, and I want to make sure that we have the capacity to retain that leadership position around the world. Absolutely – and you know that’s a that’s a not Oh does that help people around the world, but it’s a national security issue. You know, I see by the way, looking way out one one silver lining that I haven’t heard many people talk about. I think for this younger generation, this will be as defining as the space race was in mine, and I think – and I hope that we’re going to attract a lot of bright young women and men into the science fields where they may not have had any Particular motivation to do so, so all in all, I think the way you opened is exactly right. We’re gon na get through this we’re gon na learn some lessons and we’ll be even more prepared for coronavirus for ya. My lord, I do remember Walter Cronkite. He loved the space initiative. He Walter Cronkite love the space initiative. Yes, so this is Howard, Bachner, editor-in-chief of JAMA. This has been conversations with dr

Bachner, I’m reminded by Mike Berkowitz to say that next livestream will be Friday at 11 a.m. with Doug white, an intensivist and ethicist from Pittsburgh, and we’re gon na talk about a very difficult and emotionally painful issue. And that will be the potential for rationing in the US healthcare system, which is something I don’t think any of us have ever purposefully seen, and so that will be 11:00 a.m. on Friday Greg. I can’t thank you enough for joining me, be healthy, be well. Thank you our day as a journal, editor myself, I admire what you’re doing and the way JAMA has really been a resource center for all of us. So thank you Right, see you Greg bye-bye all right, bye-bye, you