Episode 160: The H5N1 Response

Chris Dall: Hello and welcome to the Osterholm update, a podcast on COVID-19 and other infectious diseases with Doctor Michael Osterholm. Doctor Osterholm is an internationally recognized medical detective and director of the center for Infectious Disease Research and Policy, or CIDRAP, at the University of Minnesota. In this podcast, Doctor Osterholm draws on nearly 50 years of experience investigating infectious disease outbreaks to provide straight talk on the latest infectious disease and public health threats. I'm Chris Dall, reporter for CIDRAP news, and I'm your host for these conversations. Welcome back, everyone, to another episode of the Osterholm Update podcast. It's been nearly three months since the US government first announced an outbreak of H5N1 avian influenza on a US dairy farm. Since then, we've seen the number of affected dairy farms climb to more than 125 herds in 12 states and three farm workers infected. While the threat posed by H5N1 to the general public remains low, there are concerns that the virus is more widespread than we know and questions about how the US is responding to the outbreak. Here's what Seth Berkley, former CEO of Gavi, the Vaccine Alliance, said in a presentation in London on vaccine development, as reported by STAT news. I live in Switzerland, but in my home country of the United States, it's been shocking to watch the ineptitude of just doing the surveillance, being able to talk about it, tracking the infections, understanding where we are. Do we have vaccines? Are they the right vaccines? It's really a challenge, so I'm not sure we've learned anything. The latest news on the H5N1 outbreak and the response to it will be the lead topic on this June 27th episode of the podcast. We'll also discuss rising COVID activity fueled by the now dominant Flirt variants, the Food and Drug Administration's change of heart on the makeup of the next round of COVID shots, long COVID, and the ongoing debate over the origins of the COVID-19 pandemic. We'll also answer an ID query on COVID vaccines and bring you the latest installment of This Week in Public health history. But before we get started, we'll begin with Doctor Osterholm's opening comments and dedication.

Dr. Osterholm: Thank you, Chris, and welcome back to all the podcast family. We're so glad you're with us again. And to those who might be visiting us for the first time, I hope we're able to provide you with the kind of information you're looking for. I'll warn you in advance that we typically cover a variety of different kinds of topics, some based on science and some not, but I hope that they're helpful to you. I also want to take this opportunity to thank those of you who have sent us very kind and generous donations that we use to help support this podcast and the other news activities of our center. Um, the outpouring of support has meant a great deal to us. One of the things that was very important for me in starting CIDRAP back in 2001, was that we would be a source of information for the entire world, everyone in the community, without regard to how they could pay. And today, there are so many paywalls out there for information that should be in the hands of the general public. And so we are committed to making certain you never have to pay a penny to get the information from CIDRAP. And with that, your support has meant everything. So thank you very, very much for the dedication segment. Today I want to discuss a recent report published by the CDC that assessed the association between social connection and mental health among U.S.

Dr. Osterholm: adults. Mental health today is obviously a very, very key part of the challenges we face in our communities. The researchers used data from the 2022 Behavioral Risk Factor Surveillance System to determine the prevalence of loneliness and mental health issues by various demographic characteristics. The main findings of the study demonstrated that stress, frequent mental distress, and depression were experienced approximately three times, as frequently by adults who also reported feelings of loneliness. Those feelings of loneliness were found to be more common among adults who identified as gay, lesbian, or bisexual compared to adults who are identified as straight as well as higher among transgender adults compared to the cisgender adults. What can be done to remedy this? Addressing social connection as a critical determinant of health is an important first step. I think there's been a major lesson from the COVID pandemic as well. We all benefit from being in a relationship with one another and knowing that our networks of care are strong. And specifically, it's important to create welcoming communities where LGBTQ+ folks feel safe and supported. There is no biological mechanism that explains the connection between sexuality or gender expression and the persistent feelings of loneliness. This association is established by social factors, by homophobia, by exclusionary policies, and by discrimination that perpetuates feelings of otherness and leads to isolation, shame, and fear.

Dr. Osterholm: In addition to building an intentionally welcoming communities, mental health care providers should be aware of the unique psychological needs of the LGBTQ+ community, as well as anyone else who experiences social isolation, because loneliness can truly touch us all. Being that it is June, the official start of Summer and Pride month, I hope that everyone feels a tug to reconnect with their communities. This can be a fun time of year to attend a celebratory event with your chosen family, travel to visit friends, spend holiday weekends outside with family, or get involved with local organizations. Loneliness can have real impacts on our mental and physical health, and although it's clearly not always easy, the remedy is simple community, community, community. Now let me move to that brighter part of the podcast that for some of you, you can check out here for a minute if you'd like. But, uh, the last, uh, podcast I noted, it was the last one prior to the summer solstice. Well, we're on the back side of it now, but we're still looking good. Uh, today in Minneapolis, uh, sunrise is at 528. Sunset is at 903. That's 15 hours, 35 minutes and five seconds of sunlight. Wow. We're losing 28 seconds a day now, though, as we now are starting to make our approach back to the winter solstice in December.

Dr. Osterholm: And now to our very dear friends and colleagues in Auckland, New Zealand, at the particularly at the Occidental Belgium Beer House on Vulcan Lane. Today your sun rises at 734. Your sun sets at 513. That's nine hours, 38 minutes and 34 seconds of sunlight. But you're now gaining a slow yes, but at 14 seconds of sunlight today, and that will only continue to rise. Now, I mentioned on the last podcast that there was something unique about this particular summer solstice on June 20th. While we don't have time to go into all of it today, I wanted to just share with you that, believe it or not, this particular solstice, this past Thursday was the earliest in 228 years. Not since 1796, when George Washington was president. And while it may seem that the summer solstice shouldn't vary that much and it is within a day, there are reasons for why it is earlier under the solstice day, or later in the solstice day that we actually hit summer solstice. I'm not going to spend time going into all of it today, because it could by itself be an entire podcast, one that could be quote unquote enlightening. But in fact, just to remind you, we just experienced the historic summer solstice, and I'm enjoying every minute of it.

Chris Dall: We're going to begin again this week with the latest H5N1 news. And there's been a lot of it. So, Mike, can you start by summarizing what we've learned since our last episode? But then I'd like you to address the way the US government is responding to the outbreak. And you heard the criticism from Seth Berkley that I read earlier. He's not the only critic of the US response, and I know you share some of the concerns that have been expressed but don't necessarily agree with all of the criticism. So can you please elaborate on that?

Dr. Osterholm: Thanks, Chris. Uh, let me say, first of all, fasten your seat belts. I'm going to try to provide you a major overview of H5N1, both historically and current and likely what might happen in the future. But before I do that, let me just share my perspective. Where am I coming from on this issue? Well, I think it's fair to say that I probably am amongst the oldsters in this topic area, given that I have actually been quite involved with it since 2003, when H5N1 influenza emerged in Southeast Asia as a real challenge. And it was because of that early work that I got involved with. That was in 2005. I was able to actually negotiate the publication of a paper preparing for the Next Pandemic to be simultaneously printed in Foreign Affairs, the New England Journal of Medicine and Nature all in the same day. And it was really an attempt to reach across a broad, broad audience, to help them understand we are not prepared for the next pandemic. And of course, since that time we've had the 2009 H1n1 pandemic and of course, COVID. And in each instance, we realized we weren't prepared. I have continued to work in this area, have published, as, you know, a New York Times best selling book, Deadliest Enemies Our War Against Killer Germs, that laid out just what a influenza pandemic would look like, and what we needed to do to be better prepared.

Dr. Osterholm: Well, I sit here today and say we're not prepared. And in fact, I believe that we're less prepared now to respond to a major pandemic than we were when COVID first emerged. And I'll go into that more in a moment. But so where are we today? And how does my perspective of this history for the past 21 years working in this area, how does that reflect on what's happening today? I believe that there are some major challenges with our outbreak investigation. I support the administration and have since its first days in office. I have many dear friends and colleagues who are part of the administration. However, I think that there are surely issues right now that must be addressed to improve upon this response. Let me give you some examples. First of all, let me just touch on the issue of pasteurization and the safety of our milk supply and assorted dairy products in terms of this virus, when we had the first cases of H5N1 documented in the dairy herd, and we saw that milk was highly contaminated with this virus. At that time, I raised issues with the Food and Drug Administration that, in fact, we needed to get on top of this immediately and to be able to demonstrate with real expert information that, in fact, the pasteurization system was more than adequate to inactivate any virus that might be found in the milk, just as we do to inactivate any other or the other infectious agents such as salmonella, Campylobacter, E.coli, etc..

Dr. Osterholm: Well, we are now looking at three and a half months out, and the FDA has not yet provided any information on how effective pasteurization is in inactivating the H5N1 virus. Other groups have done so, but not with pasteurization equipment. And that is a very unique kind of instrument where this milk goes through basically tubes, very thin tubes that allows it to get a very specific heat level and maintain it for a very specific level of time. Two different research groups who have done really outstanding work have, in fact, uh, subjected the virus to different temperatures, but not in a pasteurization machine environment. And in one of the instances, they did find that there was an active virus that made it through that temperature process. Well, we need the data on pasteurization badly, and we need it done using the kind of pasteurization machine that would be in operation for this country. And yet, here we are, three and a half months out in the FDA has not yet been able to get that work done. That's just inexcusable. We also have real concerns about concluding, how did this all happen? We know that there is active movement of young dairy cattle from the Texas Panhandle area, where they were first raised, to the farms that then milk them throughout the country.

Dr. Osterholm: And we now know that the movement of these cattle surely took the virus with them to these other states. That is the classic spillover event in Texas and then the movement of the cattle. Well, then how did it spread beyond that? And there are clearly compelling data showing that the lack of biosecurity on many farms in this various states that had animals moved to them is important. Biosecurity is where workers may work on multiple farms. They may wear, uh, their clothing between these different farms. They drive their vehicles. They live with individuals who work on different farms, including poultry. And you can really have a cross-contamination kind of event that occurs there that could account for why different farms are involved. However, we have real questions is every farm like that? And to date we have yet not seen any answers to. The fact is other farms that had no animals moved in. In other words, closed operations and farms that also did not have evidence of biosecurity breaches. The kind I just discussed. If that happened, that would be really important to know, because that would say there may very well be more than one spillover and that spillovers could continue into the future. Again, we're lacking those data three months into the situation. Another area is just the virus isolates and the sequencing data. That can be so important in trying to understand where a virus emerged, whether, in fact, it's likely a virus that came originally from the spillover in Texas or might be now a new spillover somewhere else.

Dr. Osterholm: We also have a need to enroll as many people as we can who work in these dairies. In particular, there's documented infections to understand. Might they have had infection themselves, a mild illness, one that they didn't even recognize? Well, I am happy to report that the CDC has now enrolled over 700 people who work on these farms to actually do the follow up with them to know did in fact, they actually, uh, get infected. But when you think about the number of herds that are involved, we know that there has to be many, many more people than those 700. Again, uh, this is a challenge, and I've seen too many people ascribe this to some deficiency of state or local health departments. It's simply not it's not a deficiency of them or CDC. We know that in many of these farms, the critical workforce is made up of undocumented workers. And so from that perspective, it's very difficult often to interact with them. If they fear the government, they fear public health. Uh, and, and what might happen to them. And so this has been a challenge. The lack of enrollment is in part due to the fact that, uh, the farmers and I think the USDA, to a certain degree, has not really pushed this, but a real part of the problem is just the fear of these workers.

Dr. Osterholm: When we look at where we're at today on this, this is really a research effort for an emergency response, not for some academic research situation. We need to put urgency to this and the fact that we're now three months out, lacking the information that we do, is really a challenge. And I feel very much so that there's nothing being hidden or nothing's being covered up. There's no nothing nefarious. It's just a lack of understanding of how important it is to move this information out so that we can have a better understanding of what H5N1 is doing, and might it very well become a greater challenge to human health? Might it become a real challenge to animal health? Then we get into the area of vaccines. I've heard far too many people, particularly out of the agriculture side, talk about, well, if we just get a good vaccine for humans and one for cattle, we can stop this dead in its tracks. Well, that's not true for those of us who have worked on influenza vaccines, which again, I've spent several decades on this issue. These vaccines in humans that we have for seasonal flu are ones that provide you with a fairly moderate protection against hospitalizations and deaths. But we have no data to support the fact of how much they actually prevent you from getting infected or transmitting the virus.

Dr. Osterholm: We believe that it's actually not very high. So these are not vaccines that create some kind of sterilizing immunity. And if you think you're going to stop transmission because you've vaccinated humans or animals, it's very likely you won't. You may only mask more, uh, severe illness and turning into milder illness you might miss. So again, what are our goals for vaccines? How are we going to use them? We call this the target product profile of what we're looking for. And I've seen no one talk about that. And finally, the issue of biosecurity. The USDA did put out two documents about what their findings are in Michigan, and they did document, without any question, the risk of biosecurity challenges to the spread of this virus. The problem is, is that how do you actually reduce these risks? How do you get people to wear protective equipment when it makes it so hard to work in the dairy area? What are we going to do? So by its very nature, biosecurity can improve upon preventing transmission of the virus, but it hardly means that it's going to be uniform. So let me now add some perspective here. Again, I have to say this has been an interesting experience for me because I feel like among my colleagues, I've been getting kind of shot from the front and the back.

Dr. Osterholm: When people hear me talk about this, they think I'm minimizing the this situation and I'm not. Trust me, I'm not. Uh, I've again coming at it with the same eyes that have been looking at this since 2003. At the same time, there's others that say, well, this is been a virus that's been around like that for, you know, more than 20 some years, uh, what's the real risk with this? And I don't think that that's the case either. And I can tell you, we are not prepared for any future pandemic with influenza. But let me just take a very quick journey back where I've taken you before. But I think it's worth noting today there are documented 907 human cases of H5N1, including 469 deaths that have been documented since 1997 to the current day. If you look at the early days of H5N1 and it was a different virus than it is today, it's gone through a lot of mutational changes. We saw, in fact, cases emerge, particularly in Southeast Asia and in the period of 2004, five and six, we were seeing 100 to 115 cases a year in humans, largely tied back to contact with infected poultry or ducks. And as well as the fact that there were occasionally what appeared to be person to person transmission events. And then over time we saw the numbers decrease, decrease, decrease.

Dr. Osterholm: And by 2012 we were down to 39 cases of H5N1 in humans. It was notable at that time we had two very prominent flu researchers who came before the National Science Advisory Board on Biosecurity, the national organization in the federal government with responsibility for overseeing the safety of lab research. I served as a member of that group at that time. These two researchers came to us and said, we're just one mutation away, basically from an H5N1 pandemic, and it's very likely going to occur again. We were on the edge of our seats thinking, oh my God, what's next? Well then cases continued to drop until 2015 when we saw a big peak. The largest peak in human cases since the first arrival of H5N1 back in 1997. 145 cases occurred that year, of which the vast majority were in duck farmers in the Nile River valley. We thought up, this is it. Now it is going to really do it. And then nothing happened. By 2016, 2017, we were down just to a few cases a year. And in fact, since 2017 to the current time seven years, there have been only 33 additional human cases, 11 deaths, very different than we saw in the early days. Now what happened? While we were fighting the COVID pandemic, we saw a new strain of H5N1 emerge. The 2344B clade of virus. And this particular virus had some very interesting properties in that it now affected more mammals.

Dr. Osterholm: Again, remembering that humans have a specific receptor site in their respiratory tract for human viruses, this is the alpha two six sialic acid receptors. You got to have that lock and key for the virus to get in. Whereas the other animal species have the two three receptor, which is the actual receptor for the birds. Now, one caveat to that is humans do have the two three receptors in their eyes. That's why we've seen several cases of conjunctivitis, which did not result in a more severe illness. So when we look what's happened so far, one could argue that we're actually further away from seeing human virus infection becoming a reality and particularly person to person transmitted. Do we know that for certain? No, we don't, we don't. But for me, I look at this and I think there's something going on with age five that creates a bar that makes it much harder for this virus to actually become a human virus transmitted by humans to humans. Could be wrong, could be wrong. But let me just remind you that a lot of the data that we're talking about today on this virus are not new, but they appear to some to be new. For example, we hear about cats on these farms and how this is something very different, when in fact, in 2003 and four over 100 tigers in Thailand's zoos died as a result of H5N1 because they were fed the carcasses of birds that died from H5N1.

Dr. Osterholm: At that point, you know, we've already been there before with this virus. Second of all, if you look at the ferret data, while the CDC did a study where they could show that this was fatal in ferrets and some evidence of transmission to nearby cages of ferrets surely is very troubling. But again, as I pointed out in our last episode, we've actually seen the very same data for these kinds of ferrets who are considered immune naive, meaning they never had influenza infection before. And so what happened in 2012? What happened today are virtually the same with the ferret data. And when you actually have ferrets have previously been infected with influenza challenged by these viruses, you get a very different picture. If you look at the swine studies, there have been attempts to infect swine with this virus, and they've been successful, but they don't transmit the virus to any other swine. So I'm sharing these with you not to try to minimize pandemic preparedness. We are unprepared, but we also want to be certain that we're sharing with the public the kind of nuance of this data that we need to do. And for my colleagues who think I'm minimizing this and I'm now responsible for walking away from preparedness, I'm sorry. It's not true.

Chris Dall: So, Mike, given all that, how can we be better prepared?

Dr. Osterholm: Well, the first thing we have to understand is, is that surveillance in and of itself is very important to understanding what's going on in our communities, but it will have limited impact, if any, on preventing the next pandemic. You could test every cow every day in this country. And so what happens if you find it in the cow? Does that tell you that that is about to reassort with a virus that's in the udder of that cow from both a human and another virus strain that's from a bird. No, that's not going to allow us to stop the pandemic. There's no action you can take. It can give us an early warning. The one thing that will happen is when the virus changes sufficiently to be transmitted to humans and by humans. We want to pick that up early. Why not? Because we're going to stop it. Because it won't. It's a virus with wings. It'll be gone. What we need to do, though, at that point, is now use that virus to make the vaccines for the pandemic response. And I hear people say this over and over again. We have these vaccines or we can make these vaccines. In fact, we know today that the influenza vaccine, as I pointed out, that we have, may provide 30 to 50% protection against medically attended illness, meaning you'll get that sick and has very little impact, likely on actually interfering with transmission or becoming infected. And so this virus is going to take off and vaccines, which, as we've just learned from COVID, even with mRNA technology, is going to take months to make it.

Dr. Osterholm: Uh, and and as I've said many times, I worry less about the time from the pandemic start to the first dose of vaccine, to the time the pandemic starts to the last dose of vaccine. When will everybody have access to it? And so this is really all about having vaccine technologies. And we don't we've done little in trying to get us to new and better vaccines. And this is the whole purpose of our work at CIDRAP on the influenza vaccine roadmaps, which we're doing today, which is really to an attempt to try to get us to game changing flu vaccines. And I give the NIH credit for the work they're doing right now, as well as Cepi, the coalition for Epidemic Preparedness Innovations on the flu work. They really are doing important work, but we're a long ways away from having better vaccines. So this pandemic is going to unfold much like it did with COVID. Just understand that one thing we need desperately right now is antivirals. As you may recall, in the past several weeks, I've noted the fact that we're seeing a major increase in resistance in these viruses to oseltamivir and the fact that this antiviral resistance could render this drug almost useless in a future pandemic. We need more work. So the bottom line here is, number one, we're in a tough spot right now with H5N1 in bovine. We don't know what's going to happen. We don't.

Dr. Osterholm: It could tomorrow turn into the next pandemic virus with one major reassortment. It could be our basic history with this virus tells us there is something unusual about this particular flu strain that no matter how many shots at goal has had, it just doesn't seem to get the puck in the net. And I think that that's a really important point to remember. Again, that could change. But I think also we don't want to find ourselves two years from now, having gone through what I've watched us go through in 2012 with the Nsab or even the 2015 now River Valley cases, etc., where we gin up the world and say, yep, pandemic's imminent, it's coming. And then nothing happens. I think that's the challenge that we have because then we cry wolf. At the same time, we never should stop for one second of bringing forward better vaccines, much better vaccines. That research investment is critical and we're not doing nearly enough. We'll be fighting the next influenza pandemic with all of our largely old, old types of weapons that we had, and that simply will be terribly unfortunate. So all I can say is stay tuned. Uh, I hope that I've been able to give you a sense of perspective here, one that says, you know, I worry about influenza viruses every day. I just at this point, don't put H5N1 in the same place as some people do, who believe it's just a matter of time before this particular virus becomes the next pandemic strain.

Chris Dall: So now let's turn to COVID-19. Anecdotally, I think we're now back in a period where it seems like a lot of people are getting COVID. But is that being reflected in the latest COVID data?

Dr. Osterholm: Well, Chris, I agree with you. I happen to know a number of people right now who are infected with COVID And ironically, in most instances, they only discovered they were infected somewhat by accident, or at least by persuasion. What do I mean? These are individuals who have cold like illnesses. They're not severely ill, but they have enough in the way of symptoms that they're encouraged. Why don't you just check and see if you have COVID? And in fact, they do. Now, that in some ways is bad news. Good news, bad news. You're getting infected at all. Good news is that these are milder illnesses largely. And this is something that we talked about in this podcast in the first year of the pandemic. I said, you know, I'd be very willing to accept a world where COVID was fairly commonly encountered, but it never caused anything more than mild illness. And so we'll have to see what's happening with the clinical picture right now, as we have only limited data. But let me start out by just talking a little bit about the international perspective, because I think that it gives us a sense of what we might be seeing here in the future. Um, in the Western Pacific right now, countries like Australia, New Zealand and Malaysia have reported some rises in activity, including growing deaths in New Zealand. Uh, some similar trends are happening in other parts of Southeast Asia, with Indonesia, Myanmar and Thailand seeing increases.

Dr. Osterholm: And now actually, we're also seeing in the Northern hemisphere, uh, the same kind of situation play out, particularly in Europe with Ireland, UK, Norway, Sweden, Portugal and Greece reporting recent upticks. Now, what does that mean? While case data is a bit more challenging to interpret because of the lack of widespread testing, deaths shall give us some relative sense of what's happening. If you look at deaths in countries like New Zealand, where they had 62 deaths a week last week, that's up about 27%. Australia is at 50 deaths per week. That's some still down some 60%, and Thailand is at 45 deaths per week, which is about 137% increase. Now that sounds like a big increase, but when you think of 45 deaths in a population of Thailand of 70 million, you get a sense it really is a lower number, uh, than we've had experienced throughout the entire pandemic. I'd like to give you more data from the international perspective, but it's a real challenge, and this is something we're suffering miserably with right now, as in terms of what's happening because of the lack of surveillance. All I can say is that right now, this virus is not following any one pattern. There's no seasonality to this at all. Uh, what we're really seeing is likely where the new Flirt variant, the one that we've been most concerned about, uh, is actually now taking over and becoming prevalent, as well as the fact that we just see more waning immunity.

Dr. Osterholm: Now when we look at the United States itself. We have real challenges here in terms of trying to understand the data and what's happening. And all I can say is, is that we now have evidence that is starting to increase in a variety of different states, but even there, those are real problem. And that problem is the fact that, uh, we don't have again, good surveillance and good testing. We are beginning to see the Cp2 variant, one of the Flirt variants, take off in a number of different areas. But when we even look at regional levels and try to use wastewater data, we've had some real challenges. The wastewater data from the CDC, when compared with the wastewater scan data that's combined efforts of Stanford and Emory University, supported by verily, are finding very different results. Makes it difficult, and this is going to be a topic in our next podcast, is to try to really dig into what is the wastewater data telling us, particularly when you have two different groups that are coming up with very different results. So what are we seeing here in the United States right now? Best I can tell you is yes, it is starting to creep up. Uh, when we look at the risk right now of infection, uh, here in Minnesota, for example, we're seeing about 70 hospitalizations a week in this state, down dramatically from what it was during the pandemic, but is still occurring.

Dr. Osterholm: The challenge is, is it's starting to rise. And what we'll be looking at very carefully over the next several weeks is emergency room data to look at what's happening with respiratory infection incidents, and how much of this can be attributed to COVID. So, in short, let me just say we are surely still almost at the very best we've been in the pandemic. We're beginning to see cases increase in various parts of the country. But again, without better surveillance, it's hard to know what's happening. Uh, and we're at some disadvantage of trying to interpret what's happening, uh, with the wastewater data, given that the two different groups are providing us with somewhat different results. So while the national level picture may not exactly trigger warning sounds, some of the regional and state level data are surely pointing to the possibility that we may be seeing increases. As an example again in California. Hawaii right now we know, is experiencing the highest levels of COVID activity since the summer of 2022, when Ba5 was the dominant variant. Again, trying to understand what's going on in these areas will be important, so just stay tuned. Just know that we are experiencing right now, again, some of the very lowest levels of activity that we've seen since the beginning of the pandemic.

Chris Dall: That brings us to the FDA's revised recommendation for the updated COVID shot. You may remember on our last episode, we reported that the FDA advisory committee had recommended that vaccine makers focus on the JN.1 Variant for the next round of COVID shots, and the FDA accepted that recommendation. But a little more than a week later, the FDA issued a statement saying the preferred vaccine lineage should be CP2 to ensure that the 2024 or 2025 COVID vaccines more closely match circulating strains. Mike, was that the right decision?

Dr. Osterholm: Well, first of all, I want to congratulate the FDA on this decision to change, uh, the variants included in the vaccine, from what they indicated would be the, uh, approach at the OPEC meeting two weeks ago. As routine listeners of this podcast will know, I was pretty critical of the FDA last, uh, podcast, uh, wanting to have that discussion of why we are not including CP2 in the vaccine. So it's great news. Now, let me just back this up a little bit to say I understand why the initial interest in using the JN.1 Was there because in fact, the W.H.O. on April 26th, 2024 actually issued a statement saying that's what should be in the vaccine. Well, of course, look at that was back in April. Here we are now in June. And we're seeing some real differences in virus variant activity. So to their credit, they did. In fact, uh, go ahead and say now the mRNA vaccines can contain the new KP variant. That's really important in that they can actually turn around their manufacturing capacity to basically make vaccines now for early fall. That will include the KP.2 Variant. Whereas the other issue that I think played a role in the initial FDA decision was that Novavax, which makes the protein based COVID vaccine, could not. They had already made JN.1 Vaccine, and it would take them too long to be able to actually change from the JN.1 to the KP.2 Strain. And so they're still going to be coming out in the fall with the JN.1 Strain, whereas the mRNA vaccines will have the KP.2 So again, congratulations to the FDA. I think they made a very wise choice. Uh, I can't wait to get the most current updated FLiRT variant, uh, vaccine. Uh, as soon as it hits the market, I will be past my four months of, uh, vaccine receipt, uh, when that happens to occur.

Chris Dall: So, as our listeners know, we do like to provide an update on long COVID when and where we can. So Mike, what is the latest on long COVID?

Dr. Osterholm: Well, Chris, today I want to cover two recent preprints describing experiments conducted in mice on the role of autoantibodies in long COVID. In both studies, researchers injected IgG antibodies from either long COVID patients or healthy controls into mice and observed differences in their behaviors. One of the studies found that the mice injected with IgG antibodies from long COVID patients had reduced walking distances compared to mice injected with IgG antibodies from healthy controls. The other study found that mice that were injected with antibodies from long COVID patients had an increased sensitivity to pain when exposed to heat, compared to mice that were injected with antibodies from the healthy controls. In this study, the researchers also compared anxiety, motor coordination, blood pressure and heart rate between the two groups of mice, but did not find significant differences between the mice that received antibodies from the long COVID patients and mice that received antibodies from healthy controls. These studies were very well conducted, and the findings are consistent with several previously conducted studies that suggested there could be an autoimmune cause of long COVID. But unfortunately, this still leaves us with far more questions than it does answer, and it doesn't point us directly to any particular treatment.

Dr. Osterholm: This is because, unlike a typical autoimmune disease, which we would expect to see, all patients with the disease have the same autoantibodies with a specific target the autoantibodies observed in long COVID patients vary within and across studies. This study did not answer the question of which autoantibodies cause illness or which long COVID symptoms in humans are specifically caused by an autoimmune response. Still, these results may help inform future uses of mouse models for long COVID research, getting us one step closer to providing some answers to all of those of you who are suffering from this condition. Finally, I again want to mention a National Academy report that we covered in detail in our last episode. The report was titled Long Term Health Effects of COVID-19 Disability and Function Following SARS-CoV-2 infection. And as I mentioned to you all two weeks ago, it was an incredibly thorough and well done report. I urge you all to read it if you haven't already, and we link it again in the episode description.

Chris Dall: It's time now for our ID query, and this week we have an email from Gayle who asked us about some claims made about COVID vaccines by her doctor. She wrote, I asked my doctor if I should get another vaccine four months after the last one, and he shocked me by saying that the developing data shows that the more COVID boosters one has, the greater the risk of immunosuppression in cancer, he said. When you add that data into their lack of effectiveness against COVID, he's discouraging patients from getting any additional shots, including those who would be at high risk from the disease. I was completely taken by surprise. Have you seen any data confirming a greater risk of immunosuppression and or cancer as a result of getting COVID vaccines.

Dr. Osterholm: I'm just as surprised to hear this as you were, Gayle, and I might note that you did share with us that this was a very prestigious medical clinic that you were attending, and this physician was a member and staff there. Unfortunately, this whole discussion is proof of the disappointing reality that misinformation spreads like wildfire. There is simply no evidence to support these claims. The bit about the immunosuppression and cancer may be linked to a 2022 review article, where authors claim that the mRNA COVID vaccines increase risk of both infections and cancer. First of all, the leading author of this paper had no training in epidemiology or infectious disease and had an established agenda to promote lies about vaccines. This article was no exception. The conclusions made by the authors were so harmful and off base they're not worth reiterating, but I can tell you that they were drawn based on bias and extreme misinterpretations of data from the vast database, which harbors its own limitations as a self reported set of information. A letter of concern to the editors of the Journal of Food and Chemical Toxicology said, at best. This article contains several fallacious scientific assumptions, leading to misunderstandings and thus invalidating the conclusions drawn by the authors. Several months later, former Fox News host Tucker Carlson took the misinformation to a larger platform and further perpetuated its misrepresentation of science. Even though the article was published and discredited two years ago, I fear that its poisonous effects linger further. I am disappointed that a physician is not more informed of the life saving preventive medicine of vaccines.

Chris Dall: Now to another item that we've been hearing a lot about from our listeners. A few weeks ago, there was an opinion piece in the New York Times that received a lot of attention. The article, written by Doctor Alina Chan of the Broad Institute of MIT and Harvard, laid out five key points for why the COVID-19 pandemic likely started in a lab. This article has sparked renewed debate over the origins of the SARS-CoV-2 virus. Mike, what did you make of this article?

Dr. Osterholm: Well, first of all, it's really important that we understand one very simple conclusion from all of this. We will never know if this is a lab leak event or a natural spillover event, and I'm convinced of that. Now, I come at this with a long history of being very concerned about laboratory safety and the potential for the kind of lab leak that is being suggested here by many. Again, I noted earlier that I served on the National Science Advisory Board and Biosecurity in 2012. One of the real concerns about the influenza H5N1 work that was being done in the labs was about lab safety, and I was very outspoken about that and wrote a letter to the Nsabb membership that laid out my concerns. That hopefully gives me some credibility as someone who is very concerned about lab leaks. I also having worked closely with SARS and MERS, are very aware of the challenges of working with coronaviruses and when they need to be in a biosecurity level three versus a biosecurity level two. So just in context, let me just say we will never know what happened, but it concerns me that we are so busy debating something we will never prove, which is the source of the virus in terms of how this pandemic began, that we are taking our eye off the ball of getting better prepared for both the lab leak potential and another natural spillover.

Dr. Osterholm: To me, this is such an important lesson that we're missing now just to come back to this particular piece. Doctor Chan surely has a distinguished title in her work. She's a molecular biologist at MIT and Harvard, but she has no experience in infectious diseases or investigation of infectious disease outbreaks. And we've had many individuals who have very distinguished careers in one part of science who what we call the epistemic challenge, meaning that they get out of their lane because they're a PhD or an expert in one area. I think they then are an expert in everything, and in fact, Doctor Chan has no expertise in this area. I remember very well, in 1987 debating Peter Duesberg, a very well known University of California, Berkeley expert on oncogenes, someone very respected who was convinced that HIV did not cause Aids and continued to maintain that to this very day, I could go through any number of other scientists who got out of their lane, and in doing so, they commented on things for which they had no expertise to do. But. So let me just share with you why I think that this article was really I think you're responsible for the times to publish, particularly on June 3rd of this year, the very day that Tony Fauci is going to appear before a House committee on this issue. And the first problem I have is it started out with the title, Why the Pandemic Probably Started in a lab in five key points.

Dr. Osterholm: There is no evidence to say. It probably started in a lab. You know, you could have said it possibly started in a lab, but probably started really infers a sense of, I believe, uh, a kind of authority that is just not warranted. In Doctor Chan's article, she talked about the fact that Wuhan, the world's foremost research lab for SARS like virus, is located where it is in the heart of where the pandemic began. Well, in fact, SARS viruses prior to SARS-CoV-2 are been in many labs in many countries around the world, not just Wuhan. And so from that perspective, you have to be careful to say that that's the case. I often liken what would happen if there was a new tropical disease that emerged in the Caribbean. Where might you likely pick that up first? Probably Atlanta, because that is the transportation hub and where there's going to be modern medical care. But if it happened in Atlanta because of that, everybody knows that leaked from CDC, right. That's an example of the kind of thinking that can lead us erroneously to a conclusion that's not justified by the facts. The bottom line is, I don't think that Doctor Chan's paper provides us with any new useful information. To answer. The question was, in fact, the Wuhan Institute responsible for this virus or not? As I started out, this answer with to begin with, I am certain we will never know the actual source of this.

Dr. Osterholm: So let's move on. Let's focus on how we prevent lab leaks from ever occurring with any virus in any lab. Those are the things that we need to keep our eye on. And the debate about the source is a distraction that keeps us from doing that. And finally, let me just conclude with, uh, reference here that I think you'll all find very helpful. We've linked you to a paper that appeared in the Journal of Virology by a group of distinguished authors, three who actually served on the National Science Advisory Board for biosecurity, and the paper is entitled A Critical Analysis of the evidence for the SARS-CoV-2 Origin Hypothesis. This is the kind of scientific paper that really digs in deep and goes after all the possibilities and in a very objective way, provides you with a roadmap for how to better understand what happened. And so I encourage you to take a look at this. Again. This is linked in the podcast description. Uh, and you'll be able to read the entire article. And I think you'll come away with a much better understanding of what we can say and can't say, or will ever be able to say about what happened in Wuhan.

Chris Dall: Now it's time for this week in public health history. Mike, who are we celebrating this week?

Dr. Osterholm: Well, Chris, we're wrapping up in June here, which also appears to be the LGBTQ Plus Pride month, as well as Men's Mental Health Awareness Month. I think it's fitting to feature a hero who's had a historic impact in both of these areas. John Fryer, born in Kentucky in 1937, was academically gifted, graduating high school at the age of 15. His interest in medicine led him to complete his MD and then residency in psychiatry. During this time, he faced challenges to his own mental health due to the burden of concealing his sexual orientation as a gay man from his mentors and peers. In the 1960s, he joined the team at the George W Henry Foundation, where he provided support and services to primarily gay men who were facing legal difficulties due to their sexual identity. Doctor Fryer's most notable accomplishment occurred in 1972. At the time, the Diagnostic and Statistical Manual of Mental Disorders, commonly known as the DSM, listed homosexuality as a mental illness, specifically a sociopathic personality disturbance. However, activists in and outside the psychiatric community were challenging the notion that same sex attraction was pathological. The 1972 American Psychiatric Association annual Meeting was set to host a panel discussion on this topic. On the panel were members of the gay community who were not psychiatrists as well as straight psychiatrists. What was missing from that Venn diagram, according to the committee, was a gay psychiatrist who was willing to speak on their own experience. However, psychiatrists were concerned about the reputation amongst significant homophobia of their colleagues and concerns about being discredited in their profession.

Dr. Osterholm: Lesbian activist Barbara Gittings was able to convince Doctor Fryer to appear in a disguise. Doctor fryer, nicknamed Doctor Henry Anonymous, spoke on the panel in a large rubber mask oversize suit and used a machine to distort his voice. Doctor Pfizer began his speech by saying, I am a homosexual, I am a psychiatrist. He continued on, citing that he knew there were many LGBTQ psychiatrists in practice and more work was needed to reduce prejudice not only for the public but for psychiatrists themselves. The following year, 1973, homosexuality was officially removed from the DSM, which many attribute in large part to Doctor Fryer's speech. However, it wasn't until 1994, more than 20 years later, the doctor Fryer revealed publicly that he was Doctor Anonymous. Doctor fryer continued practicing as a psychiatrist and professor at Temple University in Philadelphia. His specialty area of death, bereavement, and hospice were tragically needed in the wake of the HIV Aids crisis of the late 20th century. He often served Aids patients in his own home due to their concerns about being seen publicly in the clinic. Doctor fryer died in 2003. He was surely an incredible man with a heart for those who were marginalized by the medical system. He has certainly a public health hero for his work to reduce prejudice and advocate for access to human centered, science based care for everyone. Thank you, Doctor Fryer.

Chris Dall: Mike, we've covered a lot of territory today, but what are your take home messages?

Dr. Osterholm: Uh, stay tuned on H5N1. Uh, the whole time remembering that we will have another influenza pandemic. We have so much to do to be better prepared, particularly in the vaccine and antiviral area. I don't know if H5N1 is going to be the cause of that next influenza pandemic. That statement by itself should not be interpreted as somehow don't take this seriously. At the same time, facts are a hard thing to ignore. And in the information we have today, I think it does raise questions about just what will happen with H5N1 and human illness, I don't know. Number two, we got to do a better job of trying to understand what's happening with COVID, and we're going to try to do our part in the next couple of weeks to really dig into the various sources of information that exist, to help you understand what's happening. In the meantime, I can say that yes, we're still in a very good place compared to the pandemic years that we experienced from 2000 to 2003. Enjoy it. And if you feel at risk for any reason of having severe illness, hospitalizations and deaths, do not be afraid to wear your N95 wherever you go. Don't be afraid. And of course, last but not least, when the new vaccine is available, I urge all of you who have been four months or more under the belt since your last dose or illness to get vaccinated. I can't wait to get mine, and I think that will be a very important tool for me to continue to live every day enjoying life and not being afraid of COVID.

Chris Dall: And Mike, I think you're closing song for today is Broadway inspired?

Dr. Osterholm: Yes. In fact, today we tried to pick a song that reflects the enjoyment we all experienced watching the Tony Awards last week and how wonderful it was to see the entertainment provided by Broadway. In addition, we wanted to be true to our dedication this week and really address what I think would be, by everyone's definition, the worst kind of pain, that of loneliness and what it means to have friends. So we picked the song Old Friends, which was in Merrily We Roll Along, a 1981 American musical with music and lyrics by Stephen Sondheim and a book by George Furth. The show tells the story of how three friends, lives and friendship change over the course of 20 years. It focused particularly on Franklin Shepard, a talented composer of musicals who over those 20 years abandons his friends and songwriting career to become a producer of Hollywood movies like the play in which it is based, the show's story moves in reverse. Chronology beginning in 1976 at the friends lowest moment and ending in 1957 at their youthful best. And so I'm happy to share with you today an abbreviated version of Old Friends, which appeared in Stephen Sondheim's Merrily We Roll Along. Hey, old friend, are you okay? Old friend? What do you say, old friend? Are we or are we unique? Time goes by. Everything else keeps changing, you and I. We get continued next week. Most friends fade or they don't make the grade. New ones are quickly made and in a pinch, sure they'll do. But us, old friend. What's to discuss, old friend? Here's to us who's like us damn few. So, old friend, fill me in.

Dr. Osterholm: Slow old friend. Start from. Hello old friend I want the wind. Where and how old friends do tend to become old habit. Never knew how much I missed you till now. Hey old friends, how do we stay? Old friends? Who is to say old friends? How an old friendship survives one day chums have a laugh a minute. One day comes and they're part of your lives. New friends pore through the revolving door. Maybe there's one that's more. If you find one that'll do. But us old friends. What to discuss. Old friends. Here's to us who's like us damn few. Stephen Sondheim. Well, thank you very much for being with us again today. I hope that we were able to give you the kind of information you're looking for. Again, in keeping with the theme of today's dedication and the closing song, I hope everyone reaches out to a friend. I just to remind the friend how special they are, how important they are, and how much it means to you after you reach out to that friend for your own soul. It's a crazy time right now out there in the science world And, uh, all I can say is, is that being here with you is a place that is very special. Very special. So thank you. And, uh, be kind right now. Boy, would we need kindness. And again, thank you for all of you who support us. We so appreciate you. And it makes us want even more and more to be able to provide you with the kind of information that's helpful to you and your lives. Thank you. Be well. Be safe. Be kind.

Chris Dall: Thanks for listening to the latest episode of the Osterholm update. If you enjoyed the podcast, please subscribe, rate, and review wherever you get your podcasts, and be sure to keep up with the latest infectious disease news by visiting our website CIDRAP.umn.edu. This podcast is supported in part by you, our listeners. If you would like to donate, please go to CIDRAP.umn.edu/support. The Osterholm Update is produced by Sydney Redepenning, Elise Holmes, Cory Anderson, Angela Ulrich, Meredith Arpey, Clare Stoddart and Leah Moat.