Episode 159: Uncharted Territory

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. Hi everyone! Before we get started with this episode of the Osterholm Update, I'd like to ask for a moment of your time during the first month of 2020 for CIDRAP's team of independent, full-time news editors and internationally respected reporters and researchers have continued to publish original articles, news briefs, newsletters, reports, and podcasts reflecting breaking in-depth news of public health importance. In order to continue to report on critical infectious disease topics, we urgently need your financial support. Now is the time to act to keep CIDRAP strong and thriving. A contribution to CIDRAP in any amount ensures that we can expand, improve, and refine our offerings. The infectious disease landscape is ever-changing and with your help, CIDRAP will continue to cover the latest infectious disease threats avian influenza, COVID-19, antimicrobial resistance, the next animal to human disease, and other emerging pathogens.

Chris Dall: Please consider becoming a CIDRAP supporter today. You can donate online at CIDRAP.umn,edu/support and you can find that link on our podcast page. Welcome back, everyone to another episode of the Osterholm Update podcast. Last week, vaccine advisers to the Food and Drug Administration recommended switching the SARS-CoV-2 strain from XB 1.5 to J&J one for fall vaccine formulations. The recommendation marks the third remake for the COVID vaccine since 2022. Meanwhile, an H5N1 avian influenza news Minnesota, Iowa, and Wyoming became the latest states to see outbreaks in dairy cattle. Mexico reported the death of a man from H5N2 and an experimental infection study by the Centers for Disease Control and Prevention found that the H5N1 virus spread efficiently between ferrets, but only through direct contact. These items will be our lead topics on this June 13th episode of the podcast. Other topics will include the latest national and international COVID data and a new report from the National Academy of Sciences on long COVID. We'll also answer an ID query about dairy cattle have been infected with H5N1. Look at this year's hurricane forecast and what it could mean for vector-borne diseases, and bring you the latest installment of this week in Public health history. But before we get started, as always, we'll begin with Doctor Osterholm's opening comments and dedication.

Michael Osterholm: Thanks, Chris, and welcome back to everyone on the podcast family. It's great to be with you again. I hope you are enjoying these early weeks of summer. And to all of those who may be visiting the podcast for the first time, I hope we're able to provide you with the kind of information that you find useful. Also, information that may hopefully lift your spirits on occasion well beyond just the facts of science. Uh, today we have a full house. Uh, as Chris mentioned in the introduction, a lot of topics we're going to cover today. Uh, it's one of the things about being in the world of infectious diseases. You never have to worry about things running out for you to do or say. Today we have a rather unusual dedication for you, one that reflects what I think will happen, not necessarily what has happened, and it's one that I wish I could say it was a dedication to a more lighter note. Our dedication today was really chosen in light of the beginning of this summer. Though many of us look forward to this time of year because of the increase in sunlight, the ability to go swimming in our favorite lakes or outdoor pools. This time of the year can also bring some extreme weather events that cause a great deal of hardship across this country, as well as countries throughout the world. From January of 2023 to September of 2023, there were 183 fatalities that occurred due to wildfires in the United States.

Michael Osterholm: Additionally, there were 18 fatalities in the United States caused by hurricanes in 2023 caused by extreme heat. Unfortunately, the outlook for this year may be even worse. According to a report recently released by the National Oceanic and Atmospheric Administration, which we'll discuss more later in detail. This year's hurricane season is projected to be worse than usual because of the near-record high ocean temperatures and La Nina conditions in the Pacific. NOAA projects that there is an 85% chance that we'll see above-normal hurricane activity this year, with a predicted 17 to 25 named storms, 18 to 13 hurricanes having wind speeds of over 74mph or higher, and 4 to 7 major hurricanes either category three, 4 or 5, with wind speeds of 111 miles an hour or higher. Additionally, the Center for Disaster Philanthropy has predicted above-normal wildfire potential for 2024 due to the warmer and drier than usual weather, and this summer is also projected to be hotter than usual in the United States. This means we may see even more wildfires, hurricanes, and heat-related deaths in 2024 compared to the already very high numbers of 2023. With this in mind, we'd like to dedicate this week's episodes to all of the first responders who are risking their lives to respond to these extreme weather events, and to all of you who will suffer potential loss of life and property due to these natural disasters. Again, I want to thank the first responders who are risking their lives to respond to these extreme weather events.

Michael Osterholm: Thank you for the sacrifices you make to help keep us all safe as possible during these times. And to those of you who live in these areas, our thoughts are with you. Now, let me move on to what is really one of the highlights of the year for me to be able to do this episode in conjunction with the upcoming summer solstice. This will be the last episode of the podcast before the summer solstice, when in fact, we will see the longest days of summer. Today, June 13th in Minneapolis-Saint Paul. The sun will rise at 5:25, set at 9 p.m. we're gaining about 33 seconds a day, but that will soon level off. This next week and for a period of about two weeks, we will see our sunsets at 9:03 in the evening. For those of you who are not here in Minnesota and able to enjoy this wonderful summer light, and you happen to be living in Auckland and by chance just happened to be visiting the Occidental Belgian Beer House on Vulcan Lane. Today your sun rises at 7:31 a.m.. Your sunset is at 5:10 p.m. You're losing about 25 seconds a day, but that two will soon top off in another few days. And then you're going to start getting your sunlight back. So enjoy these long days of summer. Enjoy all the best summer offers us, and all of us can be hopeful that the summer months do not bring disaster to our home.

Chris Dall: We're going to start again this week with the latest avian influenza news. As I noted in the intro, dairy cattle in three more states have been hit by H5N1, and Mexico's Ministry of Health reported the death of a man who was infected by H5N2. Mike, can you put these items in context for our listeners?

Michael Osterholm: Well, let me footnote these comments by saying, I believe the more that I learn about influenza, and I've been studying this virus for almost 40 years, I think the less I know. And this week I will share with you what it is. I think we know what it is we don't know and what it is we have to learn and hopefully very quickly. But first of all, let me address your specific points, Chris. I consider those two items you just noted to be completely separate issues, with the H5N2 case being unrelated to the dairy cattle outbreak we're seeing here in the US. And while I don't want to minimize the tragedy of the man who died after being infected with H5N2, I do want to emphasize that I'm not concerned about H5N2 outbreaks in humans. This is in contrast to H5N1. The man who has had an H5N2 infection began to experience fever, shortness of breath, and diarrhea on April 17th before being hospitalized on April 24th and dying on that same day. He also had a number of other health issues and comorbidities, including chronic kidney disease, type two diabetes, and long-standing systemic arterial hypertension. He reported no known exposure to infected animals and 17 hospital contacts and 12 other personal contacts who lived near him all tested negative for both influenza A and B, meaning that it's unlikely that this virus is being transmitted person to person in this area.

Michael Osterholm: There was, however, an H5N2 outbreak and of a low-path virus in a backyard poultry flock in the state of Mexico that borders the state where the patient lived, which could potentially somehow be related to how he got his virus infection. Regardless, Mexico's Ministry of Health determined that this 59-year-old did not die from H5N2 virus, but rather from septic shock that was a result of his chronic conditions. All of this considered, I am not all that concerned right now about this low path H5 into outbreak in animals or humans at this point. Now shifting over to the H5N1 outbreak, which we're going to talk about in greater detail, there are now 95 affected herds in 12 states at the time of this recording. As you noted, Iowa, Minnesota and Wyoming have been added to this list. These are just the confirmed numbers. I know that there are likely many more farms out there that actually have activity currently in their dairy cattle. Like I've said before, the absence of evidence is not evidence of absence. As more and more states were added to the list, it further emphasizes the need for surveillance and testing among dairy herds, because the only way to understand what's happening with this outbreak is to know how widespread it is. So we can't do that without additional testing. So right now, we can all look to Michigan as the state, which has 25 of the 95 affected herds for the incredible job that they're doing.

Michael Osterholm: The collaboration between the state health department and the Agriculture Department has been remarkable. I think it's safe to say that there isn't necessarily more infection in Michigan. It's just that they're doing a better job of turning over the rocks and finding it. The number of human cases associated with this outbreak remains at three, with the Texas and Michigan cases we detailed last episode and an additional case in a farm worker in Michigan. The two Michigan farm workers were at different farms. All three had mild symptoms and recovered. One, however, did have some limited pulmonary-like symptoms, and it's unclear in terms of was this, in fact more of a classic mild influenza-like infection? For now, I want to emphasize that the threat to the general public, I believe, for H5N1 infection remains quite low. If you're not in contact with infected animals, you really have minimal risk. Pasteurized milk is safe to drink, not a risk at all for influenza. However, raw milk consumption may put you at some risk. I have to acknowledge we don't understand how high that risk could be. We have no evidence right now of cases of H5N1 infection in individuals drinking raw milk, but in fact, time will tell.

Chris Dall: Mike. There was an editorial published last week in The Lancet on H5N1, and I want to get your opinion on it, the editors wrote. There is nothing new in influenza strains evolving, shifting their epidemiological habits and causing infections in people, although human-to-human transmission of H5N1 is rare. Nonetheless, although developments over the past three months may or may not signal the start of a global pandemic, they are at the very least, a pressing and unwelcome reminder of the caprices of zoonotic influenza in our continued collective complacency about it. Mike, do you agree with this statement?

Michael Osterholm: Chris, let me just start out by saying it's really important to understand that no one today, and I mean no one, really knows what H5N1 influenza virus is going to do to human populations. We just don't know. And the reason we don't know is we're in uncharted territories. If all the limited history we have with influenza from a virologic standpoint, meaning that we could actually grow the virus and know what it was that was causing the illness in people. You know, we're talking about literally less than 100 years. And given that we're talking about an influenza virus that's been around for many, many, many millions of years, this is really a very uncharted territory for us to be in. But let me try to add perspective, because I've seen people over the course of the past several weeks take attempts at defining the risk, and they either put us into the camp, “Oh my God, we're all going to die!” You know, “This is this is the end. The pandemic is coming.” Or “Don't worry about it at all. It's not going to cause a problem.” And in fact, we don't know where we're at in that spectrum. I think it's somewhere in the middle. And I'll share why. Well, first of all, we are, as I pointed out, in this uncharted territory, I just got done describing the situation on the cattle where we have 95 herds with 12 states.

Michael Osterholm: If you look at the impact that the virus has had on humans, you have to go all the way back, actually to the 1996 when it first emerged in Asia. And from that time period, in the early outbreak in 1997, in Hong Kong, where there were 18 cases of H5N1, six deaths, all associated with the markets of Hong Kong, then we saw major efforts at that time to depopulate these markets and to also depopulate farms in the Guangdong province, supplying these markets with birds, it was thought, well, this averted a future pandemic. And then in 2003, we began to see activity mount again. And at that time, it was roughly the same virus that we had seen in Hong Kong. Some slight changes from 2003 to 2024. We now have a total of 907 human cases documented of H5N1, including 469 deaths, but that H5N1 virus hasn't been the same over that entirety. When we looked at what happened in the early days of the reemergence of the virus, particularly in Southeast Asia, Indonesia, we saw upwards of 100 to 114 cases a year, with in some cases very limited evidence, but nonetheless evidence of potential person to person transmission, but never more than one generation. And then over the course of the next ten years, we watched the virus activity result in fewer and fewer human cases, such that by the time we got to 2013 and 14, we were talking about less than 30 cases a year in humans, even though there was ongoing activity in the bird population.

Michael Osterholm: In 2014-15, something happened that we still can't explain. There was a marked increase in cases that occurred in the Nile River valley, uh, among duck farmers. And that year we ended up with 145 human cases, of which almost half died. And we thought, aha, this is now the next pandemic. It's coming. And then all of a sudden, it's for reasons again, can't explain. Case numbers just literally disappeared in humans such that if you look at the number of cases that have occurred between 2017 and 2020, for the last seven years, there's only been 33 human cases of H5N1, 11 deaths, quite different than we had seen in the previous history. Now, what happened over the course of the last four years, we've watched a new virus emerge on the H5N1 family. It's now the 2344B clade. And that virus has been remarkable in what it's done in infecting mammal species. We believe that there's anywhere now, depending on how you estimate this 25 to 40 different mammal species that have now been impacted by this virus, animals we had never seen before, infected with the virus. And on top of that, many of these species were devastated by the illness, meaning that these were serious illnesses.

Michael Osterholm: The animal died multi-organ involvement. And we couldn't explain based just on the genetics of the virus, what was happening. Why was this changing? Well, at the same time that we saw these mammal species hit, we saw also increased activity in birds, both wild birds and production birds. We've lost millions and millions of production birds here in the United States, in both the turkey and chicken world, in particular in the chicken world. Also among those broilers, as well as those who are egg-laying chickens. And when you look at that issue, you'd say, oh my, the risk to humans has to be dramatic. And yet, as I pointed out to you, we've seen very little activity. Now, I have lived with H5N1 in my research work and in efforts at our center, literally dating back to 2003. I was in Southeast Asia, worked on H5N1 in villages throughout a number of countries. I was on the National Science Advisory Board in Biosecurity in 2012. We surely saw this major activity in animal species, but we saw virtually no activity in swine. And in addition, research looking at H5N1 and swine demonstrated that while they could be infected and cause mild illness, there was very little evidence of any kind of animal-to-animal transmission. A very important part of a virus picture giving us a sense of impending possible pandemic.

Michael Osterholm: Well, where does this all lead us to? Here we are now. We've had three cases, as we've talked about in humans, and given all the widespread transmission out there, you'd say there probably are a number of more. That could be we could have many milder illnesses. To date, we haven't seen that happen. Uh, we've had over 80 people tested who have been in the proximity of the dairy or the individuals who were infected. Aome of them, in fact, were people who had flu like symptoms. All of these have tested negative to date. We know that at this point, the milk situation is one where it likely is causing transmission to animals on the farms, like cats who are drinking the raw milk. But we have no evidence of this infection in humans. Now, as I pointed out earlier, absence of evidence is not evidence of absence. Could there be more human cases? Yes. Could there even be more animal cases? We're missing, yes. But are we missing an emerging pandemic influenza-like illness around the country? And I don't think that's the case. Even where we have seen communities with spikes in wastewater activity suggesting influenza virus, at least influenza A is surging in that sewer system, we don't know. Is that due to human risk and human infection, or is it due to the fact that dairy operations or meat packing operations are contributing to the waste stream in that sewer system and bringing it in through the animal population? We just don't know.

Michael Osterholm: But we don't see evidence right now of clusters of severe illness and individuals. We would pick that up. I'm very certain of that. It wouldn't necessarily mean we had all cases surveyed, but we would pick that up. We're just not seeing it. So from where I sit, I look at this and say, we just don't really know. We don't know what's going on right now. I still am very much aware of the history that we've lived with, with this virus and realizing it's a different H5N1 today than it was 20 years ago, but I just don't see the evidence of any genetic changes in this virus that would support that. We have an impending pandemic. Now, when some people hear me say that, they say, oh, you are basically downplaying this and we need to get ready for a pandemic preparedness response. Well, all I can say is I hope that over the course of my last 40 years, I bought a little bit of opportunity here since I have been ringing the pandemic bell literally for almost that entire time. And I would be the first to say we need to be much, much better prepared for the next big pandemic. So what kind of information can we glean that will tell us where we're going into the future? So last Friday, the CDC scared many people initially with this, uh, report that they use the H5N1 virus from the human case in Texas, and it caused severe illness and death in ferrets.

Michael Osterholm: Not only do they say that all the ferrets in this study died as a result of being infected with this virus, but that it actually had some efficiency in spreading between ferrets via what they call respiratory droplets. The context that was missing in this report was the fact that if you take immune naive ferrets, meaning they've not previously seen influenza viruses, this is not an unusual finding to see this kind of outcome. It's of note that if you actually do these same studies using ferrets that have previously been infected with an influenza virus, that they get a very, very different results, very few become seriously ill and die with limited evidence of transmission. So to me, the results from the CDC study don't really give us any more guidance. I will say that I wish that the CDC had provided more context in this report discussing the implications of using immune naive versus previously influenza-infected ferrets. Also, just as a side note, not really directly related to these studies, but they keep talking about respiratory droplet transmission and they even make a note of it being the primary mechanism of transmission. Boy, we've been down this road so many times.

Michael Osterholm: Come on, CDC, please get your act together on this issue. It's not just respiratory droplets, it's also aerosol. It's a small particle airborne transmission. And I hope your future reports detail that. So if we look at that and we look at the sequencing data, my conclusion is we could. For this particular situation continue in the animal population where we've seen two, three, four, four be now in its second and third year of infection in wild birds, we're seeing more and more immune. Wild birds, we're seeing much less impact of this virus after it wiped through the first year or two of these animal populations. And maybe this will be like 2012 or 2015, and we will end up one day looking back and saying, what was that all about? On the other hand, we could have a reassortment event tonight where now, because we have these mammary glands on bovine that in fact have both two three and two six receptor sites where we could get a bird virus in a human virus in that same udder and result in a new virus. We could have a new pandemic virus emerge tomorrow. So please do not take my comments as saying we're not in a potentially serious situation. But at the same time, we have to be honest with the public and say, we don't know. I guarantee you, if we continue to say we're just on the edge of a pandemic and basically gin everyone up, and then a year or two from now when we don't have that happening, we will again have another loss of credibility in the public health, that armamentarium.

Michael Osterholm: And I think that by itself could be a real challenge. And none of us want to get caught surprised about what could happen. But let me just clarify one last thing. When we look at the issue of testing, which I've heard several prominent people say, if we don't test, basically we're on the verge of a pandemic. There is nothing that's going to stop a pandemic by more testing. Now, I'm an epidemiologist. I want more testing. Data is my kind of secondary four-letter word love, then data. And I want more. But knowing more about what's happening isn't going to necessarily stop this from emerging into a pandemic. I don't understand that. So let's be clear with the public, what can we do? Well, it'd be great if we had vaccines that were effective against this virus that actually prevented infection, prevented transmission of the virus. But we don't have them. We're going to have to acknowledge that if a new pandemic strain of virus emerged, it's very likely we would have to start from scratch. Making the new virus vaccine, much like we did in 2009 when we had an H1N1 vaccine, and H1N1 emerged as a new virus in Mexico, and we needed to have a new vaccine, I think that could very well be the case.

Michael Osterholm: I think what's really important to note here is that we have to better understand how is this virus being transmitted in the bovine population. I'm convinced that, yes, there was a spillover from an avian species to the cattle. And that's not surprising. If anyone's ever been in a dairy operation and seen how the animals are fed, how that often attracts birds that are in the same feeding areas as the cattle. It's not surprising. But in fact, we have more or less inferred that the only spillover event was that which occurred in the panhandle of Texas, which I think is absolutely not true. I'm convinced over the next several days you're going to find more information coming out on farms that likely had a similar spillover event in other areas of the country. These were farms that did not have any importation of cattle from anywhere in the Texas Panhandle area. Therefore, it could not be accounted for by first or second-order movement of animals. There is the possibility in some states like Michigan where we have more data, we will find that workers going between farms pose some biosecurity risk where they took the virus on clothing, boots, whatever, and that's where the possibility. But I think that what was going to really come down to is that a number of these farms actually had primary infections from wild birds, just like we saw with what happened in Texas.

Michael Osterholm: Now that's important. Why? Because if it's about animal movement, then we can shut that down. That can be taken care of. That should stop the epidemic among these cattle from spreading. But if the wild birds are continuing to contribute, then we've got a whole different situation. And then we have to figure out what that means. And then, of course, biosecurity within workers in states, regions of the country need to be really improved. And right now that's a difficult thing to do on these farms. Why? Because most farmers do not want public health on these farms. They don't want to see this happen. I'm already aware of families that have been torn apart who are owners of dairy operations. Were some of the family members want to report illness in their animals and others say, no, don't look what it will cause us if that happens. And so we also have to understand that public health is not holding back from trying to do testing. And that, again, is where I see some of the figureheads out there commenting on we're not doing enough testing, as if somehow public health is just not on top of it. We're not getting permission to go on these farms, just simple as that.

Michael Osterholm: And that's really a big issue. So stay tuned. I hope these. Comments offer some perspective. I know they're kind of all over the map in terms of the issues going on. I don't know where we're at. I don't know, we're somewhere between yep, this could be a pandemic virus tomorrow. And this could also be in two years from now, a story we all look back on and ask and wonder how we got there. What happened? Why did it do what it did? But in the meantime, we have to continue to use a science-based approach. What do we know? What do we not know? How can we stop this? Get us data, epidemiologic traceback data on why certain farms are getting hit. Is it cattle movement? Is it likely wild bird exposure? Is it movement of the virus because of workers and biosecurity? So, Chris, I think in conclusion, let me just say that we are in this uncharted territory. I don't know what's going to happen. I do know this is unlike anything we've had in the last 60 to 70 years with influenza virus in the world. We do need good data on what's happening on these farms. Is it likely animal-to-animal transmission being brought in from outside the farm? Is it in fact a bird contact and continued spillover? Or in fact, is it workers? That's what we've got to find out.

Chris Dall: Now to COVID-19 before we discuss the vaccine recommendations. I think many of us at this point are expecting to see an uptick in cases as the FLiRT variants, Cp2 and CP3, become the dominant variants. Mike, are we seeing any signs of that yet happening here in the US or elsewhere?

Michael Osterholm: From the national data we have available, we are seeing early indicators of rising cases, with CP2 and 3 now accounting for an estimated 22.5 and 25% of cases, respectively. I'm not overly surprised, although the viral activity levels in the national wastewater surveillance is currently low. We are seeing certain collection sites reporting high concentrations with massive meaning 28% to 157% change within the last seven days. A majority of those concerning areas are localized in the Western Census region, including California's Bay area, Salt Lake City, Utah, and Hawaii. Those areas in particular appear to be driving case numbers in the region. Several collection sites across Florida are also now reporting higher wastewater levels, along with several other hotspots scattered throughout the US. I'm not sure what this all means. As we've discussed over the past several podcasts, we only have limited surveillance data available to us now. By far, probably the most reliable information we have is that around deaths. If you look at recent deaths and look at the week ending April 13th, there were 550 deaths in this country. If you look at April 20th, 478 April 27th, 404 May 4th, 398. And now the most recent updated information is 303 deaths for the week ending May 11th. That's about 43 deaths a day. Now, just to remind you, from the first week of June in 2022 through March of June 23rd, we were actually averaging over 300 deaths a day. So while any death is a tragedy here, in fact you can see a great improvement in what's happening. So we also have to be careful when we talk about the numbers of cases increasing. And what does that mean? Because you can double or triple a small number and it's still a relatively small number. We're not doubling and tripling large numbers.

Michael Osterholm: And that's I think what is still good news. So, what kind of data can we look at that will give us a sense of where we're going in terms of COVID? Well, if you look around the world, remember it's the southern hemisphere's winter. I just pointed that out, you might say, in the light session with our dear colleagues in Auckland. But if you examine the case numbers there in particular, and look at the number of reported cases, realizing that these may in fact be underreporting by some substantial amount, you can see that for countries like Australia and New Zealand, they did see an increase in cases in the country over the last several months. For example, look at Australia. They were reporting about 20,000 cases a week through the period up through late winter or early spring. And then that increased to 40,000 cases. But now it's back down at 19.6 thousand cases. Same thing has happened with New Zealand. They had less than 20,000 cases reported a week. And then in April and early May they saw a spike went up to 80,000 cases. But now it's back down at the lowest level it's been since the beginning of the pandemic. So, in fact, the data from the Southern hemisphere would suggest that there may be some seasonal spike in cases, but it will be relatively low compared to anything we've seen in the past. So at this point, I will just say that yes, we have to stay tuned with these new variants. We'll talk more about that as it relates to vaccine. But in fact, I think we're still in a pretty darn good place. And I don't see at this time a major summer surge of any kind occurring here in this country.

Chris Dall: That brings us to the recommendation by the FDA's Vaccines and Related Biological Products Advisory Committee to update the COVID vaccine with the JN.1 antigen. The vote was unanimous, but there was also some discussion over whether to include the JN.1 offshoots. Mike, what are your thoughts on where they ultimately landed?

Michael Osterholm: Yes, Chris. In fact, VRBPAC did vote to switch the antigen with the currently available updated COVID from X.BB1.5 to JN.1 a clear-cut choice given overall variant trends. After the vote, however, VRBPAC asked their committee members to further weigh in on whether to include JN.1 sub-variants in the vaccine formula, which would aim to target the rising KP.2 and KP.3. As we just discussed, the variants now account for around 50% of the cases in the US and are gaining traction due to their increased fitness from added spike mutations. Although KP.2 and KP.3 are overall very genetically similar to the parent JN.1, these mutations still represent enough immunologic distance to cause problems. That is why it was disappointing for me to see the FDA proceed with recommending a monovalent JN.1 vaccine, as opposed to a multivalent one that accounts for JN.1 plus these variant newcomers, or a K.P2 monovalent. Either of these alternatives would have offered enhanced protection against variants with F.456L mutation, which we know offers growth advantage. We saw this when the XBB lineage picked it up, and we saw the rise of “Flip” variants. Despite input and pushback from the scientific community, the group chose to focus only on the already out-of-date JN.1. According to the data presented in the discussion, a JN.1, a monovalent will provide some but not the same strength of protection against variants and presumably the descendants that continue to evolve.

Michael Osterholm: One of the central factors in this decision appears to be a dialog with Novavax, in which the company stated they would not have sufficient time to pivot to a new formula, given the extended production time needed to manufacture their protein-based vaccines in time for a fall 2024 rollout. Although this concern is valid, they are not the only vaccine manufacturer in the market, and the FDA could have made an alternative formula recommendation to Pfizer and Moderna, who stated they could still pivot. They had time. On one hand, having different formulations available may be confusing to a vaccine seeker, but on the other hand, this option could provide flexibility and more robust protection against what lies ahead. Simplicity isn't always the best way forward, and I'm not convinced that just focusing on a JN.1 was the right choice. I believe that the FDA really continues to push their position that, in fact, we want a single seasonal respiratory virus vaccine, notably one in the fall for influenza, RSV and COVID. I think that that's the wrong approach. I think that we still are going to be in a position with COVID vaccines, with potentially, at least in the short term, looking at new updated vaccines every six months, not once a year. We'll have to wait and see. But I think that they missed an opportunity here to provide better protection to the public.

Chris Dall: Turn now to long COVID. Last week, the National Academy of Sciences released a major report on long COVID that provides an overview of the current status of diagnosis, treatment and prognosis. What did we learn from this report?

Michael Osterholm: Chris, this was a very thoughtful and well-done report, and we will link it in our episode description for listeners to read. The authors of the report form conclusions on nine important areas of long COVID research diagnosis, epidemiology, health effects, functional impact, and risk factors. Long COVID in children and adolescents. Management, disease course and prognosis, health equity and similar chronic conditions. I'm going to provide a very brief summary of each of these conclusions. But again, I urge those of you who are interested in this to take time to read the report. At the very least, read the full text of the committee's conclusions, which can be found in pages five through 13 of the report. I'll start with the first areas that the report covered, which is diagnosis. The report concluded that because SARS-CoV-2 infection has been so widespread over the course of the past several years, and because of the affordability, availability, and accessibility of testing has varied that a formal diagnosis of SARS-CoV-2 infection should not be required for a consideration of a diagnosis for long COVID. It concluded that a majority of those who have long COVID experienced mild illness during their acute infection, but only because a majority of those infected with SARS-CoV-2 did have mild infections. More severe illness and hospitalization still was associated with a much higher risk of developing long COVID than mild COVID.

Michael Osterholm: The next two areas, health effects and functional impact and risk factors, did not have particularly surprising results. The report found that long COVID was associated with more than 200 different symptoms, and that those symptoms can have a significant impact on daily living and working for six months to two years or more. Many of our listeners are already well aware of this because they themselves are struggling with this. The next area that the authors covered was long COVID in children and adolescents. The report found that while children and adolescents can and do get long COVID, they tend to have a better trajectory for recovery than adults. The report also noted that because children are generally healthier than adults at baseline, long COVID symptoms may present a more noticeable change from their normal state than we see in adults, leading to significant physical and mental impacts that can worsen children's performance in schools, sports, and other activities. The next area of the report covered was disease management. Sadly, as most of us already know, researchers stated that there is currently no curative treatment or disease-modifying treatment available for long COVID, though there are many in development. I surely wish we had more optimistic and positive information to share in this regards to this issue. In regards to disease course and prognosis, the researchers found that many individuals report improvement in their long COVID symptoms at 12 months.

Michael Osterholm: Data after that point is quite limited, but early research suggests after 12 months, recovery from long COVID slows significantly. The report also found that the same health equity concerns we have often discussed on this podcast inequitable access to vaccines, treatments like Paxlovid under-diagnosis of SARS-CoV-2 and long COVID by health care providers, access to long COVID rehabilitation clinics, etc., etc. all create inequalities in those who experience long COVID and what their path to recovery looks like. We need to continue to advocate for more equitable access to health care across the board in order to see improvements with this issue. Finally, the researchers concluded that COVID shares many of the features of other chronic conditions, ones that we've discussed often on this podcast. More research is needed to understand the mechanisms and management of these conditions, which may also inform our understanding of long COVID. The bottom line is that long COVID is complicated, and we still have far more questions remaining about long COVID than we do answers. And as always, I want to remind our listeners who are suffering from long COVID that we see you, we hear your concerns, and we're going to continue advocating for you and covering this issue.

Chris Dall: It's time now for our ID query. We're going to go back to H5N1 for this one. Lee wrote to us asking this question, why on earth are we not culling infected dairy cattle herds? Reassortment seems inevitable in these conditions. So, Mike, this is a very good question. Do you have an answer? And also, maybe you can explain what is meant by the term culling, which some of our listeners might not be familiar with.

Michael Osterholm: Well, thank you for this very thoughtful question. And it is one that's getting asked a lot right now. When we talk about calling an animal population, it usually refers to euthanizing the animals for the purposes of reducing their likelihood of spreading a disease, or they're in fact suffering in such a way that they will not have productive lives thereafter. And in a sense, you're putting them out of their misery. Most often when we talk about culling, we talk about that in the context of poultry, where we know that once an age 5 in 1 virus gets into a poultry operation, it spreads quickly through the entire operation. So even though a few birds may be initially infected, it could be a matter of just days before we see thousands of birds infected. So in that effort, in an attempt to minimize the amount of new viruses generated, these animals are, in a sense, culled. There's also a very important USDA program tied to that culling operation, where farmers are reimbursed for actually, in a sense, culling out these animals so that there is an additional spread of the virus. Now, what's different with bovine is the bovine don't get severely ill and die.

Michael Osterholm: They recover. And so therefore there may be a temporary period where they're out of production and theoretically could get infected with a human virus and a bird virus at the same time with the reassortment event to occur. But in fact, it would not be a practical effort in both either stopping virus transmission or in in fact, what it would do to the actual agricultural operations of the dairy industry to suddenly cull thousands and thousands of animals that are going to recover within days to weeks. So if, in fact, this was an illness that was almost guaranteed to kill the animals and it was spreading on the farm, then in fact, that's when you would want to consider this idea of culling. But in the meantime, uh, it really is not one that is going to be the practical practice or in theory, as the ag industry would obviously literally shut all public health down in terms of coming on farms, if they thought that an animal that they had temporarily out of service for several weeks was now going to be put down. And this is just simply not going to happen.

Chris Dall: Now to some other infectious disease news. And this takes us back to your dedication mic. And as you noted in that dedication a few weeks ago, the National Oceanic and Atmospheric Administration predicted above-normal hurricane activity in the Atlantic basin for this year's hurricane season, which stretches from June 1st to November 30th. Obviously, that means many parts of the southeastern and eastern US could be affected in many ways. But let's look at one aspect of it. What will it mean for the spread of vector-borne diseases?

Michael Osterholm: Well, Chris, this is worth an entire several program episode, to really get into the background of this, but suffice it to say, remember, the most dangerous animal in the face of the earth today is still the mosquito. It kills more people, more animals than any other animal species as such. And while you may not think of that as an animal, in a sense it really is. What is it that dictates the presence of mosquitoes and what populations they actually make up in a community? Little mosquito activity to a lot of mosquito activity. Well, it falls into temperature, amount of rainfall, precipitation into humidity and the potential for massive flooding. And each of those are by themselves independent variables and yet linked because if more rainfall occurs often with temperature changes, etc., humidity. And one of the things that's often missed is that in vector control programs, the effort to actually eliminate those mosquitoes that cause disease very dramatically by the type of mosquito. Take, for example, the Aedes mosquito, Aedes aegypti and Aedes albopictus. Aedes triseriatus all different mosquitoes in the 80s family. But they have one thing in common they like to reproduce themselves close to humans. They want to find dark, very closed spaces, uh, plastic wrappers thrown in ditches, garbage. They want they want to find containers of water that are basically not exposed to sunlight. Oftentimes, the Aedes mosquito will literally not fly across an open field. It won't fly across a city street. And so therefore, our control measures with 80 are all about how do you improve the living conditions of people where they're at eliminating these breeding sites? Today we live in a world of plastic.

Michael Osterholm: It has had a dramatic impact on the garbage of the world, where rainfall, when falling on it, creates these ideal little pockets of water for a mosquito to breed. Areas where water gets into what we call a tree crotch and they grow right there. So again, when we try to control these diseases, it's very different. And such as the kind of rainfall events we think of with other mosquitoes are not the case for. And let me give you that example, Culex, Culex tarsalis, which is one that transmits Western encephalitis, can transmit West Nile virus, that is one that lives more on the edges of larger water bodies, where there are the kind of organic matter that they can grow into. They love to be along kind of quiet little potholes of water. They are the most amazing fliers. I've personally been involved with. Studies where we've radiolabeled Culex mosquitoes in the Twin Cities area here, released them on a given night some 20 miles south of the Twin Cities metropolitan area. And with the prevailing winds. The next morning, we were picking up these mosquitoes in the center of Minneapolis Saint Paul, 20 miles away. So unlike 80s, they're very, very different now. They are much more affected by the kind of major rainfalls that leave bodies of water and for some period of time, allowing them to breed. And then we get into Anopheles mosquitoes again, very temperature sensitive in terms of whether they, in fact the malaria parasite will grow in them. Again, very different breeding sites.

Michael Osterholm: And so when we talk about these kind of meteorologic events, we have to be careful, understand which mosquito species are we talking about. For example, with many of the major flooding issues, it actually washes out the mosquito population for some time so that you actually see a reduced amount of activity from mosquito-borne diseases in recently flooded areas because it washed them out, even storm sewers. We know that in the early days of West Nile, in this country, in the northeast, where there were experiencing a drought that summer, we saw one species of mosquito doing very well in the storm sewers of cities where there was no rainfall for some time, nothing to wash out the mosquito population. And so in the little bodies of water hidden underneath the drains in the cooler environment underground, they were breeding all kinds of these mosquitoes that carried West Nile virus. So the point just to make here is it's the vector control is not simple. It's complicated by the different types of mosquitoes, where they live, how they live, how they move, who they infect, why they infect, etc. and so may at some point we can do an entire show on this and get into each of these different species of mosquitoes. The final one I do want to cover, though, is because I hear this all the time, and this is about tick-borne diseases, and we are seeing substantial increases in tick-borne diseases, particularly in North America. But this is often attributed to climate change. And it's not that climate change can't mean that a warmer winters in the northern states.

Michael Osterholm: Allows for a higher survival of ticks. That can happen. But what really has impacted tick populations has been the cessation of fire. Prior to the first Europeans settling in this country, we saw wildfires consume thousands and thousands of square miles of forest each and every year. And as a result of that, and the Native Americans used this to their advantage, both in terms of attracting larger herding animals and to newly burned areas with this luscious growth that reoccurred afterwards, etc., that in fact, fire played a critical role in controlling the kind of plant life and even animal populations that occurred in given areas. The white-footed mouse is an example of this, where today we see its proliferation in many parts of the northeast, the Midwest, etc. in areas that have not been burned in over 150 years. And where now the successional forests are very different than it would have been if these fires had continued. And they now really favor habitat and animal populations that favor the tick. And so I think we have to be very cautious about understanding with tick-borne diseases, how much is climate and how much is just we in our suppression of fire have resulted in kind of environment where ticks do much, much better. So on a whole this is a complicated area, but one that climate change is surely going to have an impact on in terms of the mosquito-borne to some degree, tick-borne diseases. And how that will all play out is still really not clear.

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

Michael Osterholm: This week we're celebrating the birth of a pioneer in maternal and child health. On June 7th, 1909, Virginia Apgar was born in Westfield, New Jersey. Now, some of you may recognize that last name already, but I won't spoil the ending yet. Virginia knew she wanted to be a doctor at a young age. She realized that dream by attending Columbia University and receiving her M.D. in 1933. Initially interested in surgery, a mentor encouraged her to pursue a newer field of medicine, anesthesiology. She conducted her fellowship at the University of Wisconsin and was the only woman in her program. In 1938, she returned to Columbia University's College of Physicians and Surgeons to direct their newly formed anesthesiology department as a clinician and a faculty member. She was in fact the first female faculty member to reach full professor at Columbia University. Doctor Apgar had a special interest in maternal anesthesia and its impact on the newborn. Since the beginning of the 1900s, infant mortality rates in the United States have been steadily improving. However, the rates of death within the first 24 hours of life remain consistently high. Apgar sought to develop a system that could help determine which babies were at highest risk, and may require resuscitation. This standardized scale is still used today and is known as an Apgar score. It provides a rapid assessment of appearance, pulse, grimace, activity, and respiration. Scores are taken sequentially to understand how the newborn is adjusting to the first stages of life, and help inform any resuscitation or support measures to take. I know it's something my daughter in neonatology is very familiar with. Doctor Apgar continued her legacy in public health by achieving her master's in public health from Johns Hopkins in 1959. She furthered her research on birth defects and childhood disabilities, and joined the March of Dimes National Foundation as the head of the Division of Congenital Malformations. Doctor Apgar was a prolific writer, teacher, and researcher who never retired, but remained active in her pursuits till the day she passed in 1974. 20 years later, in 1995, she was inducted into the National Women's Hall of Fame, a well-deserved honor. Thank you, Doctor Apgar, for all your incredible contributions.

Chris Dall: And now, just a quick note to our listeners as we near the end of our fiscal year, I'd like to take a moment to remind you all of how critical it is to have access to the type of high quality, authoritative, and unbiased scientific information that you get from the Osterholm Update and from CIDRAP. And it's all free. No paywalls or subscription fees. A contribution to CIDRAP in any amount ensures that we can continue this podcast and all the work we do to inform and educate the public about infectious diseases. Again, you can find that link to donate on the podcast page. Mike, is there anything you'd like to add?

Michael Osterholm: I just want to thank all of our listeners who do support this activity. You support an entire team of people that work hard every two weeks to get you the latest and most important information on these podcasts, and of course, our everyday activities with the news team, including Chris, who's a very important member of that team. And we do believe it's very important to make this information free of charge with no paywalls. I just find that unacceptable that today the public should have access to independent, authoritative and up-to-date information that they can use to make decisions for their own life. So we thank you very much for your support and hope that we can continue to provide this service to you.

Chris Dall: Mike, what are your take home messages for today?

Michael Osterholm: First point really relates to a comment I made at the beginning of the podcast. I really do believe there are moments when I feel like I know less about H5N1 today than I did 20 years ago, and it really requires a sense of humility and a sense of honesty to say we're in uncharted territories. I don't know what's going to happen, but I can tell you anyone who tells you they do know what's happening and what you need to do about it. Be careful - they may have a bridge to sell you, too. Clearly, we have to be prepared for the next pandemic in ways we were not prepared for COVID. But we have an obligation to the public to let them know what we know and don't know, and not to lead them to believe that a pandemic from this virus is going to happen tomorrow. It may, but it very well may not. And that is a hard message to get across, particularly when you're advocating for more resources to better prepare for a future pandemic, which will occur. As I've said many times, the pandemic clock is ticking. We just don't know what time it is.

Michael Osterholm: But we don't know what H5N1 is going to do to humans yet. We just don't. In terms of my second point, COVID, yeah, we will keep an eye on it. I still think we're in the best place we've been since the pandemic began, but we understand that the variants can throw curveballs at us in a heartbeat. So we will continue to monitor this closely, both here in this country and around the world. To give you the latest and best information, I will say that right now, prepare yourself. When the new COVID vaccine comes out this fall, I urge you to get it. It may not be exactly the variant that I wanted in the vaccine mix, but it still is going to provide additional information. And last but not least, we will continue to follow all the challenges that we see with climate and all the potential catastrophic events that may occur over the course of this next few months, and keep you alerted as to what that may mean for infectious disease issues. Uh, right now, again, an unknown area, but one that we have to be very concerned about.

Chris Dall: And finally, do you have a closing song for us today?

Michael Osterholm: Yes, Chris, I do have one. And it's one that is all about something hopefully positive in this world that right now gives us a challenge in terms of trying to find. This is a song by American singer Kacey Musgraves. It was released on her September 10th, 2021 album Star Crossed. It's one that she wrote as part of an inspired personal journey of heartache and healing following her divorce, and she describes in this song really the importance of looking up and knowing we can get through and knowing that there can be better days ahead. And right now, I think that's a very, very important perspective to have. Here it is. Keep Looking Up by Kacey Musgraves grew up in the sticks where there ain't no light. But the stars were big and bright. If they told me no, I would always wonder why. But I tried to be good and keep my head down. But there was too much sky around. And my daddy said keep looking up. Don't let the world bring you down. Keep your head in the clouds. Keep your feet on the ground. Keep looking up, keep looking up. They came to me in different ways. Beautiful and strange. I've seen fire burning in the sky. Things that I can't explain I've seen truths step into the light.

Michael Osterholm: And true love turn into pain. But I keep looking up. Won't let the world bring me down. Keep your head in the clouds and keep your feet on the ground. Keep looking up, keep looking up. You never know what you may find. I've seen strange things happen all the time. Keep looking up, keep looking up. Oh, keep looking up, keep looking up. Kacey Musgraves. Well thank you again for being with us. I hope this session was informative. I surely shared with you a wide range of thoughts regarding H5N1. Uh, we're going to be talking about this topic for some time to come, and I hope my comments on COVID gave you some perspective on understanding where we're at, uh, but that we're also looking at where we're going. And all I can say is, I can't wait to get that next booster dose of vaccine. So thank you. I hope you have a wonderful summer solstice. Enjoy this summer light out here. And, uh, thank you so much for being with us and we appreciate you very, very much. Be kind, be kind and keep looking up right now. We need that so badly. It's a it's a tough world, but we can make it better. Keep looking up. Thank you.

Chris Dall: Thanks for listening to the latest episode of the Osterholm update. If you enjoy 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, Leah Moat, and Clare Stoddart.