Episode 162: Class is Not Dismissed

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 Dahl, reporter for CIDRAP news, and I'm your host for these conversations. Welcome back, everyone, to another episode of the Osterholm Update podcast last week. As many of you undoubtedly know, the White House announced that President Biden tested positive for COVID-19, and it's really no surprise. President Biden is one of many Americans who are now experiencing SARS-CoV-2 infections amid a summer surge of cases, being driven by the FLiRT variants. He is vaccinated and boosted, and he is experiencing mild symptoms. A white House spokesperson said of the president in a brief statement that seemed to highlight how COVID in 2024 is being characterized. And of course, with President Biden's subsequent decision over the weekend to abandon his reelection campaign, his COVID case is now a little more than a footnote. But this is not a political podcast. So the latest summer COVID surge will be the lead topic we'll be discussing on this July 25th episode of the podcast. We'll also look at some recent long COVID news, provide an update on the latest H5N1 developments. Answer an ID query about Paxlovid access, and we'll bring you the latest installment of This Week in Public Health History. But before we get started, we'll begin with Doctor Ostrom's opening comments and dedication, which will focus this week on another big event that happened over the weekend.

Michael Osterholm: Thanks, Chris, and welcome back to all the podcast family. It's great to be with you again. Uh, it's hard to believe it's already been two weeks since our last podcast. And for those of you who join us for the first time, I hope we're able to provide you with the kind of information that you're looking for. If you're new to the podcast, you may have heard about it, and if you have, you've probably heard it. It's an eclectic mix of a lot of different things that we try to tie together here, but at the heart of it is to try to give you the kind of science information delivered in a common sense way that can help you understand what's going on in the world of public health and how it impacts you. I also want to thank again, all of you who have contributed recently to supporting the CIDRAP activity around this podcast. As I've said time and time again, I am committed to the Center's committed to providing all of our information free of charge. We never want to have anything behind a paywall and therefore needing that kind of support to keep it going. We will do everything to make sure you have instant access to the latest and the best information. Now, Chris, it was an eventful weekend, to put it lightly. There was, of course, the breaking news alerts and updated election projections spilling out of Washington, D.C., with reporters reflecting on themes of honor and legacy.

Michael Osterholm: But a bit to the north in Cooperstown, New York, there was a different kind of discussion around honor and legacy taking place this past weekend as four baseball greats were inducted into the Baseball Hall of Fame. I will warn you now that this opening is probably going to be a little bit tough for me. So if I get a little emotional through the course of it, you'll understand why. Now, Joe Mauer, a hometown hero from Saint Paul, Minnesota, and one of the best players ever to don a Minnesota Twins uniform or for that matter, any baseball uniform, was among those honored over the weekend. Joe is known to all of us here in Minnesota as a man of humility and class. Sure, he earned a Most Valuable Player award, won the Gold Glove Award three times, was a six-time all-star and three times American League batting champion. But the real story of Joe Mauer has always been his character. In light of his Hall of Fame induction, Joe's teammates recently reflected on what made him such a great baseball player. Aside from his dedication and discipline, each of the responses acknowledged what really made Joe Mauer great was his quiet leadership, the way he treated everyone from the rookie to the superstar and his positivity in the clubhouse, as well as professionalism on and off the field. I happen to have a very dear friend who is also a very dear friend of Joe Mauer and actually was in Cooperstown for his induction this past weekend.

Michael Osterholm: And this individual shared with me his observations on Joe. He said, Joe is a kind, sweet, gentle, generous soul who just happens to be one of the most skilled baseball players in history. Much more than this is his unassailable character. In all my years with him and his extended family, I have never heard one of them say an unkind word of anyone. The speech Joe gave at his induction ceremony proved that retirement hasn't changed him. In his speech, Joe spent more time thanking his mentors, family, coaches and teammates than he did reminiscing on his accomplished career. He said his late father and grandfather taught him that being successful takes more than just athletic talent, that his mom taught him that it was more important to be a good person than a good athlete. And his high school baseball coach taught him about patience and control in baseball and in life. As someone who watched him play throughout his career, I can say that Joe Mauer passed all those lessons on to all of us, the fans of the Minnesota Twins and anyone who's ever loved baseball. He is a huge source of pride for our state, and a major source of inspiration for anyone that has gotten to know him. Now, maybe more than ever, we need people like Joe Mauer in our world, people who prioritize humility and teamwork over ambition and self-interest, who remember where they're from and honor those that helped them reach success, and who earned respect by showing it to others.

Michael Osterholm: I am so grateful to him and all of you who show up in our lives with similar values. The Joe Mauer's of the world may not always get their recognition in Cooperstown, but they do make our world a much better place every day. Thank you Joe. Let's move on now to, uh, where we're at with our light. Uh, very important to this podcast. We do keep track of light here. Uh, so for today, July 24th, 2024, the sunrise in Minneapolis is at 550. Sunset at 848. That's 14 hours, 57 minutes, and 47 seconds of precious sunlight. However, we are beginning to accelerate that loss of sunlight. Today we will lose two minutes and five seconds. But our dear colleagues in Auckland at the Occidental Belgian Beer House on Vulcan Lane, we are so happy to report to you that although your sunrise at 725 sunset at 529 means you only have ten hours and five minutes and 22 seconds of sunlight, you're gaining sunlight now at one minute and 28 seconds a day. So as we have said before, we'll meet you in September, and at that point, we'll do a handoff and we'll look forward to going from sharing our light with you, to you sharing our light with us.

Chris Dall: Mike, as I noted in the intro, President Biden is one of many Americans who've tested positive for COVID-19 in recent weeks and one of many who've now had COVID multiple times. We're also now seeing some newer variants accounting for some of these cases here in the US. So what do wastewater levels and other markers tell us about this surge in cases in the US? Is it anything like we've seen in previous summers?

Michael Osterholm: Well, Chris, as we've discussed, we've all heard of a number of people who have been testing positive for COVID recently, and I'm sure that many of our listeners are aware of similar situations, including themselves being positive. Many of the people who are positive are often asymptomatic and only tested because they were in contact with someone who was a case, or they're very mildly ill, whereas I've heard it described time and time again cold-like symptoms, not flu-like symptoms, cold-like symptoms. So at this point, all I can say the uptick in people that I know being infected is consistent with all the data we have. Wastewater levels have now surpassed the levels we saw during the last summer's uptick and continue to trend upward. A total of 36 states, including the District of Columbia, that 71% have high or very high wastewater activity. This is up from 26 the previous week. Minnesota is one of the states that has jumped from high levels last week to very high levels this week. The current wastewater levels were seen in Minnesota are inching closer to the levels reached this past winter. This increasing viral activity in wastewater is consistent with hospitalization data. There are currently approximately 140 Minnesotans hospitalized with COVID-19, up from 50 just a few weeks ago. A couple of other states have notable trends, including Oregon and Florida.

Michael Osterholm: Oregon has seen a dramatic increase in the last couple of weeks, and are now seeing their highest level since February of 2023, and Florida has seen a ninefold increase in wastewater concentration since late April, making their highest levels since January of 2022. During the initial Omicron descent regionally, wastewater activity is highest in the western United States, with another jump there after a brief plateau. Things in the southern U.S. have also continued to climb in the Midwest and Northeast levels have also increased these past several weeks, but it's been more gradual compared to the South and West. Overall, the national average has climbed since late April, equating to about 11 straight weeks of rises. The wastewater trends are similar to what we're seeing with hospitalization data, which isn't representative of the US, but it's the best we have. Hospitalizations have increased since mid-May when we saw all-time lows. There are currently just under 3000 Americans hospitalized with COVID-19, up from 2500 a week ago, and just under 290 of those were in ICUs, up from 230 a week ago. These numbers, however, only represent about a third of all the US hospital's COVID deaths, which are a lagging indicator, seem to be following a similar trend, and we can expect increases in the coming weeks and months from mid-January to early June, about six months.

Michael Osterholm: Weekly deaths consistently declined. In that time, we went from nearly 2600 weekly deaths to an all-time low of 294 weekly deaths the week of June 8th. However, weekly deaths rose to 342 the week of June 15th and 385 the week of June 22nd, which is the latest week we have nonpreliminary data for preliminary data shows that there were 540 new COVID deaths reported over the last week, which is the highest since early May. Now, to put this into perspective, however, if we look at deaths during the peak of what we saw during the pandemic, we were at that time averaging close to 26,000 deaths a week. So I just want to compare the number of 540 to 26,000. Still a real challenge, but clearly we're not back to anywhere close to what we were during the pandemic. Looking at the variant proportions, it seems that the FLiRT variants continue to grow with KP.3 and KP.3.1.1 variants accounting for the majority of new cases. KP.3 accounts for 32.9%, and KP.3.1.1 accounts for 17.7%. These variants are the target of the updated RNA vaccines, which we'll talk more about in a moment, so we can only hope that vaccines start going into the arms as soon as possible.

Chris Dall: Okay, so to that vaccine question, we talked last episode about whether people who are more than four months out from their last vaccination should get a dose now, or wait until that updated vaccine is available, and that should be in late August or early September. But with this uptick in cases, this is a question that keeps coming up. Acknowledging up front that there is no easy answer to this question. Mike, what factors should people consider in making this decision?

Michael Osterholm: As we also discussed last episode, as a result of the timing since our last doses, many of us are heading into this surge with very little protection. There are so many different opinions about what to do so far as vaccines go. Anyone who is at least four months out from their previous dose will be eligible to receive a dose of the updated vaccine when it becomes available. With the new timeline looking like RNA, vaccines will be available in September, which is about six weeks away, and that the Novavax protein vaccine will be available potentially in the next 2 to 3 weeks. However, neither of these are confirmed timelines. Combined with the increasing COVID activity, we have to actually ask ourselves what is it that we're trying to accomplish with these vaccines? Remember, we have several studies now which show that it's not the number of doses of vaccine you've had, it's when did you receive your most recent dose? And once you get 4 to 5 months out, the protection against even serious illness begins to decrease substantially. Let me just say, at this point, I have been putting a lot of thought in this in terms of personally, what should I do? Let me remind you that I'm not making any recommendations providing medical care. I'm simply telling you the factors to consider and how I am personally choosing to proceed. As a 71-year-old who has had COVID, followed by four months of long COVID symptoms and are now five months out from my last dose. And let me add, my approach is surely influenced by my many conversations with people who I believe are far sharper in this topic than I am, there are a lot of factors to consider when making the decision.

Michael Osterholm: I want to lay some of them out to potentially help others with their decision as well. The first factor is the increasing COVID activity that we're seeing right now. As we talked about earlier in the episode, COVID wastewater data is showing levels as high as they were at in the peak of last summer's surge and increasing, but this is occurring about a month and a half earlier than that surge. These levels are lower than the levels we were seeing during the winter surge, but are heading towards those levels. As regular listeners know, I will be the first to tell you that this is not a seasonal virus. It is unpredictable in its timing as well as the unpredictability of when variants come and when they decrease. Planning to vaccinate seasonally for a virus that is not seasonal is not a good idea, but this is a discussion of another day. But I digress with the high viral activity we're seeing, I understand an urge to receive a vaccine now, because waiting for six weeks until you actually can get the mRNA with the new variant included means you have maybe no or little protection between now and that time. That will show up sometime in September. Now remember, one of the things that's happening, though, that I think is notable is the Novavax protein vaccine will be available likely within the next several weeks.

Michael Osterholm: This is a vaccine that has an adjuvant included. This is a chemical that boosts the immune response, and the Matrix-m antigen has been very successful in getting a better response. Now, however, the Novavax vaccine will include the J&J one variant, the parent of the lineage that we're seeing most frequently now. Some will say, well, I want the most current lineage of variant in my vaccine. Others will say, you know, the Novavax may be the ideal because I can go with it right now when it comes out. And hopefully, as I said, it'll be very shortly. And there is an advantage to the adjuvant present, as well as the fact that we have had many reports of people having received both mRNA vaccines and the Novavax protein vaccine. That report substantially increased side effects from getting the mRNA vaccine versus the Novavax vaccine. My last dose was the Novavax. So I have personally decided, and I just want to be clear as a personal decision, I'm not giving you medical advice, but I am going to get the Novavax vaccine as soon as it comes out. I'm getting this vaccine knowing that I then have to wait four months out from that dose until I'm eligible for the new vaccine dose that will be included in the mRNA vaccine availability. I'm willing to accept that and say that I think I'm going to get sufficient enough protection immediately, which I would not get potentially for another six or more weeks with waiting for the mRNA vaccine and then get the Novavax vaccine with the adjuvant.

Michael Osterholm: Then at four months, get the mRNA vaccine. So I hope that that is going to be a successful approach. I again want to emphasize this is not medical advice, but it surely makes sense to me and it makes sense to a number of my colleagues. So at this point, your choices are, do nothing, which I hope none of you choose that option. And I'm unfortunately aware of many who said I'm just done getting vaccinated. I'm not going to get it again. And you know, these vaccines can surely help prevent serious illness, hospitalizations, and deaths, and particularly for those who are older, I might add that we've now begun to see in Minnesota and other locations like this, an increasing number of outbreaks in long-term care facilities. So this would be a time to make sure that grandpa and grandma or your mom or your dad, or in some cases, your brothers and your sisters, aunts and uncles are there, and that they really do need to have better protection. Many of the individuals in long-term care are at least 6 to 12 months out from their last dose of vaccine, and this recent CDC data shows that just 1 in 3 nursing home residents are up to date with their vaccines, meaning they've received either two doses of vaccine or a dose within the past four months. Unfortunately, many of those qualify using that definition. They've had two doses of XB vaccine before, which again, as I just pointed out, should probably be excluded from this context of what is up to date, because it really comes down to when did you get your last dose? And if you were to use that criteria only, I think that many more people would also fall into that category of not being up to date.

Michael Osterholm: So unfortunately, with the vaccine coverage so low in residents and even lower in long-term care facility workers, which CDC estimates right now to be just 1 in 10 are considered up to date. And again, that includes if you previously had two doses, but it was more than four months ago. So at this point we're seeing about 500 deaths a day. Uh, this is surely a challenge relative to, uh, particularly those who are older, long-term care. Many of the deaths are in the 65-year-old age group and older. So stay tuned. The most important thing is get the vaccine, get the vaccine. And I would urge anyone who is eligible for the vaccine. In other words, everyone, uh, except for the Novavax, it's only 12 and older. Uh, get it when you can and even avoid, uh, potential illness, serious illness, hospitalizations, etc. this is really no different than the approach we take with flu, so hopefully this is helpful information. Uh, I can't wait till Novavax is available. I can't wait then to get four months out and get the mRNA vaccine with the new variant. And just know that we're still undergoing a lot of questions about what should be the path forward for coronavirus vaccines. And we've got a lot to do to get a better handle on how to approach that.

Chris Dall: So even though most COVID cases are now mild, long COVID remains a concern. But a study published last week in the New England Journal of Medicine found that the risk of long COVID has decreased over time, most likely due to the impacts of vaccination. Mike, what did you make of this study?

Michael Osterholm: Well, first of all, let me just say that this study was conducted by a research group that have really contributed a great deal of information in terms of understanding the clinical course of COVID and what we can do about it. It's led by Ziyad Al-Aly, who is the director of the Clinical Epidemiology Center and chief of research and education services at the VA Saint Louis Health Care System. Ziyad has done an amazing job of putting information forward that's useful, and that can help provide context to why vaccine is so important. So I was very pleased to see the results of this study, which you noted found that vaccination is associated with reduced risk of long COVID and is likely responsible for most of the reduction in long COVID we've seen in the past couple of years. The researchers who conducted the study used medical records from the Veterans Affairs Health System from March 1st of 2020 through January 31st, 2022 to compare five different groups of infected individuals unvaccinated individuals who were infected with the original strain, Delta variant or Omicron variant of SARS-CoV-2, and vaccinated individuals who were infected with either the Delta or Omicron variants. The researchers found that during the time when the original strain of SARS-CoV-2 was dominant, about 10% of those infected developed long COVID during the time when delta was dominant, about 9.5% in 100 unvaccinated individuals developed long COVID, compared to 5.3% in vaccinated individuals during the time when Omicron was dominant.

Michael Osterholm: About 7.8% of the unvaccinated infected individuals developed long COVID, compared to 3.5% among those who were vaccinated infected individuals, according to the researchers' analysis. This means that about 28% of the decrease in long COVID risk is attributable to the change in variance, and about 72% is attributable to the use of vaccines. Let me repeat that this is a very important summary statement. According to the researchers' analysis, this means that about 28% of the decrease in long COVID risk is attributed to the change in the variance, but a whole 72% is attributable to the use of vaccines. The researchers also found that the symptoms of long COVID have changed over time, with metabolic symptoms more common during Omicron dominance than before. Omicron dominance and cardiovascular, neurologic, pulmonary, and mental health symptoms less common during Omicron dominance than before Omicron dominance. This was true for both vaccinated and unvaccinated groups. These results do have to be interpreted somewhat cautiously as the sample, which was 90% male, 74% white, and had an average age of 64, is far from representative of the US population. Still, this was a very well-conducted study, and these results serve as a critical reminder of the importance of vaccination, not just for preventing hospitalization and death following an acute infection, but for preventing long COVID, as well as someone who went through long COVID. I can tell you I so appreciate the power of what these vaccines can do.

Chris Dall: Let's turn now to H5N1. On July 15th, the Colorado Department of Public Health and Environment announced that five workers at a poultry farm had been infected with H5 avian influenza. Since then, two more poultry workers in Colorado, including one at a second farm, have been infected. These are the first poultry workers to test positive in the US since 2022. Mike, is there anything noteworthy about these cases?

Michael Osterholm: Well, I think the whole situation is noteworthy in that, as I have shared with the audience over the past several podcasts, we're not really sure where this is going, but I don't see at this time that it's going towards the likelihood of becoming the next pandemic virus. But let me add some context here. First of all, it's important to just say that the numbers of cases that we're seeing in humans and the number of infected animals in dairy operations really are remarkable in how they're concentrated in just four states. As of today, we have 169 farms that have evidence of infection in the cattle. Of these, 125 are almost 75% are in just four states Colorado, Idaho, Michigan and Texas. Now, does that mean that it's absent in all these other states out there? I can't say for a fact that that's true. We could have some additional states where we just have not yet picked up the activity. But I think it's fair to say that it is not equally widespread throughout most of the country. That takes us back to then. How did this all begin, and what does that mean? And I think it still speaks to the fact that it's been a single spillover event that occurred from wild birds to dairy cows in the panhandle of Texas. Those cows were then moved to various states as part of the normal work practice of supplementing dairy herds with dairy cattle from the Texas Panhandle, where as younger animals, they're raised.

Michael Osterholm: Now, what I think is important here is, is that if you look at the genetics of this virus that we're seeing, it continues to be the same set of sequences of very much supporting that this was a single spillover event from Texas, meaning we're just not seeing it elsewhere. This is also borne out by information that we have now have from Canada and Europe, where they have been doing market shelf surveys of actually going out, buying milk and testing it for the presence of H5 antigen. And of course, as we know that this does not mean the milk is in fact contaminated with live virus. It's not, but it gives you a sense of what else is out there, and we're just not seeing it anywhere else around the world. So I think that this was an isolated at this point, one spillover event kind of phenomena. And what we're seeing now is a combination of where did the animals move from Texas. And then once they were in a new location, what kinds of cross contaminating events occurred because of a lack of good biosecurity, meaning that people went from one farm to another, including in some cases working both on dairy farms and and poultry farms. Uh, not changing clothes, having contaminated shoes, any number of things that could move those virus around. And I think that's what's been happening now in terms of the human cases.

Michael Osterholm: There are actually 11 human cases now. Uh, seven are in Colorado, three are in Michigan, and one is in Texas. All of these cases to date have been a much more classic conjunctivitis situation, not a classic influenza. Now, this is important because as I think all the listeners will know by now that the influenza virus that avian species carry and have transmitted on to other mammal species, like the cow, basically have a need for two three receptors for them to actually bind to cells in the new host species. So in this case, two three receptors are common in a number of animal species. And it also is found in the human eye. And so it's not surprising if you're in an area where two three virus may be in the environment, either in the dairy barn or in the poultry barn, that you might get infected in the eyes. We have yet to see any evidence of classic what we call two six like illness. This is the receptor site that's in the human lungs. It's in the pig lungs. And also now we know it's in the udder of of cows. This is where the viruses that cause human illness, where humans can actually not only become infected but transmit the virus, are located. And we've just not seen that activity. Uh, several recent papers have also demonstrated a lack of two six receptor binding with this virus. Um, and I think that that's an important context also.

Michael Osterholm: So what is going to happen with humans? I don't know why seeing the increase in cases now, uh, that we're seeing, I don't know how much of that is ascertainment bias where meaning that, uh, you know, these de-population events and the poultry-related human cases are all involved with depopulating barns that had, uh, at that time, poultry dying because of H5N1 infection. So I think we're still far too early to say that this is going to continue to occur throughout the country. It surely could if cattle were moved from one area to the other with infection, but hopefully with USDA efforts, that is not likely to happen. And I think we're at a time when, uh, we're just still trying to understand what this means. The CDC and the W.H.O. have yet to raise the risk factor for this. They still consider this a low risk to the general public. I agree with that assessment. I have no doubt none. There will be a future influenza pandemic that's going to happen. Will it be H5N1 that causes it or a reassorted H5N1 or a mutated one? I don't know, I don't think so. I think that there's something about this virus that after 20 some years of trying to infect humans and causing humans to transmit to others, it just hasn't successfully happened. So stay tuned. At this point, I think the news is generally good.

Michael Osterholm: I'm not concerned about these increased number of cases that we've seen. And in fact, I told several reporters eight weeks ago that I thought it would not be unlikely to see 15 or 20 conjunctivitis cases associated with this virus In terms of what was happening within agriculture, but it is one that surely we have to stay on top of. Uh, and uh, again, we'll tell you, uh, first and foremost, if we think that there's an increasing risk to humans at this point, the human risk is really associated with those working in the, uh, depopulating activities of the poultry barns and still working with the cattle. One area that we are yet really unclear about in terms of risk what happens come seasonal flu time in the winter, and we have dairy barn workers who are bringing in influenza viruses that are of a seasonal nature, and the dairy cows are still infected with H5N1. If that seasonal virus and the H5N1 get together, and that udder, which now we know, by the way, has receptor sites for both two three and two six receptors. Um, that could be a real challenge. Uh, and, uh, could that be where we get a reassortment, where the two viruses get together in one udder and actually go through reassortment, where they both get together and create a third new virus? That could be a challenge. We just don't know at this point what that means.

Chris Dall: It's time now for our ID query, and this week we've received several questions about access to the antiviral medication Paxlovid. We've had some listeners, even those over 70, say providers will not prescribe Paxlovid to them because they don't qualify. So, Mike, can you review the guidelines and recommendations for Paxlovid?

Michael Osterholm: Well, Chris, let me start out by saying this is a very frustrating topic for me. I feel like to a certain degree, the medical community in this country has done a very poor job of understanding the importance of Paxlovid and how to use it in the context of COVID, and I have personally been involved with recent experiences where people came to me who I know who should have been prescribed Paxlovid for what their risk factors were, and the fact that they just recently been infected and their physician said, oh no, I wouldn't get it, and had a myriad of reasons why none of them which had any biologic basis. I want to express my real support for all the listeners who have reached out, sharing their frustrations about this challenge they faced trying to access Paxlovid. We may not get a chance to reply to every email that comes into our mailbox, but please know we read every single one of them and we are listening to your stories. I'm going to dive into some of the issues regarding disparities in Paxlovid uptake and reasons for Paxlovid hesitancy in just a moment. But first, I want to review the eligibility criteria for Paxlovid treatment. In order to be eligible to receive Paxlovid, individuals need to meet three criteria. The first is that they need to have mild or moderate COVID-19. This is not for treating as such in the hospital when you're critically ill.

Michael Osterholm: Paxlovid is not available as a pre-exposure or a post-exposure prophylaxis medication, meaning individuals need to actually have COVID and not just an exposure or a potential future exposure to be eligible to take it. The second criteria is that they need to have symptoms for five days or fewer. This can be a real challenge when many individuals don't test positive until several days after symptom onset, and also presents a challenge for the fact that 1 in 3 Americans that lack access to primary care are unsure of who to turn to for a prescription. This is very different today than it was when it was readily available during the main part of the pandemic. The third criteria is they need to have a high-risk factor for severe disease, hospitalization or death due to COVID-19. These risk factors include being over the age of 50, which a whole lot of us are. Being overweight or obese. Having type one or type two diabetes. Having a mental health condition, heart condition or lung condition, being a current or former smoker or having a sedentary lifestyle. Let's put this into context. Over a third of the population in the US is over 50. Nearly 3 in 4 US adults are overweight or obese, over 1 in 5 have a mental health condition, and nearly 1 in 4 have a sedentary lifestyle. The only people in the US who don't qualify for Paxlovid are those adults under age 50 and who are not overweight or obese, have never smoked, have no physical or mental health conditions, and get at least some physical activity on a regular basis.

Michael Osterholm: For all of our listeners who are told they didn't qualify, especially those over age 50. You received incorrect information. That said, there are certainly cases where people can meet these criteria and still not be able to take Paxlovid. There are several medications that can cause severe interactions when taking Paxlovid, and in many cases, it's not safe or feasible to discontinue taking these medications to take the Paxlovid. In these cases, it's important to consider the use of molnupiravir, another antiviral with SARS-CoV-2, which is often safe for individuals that can't take Paxlovid. While medical contraindications may account for some of the low uptake in the US, we know that this isn't the case for many individuals who are denied a Paxlovid prescription. Misinformation about the risk of a Paxlovid rebound has resulted in a lot of hesitancy surrounding the drug from both patients and providers. Studies that have assessed the risk of COVID-19 rebound have found that it occurs regardless of whether someone takes Paxlovid or not. There are some studies that have found a slightly higher risk of rebound among Paxlovid patients compared to those who aren't taking the medication, but there are a number of others that have not found any increased risk More research is needed in this area to fully understand the risk factors associated with COVID rebound, but it is clear at this point the rebound is not a valid reason not to take Paxlovid.

Michael Osterholm: Unfortunately, though, as I previously mentioned, fears about rebound as well as some of the side effects of Paxlovid, including the unpleasant taste of the medication, have led both patients and providers to avoid the drug. Uptake has varied widely across states, with Rhode Island having the highest uptake of 8011 units of Paxlovid per 100,000 population administered since December of 2021. This is over five times higher than the amount of Paxlovid prescribed in North Dakota, the state with the lowest uptake in general uptake as high as the northeastern states and lowest in the Midwestern states. I also want to note that, as with many other public health issues, there are some clear equity challenges present with Paxlovid distribution. A February 2024 study found that a disproportionately low percentage of Black and Hispanic individuals with COVID were prescribed Paxlovid, as were individuals living in low-income neighborhoods. As we continue to advocate for higher uptake of Paxlovid, we need to emphasize the importance of equitable distribution of this treatment across all states, races, and income groups. Finally, we're on the topic of COVID treatments. I want to remind listeners about an important study we covered several months ago on the use of metformin, a commonly prescribed diabetes drug for treating acute COVID-19 and preventing long COVID.

Michael Osterholm: The study was conducted by researchers at the University of Minnesota, and they found that metformin treatment during the acute phase of a COVID-19 infection reduced the risk of hospitalization by 58% and the risk of long COVID by 41%. Wow. This is incredibly promising, especially considering the fact that metformin is already FDA approved to treat type two diabetes and has a very strong safety profile, so I look forward to seeing more research done on this in the future. But in the meantime, if I were to get COVID infection again, I would immediately get both my Paxlovid and Metformin prescriptions. So what is the bottom line with all this? Well, it's clear that far more Americans with COVID-19 do qualify for Paxlovid treatment than don't qualify. And yet, Paxlovid is still being widely under-prescribed, particularly among demographics that already have higher rates of COVID-19 mortality. We need to make sure that healthcare providers are properly informed about the benefits of and guidelines for Paxlovid treatment, and we need to continue advocating for changes in our healthcare system that will make it easier for patients to seek and get treatment. Paxlovid is an incredible tool for preventing severe disease and death. But just as we've discussed dozens of times with vaccines, these tools are only effective when we actually use them.

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

Michael Osterholm: Well, Chris, this is a topic that is somewhat near and dear to my heart, and I say that and I hope it doesn't sound a bit weird, but this is one that I actually worked on in my first year of public health activity. And as you'll see in a moment, I even had a much more, uh, intimate experience with this whole situation, uh, several years later, this week, we're featuring a notable public health event rather than an individual. We're headed back in time, almost 50 years to July of 1976. That was in the first year that I was working at the Minnesota Department of Health. Our US listeners may recognize this as the bicentennial celebration of the signing of the Declaration of Independence. The American Legion, a veterans service organization, was hosting its annual conference in Philadelphia in the historic Bellevue-Stratford Hotel. To coincide with this occasion, more than 2000 of the organization members, known as Legionnaires, would be in attendance, but in the days following the convention, things took a turn for the worse. By late July, a number of conference attendees began to fall ill. Retired US Air Force captain and American Legion bookkeeper Ray Brennan, age 61, died of what appeared to be a heart attack. The American Legion began receiving additional notices of more than 130 hospitalizations and 25 deaths. It became clear that this required urgent action. The Pennsylvania Department of Health and the CDC launched one of the most extensive epidemiologic investigations in the country's history.

Michael Osterholm: While most cases of this mysterious pneumonia were attendees at the American Legion conference, there were some outliers as well. A bus driver. A bank teller from across the street of the hotel, and even some pedestrians who had merely passed by the outside of the hotel. Even without a known agent. The media frenzy around this event led to the naming of the mystery illness Legionnaire's disease. It was almost six months before public health officials were able to uncover the culprit in this devastating outbreak. There were numerous theories floating around as to the cause of this influenza like illness. From a new strain of swine flu to contaminants in the building's wallpaper or elevators, to the cadmium content in the pictures used to serve the attendees Bloody Marys. Microbiologist Joseph McDade, after being heckled by his superior officer at the Christmas party for not yet finding the diseases caused, canceled his vacation and doubled his efforts in the laboratory. Describing his attempts to reexamine his microscope slides, he said to the New York Times, It's like looking for a contact lens on a basketball court with your eyes four inches above the ground. Finally, he and his colleague Charles Shepherd were able to identify the cause, a bacteria that they named Legionella pneumophila. This organism thrives in hot environments and soil and water. In this case, the bacteria made its way into the cooling tower of the building and was transmitted to others through aerosols and mist within and along the exterior of the building.

Michael Osterholm: Legionella remains a public health threat across the globe. Proper surveillance and maintenance of water sources and air conditioning systems is critical in identifying and addressing the bacteria. Most notably in recent history. The bacteria was found in large quantities in Flint, Michigan's water supply, compounding the already dire public health threat of lead contamination. Now, as Paul Harvey would say for the rest of the story. So, as I noted in the summer of 1976, I was one of those people out collecting samples from Minnesotans who had been to Philadelphia during the time period of the Legionnaires convention. Uh, looking for whatever might be the biologic cause of the outbreak. More importantly, one of the associate directors of the CDC contacted me in late 1976 and asked if I was aware of an outbreak called Austin pneumonia. I wasn't. It had occurred in Austin, Minnesota in 1957. It involved 78 individuals. Two died, over half were over 55 years of age, and a majority of them worked at the Hormel meat packing plant in Austin. As it turns out, this large outbreak was under investigation by CDC at the time. In the summer of 1957, when, in fact the 1957 influenza pandemic began and they literally were required to put the research materials that they were working with, tissues and so forth, aside at what was then known as the CDC Kansas City Laboratory, and they were all diverted to working on the influenza pandemic.

Michael Osterholm: Well, not long after that, the CDC lab at Kansas City closed down, and all of the specimens and all the paperwork was shipped to a federal depository in Saint Louis, where again, they were available to anyone who wanted to use them. But at that point, we had moved on. Well, it turned out that in 1973, there was a major fire in Saint Louis, and the depository burned down, destroying more than 18 million records of Vietnam War veterans and other military specialists, and all the materials related to the 1957 outbreak in Austin. Well, being as curious as I was, I decided I was going to try to resurrect this, and so I contacted the Hormel plant in Austin, uh, to the senior leadership in Hormel working with CDC, and said, do you have records on who might have been a case of Austin pneumonia in 1957? Hopefully, they were younger, under age 55, because now we're in 1977 78 and there are still around Austin, we were able to find 15 such individuals who had worked at Hormel who were cases and who were still alive, living in the Austin area. With that, we launched a study of which I followed up with those 15, as well as 30 age and gender-matched controls, both in terms of whether they worked in the Hormel plant or they were neighbors in the community.

Michael Osterholm: Lo and behold, it turns out that when drawing blood samples from these individuals, it was clear, statistically and otherwise, that those who had been cases had much, much higher levels of Legionella pneumophila antibody than those who are not. And as such, what the records that we could find from people's old files, people who had worked with CDC had not put the materials in the federal depository, etc. we actually resurrected this entire story, and it was then published in the American Journal of Epidemiology in 1983 as the 1957 outbreak of Austin pneumonia, which would have gone down in record as the very first outbreak of Legionnaires disease in this country. And I'm very proud of this piece of work. It was truly shoe leather epidemiology. Uh, and unfortunately, a number of my coauthors of this paper are no longer with us because they, too, have aged to the point of, uh, uh, their careers were many, many years behind them. So this week, we celebrate the incredible work that was done in Philadelphia with Legionnaires disease and the outbreak that occurred there. And I want to acknowledge, my dear co-investigators, those who helped us so much resurrect the 1957 outbreak of Austin pneumonia some 22 years later, and show that in fact, that was and still is, the first recorded outbreak of Legionnaires disease ever in the world.

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

Michael Osterholm: Chris I wouldn't have a take-home message if it wasn't about COVID, right? That's how this whole show started. Well, COVID activity is increasing, but orders of magnitude below the pandemic peaks. But still, it is an illness for which we should be able to avoid severe illness, hospitalizations and deaths. And so it is one that for me in particular, for those who are older, we need to continue to double down on vaccination status. We need to continue to emphasize that if you are someone at increased risk for serious illness, particularly the elderly, long term care besides vaccination, we still have to look at respiratory protection. If in fact, you're going to go see grandpa and grandma, you know, don't go if you have any symptoms at all of a respiratory illness, at least test before you go. And because this is a milder illness in so many people right now, they have no idea that they actually have COVID. And they go to an event with grandpa and grandma, who now they're at a much higher risk of having a serious illness. So we can still do a lot about this. In addition, we need to continue to push the Paxlovid issue. This can help save lots of lives and can reduce long COVID.

Michael Osterholm: My second point really is there's nothing new to report on the H5N1 in terms of changing the public health risk assessment. Yes, we've seen some additional cases of conjunctivitis. We we talked about that last time. Why that was a concern that these very hot barns that people were working in, it's very hard to use PPE. Uh, and in addition to that, of course, the human eye is this incredible receptor site location for the avian bird viruses. So we should not be surprised we're seeing cases there. But again, I don't see a major change in the risk picture. And the final piece of it is we're all trying to figure out right now from a public health perspective, what are the priorities. And I thought about it today. I could have covered at least 7 or 8 different topic areas from impacts, etc. antibiotic-resistant infections, uh, dengue virus infection and people traveling around the world right now. Um, and so just stay tuned. We'll try to always focus on the 1 or 2 major issues of the day. But this is not a time to take a vacation. And infectious diseases. We still have a major challenge with the infectious diseases of the world.

Chris Dall: And finally, what is your closing for today, Mike?

Michael Osterholm: Well, in keeping with my dedication to Joe Mauer and all the Joe Mauer's of the world, I just wanted to go back and share again, uh, some words that had come to me in a great deal to me, uh, and spoke to what Joe Mauer and people like him are all about. I think some of you may recall that in the past, I've referenced, uh, commencement address that I gave at Case Western Reserve University on May 17th, 2023. And in that particular address entitled lessons from Nana, I talked about, uh, the my early childhood and how it shaped me and becoming the person I am today. As you know, I was born in a small northeastern Iowa farm town, the oldest of what would be six kids. My father, a photographer at the local newspaper, was an alcoholic and a deeply emotionally troubled man who had a primary way of expressing his fierce internal anger with the world. It was through his fists and his mental intimidation, without regard to your age or gender. And I've said, I'm sure my childhood was not different from some who are listening to this podcast right now. But for certain, I also did have what may very well be one special difference. I was adopted spiritually at an early age by the wife of the owner of the newspaper where my father worked. She went by her family name, Nana. She had a degree in journalism was the very essence of a Renaissance person. She was in her mid 40s when I was born, and although she was not biologically related to me, she did become the mother of my soul.

Michael Osterholm: I can only conclude that in this case, the spirit was thicker than blood. Her spiritual DNA remains in every cell of my body. One of the most painful yet appreciative days of my life occurred when Nana died from cancer in January of 1980 at the age of 72. I miss her dearly, even today, some 43 years later. But she left a legacy for me which I will never be able to repay. It was in the form of many hundreds of hours of endearing conversations and literally hundreds of typewritten notes and letters. I want to share with you now one example of that communication back and forth, and how the story that I'm about to share with you is shaped by her perspective. My commencement address. Finally, let me say a few words about class. It's the ability to never forget who you are or what is most important in life. Classes that status you earn when your achievement allows you to go to the head of the line, and you don't think twice about standing in the back of the line because others were there first. Nana taught me that class comes in many different packages and under many different circumstances. When I asked her once to better describe class to me, she replied, you'll know it when you see it. She was right. An experience a few years ago provided me with such an example. I was given an endowed lecture at one of the largest teaching hospitals on the East Coast. The Chief of medicine at this prestigious institution is an internationally recognized expert in his area of medical specialty and was in charge of the day's activities.

Michael Osterholm: The only way I can describe him is to say he is a brilliant clinician and a wonderful gentleman. As we walked the halls, fellow physicians, nurses, security guards, nurses, aides, and even station clerks addressed him by his name, Jack, or an affectionate doc. This lack of formality might be viewed by some as a lack of respect for someone of such stature. Nothing could be further from the truth. Jack seemed to know every one of them by their first name, and address him as if he were talking to a dear friend or neighbor. The deep admiration and respect for the chief was obvious. After my lecture in the hospital's auditorium, Jack and I were taking the back roads to get to his office. It seemed like endless maze of hallways. Suddenly, in a relatively out-of-the-way hallway near the lab, we encountered an older gentleman who appeared lost and was quite distraught. Jack asked him if he could help. The older gentleman seemed almost surprised. Someone in a white doctor's coat would ask, he blurted out in a painful acknowledgment that his granddaughter had just been admitted to the pediatric intensive care unit, and he was trying to get there. He was desperately lost. Jack looked at me and his eyes told me just to follow him. He asked the grandfather if he might take him some stairs to save time. He replied, anything to get me to my granddaughter. After more hallways and two flights of stairs, we were in front of the intensive care unit.

Michael Osterholm: Jack put his hand out to the man and said, please know the staff of this unit are remarkable. Your granddaughter is getting the best care possible. The grandfather got huge tears in his eyes, grabbed Jack's outreached hand with both of his and held it for a moment. I'll never forget that silent but heartfelt gratitude. Obviously, the grandfather had no way of knowing that the physician whose hand he held was a prestigious and powerful individual in his field of medicine. But that was not the jack I saw standing there either. As we walked away, making another attempt to get to his office and continuing our previous discussion, I realized again that Nana was right. I would know class when I saw it and I was in the presence of real class. Well, that hopefully ties together the fact that Joe Mauer and people just like Joe Mauer also what it's all about with class, if there's anything today that the world needs, it's more kindness in class. So thank you for being with us again. I hope we're able to provide you with good information. Uh, again, I remind you, with regard to the vaccine status, uh, you know what I'm going to do? Uh, that's not medical advice, but, uh, you can consider it for whatever it's worth. And thank you so much for your support. Thank you for being part of this podcast, family. It means so much to us to be able to share with you what we know and learn from you, what we should know. Thank you very much. Be kind. Be gentle. Be safe.

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.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 and Elise Holmes. Our researchers are Cory Anderson, Angela Ulrich, Meredith Arpey, Clare Stoddard, and Leah Moat.