July 13, 2023

In this episode, Dr. Osterholm and Chris Dall discuss recent studies on the neurologic effects of COVID-19, the newly approved RSV vaccine, and locally acquired malaria cases in Florida and Texas.

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Chris Dall: [00:00:07] Hello and welcome to the Osterholm Update, a podcast on COVID-19 and other infectious diseases with Dr. Michael Osterholm. Dr. 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, Dr. Osterholm draws on nearly 50 years of experience investigating infectious disease outbreaks to provide straight talk on the latest infectious disease and public health threats. I'm Chris Dall, reporter for CIDRAP News, and I'm your host for these conversations. Welcome back, everyone, to another episode of the Osterholm Update podcast. On June 26th, the Centers for Disease Control and Prevention issued an alert to health providers and the public about locally acquired malaria infections in Florida and Texas. The first locally acquired cases of the mosquito borne illness reported in the United States since 2003. Although the risk of acquiring malaria remains low for most of the country, it's still a reminder that while COVID has dominated our lives for most of the past three years and will continue to have a significant public health impact in the coming years, SARS-CoV-2 is just one of many infectious diseases we have to deal with. The malaria cases in Florida and Texas are one of the topics we're going to discuss on this July 13th episode of the podcast. After we take a look at the international and national trends, we'll also discuss some recent studies on the neurologic effects of COVID-19 and an infectious disease query about whether and when to get the newly approved RSV vaccine. And talk about the continuing drug shortages that are impacting health care around the world. And we'll share our latest moment of joy submission. But before we get started, as always, we'll begin with Dr. Osterholm's opening comments and dedication.


Dr. Osterholm: [00:01:58] Thank you, Chris, and welcome back to all of the podcast family. It is always a wonderful experience to be in contact with you, even if it's merely through the internet. I hope you all have had a good summer so far, but as I will note in my dedication today, there surely have been some challenges with regard to that. And I also want to welcome anyone who might be new to the podcast if you haven't listened to it before, I hope that what we're able to provide you is what you're looking for and that you'll come back again. I will tell you it's a very special group to be part of this podcast family. We hear about it week after week after week from the wonderful notes, the kinds of feedback that we get very constructive sometimes with, you know, really very pointed recommendations about what we can do better, which we surely appreciate. So again, thanks to all of you. One footnote to Chris's introduction, which demonstrated the number of different infectious disease issues that are before us today. I want to say that sometimes I think the more I know, the less I know. And with almost 50 years of experience now, you'd think I'd seen most things. But I'm going to share with you today some information that frankly, is, I think, stunning in terms of what it represents, what we might be confronted with with regard to that information and how we have to take a look at the future of infectious diseases, not just for us in this country, but for the rest of the world.


Dr. Osterholm: [00:03:28] It is going to be a very interesting time. The dedication today is really about now, but it's also clearly about the future. And what I'm dedicating this podcast to is everyone who is trying to escape the heat or the flooding related precipitation or the droughts throughout the world, and what this means to our future. We can no longer as a world. Deny or not quickly respond to the issue of global climate change. And I'll mention in a moment why I believe this to be the very key issue. But if you just take this past two weeks, July 4th was the Earth's hottest day in over 100,000 years, breaking a record for the second day in a row. The average global temperature of 62.92°F beat the previous record of 62.62 degrees in Fahrenheit, which may not seem like a lot, but on a global basis, that's huge. Nature Medicine actually reviewed the heat related mortality in Europe during the summer of 2022, which this year will even be worse. And they estimate almost 62,000 heat related deaths in Europe for June, July and August of 2022. In the US there has been an average over 700 heat related deaths, 67,500 heat related emergency room visits and 9200 heat related hospitalizations per year.


Dr. Osterholm: [00:04:59] Now you add in flooding and drought. At least 35 million people worldwide have been impacted by flooding just in the last two years. Drier regions are getting even drier and wet regions are getting even wetter. 55 million individuals have been impacted by droughts. The inability to get water to survive for them or their farm animals. It's estimated by 2030, over 700 million people in this world will be severely impacted by drought. Now I lay this out because, again, infectious diseases sit on top of this. And as we get into the program, we can we'll talk more about that. But people today don't believe that what is happening is different. They say we've always had hot days. We've always had wet periods. We've always had cold days. But I'd like to use an example of what's happening right now and just looking at the whole issue of global temperatures and what this means. And I'm using an example that I mentor to me in communications, Don Shelby, a Twin Cities newscaster, now retired, a Renaissance individual in every regard, every regard, and trying to understand, well, is this different today if we have a bad storm? Is this just not like bad storms we've had all along? He shared with me one day an example of understanding this by understanding what happened with Sammy Sosa, the very well known Major League Baseball player from the Dominican Republic.


Dr. Osterholm: [00:06:41] He first broke into the majors in 1989 with the Texas Rangers. He played his last game in September of 2007. And you may recall Sammy was one of two people in particular, Mark McGwire from the Cardinals and him that were really at the center of the use of steroids in baseball and what that meant in terms of hitting home runs. Now, Sammy Sosa, when he came in to the major leagues in 89, he was really already a very, very good player. But if you look at his home run production during the time from 93 to 97, when he was really just beginning to become a home run hitter, he averaged between 25 to 40 home runs a season. And then something happened in 1998, 99, 2000, 2002, and even just in the cusp of 2003, he goes to 66 home runs in 98, 63, home runs in 99, 50, home runs in 2000, back to 64, home runs in 2002. And then he starts to slip again. And from 2004 to 2007, he again only hit 14 to 35 home runs a year. Now, there was no question Sammy Sosa, before he ever used steroids, something he's denied but has been now confirmed, he tests positive. It's well known in Major League Baseball about this situation. He could hit home runs before he ever juiced.


Dr. Osterholm: [00:08:12] He could do that. But if you look at what happened when he juiced, basically the home run production increased substantially. So today, when storms occur, droughts occur, temperatures are very hot or very cold occur. You can say, is this really different? Well, we know the world can be hot. We know the world can be cold. We know that it can be wet or dry. But this is like juicing. This is a very, very different experience. So now instead of hitting 25 to 40 home runs a year, Sammy went to hit 65 or more home runs a year. What does that mean? Well, it means that some of those hits would have occurred no matter whether he had juiced or not, but surely some of them related to the juicing. Today, the earth is juiced. It is juiced. We have to understand that. And so not every hurricane, not every flood, not every drought can be laid at the hands of climate change, but the juiced ones can. And they are. I just want to cover this issue today because of all the things I've ever talked about on this podcast, all the things that we have shared as a podcast family, nothing means more to our kids, our grandkids and even our great grandkids. Then this topic here we have to understand how serious and significant this is. So for all of you who are suffering the terrible, terrible pain from the heat, the flooding, the drought, please know that this is real.


Dr. Osterholm: [00:09:50] Your lives have been upended in many cases, and we as a world must see this and act accordingly. And so I give everyone out there who is trying to do their part to limit their energy use, to support global energy policies that actually use renewable energy. And that, in fact will help us at least try to tame a bit, a bit, not a lot a bit, this rising juiced weather events that we're seeing today. So now moving on to a very special part of the podcast for me. I'm happy to report today that we're still seeing lots of sunlight here in Minneapolis-Saint Paul on July 13th. The sunrise is at. 538 sunset at 858. We still have 15 hours, 19 minutes and 21 seconds of sunlight, but we are losing our sunlight at about one minute 30s a day. That number will continue to increase up until September, and then it will back down into December. And our dear colleagues today in Auckland will see sunrise at 7:31 a.m. and sunset at 5:21 p.m. for nine hours, 49 minutes and nine seconds of sunlight. You're gaining at about a little over a minute a day in sunlight. We'll soon meet somewhere around September 21st, and then you will have the benefit of what we have just had.


Chris Dall: [00:11:19] Let's start with the international and national COVID trends. The most recent updates from the W.H.O. show that some countries are reporting upticks in COVID hospitalizations, while the CDC last week reported increases in emergency department visits and test positivity measures that the agency uses as early markers. We've also had some reports on upticks in COVID wastewater levels in parts of the country. Mike, what's your read on the latest data?


Dr. Osterholm: [00:11:46] Well, Chris, let me just start out by saying that in general, we are still very much in this good news segment of the COVID experience. It's much, much better than we were a year ago. However, as I have said time and time again, we have to learn to expect the unexpected. And while I don't see any major catastrophic type of surge of cases occurring any time soon, it is nonetheless one that, as you just pointed out, we have to watch. Clearly, COVID hasn't gone away. And some of the points that you mentioned in the lead up to your question, speak to that. As I've mentioned time and time again, things like underreporting have really made it increasingly difficult to understand with certainty what's going on. However, despite that reality, I do think the general trends as far as activity goes, are still quite favorable relative to where things have been in the past three years. To that point, when you look at the show's most recent weekly COVID update, which was published on Thursday, July 6th. It shows that over the latest 28 day period, spanning from June 5th to July 2nd, there were a total of 885,000 cases and just over 4900 deaths. Now, this is the seventh consecutive 28 day period with overall global declines, both in terms of cases and deaths. It's a trend that began right around the new year and has continued to date.


Dr. Osterholm: [00:13:12] Also worth noting was that essentially all five W.H.O. regions reported declines. For example, if you look at the numbers of new deaths reported in the past 28 days and comparing it to a period prior, you see that Europe has reported a 64% decline in new COVID deaths. The Americas reported a 60% decline. There was a 58% decline in the eastern Mediterranean, a 55% decline in Southeast Asia, and a 41% decline in the Western Pacific. Now, there was one exception to this, which I have noted in the past, and is really a function of the infrastructure for case detection and reporting. That was, in fact Africa, which reported a 17% increase in deaths. However, the total number of deaths there throughout the entire 28 day period was only 21. And again, throughout a region with a population of 1.2 billion people, I wouldn't read much into this increase. Again, a big part of the challenge has been underreporting and it's continues to be that, as I mentioned in our last episode and which still happens to be the case, almost half of the world's countries do not report even a single COVID case at any point throughout this period from early June to July. That should never be interpreted as the absence of evidence is evidence of absence, meaning that in fact there clearly are cases occurring out there, but we're not detecting them.


Dr. Osterholm: [00:14:41] But overall, I think these general trends globally and regionally are very, very reassuring. Be that as it may, if you zoom in a little bit closer from the regional picture, like you said, Chris, we can see some countries where things haven't necessarily been cooling off. In fact, directly from the W.H.O. report reads the following Some countries continue to report high burdens of COVID-19, including increases in newly reported cases and more importantly, increases in hospitalizations and deaths, the latter of which are considered more reliable indicators given the reductions in testing. A few examples include Bangladesh, Japan and Malta. However, to be clear, and I know we'll touch on this more in a little bit, I personally have not seen any evidence that the activity in these places is being driven by some new variant. However, we are obviously keeping an eye on some of these places that are exceptions to the trend. I don't know what they mean. I don't know why it's happening. I don't know what this virus is doing in places like Bangladesh, Japan and Malta and why it's not doing it in other places. I still have so much to learn about this virus. Now, moving on to the US, obviously a lot of the caveats I just mentioned in terms of things like underreporting still apply.


Dr. Osterholm: [00:15:59] However, overall, I think there are still some very encouraging signs at this point. First, COVID hospitalizations have continued to drop and reach new all time lows since the start of the pandemic. Right now, if you look at the CDC data, it shows that on July 1st, which is the latest date we have data for, there were less than 5200 Americans hospitalized with COVID nationwide. For context, that's down from 6800 hospitalizations in early June just a month prior, and is well below the 41,000 hospitalizations we saw at the beginning of this year. In fact, we are now in the 25th consecutive week of declining hospitalizations, according to the CDC data. Of course, there is a possibility that the number for hospital. Organizations has also been influenced a bit by changes in COVID testing and screening policies as some health care institutions. But overall, I think these declines were seen in hospitalizations are real. At the same time, we fortunately seen continued declines with COVID deaths, which have also reached new record lows, according to the latest complete data published by CDC, which is for the week of June 10th, there were a total of 568 weekly deaths from COVID. For context, around a month prior in early May, there were 913 deaths in a span of a week.


Dr. Osterholm: [00:17:20] So now down at 568 versus 913 two months prior, in April, there were 1350 weekly deaths and again just three months ago, in March. Weekly deaths stood around 1350. So we're at less than a third of the deaths we were at in March. So some good news is that overall, we've seen 15 consecutive weeks with declining deaths. However, as I have said time and time again on this podcast, every one of these deaths is somebody's mother, father, brother, sister, aunt, uncle or son or daughter. And so we can never lose sight of that. We can never lose sight of that. And on that note, we know that with this virus, declines aren't a guarantee, As you mentioned in the lead up to your question, Chris, there are some metrics where we've seen recent, although subtle, increases. This includes test positivity, which rose from 4% in mid-June to 4.8% in early July. Honestly, I don't know how to interpret that. There also includes a percentage of emergency room department visits with a positive COVID test, which grew from 0.51% in early June to 0.55% in early July. Again, not sure what that means could be impacted by who's getting tested. And finally, there are some US regions with slight increases in wastewater positivity. Got to keep our eye on this. Now we also have to be careful not to overreact in terms of making it sound like the surges of 2021 2022 are going to happen again.


Dr. Osterholm: [00:18:57] We could double the case numbers, which could still be a very small increase because we're doubling a small number compared to what happened if we doubled a very large number. So I want to keep that in perspective and to say that we could see little bumps up and down. But again, the trend is not back towards these very large surge numbers we've seen in the past. So in conclusion, let me just say we're at a point in this pandemic where it surely is possible that with waning immunity in humans overlaid with a new variant that might emerge, that could escape some of the immune protection we have, we could see a substantial increase in cases. But again, I don't see any evidence that would be similar to what we saw with the Alpha Delta or Omicron surges. I just don't think that's going to be the case. So Chris will leave it here and just say that I hope that people are finding more freedom in their life from COVID able to enjoy it more and whether it be family events, public get togethers, etcetera, but know that this virus has not disappeared, but it surely has changed its course over the last months.


Chris Dall: [00:20:05] And has the variant picture changed much?


Dr. Osterholm: [00:20:09] Well, obviously, this is one that we follow closely because it could be a change in a variant that could really change the path of what we now are calling the backside of this pandemic. Just to note that there are two deemed variants of interest by W.H.O., the XB 1.5 and XB 1.16. Both of these are variants I discussed in the last podcast. There are six other variants under monitoring throughout the past couple of months. Xb 1.5 was actually the dominant variant globally and in the US. However, it's been declining fairly steadily all the while. Xb 1.16 is increased and just recently. Xb 1.16 actually took over as the new leading variant globally and in the US. However, with only a 21% prevalence globally and 18% prevalence in the US, it's still justrillionepresents around 1 in 5 cases. So this is part of living in this variant soup that we live in. But I think the important take home message here is we don't see a variant right now that appears to have increased transmissibility and an increased ability to escape immune protection. And so I think we will continue to be in kind of this steady state situation for at least the next weeks ahead.


Chris Dall: [00:21:27] Last week, CIDRAP News reported on some new studies exploring the neurologic effects of SARS-CoV-2 infection, including the possible mechanisms behind long COVID's impact on the brain. Mike, what can you tell us about these studies?


Dr. Osterholm: [00:21:42] Well, the first thing I want to tell you is that they mean a lot to me because as so many of our listeners know, I had COVID in early March and suffered some of the consequences of a long COVID like picture since that time. I first want to report that I feel like I have fully recovered and I feel very blessed with that. I've got my energy back. I'm not fatigued. My memory loss issues seem to have been resolved and I'm as forgetful as I've ever was, but not as bad as I might be. And I think that at this point, it's fair to say that for the me too experience that really brought home what so many of you are experiencing, I happen to be better, but I know many of you are not. The studies that we're talking about really, I think are quite important. There was a set of studies presented at a conference in Brazil last week, and the CIDRAP news piece you just mentioned focused on three studies from that conference. Each of these studies linked COVID-19 infections to neuropsychiatric conditions like depression, anxiety, fatigue, as well as interfering with a person's well being and ability to work. Using different methods. One study analyzed MRIs of patients three months after their COVID infection. The MRIs of the patient experiencing long COVID showed changes in the brain, including deterioration of gray matter, as well as cerebral hyperconnectivity changes that are associated with anxiety and depression. So what you're feeling actually has a physiologic basis if you are in that group.


Dr. Osterholm: [00:23:17] Another study which involved analyzing questionnaire responses from 607 comparable individuals, all who had COVID, who all worked in banks. The questionnaire results found that more than half, 52% of the individuals were still experiencing memory issues. 48% were experiencing fatigue and 38% were experiencing anxiety. An average of 200 days after their COVID infection. The final study covered from the conference in Brazil included a series of tests that aimed to define fatigue associated with long COVID. They found motor skill impairment in long COVID patients suffering with fatigue. But interestingly, reaction time was not affected. They also found that long COVID patients did not perform as well with their dominant hand compared to participants without long COVID. The other major study from the CIDRAP news piece was one from Shanghai Normal University and the University of Hong Kong, which was published in Cell Death and Discovery. This study aimed to understand potential mechanisms in which long COVID impacts the brain. The three routes the authors propose, which I'll explain in depth, are via the nasal cavity, the lungs and the eyes. The first mechanism is the virus entering the sensory neurons via the nasal cavity to the olfactory nerves, then on to the olfactory bulb route to is that damage to the respiratory tract that allows SARS-CoV-2 to spread throughout multiple organs and ultimately may cross the blood brain barrier through the angiotensin converting enzyme facilitation and ultimately reach the central nervous system.


Dr. Osterholm: [00:24:57] And the third route is through the eyes and the optic nerve to the brain, although viral loads in the eyes are typically quite low. There have been reports of conjunctivitis being the only COVID symptom experienced by a patient. These different routes all have effects on the brain leading to different symptoms, many of which affect memory. The authors explain some of the symptoms of memory impairments as short term memory, working memory, concentration, decision confusion, problems with daily activities and other related memory problems have been widely reported in COVID-19 patients. One point that the researchers of this study brought up that I think is important to note is that the memory problems caused by COVID-19th May be more harmful to children than adults because of the stages of brain development that happen throughout childhood. This is incredibly concerning and something we certainly have to monitor going forward and in the coming years. Finally, these are the types of studies we need going forward to bring awareness to the issue of long COVID. There are so many people suffering, and just because the general public and the majority of the world has moved on from COVID does not mean we all can forget about the long term effects that COVID is still having on so many people. These people do not have the luxury of just leaving the pandemic behind. And we'll continue to bring you as much information about long COVID as possible. We are together on this one.


Chris Dall: [00:26:28] There's also some new research out from the US Department of Agriculture this week about the spillover of SARS-CoV-2 from humans into the deer population. Mike, what is the significance of these findings?


Speaker3: [00:26:41] Chris, This.


Dr. Osterholm: [00:26:42] Is one of those situations where the answer should be, I don't know. But the answer also is I think it's important. And what I mean by that is, is that this is one of those events within this pandemic that has just left me in awe of the powers of Mother Nature, infectious diseases and the issue of different human and animal populations and their susceptibility to these infectious agents. As we have reported previously on this podcast. We have seen the spillover of SARS-CoV-2 infection to whitetail deer, and I have not yet understood how that happens, where the contact occurs, what is the actual inciting event? You know, could it be wastewater? Well, we have many areas of the country where there are a limited number of wastewater treatment facilities, and much of the waste is through septic systems, etcetera. Yet we still see the same intensity of infection in the deer populations there. It can't be close contact with humans beyond a very limited number of locations where humans are in, you know, deer farms or other kinds of zoo settings where they're actually potentially almost touching the deer. First of all, let me just say this was a remarkable piece of research and my hat goes off to this research group. It was based on 8830 respiratory samples from free ranging white tailed deer across Washington, D.C. and 26 states from November 2021 to April 20th, 22. A total of 944 samples were positive for SARS-CoV-2, and researchers sequenced the genomes from 391 of these samples. What did they find? Well, first of all, sequencing showed Alpha Gamma, Delta and Omicron lineages and multiple lineages were circulating among deer at the same time. So they were seeing in as much diversity of the virus as we were.


Speaker3: [00:28:47] Out of the 282.


Dr. Osterholm: [00:28:48] White tailed deer viruses analyzed, 238 were found to be grouped into 109 clusters that also contained human SARS-CoV-2 viruses. For each cluster, a SARS-CoV-2 genome sequence from a human was identified as the precursor virus with at least 99.85% nucleotide identity, indicating that at least one independent spillover event from humans to white tailed deer. Now, when you look at that, the numbers that they came up with is at least 109 spillovers just in this sample of deer that they had. So it was moving readily from humans to white tailed deer. But even more concerning were three really convincing situations where there was evidence based on the genetics of human to deer transmission and then back to humans, three of them. Now, why do you say that's important? Because if we see this kind of virus circulating in these animal populations, what is the possibility for the genetic changes that could occur that bring us back a new variant that would come back into humans that could be so different that it could challenge the immunity that we already have and give us another wave of infection.


Dr. Osterholm: [00:30:04] I don't know that could happen. But no one no one can tell you it wouldn't happen. So we're watching this situation very closely. It also calls into question what other animal populations out there who might be in close contact with humans are also experiencing this very same situation? And could this mean that as much as we've been following variants and sub variants in humans looking for the next concerning variant, could it be that the next concerning variant is going to jump from an animal back into humans? We don't know that. We just don't know. So for now, I would say, you know, I would not get too worked up about this. I wouldn't, you know, say, oh my, the sky is falling. But this is one that we have to watch very carefully. I don't know what this represents, but it sure is something I have never seen in my public health career. To see this kind of jump from humans to a wildlife species and then back even to humans like this. So this is going to be an ongoing challenge.


Chris Dall: [00:31:09] Now it's time for our infectious disease or query. And just to note for our listeners, this is what we are now calling the COVID query, and it reflects the widened scope of this podcast. And this week our query is about the respiratory syncytial virus or RSV vaccine. And just to back up for a moment, because I don't believe we've covered this. On June 21st, the FDA's Advisory Committee on Immunization Practices recommended the newly approved RSV vaccines for use in people ages 60 to 64 and 65 and older. Based on a shared decision they make with their doctor. That recommendation was then endorsed by outgoing CDC director Rochelle Walensky. But when people in these groups should get the shot and whether they might get it at the same time they get their flu and COVID shots appears to be undecided at this point. So Yvonne wrote to us. Could you share your thoughts on whether to get the new RSV vaccine this fall and also the timing of receiving that vaccine in relation to the timing of the influenza and upcoming new COVID-19 vaccines?


Dr. Osterholm: [00:32:13] Thanks for your question, Yvonne. We've talked about RSV quite a bit on the podcast, so it's exciting to discuss opportunities on the horizon that can better prevent severe illness, according to the CDC each year in the US. Rsv leads to an approximate 60,000 to 160,000 hospitalizations and 6000 to 10,000 deaths among adults 65 years of age and older. As Chris mentioned, two vaccines from Pfizer and GSK were recently recommended for adults aged 60 and older. This past May, it is expected that these vaccines will be available this coming fall, with a similar timing to influenza vaccinations around September or October. I have not seen any evidence yet of cross-reactivity between the RSV vaccines with flu or COVID vaccines weighing the strong safety profiles detailed in the FDA and the serious risk of this disease to older adults. I think that those who are eligible should speak with their providers about getting this immunization in the fall. And I'll weigh in on the timing of how we might consider these three vaccines in just a moment. In addition to older adults, we also concerned about the severe impacts of RSV on children, especially infants, under six months of age. According to the CDC, surveillance RSV causes over 2 million outpatient visits in children under the age of five and 58,000 to 80,000 hospitalizations in that age group. Rsv is also one of the top causes of death of young children in low and middle income countries worldwide.


Dr. Osterholm: [00:33:44] The good news is that more preventive measures are going to be available in this age group as well. The same Pfizer RSV vaccine available to older adults is also a candidate to be given during the third trimester of pregnancy and offers protection for the infants up to 24 months after the birth. Vrbpac has also recommended an antibody shot would actually be given directly to newborns and infants entering into their first RSV season. This is different than actually giving a shot for the infant themselves to make the antibody. The single shot could be more affordable in a convenient option compared to other preventive antibody shot that is administered monthly and only given to children at highest risk. The FDA is not required to follow the recommendations of Vrbpac, although it typically does. We'll see FDA's response sometime in the third quarter. There'll also be review by the CDC's advisory committee, the Acip, and how this particular approach would be rolled out to the public, including considerations for any special populations. Overall, I'm really pleased to see more tools in our toolbox to prevent and fight RSV. As we've discussed previously, vaccinations are only valuable if we can actually get shots in arms. So we'll still need to see whether people will come out to be immunized. This past winter, 71% of older adults did receive their influenza vaccination, while only 43% got a COVID booster.


Dr. Osterholm: [00:35:14] And at this point comes the challenge of trying to message do we get all three shots at once or do we actually take them at different times? As you have heard me time and time again on this podcast say, I have no evidence at this point that COVID in of itself is going to be a seasonal disease, at least for this next year. I mentioned that already in terms of activity in the southern hemisphere, where we're seeing lots of influenza, a limited amount of COVID. So at this point, to me, the COVID immunization should be all about when were you last vaccinated or last had an infection? Get it? Don't make it seem to be a seasonal shot. Get it as soon as you can. Rsv in some ways is the same in the sense that we do expect protection to persist with this vaccine. So getting it early into the fall, as soon as it's available is a great idea. And I urge you to do that where I have more concern is with the influenza vaccination. And let me be very clear about this. I am a very strong supporter. I have gotten my flu shot every year for many, many, many years. But as you've heard me also say, here in last year was an example of this, where I wait until there's early evidence of flu starting to circulate, because getting it early in August, September, October, with the known overall loss of protection with time up to 7 to 10% reduction in protection by month following getting the vaccine.


Dr. Osterholm: [00:36:49] So if I get it in August, what kind of protection do I have if, in fact the season starts in January? And so I would say get the COVID and the RSV shots as soon as possible. That'll be just fine. But again, I would wait until I had some evidence that flu was taken off last year. It was early in November. I got my shot in. In the late part of October this year. I could go into November even before I get mine if we're not seeing flu activity because I want as much protection at the time, I'm most likely to encounter flu. So I hope this isn't confusing. I want to make it clear all three vaccines are important, but I would take RSV and COVID as soon as I could get them as the new vaccines, which I expect will be by September, and I would get my flu shot closer to the actual advent of the flu season. Watching carefully and we'll tell you on this podcast, I'll tell you, you know, it's time right now. Get it? I just went and got mine. And that'll help you with your flu protection by getting the immunization much closer in time to when the risk in the community is at its increased level.


Chris Dall: [00:38:06] Mike is a follow up. There is an article in The New York Times that suggested that the CDC will likely encourage older and immune compromised Americans to get all three shots in the fall to prevent a repeat of last year's tripledemic. Can you explain why you continue to push back against this notion of the Tripledemic?


Dr. Osterholm: [00:38:25] Well, first of all, I think it is not an accurate description of what's happening. And I think it's a catchy phrase that some of my colleagues have used. The New York Times seems to like it, but I don't think it is an accurate portrayal of what we're up against. And it creates more of what I would call a sensational message to the situation. Almost every year we have a flu season. COVID obviously disrupted that a bit. Now, when is it an epidemic? You know, when is it what we would just expect? And if you look last year, it was a classic example of where we actually had people using this, oh, my, here comes the tripledemic, because the flu season started earlier. By the way, in the southern hemisphere, six months before we saw the same thing in the United States. Flu really picked up in late October, early November. Usually we think of it picking up in December and January and people went, oh, this is going to be the worst flu season ever. But, you know, having watched what had happened in the southern hemisphere, they too, had a season that started 6 to 8 weeks earlier than normal. But in the end, they didn't have an increased number of flu cases. It just got displaced earlier in the season.


Dr. Osterholm: [00:39:36] Well, that's exactly what happened here in the United States. We didn't have a big epidemic of flu last year. We got hit with seasonal flu. It started earlier, but the case numbers weren't higher. That's hardly a flu epidemic as such. And so I think that there is an example right there. Then when you overlay RSV and then they overlaid COVID on that, which there was no evidence of increased occurrences with COVID during that winter flu season in the United States last year. If anything, case numbers were continuing to drop. So I think when we communicate to the public, we have to give them a sense of when I talk about an epidemic or a tripledemic, what am I really talking about? It's a bad term. It's kind of scares the hell out of you, you know? And I think we should have learned by now with dealing with COVID how we communicate to the public and what we share with them is important because, in fact, if they look at this and say, well, wait a minute, what's different about this or what happened here, you lose credibility. And I think the media is a big problem. I think The New York Times stories this past week were not at all responsible, and I don't think they were helpful.


Dr. Osterholm: [00:40:46] And so I would leave it with the fact that, as I said in the previous question and answer, getting RSV, COVID and flu vaccinations are very important. Get them. But look at both getting RSV and COVID. When the new booster becomes available for COVID and the newly approved vaccines for RSV. You want to get COVID earlier because most of us now have been at least six months out since our last encounter with either vaccine or infection. And you want to get RSV because we're coming into the season. And with this vaccine, you have a good chance of protection, even if you get it in August or September. And flu, you want to wait until you see what's beginning to happen in the community. And once you have that first suggestive triggering activity, then get the flu shot. And at this point, we do have weeks, sometimes three, four weeks where we should start to see flu coming up. It's not like you have to say, oh, if I don't get it tomorrow, I'm done. And so I hope that this brings some sense to this. Get rid of the term tripledemic. It's, I think, irresponsible. Number two is get your vaccinations, but get them in terms of timing that are most going to protect you.


Chris Dall: [00:42:03] Now to malaria. As I mentioned in the introduction, the CDC on June 26th issued an alert about locally acquired malaria cases in Florida and Texas, the first in the US since 2003. Mike, how surprising was this news and how concerned should people in those states be?


Dr. Osterholm: [00:42:25] Well, Chris, this is not surprising news, and I think that's an important message to get out. I've already seen people hinting that, oh, because of climate change, something which, based on my dedication, I hope people realize, I think is very important, but that somehow climate change is now suddenly going to make malaria widespread through the United States. That is just simply not the case. As you noted in the question leading in here, we have now had a total of six cases in Florida and one case in Texas through the summer. We have to understand that malaria is endemic in many parts of the world. So it's not entirely surprising that we're seeing this particular parasite transmitted here in the United States by what we call the anopheles mosquito. Anopheles are the vector for malaria. There are a number of species of Anopheles that reside in the southern part of the United States. And at one time, North America was a hotbed for malaria transmission. That's how CDC got started. They were originally a malaria control organization in Atlanta and built from there. And so from that perspective, we have had the historic data showing of this. And in fact, right here in Minnesota, around the time of the Civil War, we had lots of malaria here. But if you look at the different kinds of mosquitoes and what they transmit, the anopheles mosquito is one that lays their eggs basically in more open waters, larger ponds, lakes, that type of thing, such that it's very different than the 80s mosquito, which is what we kind of call the household mosquito.


Dr. Osterholm: [00:44:01] It loves discarded garbage, plastic, a little bit of water in a McDonald's wrapper in a ditch is more than adequate breeding site for it. 80 is what transmits the dengue virus, Zika, Chikungunya and La Crosse Encephalitis. If you look at Culex, another mosquito species that even has a different range where they are at and how they breed, they're the ones that transmit Japanese encephalitis, Saint Louis encephalitis. And in this country, a disease of real concern, West Nile virus. So the mosquitoes are here. But what has saved us over the course of the past number of years with malaria, with people coming into the country from malaria endemic countries where they acquired the parasite, is the fact that we largely live in buildings with screens. We do have more air conditioning, although surely not enough, as we have demonstrated with heat related injury. But by keeping the mosquitoes from us at night and Anopheles tends to be a nighttime biter. And that's why Bednets, for example, have been important in many countries around the world where malaria is a serious public health problem. So we have had examples over the years. I remember early in my career here at Minnesota where we actually had concerns because we had a number of returning Vietnam War veterans who were infected and moving back to the United States. We actually had several outbreaks occurring in neighborhoods where that individual who was infected, local anopheles mosquitoes fed on them, got infected and then transmitted to other people in that area.


Dr. Osterholm: [00:45:36] And these were very quickly put out. They were they were not sustained problems. So I think the message here is, is that this number one by itself doesn't mean it's climate change difference. It means that we just have more people from around the world going to more places where malaria is present, not being adequately treated either from a prophylaxis standpoint or from an infection standpoint. And then the mosquitoes feed on them. Now it still means we should do everything we can with vector control. This means including improved sanitation, looking at certain kinds of insecticides that can safely be used in breeding sites for Anopheles and addressing that and of course following up on cases and of course following up on potentially suspected cases of malaria in areas where other cases have occurred. So it wouldn't surprise me to see more cases of summer, but we're talking about numbers at the very, very, very most in the two digit level. We're not talking about thousands and thousands of cases like we might be talking about with West Nile virus. So I hope that you don't delay travel to Sarasota County, Florida, or to Texas based on this situation, but be mindful of just trying to avoid mosquito bites. And I can tell you that while it may seem somewhat inconsistent to say how could such a tiny little thing be so dangerous, but in fact, mosquitoes are the most dangerous animal in the world for human health. They remain that. And we have to understand that.


Chris Dall: [00:47:11] Mike, As you know, the COVID-19 pandemic created a real disruption to the pharmaceutical supply chain, resulting in a variety of drug shortages. But unlike other supply chain disruptions that have been resolved, we're still seeing drug shortages. More than a dozen cancer drugs are currently in short supply, as is an antibiotic for treating syphilis. So what is going on with the drug supply chain and how do we fix it?


Speaker3: [00:47:35] Well, Chris, this is.


Dr. Osterholm: [00:47:36] Certainly a very serious concern and one that we've been thinking a lot about here at CIDRAP. As you know, we had over the past four years a program looking at resilient drug supplies and what's happening with global marketing and manufacturing. And this is a real challenge. According to the American Society of Healthcare Pharmacists, we're currently seeing shortages of 243 different drugs in this country. And some of these drugs are critical life saving drugs that we can't get. Today we have children who can't be treated for their cancers. Accordingly, I can't even imagine the nightmarish situation that must be for their physicians and their family members to know that they have a young child who needs a certain cancer drug. They can't get it. I mean, that that is scary. But, Chris, when we look at where we're at today, I fear that we're just getting started in terms of the shortages. Well, why is that? Well, because most of these drugs today are in fact, generic, for which they basically are manufactured throughout the world, primarily in China and India, and for which there is very, very, very little margin of profit with these drugs. And so there's not a lot of investment in these areas. And I think that this has been a challenge to say, well, what are the supply chains you need to have and how much will they cost? So let's let's just dig down a little bit further on the buy, sell and shortage. Noted. Pfizer announced the buy, sell and shortage last month, stating that the shortage is a result of a complex combination of factors, including significant increases in demand due to an increase of syphilis infection rates as well as competitive shortages.


Dr. Osterholm: [00:49:21] What this means is they just couldn't make enough, didn't have enough. And that's the challenge. Both the adult and pediatric forms of bicylinder are in short supply as Pfizer has slowed production of the pediatric form of the antibiotic in order to increase production of the adult medication. Though the demand for the pediatric form of the medication is typically low. Now we've had shortages of amoxicillin, another common antibiotic, and therefore the second line drug you would use is selling, which now is also being challenged. The CDC has stated that most syphilis patients who cannot access by selling should take doxycycline as an alternative treatment. But it's important to note that for pregnant individuals infected with syphilis, there is no alternative treatment. This is particularly concerning as congenital syphilis rates have already increased roughly 700% over the past decade. The reality is that as long as these shortages continue, we should expect to see more untreated syphilis and more transmission. And this is going to be true with other infectious agents. So what does this mean going forward? Well, I worry that there's going to be an additional layer of challenge thrown at us very soon. And that is you're going to be hearing about more and more major infectious disease related research development and product licensing and manufacturing from some of the biggest pharmaceutical manufacturers in the world. Why? Why are they getting out of this area? Well, if you look at the infectious disease market for drugs in 2031, not that far off, it's estimated it'll be about $120 billion a year.


Dr. Osterholm: [00:51:04] A lot of money. But if you look at the oncology market in 2031, it'll be 471 billion. And if you look at the neuroscience market in 2026, just three years off, it's 721 billion. If I'm a pharmaceutical company and I have so much money to invest in research and development, what are my opportunity costs if I go into infectious diseases when I could have a much, much higher return on investment potentially in these other markets? So I think that even as we're talking about drug shortages for these other markets, ID is going to take a bigger and bigger hit. And I don't think the world realizes that. You know, these are private companies. They are not in any way, shape or form following what the government says. You've got to do this or this or this. That doesn't happen. It's open to, you know, the free capital society. And so I think this is going to be a real challenge. And it's not at all clear to me what it might look like in a few years, which could even be a lot worse. So what do we do about it? We are going to need government intervention here to assure that these supply chains exist. Wouldn't it be such a horrible, horrible, horrible outcome to know that we have drugs that could be effective, that could save lives, but nobody can get them because somehow nobody wanted to pay that extra $0.03 per tablet, whatever, to make a generic drug. Available.


Chris Dall: [00:52:38] Now for our latest moment of Joy submission. Mike, who did we hear from this week?


Dr. Osterholm: [00:52:44] This may be one of the most special moments of joy that I've had the opportunity to share with the group here. You know, I work with incredible people at CIDRAP. Incredible. This podcast team is is exactly that. And I rest on the shoulders of so many people there. And one of the people who is a member of our CIDRAP team, Elise, who is referenced each week in the podcast Acknowledgment as part of the team and who has been a very important member of our CIDRAP team, as you may know, recently had a baby and her first child, Tommy, someone that if you saw the pictures, you couldn't help but just break it into a smile. Beautiful pictures. So Elise actually has shared a moment of joy with us as she has just come back to work in the last week and a half. And so I'm going to share with you that. And it has a very personal connection here, as you'll see in a minute. One that I can't tell you how proud I am as a father. So here is Elise, moment of joy. Thank you, Elise. My moment of joy from this year was welcoming a new baby and after a very busy, often draining few years of working in public health, emergency response, bringing a new little person in the world is such a ray of light.


Dr. Osterholm: [00:54:03] It came with its own challenges, from trying to navigate the Minnesota State Fair with first trimester morning sickness to having a difficult first week after birth in the neonatal intensive care unit. We are incredibly grateful for all the amazing staff at the University of Minnesota Women's Health Specialist Clinic and the University of Minnesota Masonic Children's Hospital, including the other Doctor Osterholm. We look forward to the many adventures ahead of us as a family and with our happy and healthy little boy, we may even have a future epidemiologist on our hands. Thank you, Elise, for sharing that. Again, Tom, he's a beautiful boy and we're so pleased he's doing well. Now, noted here in this, of course, is, as many of you know, my daughter, Dr. Erin Osterholm, who is the real doctor in the family, by the way. I just play one on TV. She actually is the medical director of the NICU at the University of Minnesota and someone who I'm incredibly, incredibly proud to be her father. I'm so glad that she could be there with Elise and her husband to bring Tommy along into this world and now doing very, very well. So what a moment of joy. It really is a very, very special moment.


Chris Dall: [00:55:19] And just a reminder to our listeners that we would love to hear from you about your moment of joy even as we move past the pandemic. We know that we live in challenging times and finding the thing that brightens your day, even if just for a moment, is so important for our mental health. So what is the thing that you look to for a little bit of joy? It can be a place, a person, a pet, a piece of art, a memory. It can be whatever you want it to be. You can share it with us at Osterholm. Update at Umbn. Edu. Mike, what are your take home messages for today?


Speaker3: [00:55:49] Well, Chris.


Dr. Osterholm: [00:55:50] Kind of on a theme here that we've had for the past few podcasts. The first one is clearly we continue to have good news about COVID, not perfect news, but good news. And I think that everything I'm seeing right now still tells us that we're on the backside of the pandemic. I haven't seen any evidence yet that we are going to see a new emergent variant that could cause us nightmare moments. But we'll have to wait and see. And I want to be very clear about that. As I shared with you with regard to the data on whitetail deer, for example, what does that mean? What could that represent? And so we'll have to continue to monitor it. But even with the deaths we have, which are too many, we've come a long, long ways. Second of all is the fact that we do need to expect the unexpected. And that is what we're really talking about in terms of the whitetail deer population. Example. And, you know, I still need to sleep with one eye open, even if my crystal ball isn't necessarily caked with five inches of mud right now. It's still got 3 or 4in. And I think that this is where the public expects us now to provide them with the current information about what might be happening.


Dr. Osterholm: [00:57:09] And if things are improving, share that if we have reason to be concerned, share that. And so we'll see. Finally, I just want to say that the RSV, COVID and influenza vaccine scenario I talked about today is actually a positive thing to be able to have these vaccines. But also, I think it's very important to be very, very careful about the assumption that COVID is a seasonal disease, which it's not. It should be one at this time. It should be interpreted at this time as one where you need that booster likely every six months, whenever the season might be. And with influenza, you don't want to get the vaccine too early. You just don't. So I think those are the main points. I would add a caveat. Fourth one that I think is also something is doesn't really need to be stated, but long COVID cannot be forgotten. We have to continue to emphasize the research agenda to understand why it happens and what we can do about it. There are far too many of us who have been through long COVID symptoms and I dare say for those who continue to have them, I'm so sorry, but we need to clearly do much more to to emphasize research and understanding what's going on and what we can do about it.


Chris Dall: [00:58:38] And I understand you have not one but two closing songs for us today.


Dr. Osterholm: [00:58:45] Well Chris, after I  started this dedication for the podcast, it should be clear to people that I'm very concerned about what's happening with climate change and these high intensity precipitation or drought moments, what's happening with heat, etcetera. So yeah, I think we've got some real challenges, but how could you not how could you not be taken in by Elisa's moment of joy? You know, what a special, special moment. And so I would like to reflect both of those today in our closing. And the first one I've picked is one that if you are a baby boomer generation, you recognize this one right away. This is one from the late Marvin Gaye. It's the second single from Marvin Gaye's 1971 album, What's Going On? Following breakthrough of the title track Success. The song, written solely by Gaye, became regarded as the popular music's most poignant anthem of the sorrow regarding the environment. This song basically went to number one for two weeks on the R&B singles charts in August of 1971. Here are the lyrics. Mercy. Mercy Me. Marvin Gaye. Mercy. Mercy Me. Things aren't what they used to be. No, no. Where did all the blue skies go? Poison is the wind that blows from the north and south and east. Mercy. Mercy! Me. Things aren't what they used to be. No. No oil wasted on the oceans and upon our seas. Fish full of mercury. Mercy. Mercy. Me. Things aren't what they used to be. No, no. Radiation underground and in the sky.


Dr. Osterholm: [01:00:30] Animals and birds who live nearby are dying. Mercy. Mercy me. Things aren't what they used to be. What about this overcrowded land? How much more abuse from man can she stand? Marvin Gaye. Now, clearly the issues are a bit different today with climate change relative to what he talked about, but I think they really share that same anthem about what are we doing to our earth? And in the second closing song here, I just had to use this song as a sense of feeling and thinking about Elisa's moment of joy. This song I've used before. What a Wonderful World Is, a song written by Bob Thiele as George Douglas when he wrote it, and George David Weiss. It was first recorded by Louis Armstrong and released in 1967 as a single in April 1968. It topped the pop chart in the United Kingdom, but performed poorly in the United States because Larry Newton, the president of ABC Records, disliked the song and refused to promote it after it was heard in the film Good Morning, Vietnam. It was reissued as a single in 1988 and rose to number 32 on the Billboard Hot 100. Armstrong's recording was inducted to the Grammy Hall of Fame in 1999. This song reflects that feeling, that moment of what we captured today in a Lisa's note. So here it is. What a wonderful world. I see trees of green. Red roses, too. I see them bloom for me and you. And I think to myself, what a wonderful world.


Dr. Osterholm: [01:02:15] I see skies of blue and clouds of white. The bright blessed days, the dark, sacred nights. And I think to myself, what a wonderful world. The colors of the rainbow, so pretty in the sky are also on the faces of people going by. I see friends shaking hands, saying, How do you do? They're really saying, I love you. I hear babies cry. I watch them grow. They'll learn much more than I'll ever know. And I think to myself, what a wonderful world. Yes, I think to myself, what a wonderful world. Louis Armstrong. Thank you, everyone, for being with us. Again, another podcast. I hope we've provided you with the kind of information that you find helpful to the podcast family. Thanks again for this opportunity to be in your homes wherever you are listening to this, it's a real honor and privilege. And again, we welcome your comments. Everything sent to us is read by the team. We appreciate it very, very much. And as I close and celebrating, what I do believe could be the back side of this pandemic is still never, never a time to forget how important kindness is, how to think about how someone else will feel when we are kind to them. Thoughtful in a world that has so many challenges today. What a beautiful commodity that is. What a beautiful commodity. So thank you for listening. Be safe. Be kind. Talk to you soon. Thank you.


Chris Dall: [01:04:00] Thanks for listening to the latest episode of the Osterholm Update. If you enjoyed the podcast, please subscribe rate and review wherever you get your podcasts and be sure to keep up with the latest infectious disease news by visiting our website CIDRAP.umn.edu. This podcast is supported in part by you, our listeners To contribute, please visit CIDRAP.umn.edu/support. The Osterholm Update is produced by Sydney Redepenning, Elise Holmes, Cory Anderson, Angela Ulrich, and Meredith Arpey