More than two years into the COVID-19 pandemic, there are still many questions that we sort of think we know the answers to, and many others we don’t. We do know vaccine effectiveness wanes, and that vaccines need to be updated to keep pace with an evolving virus. We don’t know if next-generation vaccines will be as effective against current variants as the original shots were against COVID Classic. We do know that the virus is substantially less deadly now that we’ve built up a big wall of immunity, but it still manages to infect most people, sometimes even multiple times a year. Is this a level of disruption we’re just going to have to tolerate indefinitely? Would anyone really be satisfied with the existing level of COVID risk continuing in perpetuity? And is our healthcare equipped to deal with the ongoing and compounding effects of long COVID? Dr. Peter Hotez, professor of pediatrics and molecular biology at Baylor College of Medicine and co-director of Texas Children’s Hospital Center for Vaccine Development, joins Brian to discuss the known knowns, known unknowns, and the unknown unknowns of COVID—and whether ongoing research can provide the answers we need.

TRANSCRIPT

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Brian Beutler:  Hello and welcome to Positively Dreadful. I’m your host, Brian Beutler. So if you’re listening to this, it’s probably Friday, September 16th, or maybe Saturday the 17th. But I recorded the episode on Monday, September 12th, and on Sunday the 11th, I got my latest COVID 19 booster shot. Specifically, I got Moderna’s so-called bivalent booster, which has been reformulated to target or neutralize the BA.4 and BA.5 Omicron sub variants. So I feel a little crummy as I record this. Not too bad. Mostly I’m just relieved to have received the booster. I have some leisure travel coming up, my first trip abroad since before the pandemic, and it’s nice to think I’m that much less likely to get sick with COVID before my trip or during my trip. One thing I definitely do not feel, though, is the same sense of permanent ground shifting change that I think we all felt when the first gen vaccines became widely available early last year. And part of that is that we’re all a bit snake bit by that initial exuberance that the vaccines might make COVID an actual non-factor in our lives. But another part is that we don’t have the same assurances this time. Remember back then, we’d hear the Moderna shot is 94, 95% effective against COVID infection, Pfizer’s 90%, etc., etc.. We don’t have those numbers, at least not yet. And that’s in part because back then nobody had been vaccinated and relatively few people had had COVID. And now we have this big immunity wall where nearly everyone has at least some immunity. So one’s response to the updated vaccines is probably going to be a function of what baseline of immunity they were boosting from. And then there’s this newish concept, or at least it’s new to the masses called original antigenic sin, which might complicate things further. What is that? Well, I’m mostly going to leave it to Dr. Peter Hotez to explain. But my understanding is that later variants of novel viruses can be harder to immunize against because the body has been primed through prior infection or prior vaccination to respond to the earlier variants. And as we know, Omicron substantially different from wild-type, COVID and the Alpha variant and even the Delta variant. So it’s pretty confounding if that’s true, especially if you’re hoping to gain some sense of how long will be in this phase of the COVID pandemic. Right. In the world of COVID prognostication, you’ll find people who are concerned more virulent strain could upend things all over again. You have others who are just as certain that COVID will eventually mutate into some harmless form, like the Spanish flu eventually did. But to my mind, the only thing we can truly reckon with is how things are now. Would anyone really be satisfied with the existing level of COVID risk continuing in perpetuity or even just for a few years? We think of Spanish flu as something that killed a lot of people in the middle of World War One. But the data from that time shows that excess deaths remain significantly elevated well into the 1920s. It’s not my favorite piece of historical trivia, but it’s true, and it is what it is. So let’s assume we’re just on a something like a similar trajectory where COVID remains substantially less deadly than before we built up all this immunity, but still manages to infect most people, sometimes even multiple times a year. Is that a level of disruption we’re just going to have to tolerate? And what does that suggest for the overall toll of COVID, which includes not just people who are acutely sick with it or who die from it, but people who remain sick with post-COVID illnesses for months or years. Even after all this time, there are just basic questions about pandemic illness that we sort of think we know the answers to, but maybe we don’t, actually. So that’s why we wanted to talk to Dr. Hotez. If you followed the pandemic through the news, he’s been a vital experts source of information. He’s a professor of Pediatrics and Molecular Biology at Baylor College of Medicine and co-director of Texas Children’s Hospital Center for Vaccine Development, and has particular expertize in vaccines, including COVID vaccines. So if there are answers to these questions, he should have them. So, Dr. Hotez, welcome to Positively Dreadful.

Dr. Peter Hotez: Oh, great. Well, thanks so much for having me.

Brian Beutler: Okay. Can I start with my only stupid question and then we’ll get into smart questions?

Dr. Peter Hotez: There’s no stupid questions. I may not give you the best answer—

Brian Beutler: No, I think you will. It’s kind of stupid, only because I have doctors in my family that I could ask this. But for the benefit of listeners, are doctors trained to practice under pandemic conditions is like is pandemic provision of care part of the training that doctors and other health care providers go through at medical school or nursing school or wherever else?

Dr. Peter Hotez: Well, the short answer is no. And the reason is, is because we were the the our age of pandemics is relatively new. And it’s something that in my last book, Preventing the Next Pandemic, I’ve been writing that that just came out last year. I’ve been writing that that we are starting to see an increase in pandemics starting around 2013, 2014, and that’s when we’re starting to see the big upturn. And so medical schools and residency trainings, they’re not really attuned to all of this new normal.

Brian Beutler: Is it something that you think just going forward as we reassess how we do provision of care in the age of pandemics, that training under these conditions, providing care when there’s communicable diseases around that everyone’s susceptible to that are dangerous, are something that the people who work in hospitals are prepared for and don’t sort of see the COVID experience as a as a one off.

Dr. Peter Hotez: Well, I would broaden it a bit more to say that I think we have to recognize now that disinformation and is is at an all time high in how we now practice medicine in this new era of disinformation and the fact that physicians and physician scientists are not out there communicating with the public on a regular basis. You know, too many of us are still largely invisible. I think that that’s got to change. I think dealing with all of all health professions and the fact that people are leaving in droves and understanding the forces that are that are driving that. So no question about it. We’re going to have to make some adjustments moving forward if we’re going to handle this pandemic better than the current one.

Brian Beutler: Yeah, the next one right— [both speaking]

Dr. Peter Hotez: I mean, the future pandemics better than the current one.

Brian Beutler: So quick u-turn back to technical questions about COVID and vaccines. Should we expect the new bivalent vaccines to be as effective against the current variants as the original mRNA shots were against wild-type and Alpha variant?

Dr. Peter Hotez: Well, there’s a lot of unknowns. So right now, so the the new booster, which is a combined mRNA that targets the original lineage coming out of central China, plus the second one that’s targeting the BA.5 sub variant. Here’s what’s happening. BA.5 Is starting to go down now. So it’s it’s slow with a long tail, but there’s no question it’s starting to go down, which is good. But the question is, what are we vaccinating against at this point? Because I think the the bigger unknown question is what’s around the corner? I think, you know, if you’ve looked at this pandemic, we’ve had these big waves during the winter. So last winter. We had the big Omicron BA.1 wave and the winter before that we had the big Alpha wave and those were incredibly deadly with two to 3,000 deaths per day. So what’s what comes this next winter? And I don’t think anybody knows. And unfortunately, we don’t have good surveillance mechanisms to understand what’s out there. We don’t have good forecasting mechanisms to understand what drives at a very granular level the new variants, other than the fact that they mostly are coming out of low and middle income countries and we have failed to vaccinate the world’s low and middle income countries, so we should expect another one. So the hope and this this is not an easy concept to explain for a lot of people because we haven’t really done this before. The hope is that whatever is coming along by having a vaccine with two components against the original lineage and the BA.5, it gives us two shots on goal to hope that whatever is coming along might look either more like the original lineage or BA.5 And therefore make it more likely that it’ll it’ll prepare us for what might be coming ahead. And and although that’s not really articulated, I think that’s driving a lot of it. We’re actually moving slowly towards a universal coronavirus vaccine, which in addition to our current vaccine, that’s something else we’re working on, but we don’t really frame it as such.

Brian Beutler: You have me here hoping that the next wave is going to BA.5 because I just got my bivalent booster yesterday. I guess the good news personally is that I feel basically okay today, previous boosters, not so much, but—

Dr. Peter Hotez: You did the right thing. And and and I definitely support this new booster that but what’s not being articulated so well is what are we actually immunizing against if the BA.5 Is starting to go down? Well, first of all BA.5 If I still going to be with us for a few more weeks anyway, so so take that at face value. But the other issue is what’s coming in this winter if we get another big wave? And the hope is by now you’re having immunity against both BA.5 and the original lineage, it might put you in better shape for whatever comes down the pike next.

Brian Beutler: So can you explain a concept that I’ve read a little bit about in recent weeks but had never heard of before of original antigenic sin?

Dr. Peter Hotez: Yeah. And we actually see it in our laboratory, in our rodent mouse models of of COVID 19 as well. So basically what it says is whenever you’re initially immunized with and boosted, thats, it’s basically steering your immune response towards that. And the worry is that by doing so, it may not respond. Your immune system may not respond as well to something that sort of resembles it, but is also different. In other words, all of our immunity is being steered towards the original lineage and that it may not pick up the signals to respond adequately to BA.5 even though BA.5 is in the booster, it’s still more of a theoretical concept than something hard and fast. And the answer is, we don’t know. We we’re hoping that there’s still going to be an immune response to BA.5. But let me give you an example of it. So in our efforts to make a universal coronavirus vaccine on top of the one we’ve already made, we’re looking at combining the original SARS that emerged back in 2002 with this COVID 19 original lineage, the second one and maybe two or three others, or one or two others that correspond to what people are finding in bats right now, etc.. What we find in the laboratory, in mice is that if we immunize with the original SARS, call it SARS-1 that emerged out of 2002 and then we boost with SARS-2. We don’t get much of an immune response to SARS-2, we still continue to get a predominant immune response bias against SARS-1, and if we reverse it and immunized first with SARS-2 and then boost with SARS-1, we’re steering the immune response to SARS-2.

Brian Beutler: Wow.

Dr. Peter Hotez: And you might say, Oh my God, so what does that mean? Why did I get this booster? Well, the answer is, you know, we have a we have an expression in biomedical science, which is that mice lie and that what’s true in mice may not always be true in humans. So I don’t think, you know, the good news is that we although we don’t have data on BA.5, the FDA and others have looked at other types of boosters like the original BA.1 booster in human trials and humans do respond to it. So—

Brian Beutler: That’s good. I’ll take that.

Dr. Peter Hotez: —so, so the idea of a, so the original antigenic sin idea, you know, has been shown to be the case on occasion. But there’s no way, I think, to predict in this human immune response to coronaviruses whether that’s going to pan out or not.

Brian Beutler: Do you take any solace in the fact or do you think it’s significant at all that we’ve been in this kind of Omicron family of variants and subvariants for ten months without it shooting out to either go to be more like the wild-type virus or something new and newer altogether?

Dr. Peter Hotez: Yes, but on but it’s tempered by the fact that if you look at the immune responses to the original Omicron BA.1, it doesn’t protect that well against BA.5. So they really are quite different. We call them subfamilies rather than a new Greek letter. But for all practical purposes, they’re operating like a new Greek letter in many respects.

Brian Beutler: Wow.

Dr. Peter Hotez: So so we’ll see what what’s what’s coming down the pike next. I mean, I think the long the long range answer, I think, is to develop a universal coronavirus vaccine, not only against any new subvariants or variants of the SARS-2 virus, the COVID 19 virus. But remember how this works. We’ve had SARS in 2002. We’ve had MERS in 2012, Middle Eastern Respiratory Syndrome, which is another coronavirus. Now we have COVID 19. We still don’t understand at a granular level how these viruses have emerged from bats and jump to humans. So guess what? We’re going to have a fourth COVID pandemic or a serious epidemic, I predict, and maybe a fifth. So and I can’t tell you where that’s going to be in 2026 or 2032. But at some point, we are likely going to have another fourth major coronavirus epidemic slash pandemic. And so if we can make a universal vaccine that will get all of the beta coronaviruses, somebody sometimes called the sarbecoviruses, I think that will put us in good shape. And that’s one of the things in addition to our vaccine technology like the Corbevax now in use in India and IndoVac in Indonesia, making a universal one we think is the long range to go. The problem is there’s probably a couple of years away. So then the question becomes how do we navigate this space for the next couple of years? And people have different opinions about that.

Brian Beutler: So I want to get into that in a second. But first, there’s an idea that I have seen pop up and kind of bubble out of fashion since the since the pandemic began. The idea that over the long haul, viruses tend to mutate to be both more more contagious, but less virulent. Is that is there any truth to that? Is it just a myth? Are we just lucky that in the course of human history, a virus hasn’t emerged and just become increasingly lethal?

Dr. Peter Hotez: Well, the virus will evolve whatever gives it some fitness advantage so that that that makes sense that it is becoming somewhat more transmissible. And I think we have human transmission data to document that, that it’s becoming now the if you look at the reproductive number of this BA.5 subvariant, it’s it’s quite a bit higher than it was with the original lineage and reproductive number refers to how many people on average will get infected if with a single index case. And so it was around, you know, two for the original SARS, which is still pretty high and now it’s upwards maybe over ten. So that’s significantly more transmissible, but there’s no reason why it has to be less severe in terms of illness. And quite honestly, I’m not convinced that the severity of illness with each successive wave has really decreased. I’m not convinced of that at all. You might say, well, hang on before we are to having two to 3,000 deaths a day. Now we’re at, you know, 500 deaths per day. So it’s still pretty serious, but not as high. And I think part of that is being mitigated on a population level that so many people in the United States have either been infected before, vaccinated before or or more likely infected in vaccinated or vaccinated infected population level that has had some mitigating effect on the number of deaths. The problem is the mistake people make is they translate that to individual health decisions. They assume that means that there’s that the virus is less lethal and they’re out of the woods. It’s not the case. You have to be mindful of your vaccination status. So if you’re unvaccinated, you’ve just gotten lucky and you could get a BA.5 infection that will land you in an intensive care unit. And even if you’ve gotten now two immunizations, but not gotten your booster or in some cases not gotten your second booster, then you’re still at risk of hospitalization. So when you’re making individual health decisions as on a population level, yes, there’s some mitigating effect, but it doesn’t really inform you very well for individual health decisions. The bottom line is the single most important thing you can do to protect yourself and your family is to be mindful of your vaccination status and max out the number of boosts that you’re eligible to get. That’s the probably the single most impactful way you keep yourself or your loved ones out of the hospital.

Brian Beutler: Is there a theory, though, about why we haven’t seen this operate in reverse? Where like the Spanish flu, for instance, fizzled out after several years. It mutated, I think, into a less harmful mutation or variant and then stop killing people.

Dr. Peter Hotez: Except not really. Right. Because we still saw I mean, we still have regular waves of flu, including some devastating flu epidemics in the out years. So. Um—

Brian Beutler: And and those are and those are of the same lineage as the Spanish?

Dr. Peter Hotez: —well, they’re either the H3N2 or the H1N1 or or some combination of those. So. So I wouldn’t I think I wouldn’t count on that at all. That that what’s lurking out there is somehow more benign. First of all, a brand new coronavirus could come along that’s that has the same transmissibility, a beta of BA.5, and yet actually causes much more severe disease. I mean, let’s let’s look at the original SARS that had about a 10% mortality. The same with MERS with with SAR-2 at about a 1% mortality. But it had the other disadvantage of so many asymptomatic people. So it made it made it much harder to do contact tracing and transmission control. The next either subvariant of SARS-2 could be 5% mortality. And the next big coronavirus that comes out of the bats across the face of Asia and elsewhere could also be like that. So. So we have to be extremely mindful.

Brian Beutler: So it does sound like you’re saying that it is sort of just an accident of history that at no point along the way has a novel pandemic virus emerged and then mutated into something that—

Dr. Peter Hotez: Well, it may be like, for instance, look at I mean, prior to, you know, when I was being trained in pediatric infectious diseases. Way back when, I mean, the teaching was that there were four upper respiratory coronavirus infections. And they caused generally they were considered a less common cause of the common cold compared to something like a rhinovirus, and then occasionally did cause severe disease. But it was rare. Now, the question is, how did those begin? Did those begin with something that resembled, like COVID 19, back in the 1920s or back in the 1800s, and then evolved to become something more to less severe. I think that’s a possibility, but we don’t really know that.

Brian Beutler: Has COVID improved our understanding of I believe I believe I’m pronouncing the term right post-viral sequelae in general, is there a reason to suspect that long COVID is a novel form of post-viral sequelae?

Dr. Peter Hotez: I think things like long COVID do happen with other serious viral infections like Epstein-Barr virus or influenza, but I think seeing it in the pandemic form like this has made us so much more aware of it. And now what’s really exciting in the field is there’s some fantastic basic research going on to understand the mechanisms of it. And there are things like autoantibodies to the virus or what’s called micro glial activation, or even in some cases maybe latent virus, although I think fewer people believe that. But the reason I say that is now with with the mechanisms being uncovered associated with long COVID from the stars to coronavirus, maybe that gives us ideas of going back now to people who have chronic fatigue syndrome or fibromyalgia, possibly something that started after another viral infection. To help us understand what the mechanism is there.

Brian Beutler: Do we know yet if the people, generally speaking, are equally susceptible to long COVID or other post-viral sequelae?

Dr. Peter Hotez: Well, we’re actually looking at that to model it with a group out of City University of New York headed by Bruce Lee at this different Bruce Lee [laugh] at at the School of Public Health Bruce Y. Lee and his team. And, you know, looking at the you know, the published literature on long COVID, first of all, any any COVID case could ultimately lead to long COVID, but including asymptomatic illness. But on average, the risk seems to be go up with severe COVID. So severe COVID is is more likely to, you know, create susceptibility to long COVID than non severe COVID. That’s one. Second diabetes, underlying diabetes appears to be a risk factor, but that may also because people with underlying diabetes get more severe COVID. So could be the severe COVID thing. And conversely, vaccination seems to have some mitigating effect. And that could be because vaccination makes you less likely to get severe COVID. So all of those things are being looked at right now. So even a mild COVID, even asymptomatic COVID, could give you long COVID. But on average, the risk of long COVID seems to go up with more severe illness.

Brian Beutler: I ask for for a couple of reasons. One is, I wonder if if we’re just going to wait and hope that COVID burns itself out and thus nearly everyone will get it at least once, then then it matters whether there’s like a lid of sorts on how many people will end up with some sort of debilitating long term condition from it versus if, if it’s really just like everyone’s, you know, similarly susceptible to it, that the more it churns through the population.

Dr. Peter Hotez: If it turns out that I’m correct, that that severe COVID predisposes you to a greater likelihood of long COVID, then you’d expect long COVID, the the the prevalence of long COVID will be higher in areas of the country where vaccination rates are lower, which tends to be in the part of the country that I’m in, in Texas, in the southern United States, where people have been defiant about vaccines. So in addition to the higher death rates in the southern states and where where people are not getting vaccinated, we’re going to see more long COVID as well. And unfortunately, a lot of the southern states are not as wealthy as some of the northern states, so they’ll be less able to handle it on the health systems basis as well. So that’s the next, other shoe. I think that’s a lot of shoes that are falling these days and I think that could be one of them.

Brian Beutler: The other reason I ask is, and this is slightly more personal than I normally get on on the show, but my wife and I got COVID just before the mayor issued the shutdown order for Washington, D.C. in 2020. So we were like we were among DC’s inaugural infectees and we were both mild to moderate illness, then maybe a month of COVID pneumonia. And then we were better, except I lost basically all of my physical conditioning. So I tried to go on a run and I couldn’t get more than a couple of blocks. And then I tried again and a few days later the same thing. And I remember the news reports at the time suggested post-COVID exercise intolerance was fairly common. They were already getting lots of reports about it and it was probably just heart inflammation and it would go away. So don’t rush out to the hospital, just give it time. So I gave it time, but weeks became months and it didn’t get better. So eventually I asked my doctor to investigate, and after several scans and several more weeks, he found blood clots in my lungs that had become chronic. And it’s been a whole ordeal. [laugh]

Dr. Peter Hotez: Sorry. Yeah. No, this is. This is not an unusual story, unfortunately—

Brian Beutler: Yeah, well, and so, you know, when I have written about it, I’ve gotten emails from people who have experienced basically a similar situation. But one thing I think back on, the one thing I could if I could go back and change anything, I would would have been to ignore that advice about not going to the hospital if you’re having post-COVID difficulty exercising, because if they’d caught on to what was happening sooner and were able to lice away the clots before they did permanent damage, then it would have had a big impact on my, you know, future health.

Dr. Peter Hotez: Potentially—

Brian Beutler: Potentially, yeah.

Dr. Peter Hotez: —and now hopefully, you know, we’re and there’s still a lot of variation in terms of degrees of sophistication and understanding long COVID depending on what medical center you you go to, you know, some medical centers have created long COVID, long haul clinics that are specializing in this, but not enough.

Brian Beutler: Yeah.

Dr. Peter Hotez: And so so I think this is going to haunt our already messed up health system for a long time. And and then not only on the medical side of things, because it’s first of all, it’s multifaceted, right? It’s long COVID could be, you know, chronic brain fog or neurologic and cognitive deterioration or it could be, as you described, exercise, intolerance or pulmonary insufficiency. So it’s going to require multidisciplinary clinics. So so it’s a complicated issue from the medical side, but then we’re going to have to deal with what the insurance companies are going to do? What what are we going to do about people who have to go on disability? It’s it’s you know, we’ve already got a dysfunctional health system in this country despite it being so expensive. And this is only going to show yet another aspect of our depleted health system and the mental health effects of that’s depressing as hell not to be able to—

Brian Beutler: I will say that for me. Yes—

Dr. Peter Hotez: —I mean, if I if I don’t go on the treadmill for 20 minutes every day and do my walks, I get I get into a funk, you know.

Brian Beutler: Yeah.

Dr. Peter Hotez: I can imagine what that’s like having that taken away for. So the mental health effects and how we deal with that and not just the mental health of people suffering from long COVID, but the mental health of people who have lost loved ones or you know, we’ve seen now a whole generation of orphaned of COVID orphans because of this. So and you know what? As bad as our health system is, it’s not nearly as bad as our mental health system, which is which is nonexistent. Right. So so this is this is going to be serious business.

Brian Beutler: Yeah. You know, in my personal experience, when I when I realized I couldn’t run anymore, I, I kind of modified my exercise routine to to be something that my, you know, new condition allowed for shorter bursts of work instead of steady state running. And that, you know, allowed me to continue exercising. So I didn’t have the sort of what you were describing that when when people who want exercise can’t it affects their brain chemistry. But, you know, when when the doctors came back to me and were like, you got blood clots in your lungs and it’s like a lifelong condition and it’s really dangerous. I mean, that was terrifying, right? Like that. The knowledge that there was something something physically wrong with me was in itself a kind of trauma. And at least they were able to tell me what it was, because I think a lot of people with long COVID, you know, they they go in, they get scanned and their scans come back normal and—

Dr. Peter Hotez: Yeah, and and then and then we’re hearing reports of increased susceptibility to heart disease or cerebrovascular events. So we’re, we’re still on a steep learning curve understanding. I mean, remember, this is a disease we didn’t know about three years ago. So we’re still on a steep learning curve. Understanding all of the ramifications. I’ve said this in public before. I’ll say it again. This is going to change the way we think about medical practice and not just from the that’s how we started this conversation about the physician burnout issues, everything else. But even just the pure raw medical side of the practice is going to change because of COVID. Just like HIV/AIDS was a game changer for internists, you know, in the and neurologists in the 1980s. I think it’s going to be the same for COVID.

Brian Beutler: What would you tell your patients, any patients about, you know, if. If somebody has COVID and then they get over their acute infection and they have brain fog, for instance, you know, when would you tell someone, you know, just you’re going to have to work through that on your own and hopefully it’ll go away versus this sounds more serious. You should go have a doctor do get imaging or tests taken to determine what’s going on.

Dr. Peter Hotez: Yeah, well, I think I think there’s there’s two components to that. I think in terms of the brain fog. One is the studies coming out of, you know, the Oxford University Neurology Group showing gray matter brain degeneration. So should you get an MRI or a functional MRI and a neurologic evaluation? I think that’s one. Second, you know, and documenting any cognitive decline that you might be having. But third is that in itself could lead to depression or other psychiatric issues. And so we’re going to need a mechanism by which neurologists and psychiatrists talk to one another to provide that kind of interdisciplinary care.

Brian Beutler: What? I guess so what happened to me, like I said, is something that doctors could see. I mean, they did the imaging, they found the clots. They were able to give me a diagnosis then, and they had preexisting tools to address it, which has allowed me to get much better. I don’t know how true that is of other forms of long COVID or post-COVID sequelae. Are there, you know, are there ways of detecting? What what is causing the brain fog testing to to document that it’s this class condition and thus might respond to these therapies or an experimental therapy.

Dr. Peter Hotez: Well, the way the Brits found it was because they have a real health system. Right. The National Health Service. And as opposed to us, we have Amazon pharmacy. Right. So. But what what they what the Brits were able to do, the Oxford Group is they had 40,000, they had a registry of 40,000 brain scans, MRI’s, before the pandemic. And people who they’ve documented got COVID, they could invite them back and get an after image. And so it was a sort of a perfect lead design study in some ways, before and after they could see the documentation of the gray matter, brain degeneration and a picture that resembles somebody with cognitive decline. So that’s extremely useful. We unfortunately, we don’t have anything quite like that in the U.S., but it’s still something that could be followed potentially with imaging studies. The problem is, I don’t know that it’s being done systematically. You know, if there is an investigator, a neurologist in an academic health center in your city that has a personal interest in it, that person can follow it. But right now, as far as you know, it’s not been universally adopted into clinical algorithms for all neurologic care or psychiatric care, etc..

Brian Beutler: So what are the prospects as far as, you know, of the scientific community, the medical community making progress on treating the most common forms of long COVID so that the risks associated with getting COVID can go down?

Dr. Peter Hotez: I think now that, you know, there’s work done, for instance, by Akiko Iwasaki’s group at Yale looking at the mechanisms of long COVID, the antibodies and microglial activations, others as well. Once you know that, in theory you could start designing intervention strategies, you know, if it really does have an inflammatory basis or an autoimmune basis, you can start design, looking at testing different drugs that work, that are anti-inflammatories, that work in reducing autoimmune sequelae to see if that has a beneficial impact on long COVID. The problem is it’s not quick. It’s going to take time to to do that. So I do have some optimism and the need is going to be huge because if you do the back of the envelope calculation, right, the fact that virtually the entire country’s, you know, probably has been infected at some point, or, I mean I shouldn’t say that. There probably, you know, three quarters of the country had been infected. It’s a lot of people and that’s a lot of long COVID. So there is some urgency to address this. I know the NIH is starting to look at this as well, but that all those studies have to be accelerated. And when the new NIH director comes on board, since Francis Collins has stepped down, it’s going to be really important that that becomes a big priority.

Brian Beutler: So when do you anticipate excess deaths returning to their pre-COVID baseline? And do you think it will be thanks to human ingenuity or to the sort of natural wonder of viral evolution?

Dr. Peter Hotez: Well, I think, you know, if if we get lucky and we don’t see a big winter wave, that’ll help a lot, you know. So we’ll see. We can’t, I’m predicting we’re likely going to see it, but it’s not inevitable. So the key is, you know, in the fate’s in our hands as well. So if all of the entire country did what you just did and got boosted with this new booster will be in a much better position to weather what’s coming down the pike. So again, that’s the most impactful part about reducing both COVID and long COVID and reducing the excess deaths. As if you’ve not gotten vaccinated. Get vaccinated. If you’ve got vaccinated, get boosted. If you get boosted, get two boosts. And if you got two boosts and eligible for your third boost, get that as well. And if people more people were doing that, I think will we have the ability to reduce the number of excess deaths. The unknown is going to be even among people who have been vaccinated before after they got COVID. What is long COVID mean in terms itself of excess deaths, in terms of ongoing heart disease or cerebrovascular disease or pulmonary disease or kidney disease? I don’t think we have a full understanding of that by any means yet.

Brian Beutler: And it also sounds like the sort of thing that it’s happening so much on its own separate track, that it’s what we learn or what we develop to to treat long-covid or reduce its symptoms may not emerge at a time when COVID is still pandemic in its incidence right so that people, as they go about their lives, they know that they have some risk of getting COVID. They know that entails some risk of getting long COVID. But if you also know that there’s ways to treat long COVID, maybe that makes it a little less scary.

Dr. Peter Hotez: Yeah, as I say, I think the specter of long COVID is going to haunt us for quite a while, even after the pandemic subsides and even before the next big coronavirus comes along, the fourth one after SARS, MERS and COVID long COVID is still going to be with us for quite a while. And by the way, we haven’t even talked to my kids. So I’m also concerned about, you know, long term neurodevelopmental outcomes in kids with long COVID. You know, everybody’s so focused on the and the lower death rate of kids. I just wrote a piece for Science Magazine about this and that long COVID is still going to be there among kids. And we’re going to need a whole new generation of pediatric neurologists and child psychiatrist to continue and and psychologists to continue to follow that among the kids as well.

Brian Beutler: So what are the what are the most hopeful and optimistic things that you see happening in either scientific development or provision of medicine or just the the nature of how this virus is spreading that people can can look to if they’re trying to see what, like the next phase after we’re through this liminal Omicron phase looks like, and that it’s maybe less disruptive and less scary.

Dr. Peter Hotez: Well, I’d say new and improve antiviral drugs for the acute stage of the illness. We’ve already got some good candidates. Better ones will come along. Remember, it’s still pretty early. You know, this is only been three years. And so the pace has been impressive. Improve vaccines in turn and also universal coronavirus vaccines. There’s some interest in alternative delivery mechanisms such as under the tongue or intranasal or oral. So I think there’s a lot coming down the pike and then some specific interventions for long COVID based on our understanding of the mechanisms, I think that’s going to be extremely important as well.

Brian Beutler: That is all great to hear. I will leave it there. But Dr. Peter Hotez, thank you for spending so much of your time with us today.

Dr. Peter Hotez: Thank you so much. I really appreciate the opportunity. [music break]

Brian Beutler: I alluded to this briefly in my intro, but the really confounding thing about trying to get your arms around the future of this pandemic is that there’s very little certainty about anything, even a problem as big and complex as, for instance, climate change provides us greater certainty because we can model it and we have reasonable confidence in what the inputs are and what outputs those inputs entail. COVID isn’t really like that. We could wake up tomorrow to news of a terrible new variant of extreme concern. Or we could see zero more infection waves. We could see daily death rates drop. For all intents and purposes, we’d be done with it. All we really know is what’s happening today, and assuming that doesn’t change much on its own in the near term. We know what we can do together or what scientists can do to get us closer to a pre-COVID baseline than we are now. And really, for all intents and purposes, I think we’ve collectively decided that that’s a question for the scientists, not for the larger culture or society. For better and for worse, society has chosen to act as if we’re mostly back to the time before COVID already, even though empirically we’re just not. And the truth is, I think that’s more or less defensible under the current circumstances. Individual and group risk is much lower now than in 2020 or much of 2021. Deaths are way down, though. If if we’re honest with ourselves, I don’t think we would have imagined tolerating as much death and disease as we’re facing today before we all became a bunch of boiled frogs. But we have become a bunch of boiled frogs. And so there’s tons of cultural and political and peer pressure to carry on under a minimal set of precautions. And that’s left us with a status quo where, as done with COVID as we might feel, it’s not really done with us. It can still throw a grenade into your best laid plans. It can keep you out of work for multiple weeks every year. And we basically said, okay. We’ll wait for next gen vaccines or we’ll wait for better therapies or we’ll wait for long COVID treatments. And the message I took from Dr. Hotez is those things are probably coming, which is great, but they’re also probably quite a bit further away than we realize or would prefer. And the problem is our collective blasé attitude about how tolerable the status quo is is contributing to that long lag. If we want things to get better faster, we need to convey a greater sense of collective urgency about our dissatisfaction with how things are now. But we’re not doing that. And unless that changes, the real blessing here is that there are still scientists like Dr. Hotez doing the best they can in a climate of political and social apathy to hasten a better new normal. [music break] Positively Dreadful is a Crooked Media production. Our executive producer is Michael Martinez and our producer is Olivia Martinez. Veronica Simonetti mixes and edits the show each week. Our theme music is by Vasilis Fotopoulos.