Akiko Iwasaki: What Have We Learned About Long COVID?

Transcript

Harlan Krumholz: Welcome to Health & Veritas. I’m Harlan Krumholz.

Howard Forman: And I’m Howie Forman. We’re physicians and professors at Yale University, and we’re trying to get closer to the truth about health and healthcare. Our guest today is Dr. Akiko Iwasaki, but first, we like to check in on current hot topics in health and healthcare. Harlan, what do you have?

Harlan Krumholz: Well, Howie, I was going to talk today about an editor’s page I did for the Journal, because it was kind of a little orthogonal to everything else going on in the world. There’s an area of medicine where it gets very little attention, but I think is very important, which is what do you do when your patient dies? How do you manage the conversations and how do you navigate the families and your own maybe sometimes feelings of guilt and how do you reach closure about that? And so I’ll just point that out. We’ll put it in the notes if people are interested in it.

But then I start thinking, you’re asking me what’s new and what’s going on, and I thought, how can we really acknowledge what really is going on right now in the world, Howie? It’s like I’m really concerned about the world’s and the U.S.’s sort of state of mind, mental health. I was in China for a couple of days, and I was sort of isolated from the news a little bit, in part because it’s hard to get the New York Times over there, that they’re banned still over in China. But also just because I was so busy.

And I came back and wow, just, I don’t know what, they’re knocking down the East Wing of the White House. They’re picking off people in Canal Street with people who look like they’re stormtroopers. The country just feels like it’s in mess. The shutdown is still there. My son is at the Department of Justice working for free, because he’s not getting paid. I looked at, there’s these food lines in D.C. for federal workers trying to get food. Food stamps are about to run out. If we can’t get this thing resolved, health insurance premiums are going to go up.

And then I saw this thing from Gallup that came out just yesterday that was talking about how Americans are perceiving federal agencies. And if you look at a lot of the agencies, by the way, this is emblematic of this, the agency that gets almost the highest rating right now is the post office. Who could ever imagine that would be the one that people would look to as the one that they trust the most?

But if you looked at agencies which are so important to our health that we really should be looking to for direction and feeling a great degree of trust, like the Centers for Disease Control and Prevention or the Food and Drug Administration, we are almost at historic lows for Americans rating them as doing an excellent or good job. Right now for CDC, and this is understandable given what’s happening, but I think this is a crisis in itself because there’s no authoritative, trustworthy source of information for people. So CDC is now down to 31% of Americans. Now they were never at a hundred, maybe they were hovering around 60 to 70, maybe 60% before, but it’s half of that now.

And as you know, the MMWR, the sort of beacon of information from the CDC, is on life support. Even to the point where The New England Journal of Medicinenow has said that they are going to partner with another organization to put out public health reports to fill that gap. And if you look at the Food and Drug Administration—CDC, 31% of Americans saying they’re doing good or excellent work, Food and Drug Administration’s down to 27%. Now they were never as high as CDC before, you go back to 2003, 2005, they weren’t quite as high as CDC, which had a lot of the trust of Americans. But these are historic lows.

So these organizations which provide such important information, they do such important work on behalf of the health of the nation. And there are very few people right now who think that they’re doing a very good job. And of all the federal agencies, like the top still are Postal Service, Department of Defense (which now is called the Department of War), NASA. But the bottom are these, and the very bottom is the VA, the Department of Veteran Affairs.

And you may say, well, how relevant is that to people at large? But for veterans who depend on those services, the fact that people are so dissatisfied now or feeling that the work that’s being done isn’t so good, and if you look at other surveys just about trust, it’s just been eroded. And I think it’s part and parcel of this fragmentation, this brinksmanship that’s occurring in the country, the polarization. But I worry that it has—nobody knows what to do. And I’ll just say finally there’s another measles outbreak in, where is it now? In South Carolina, I think, and that—

Howard Forman: There’s multiple right now, there’s several small outbreaks.

Harlan Krumholz: But I saw one in two schools and they were saying, I couldn’t believe this. They were saying in these schools the measles vaccination rate was only 17%, down to 17%. And so this thing is spreading like wildfire in that area, and of course threatening health and so forth.

So anyway, you asked me what’s going on. I came back, I had a great trip to China. By the way, there’s lots of great science going on, very interesting. Obviously its society itself has got its challenges too. But just in terms of the cardiology world, and it was almost like four or five days of being away from day-to-day news because I’m immersed in the news when I’m here. And I came back and it was almost like you get smacked in the face because, oh, my God, I almost can’t watch the news.

And whether you’re Republican or Democrat, this isn’t even a partisan issue. I’m just saying there’s so much strife and tension in the air in the country, let alone we’re facing the shutdown and with no prospect of resolution at the moment. So I don’t know how you’re encountering this, but I think this has got to be affecting people at work, at home, in relationships. It’s just adding to this, a layer that—

Howard Forman: I do think that there’s a lot of anxiety over a lot of this. And for me, personally, I’ve just learned to limit my intake to mostly the newspaper and checking Twitter infrequently, whereas I used to be on it all the time. So I agree with you, it’s a very divisive time.

Harlan Krumholz: But you want to be engaged, and no matter where you sit on the spectrum of politics, I urge people in a democracy to express yourself. And we had big protests over the weekend by one side and then the other side with artificial intelligence memes countering it, the president countering it. But yeah, I don’t know, it’s hard to know how to proceed. Sorry, I don’t know. It wasn’t an upbeat thing. Have you got an upbeat thing for me?

Howard Forman: I do, I do.

Harlan Krumholz: All right, well, you’ll have it at the end, right?

Howard Forman: I will.

Harlan Krumholz: We have Akiko Iwasaki today, which is a great joy. And so maybe we should move to the interview, and she’ll be a spark of insight for us. Then we’ll get to your thing at the end and you can lead us onto a high note. All right, let’s get to the interview.

Howard Forman: Dr. Akiko Iwasaki is a Sterling Professor of Immunobiology and Molecular Cellular and Developmental biology, and the Director of the Center for Infection and Immunity at Yale University. She’s also an investigator at the Howard Hughes Medical Institute. Dr. Iwasaki’s research centers on how the immune system defends against viruses that infect at mucosal surfaces and on developing vaccines that harness these protective mechanisms.

Since the COVID-19 pandemic, she has become one of the world’s leading scientific voices on COVID-19. And through her own lab’s discoveries and through collaborations with colleagues near and far, including our own Harlan Krumholz, she has substantially advanced the understanding of COVID-19, long COVID, and the means to prevent and treat it. She’s also passionate about combating sexism in academia and about advocating for, sponsoring, and mentoring women in science.

Dr. Iwasaki received her Ph.D. in immunology from the University of Toronto and Canada and her postdoctoral training from the National Institutes of Health. In 2024, she was named one of Time Magazine’s 100 most influential people in health. In February of 2022, she joined us on the 19th episode of the Health & Veritas podcast in the midst of the Omicron outbreak.

So much has happened in COVID science, immunology, and the world since that time. And we’re really just so grateful to have you back on the podcast today. And I want to start off by asking, there’s so much progress made on the long COVID front, and you and Harlan have worked on this, and very recently you’ve testified in front of HHS and Congress about the progress that’s been made. Can you give our listeners some general idea of what the progress is and what hope there is for the many, many suffering long COVID patients out there?

Akiko Iwasaki: Thank you, Howie and Harlan, for having me back on this show. It’s really an honor to be back here. Yeah, so the question about what we’ve learned over the last two years, there’s been so much progress that’s been made in this area of long COVID research, but what I had shared with the audience back then still remains. These are the hypotheses that we’re testing, both at the basic science level and through collaboration with Harlan using randomized clinical trials and other sort of human investigation methods. And so that remains to be the persistent virus idea.

Where SARS-CoV-2, even though it was thought to be an acute respiratory infection, it’s able to infect multiple different organs and remain and replicate in some people. And that’s sort of the idea why we did the Paxlovid trial together with Harlan.

There’s also the autoimmunity hypothesis where infections can trigger bystander or cross-reactive antibodies and T-cells that can target the host cells and that can be mediating chronic conditions in some people.

And then also there’s the reactive herpesvirus hypothesis where latent viruses like the herpesvirus family members can reactivate in response to SARS-CoV-2 infection, and now that may be causing the pathology.

And finally, there is also the sort of tissue damage that’s not repaired. And chronic inflammation is persisting in patients, and that may be triggering the disease. And these are not mutually exclusive hypotheses and could be happening, all of this could be happening in some patients while one of them or two of them are happening in others. And so the challenge in the field is to identify patients who suffer from one or two or more of these root causes so that we can diagnose and treat them properly.

Howard Forman: And just one question before I’ll let Harlan speak, are you seeing progress made? I know that there are new antivirals that are coming out soon or at least being developed. Can you speak to the progress and the hope for people with long COVID right now?

Akiko Iwasaki: We believe that further research will lead to some actionable things that we can do to help people, especially identifying these root causes and utilizing either existing or new medicines that target these root causes. For example, we are collaborating with a company called Invivyd which makes Pemgarda, which is a monoclonal antibody against the spike protein that’s being used as a prophylactic therapy for people who are immunocompromised.

But they have another version, a next-generation monoclonal antibody, that target the spike protein. And we’d love to be able to do a randomized clinical trial of patients with long COVID with persistent virus antigen to see if that eliminates the cause of the disease, in which case this would dramatically improve the health of individuals. And we still remain very hopeful to find therapies that really help the patients.

Harlan Krumholz: Akiko, one of the great things that you and I both face are the large number of people who email us who are really out of hope. They have trouble finding a place where someone will listen to them, let alone can pursue a course of diagnosis or treatment. And in part the medical profession I think is stymied because there are no tests for this condition.

So it’s really a matter of trying to piece it together by someone’s story. They had COVID, and sometime after that they developed or continuing from that infection, they had symptoms that were overwhelming them and disabling them. And they’re really coming from all sorts of different directions that can be pain, that could be fatigue, difficulty concentrating, cognitive issues.

I’ve watched you navigate this with compassion that as busy as you are, you tend to find ways to respond. But I find it increasingly frustrating. A trial just came out last week that showed colchicine didn’t work. Our trial of Paxlovid was negative, was stone-cold negative. It wasn’t just negative with maybe some signals; it was stone-cold negative. We had been hopeful, and it took us so much effort to try to do that trial.

What are you telling people now? In terms of, because people are saying, “What should I do?” And just so people hear your approach, what are you saying when people are saying, “I don’t know where to go and what to do?” What’s your usual approach to that?

Akiko Iwasaki: Yeah, I totally understand that it feels hopeless sometimes because of all these trials that are not providing any sort of positive impact on people. But I remain hopeful because I think the reasons why some of these trials fail is either that the medication or the drugs that are being used did not change the root cause of the disease because it was too short or didn’t have the accessibility or whatever it might be.

And I think the four hypotheses that I raised, they still remain very plausible. There’s so many papers demonstrating evidence for these things. So I think it’s just a matter of doing the right trial with the right drugs for the right duration to be able to see an effect. And I don’t know, I still remain very hopeful.

Harlan Krumholz: I wonder if you could just share with people listening your concept of these post-infectious syndromes. Because I think one thing that you’ve been able to do is lift this up from a singular issue in long COVID and try to generalize it to say that we’ve seen this before. This isn’t about something that’s odd related to the pandemic, that there is a large group of conditions that appear to be related to something triggered by an infection. This is an area that you’re arguably either the world’s leading or one of the world’s leading experts in.

I just wonder if you could share your conceptual framework for this idea that people get an infection and then these chronic conditions can follow. And it’s not just about long COVID, it’s about understanding the sort of family of conditions.

Akiko Iwasaki: Yeah, absolutely. So long COVID is the most recent to join the list of diseases that have been documented for centuries and haven’t been really paid much attention to. Because when they emerged, there was very little recognition of these diseases or that there was no technology to go after these diseases. But this post-acute infection syndrome is what I believe is the fourth outcome of infectious disease.

So the first outcome is recovery, second is death, and third is chronic infection for viruses that are persistent, like herpesviruses or HIV. But then this fourth dimension of infectious disease, which is a post-acute infection syndrome, are the chronic conditions that follow after a variety of infections, many including viruses like Ebola, chikungunya, EBV, SARS, but also bacterial and parasitic pathogens.

So it’s not unique to COVID at all. It’s an outcome that’s been known but have been ignored largely due to that’s the sporadic nature of these things that are happening in the absence of a pandemic as well as a lack of real recognition because many people who suffer from these diseases are women.

Harlan Krumholz: We should explore that, but I just want to just, because that’s a very important issue, let me just tag on one quick thing and then I’ll let Howie get a word in edgewise. So are you also including in that cluster things like diabetes, type 1 diabetes and multiple sclerosis? Is that a different kind of vector into this, which is that....because this chronic thing can sometimes be kind of multidimensional, like we see where people are affected with cognitive dysfunction, fatigue, pain, all these other kinds of syndromes that are harder to find, but there also are well-defined diseases that appear to be triggered post-infections. So you put those all together or do you think about them separately?

Akiko Iwasaki: Yeah, some people put them all together, but I think about them separately for reasons that are for the patient as well as the research community. Because type 1 diabetes, multiple sclerosis, lupus, these are well-defined autoimmune conditions that can be triggered by infections. Absolutely. And in fact, there’s a very strong link between Epstein-Barr virus infection and multiple sclerosis.

However, these are medically well-defined conditions. What I’m talking about is these medically undefined conditions or unexplained conditions that really didn’t have a name before. There was this sort of myalgic encephalomyelitis or chronic fatigue syndrome that clearly belonged to this post-acute infection syndrome. But MECFS is just one of the many branches of post-acute infection syndrome. So we came up with this term, but other people use other terms to describe it.

I think it’s a useful framework to think about post-acute infection syndrome separate from the well-defined autoimmune conditions or neurodegenerative conditions.

Howard Forman: You highlighted on Twitter or X just in the last couple of weeks, an article out of Europe in Nature Medicine about how patients that have been treated or given the Shingrix vaccine or the shingles vaccine have some protection against dementia and two doses even better than one dose. And I was just struck by that because it fits neatly into what you’re talking about with Harlan right now.

Can you say a word about how we should be thinking about these things? Because very often when we think about vaccines, people think about just the immediate effects, just the fact that it prevents hospitalization, death, emergency room visits. And yet here you have an example now where, long-term benefits. And when it comes to COVID, people are very often ignoring long COVID when they talk about what the effects are. Can you speak to either that paper in particular or what our efforts are with vaccination and trying to be more inclusive of long-term benefits?

Akiko Iwasaki: Yeah, thank you, Howie. Yes, I highlighted that paper because it’s kind of adding to emerging evidence that... actually it’s more than emerging; it’s probably consensus now that there are certain latent infections that when they reactivate cause diseases beyond what’s visible. For example, shingles, obviously you can see the lesions and patients undergo a lot of pain and suffering from that, but then they don’t often associate that with dementia.

But in fact, a lot of population studies as well as some basic studies are showing that shingles, the reactivation of varicella zoster virus is really associated with increased risk for dementia. And there are many other studies that contributed to this. So I feel that the vaccines against shingles are kind of really preventing significant risk for some people from developing dementia. And that is something to be highlighted. It’s not just for shingles prevention, but potentially preventing Alzheimer’s and other neurodegenerative diseases.

And that may not be that surprising to people like us who are studying virus infections because many of these viruses, they become latent within nerve cells. And when they reactivate, it induces significant damage to the nerve cells as well as immune cells that infiltrate and try to clear the virus but in that process are becoming toxic to the host.

And so if we had vaccines against Epstein-Barr virus or herpes simplex viruses, we could probably prevent a lot of these other outcomes like neurodegenerative diseases if we had them. And we don’t have them, unfortunately. But the shingles vaccine is really illustrating the sort of the breadth of diseases that occur after reactivation with a herpesvirus and preventing that with a vaccine. Two doses are better than one because it mounts that robust immune response after the second dose. So it’s really kind of demonstrating that the link between the virus and chronic diseases is just stronger and stronger every day, right?

Harlan Krumholz: And that response, Shingrix right now, the recommendation is you just need it once. Do you think that that’s right or will it ever need more than one shot? The two shots, what I mean is a series, one series, yeah.

Akiko Iwasaki: Oh, I see. Yeah, I mean that’s something to be considered in the future. So the age group for eligibility is getting lower and lower, right? And I think that that’s a good thing, but at the same time, people are living longer and longer. So does it mean that we need another series of Shingrix, 10 years, 20 years from the original dose? That’s something that I think we should be investigating in the future.

Harlan Krumholz: We don’t know yet. One thing I want to raise with you is that you and I, on this journey that we were on, encountered another group as we started to look into people with long COVID. We encountered people who were really experiencing a lot of the same symptoms, although we’d subsequently learned that they’re a little bit different, but after getting the vaccine. And so after their vaccination, they were reporting a wide range of symptoms that were very disabling. And in many cases they were very healthy individuals, and it was just the timing and the sequence. Something which we ultimately started calling post-vaccination syndrome.

And then we found out that we were sort of encountering a political milieu that was quite charged where we were just trying to surface the experience of these individuals and to suggest that it needed to be studied. And we found ourself in the middle of this vax, anti-vax or this, that. But meanwhile, these people weren’t intrinsically anti-vaxxers, because they all got vaccinated, but were experiencing something, and they were also being rebuffed by the medical establishment who didn’t know what to do with them. And so they were kind of isolated by that.

We have subsequently tried to pursue work and pre-printed work. We found journals weren’t very receptive to papers that were looking at this. Albeit our papers were very preliminary. And we’ve tried to play down our results in the sense that they’re very early and some groups have run with them as more definitive than we believe they are. And some groups have tried to dismiss. We’ve been dismissed by both sides, you know, people who are pro and anti for various different reasons.

How have you experienced this and what is it that enables you to persist despite the headwinds that we’re getting that seem not about the science as much as about the politics?

Akiko Iwasaki: Yeah, Harlan, this is one of the most difficult things I’ve dealt with in my career, I would have to say, the types of attacks we’re getting from all sides. But first of all, I want to say that I’m an immunologist studying vaccines for the last 25 years, at Yale, we try to develop better and safer vaccines for prevention of diseases and therapy of diseases. So this is really a... heart and soul of what I do is vaccine research. And we do this because we truly believe the benefit of vaccines for the population.

However, at the same time, we have to acknowledge even when a small proportion of people suffer from shots, it doesn’t have to be COVID even, it could be any vaccine, any medical intervention carries some risk, no matter how little. And when that happens, it’s our duty to study the mechanism behind such illnesses in order to make vaccines even safer. And also to acknowledge these people who are suffering because as you say, Harlan, they took the vaccines because they believed in vaccination.

And so I am still standing here with you studying post-vaccination syndrome because these patients really deserve recognition and that they deserve some therapy that could help them. They’re still suffering and we cannot ignore these patients just because it’s inconvenient.

Harlan Krumholz: Yeah, I think the thing for me—I just reflect one quick thing, Howie—that also I think is one of the more difficult situations that I’ve experienced as well. Just the ferocity of the blowback on all sides that seem not to be open to how science can progress, but more about what this is saying or what the implications are and depending on what side you’re on.

But when you meet these people, their humanity comes through, their suffering comes through and you don’t—I’ve not detected in any of the individuals that I’ve spoken to who are suffering from this an ulterior motive, any sort of motivation to be political. Actually, I find that they are apolitical. They just want to feel better, and they’re trying to figure out why don’t they feel well.

And if people would take a moment to try to talk to some of these individuals, I think they would see that these aren’t people being put up by others or they’re not people who are trying to tear down anything, they’re just trying to get better. And you and I sort of holding hands as researchers and colleagues and with other colleagues, David Putrino and others, are just trying to say, “Can we just focus on the science and try to understand this?”

We have a group of people who are suffering. We ought to be able to move forward and we ought to have scientific humility about what we’re finding. We are not finding anything definitive yet. So don’t co-opt this for other purposes or try to overreach, but let’s just try to make progress. We need funding, we need funding to do it. And that doesn’t diminish the net value of vaccines. But we would be silly to think that vaccines wouldn’t affect some people adversely, just like anything else in medicine. But it is a challenging moment, for sure.

Howard Forman: I wanted to pivot to a different topic and the topic that you, again, from Twitter from four years ago, you first talked about it, and that is that at the time at least you suffered from alpha-gal syndrome, which is effectively a tick-borne disease. But it’s a tick bites you and induces an allergy to mammalian meat, I believe is probably the simplest way for me to describe it. You can do a better job on that.

It’s also true that, first of all, it’s become a much wider syndrome. There’s maybe 400-plus, a thousand people in the country that have it, it’s growing, more ticks seem to carry it. But one thing I learned recently is it actually can resolve in many people over months or a few years sometimes. So one, I wanted to ask you if you have even tested whether you continue to have alpha-gal syndrome? And just secondly, a little bit about what that is and what our listeners might want to know about that?

Akiko Iwasaki: Yeah. That is something that I have made public that I suffer from this alpha-gal syndrome. And it’s becoming less uncommon because of global warming and other issues that enable these ticks to spread throughout the U.S. and Europe and other countries. So what it is, is that these lone star ticks and other tick species, they carry in their saliva something that induces very strong allergic response to mammalian meat.

So humans and primates lost the enzyme to decorate our proteins with this particular alpha-gal moiety, but meats like beef and pork and lamb and other mammalian meats, they contain this antigen. And people with alpha-gal syndrome make strong IgE response to this sugar molecule on the surface of the proteins. And that causes anaphylaxis in some people and GI issues in other people. And it’s really a severe disease that could be lethal if not treated quickly.

And it’s becoming more of a problem because many more people are developing. And I heard that in some areas in Martha’s Vineyard, for example, there are shops that have signs and saying, “Alpha-gal safe food,” because so many people are developing it. And so I don’t even have the courage to test whether I have not recovered from this disease.

But occasionally I get tested by accident even though I request in restaurants, no mammalian meat. Sometimes they sprinkle some bacon bits on my Caesar salad without me knowing. And when that happens, there’s severe consequence afterwards. So I know I’m not recovered, Howie, I still have it. And you can do IgE tests, but not everybody turns positive. It’s really a trial and error of testing different foods and seeing what you’re allergic to. It took me months to diagnose what it was, but once I knew, then I don’t eat any mammalian meat.

Harlan Krumholz: Of course, these people could have lower cardiovascular risk now because they’re all vegetarian and they’re—

Howard Forman: Well, let me just say two things about that. One is that you said it takes months. I was reading an article that said that the average person takes seven years to figure out that they have this. So you’re doing pretty well there.

Akiko Iwasaki: Well, I am an immunologist, yeah.

Howard Forman: And to Harlan’s point, there is a bioethics paper out there where a scholar in, I think, Michigan makes the argument that we should purposefully let people get bitten by the ticks because eating meat is immoral to begin with and this is a movement in the direction of stopping us. It was a remarkable paper. We’ll put it in the show notes for—

Harlan Krumholz: You do realize, Howie, that this thing doesn’t bother cannibals. That’s the thing that—

Howard Forman: Incredible. It’s true, right? Primates, yeah.

Harlan Krumholz: ...is very interesting is that the human meat, the human, our muscle doesn’t—

Howard Forman: Primates. Yeah. No, it’s fascinating.

Harlan Krumholz: That’s a fascinating thing. Akiko, I want one more thing because we’ve taken you so long. You’ve been so kind to indulge us with a long session, but you’re so good. So you’re a great influencer, and you’ve raised so many issues worldwide. You stand up for women and many other issues that are so important in society and in medicine and in science. But your principal platform is X. And X has evolved since you’ve been on, but you accumulated more than 250,000 followers, which meant it was sort of hard to leave X because that’s your large community.

As X has evolved, how have you thought about that? There’s so many people who have left it, but it’d almost be silly for you to leave it because, actually, you’ve got such a following. I don’t know. Have you thought about your presence and whether that’s the right platform for you and if you’re going to continue on it?

Akiko Iwasaki: Yeah, I’ve thought about it a lot, Harlan, and many of my academic colleagues have left X already and they’ve moved over to Bluesky and other platforms. But I remain on X because many of the patients who follow me are only on X and not other platforms. And it’s a great platform to communicate science to the public. Generally with Bluesky and other more academic-leaning platforms. I don’t reach everyone that I need to reach.

And I also want to reach people of many different political spectrum because everyone needs to know the benefit and risks of various different treatments or that, I believe, there is hope for finding a therapy for long COVID and post-acute infection syndrome in general. So for that I remain on X, even though it is becoming more hostile. I have to develop a thicker skin.

Harlan Krumholz: I do find you get more views still on X, but how about—

Howard Forman: She’s highly effective.

Akiko Iwasaki: Thank you.

Harlan Krumholz: ... have you thought about Instagram and TikTok? Are you ever going to expand into those areas?

Akiko Iwasaki: So I’ve been banned from TikTok by my daughters, so that’s their platform and I’m not allowed to be on there.

Howard Forman: That’s fair.

Akiko Iwasaki: But Instagram, I have an Instagram account. It’s mostly for personal things, like travel and food.

Howard Forman: Before we let you go, I just want to say Harlan said some nice things about you. Neither of us can say enough nice things about you in every possible sphere, but we should not pass on the moment to say that you’ve just been awarded the Science Prize from Keio University in Japan. You’re the first Japanese woman to receive this very, very prestigious prize. Twelve Nobel laureates have received this prize in the past, and it is just one among so many prizes.

We could have filled the entire segment talking about your awards that are all justly deserved. And so I can’t say enough about how amazing you are both for the world, but also for Yale, your students. You have a devoted lab, you have a lot of people that do great work for you, and they speak the highest words for you and praise for your sponsorship and mentorship. So thank you.

Harlan Krumholz: Thanks for joining.

Akiko Iwasaki: Thank you so much, Howie. By the way, they don’t work “for me.” We work together.

Harlan Krumholz: With her. With her. I know—

Howard Forman: It’s a valid point, valid point.

Akiko Iwasaki: No problem. But I really feel that way. We are just a team.

Howard Forman: That’s great.

Akiko Iwasaki: But thank you so much for saying that.

Howard Forman: Thank you.

Akiko Iwasaki: We appreciate it.

Harlan Krumholz: Well, I’m so glad we had Akiko on today. That’s the boost I needed. And now, okay, Howie, you promised me something good here at the end that’s going to raise my spirit.

Howard Forman: Yeah, no, I think this is actually pretty good. So we’ve not talked about H5N1, which is the highly pathogenic avian influenza or bird flu in a while, but it’s not gone away. The good news is that human cases have basically been stable at around 70 for a pretty long while, and there’s only been one new cattle outbreak in the last month. But there remain lots of wild birds and poultry outbreaks, commercial poultry farms. And in the last two months alone, seven million poultry were affected.

I still believe this remains a future risk to humans if and when the virus modifies to become capable of human-to-human spread. But when that happens remains a very open question. And while it could happen very soon, it could also be many years off, which is why an article in Nature Communications brings a ray of hope.

Researchers out of Bern, Switzerland, used an RNA replicon vaccine to vaccinate a wide array of avian species and induced very high neutralizing antibodies, mucosal immunity, and seemingly a durable protection not only against severe disease but also against viral shedding. That is so critical, it means it could stop spreading.

It bears reminding our listeners that with hundreds of millions of birds already infected and wild birds clearly playing an active role in spreading disease between farms and regions, we have been dealt an almost impossible task at containment and have mostly been trying to limit human exposure and symptoms while euthanizing cattle and birds at a frightening rate at times, at least early on.

What this approach offers is a means to slow and then stop the spread. You’ll not be able to eradicate this from wild birds with this technique. No one’s suggesting that we’re going to go out and try to vaccinate wild birds. But if you can begin to slow and even stop the spread on the farm level, you no longer have a reservoir. And a wild infected bird may continue to bring the virus to a farm, but if there are no animals that will become infected, it’s not a real concern. Over time, this could lead to true eradication.

It is also just the first step. They need to do further studies to refine the dosing, continue to test in more species, including eventually mammals. They also got to figure out better routes of administration as giving two shots to every chicken on a farm is logistically impossible. But there are things like ocular routes of administration that are mentioned. This is all to say that science moves forward and brings us closer to curtailing H5N1, even as the virus is also mutating in ways that makes it more likely at some point to be a true threat to us. So that’s my good news.

Harlan Krumholz: I think we should commit to only talking about good news on this podcast.

Howard Forman: That would be impossible. But I do think we had a lot of good news today. I feel like there’s a lot of progress in immunology, vaccinology, in our science coverage, and I do think there is a lot of good out there. And I completely am still optimistic even during dark times.

Harlan Krumholz: Yeah, I think, look, on the science front, there is a lot of good things to do. I don’t know, for some reason I was just reflecting in the beginning on some of the things that I felt were—

Howard Forman: It’s a hard time.

Harlan Krumholz: I just encountered, after being away from it for a couple of days, it just sort of put it into bright relief for me. But this is indeed good news and there’s a lot that we can be thankful for. So thanks, Howie. That was a good statement. You’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman.

Howard Forman: So how did we do? To give us your feedback or to keep the conversation going, email us at health.veritas@yale.edu or follow us on any social media.

Harlan Krumholz: And we appreciate your feedback. It helps people find us. We respond, and it helps us get better. So keep it up.

Howard Forman: And if you have questions about the MBA for Executives program at the Yale School of Management, reach out via email for more information or check out our website at som.yale.edu/emba.

Harlan Krumholz: Health & Veritas is sponsored by the Yale School of Management and the Yale School of Public Health. We are fortunate to have two superstar undergraduates who are helping us, Tobias Liu and Gloria Beck, and a remarkable producer, Miranda Shafer, who somehow makes us sound good every week. And I’m here with the best co-host in the business, Howie Forman.

Howard Forman: We’ve got a good team, the entire team, and I love working with you, Harlan.

Harlan Krumholz: Talk to you soon, Howie.

Howard Forman: Thanks, Harlan, talk to you soon.