Respiratory Viral Vaccines and Personalized Vaccinology

Podcast Transcript

Raed Dweik:

Hello, and welcome to the Respiratory Exchange Podcast. I am Raed Dweik, Chairman of the Respiratory Institute at Cleveland Clinic. This podcast series of short, digestible episodes is intended for healthcare providers and covers topics related to respiratory health and disease. My colleagues and I will be interviewing experts about timely and timeless topics in the areas of pulmonary, critical care, sleep, infectious disease, and related disciplines. We will share information that will help you take better care of your patients today as well as the patients of tomorrow. I hope you enjoy today's episode.

Dr. Steven Gordon:

My name is Dr. Steven Gordon, I am Chairman of the Department of Infectious Disease, and this is a very exciting podcast we have on our RSV series. Today it's a great privilege and honor for me to introduce a friend and one of the world's experts in vaccines. I want to welcome today, Dr. Greg Poland, who is the Mary Lowell Leary Emeritus Professor of Medicine, distinguished investigator at Mayo Clinic and he is a physician, scientist and the founding Director of Mayo Clinic's Vaccine Research Group, lifelong passion, and career in vaccines, so Greg, welcome.

Dr. Greg Poland:

Thank you, it's great to be here. My first time to Cleveland Clinic.

Dr. Steven Gordon:

So, you are a self-described vaccinologist, how would you define a vaccinologist?

Dr. Greg Poland:

We are a bit of a rare breed, but what a vaccinologist does is really devote his or her professional time and attention to the development and the study of vaccines. It is a pretty broad area, because vaccines of course, encompass all the way from chronic diseases, oncology, to viruses, bacteria, parasites, fungi, etc., so it is an uncertified sub, sub-subspecialty.

Dr. Steven Gordon:

Well, thank you for that, and again, you have devoted your career as you are passionate about disease prevention. There is probably no other public health intervention going back to Jenner and the smallpox vaccine would you still agree with that?

Dr. Greg Poland:

I would. In fact, a few years' ago, CDC published something where they acknowledged that there are three things that have happened that have immensely improved the human lifespan and wellbeing. Those were clean water, access to food, and vaccines.

Dr. Steven Gordon:

Well, that is a food for thought here and thank you. Now I want to pivot to respiratory viral vaccines and respiratory viral diseases. In particular, we are going to focus on respiratory syncytial virus vaccines, the new kid on the block. Can you give us an overview when we talk about respiratory viruses in 2024, the big three, so to speak?

Dr. Greg Poland:

Yes. Well, I think the ones that are absorbing our attention right now are COVID-19 still, RSV, as you mentioned, which for the most part has been ignored in adult medicine. You and I were taught basically that this was a pediatric disease, turns out it isn’t so. Then of course influenza which never goes away.

Dr. Steven Gordon:

Pivoting to RSV, can you just underline what the why is? So, what was the public health imperative, in terms of development of vaccines for adults?

Dr. Greg Poland:

Well interesting it was not an imperative up until recently for a couple of reasons. Number one, the ability to diagnose it and really understand how much morbidity and mortality was happening in adults due to respiratory syncytial virus. The second are very elegant structure function and atomic crystal level studies of the fusion, the F protein of the RSV virus allowing the development of a so-called pre-F vaccine. What had happened is in the '60s, started in the '50s, an inactivated RSV vaccine was developed but it caused enhanced disease in the kids that were in the clinical trial that got the vaccine. And it turns out that it was due to the fact that what they actually received was the so-called post-fusion F protein vaccine because the pre-fusion protein is metastable unlike a highly stable post-fusion confirmation of that F protein, the fusion protein that joins to human receptors.

So all of these developments have enabled the development of a RSV vaccine and what's fascinating to me, is in very short order, in fact, I think it was a month apart, both the GSK and Pfizer [RSVPreF3 (Arexvy) and RSVpreF (Abrysvo)] vaccines were approved and undoubtedly very shortly, the Moderna mRNA-based RSV vaccine will be approved, so we will have three different products.

Dr. Steven Gordon:

Thank you. If we back track a little bit, I have heard you refer to this as a precision vaccine.

Dr. Greg Poland:

Yes.

Dr. Steven Gordon:

And implied in this is the understanding of basic science.

Dr. Greg Poland:

Yes.

Dr. Steven Gordon:

So, the days of swabbing and then doing a live, attenuated vaccine, although that was successful, this is beyond that, so can you elaborate a little bit more on the precision vaccine?

Dr. Greg Poland:

Yes, so precision, in this case, in the sense of knowing at the atomic level, what are the antigenic epitopes? And they turn out to be epitopes displayed as I say in that pre-F confirmation. We really had no knowledge of this until an investigator down in Texas and Barney Graham, at the Vaccine Research Center at NIH, worked and worked and worked on this to determine the structure. Those structure function studies informed the development of COVID-19 vaccines, so precision in that regard. The next step in precision or personalized vaccinology is to understand the immune phenotype and genotype of individuals, what some have called the immune biography of an individual and select the right type and dose of vaccine for that individual. Much as we are now doing with individualized drug dosing.

Dr. Steven Gordon:

Very, very, very interesting. Again, to step back, can you give us the definition for the listening audience of immunity and then talk about what you would say disease blocking versus prevention of disease?

Dr. Greg Poland:

Immunity, as it turns out is sort of a wastebasket term and we use it very broadly. When, in fact, we should be talking about innate immunity, humoral immunity, cellular immunity, durable immunity, and the idea that immunity can tip over or be directed in an adverse way. So, you have really got a very broad playing field here of what we mean by immunity. For the vaccines that we currently have, with very few exceptions, I think what most healthcare providers and certainly the public does not understand, and in fact they have been miscommunicated to, in particular with COVID-19 vaccines; is these vaccines' biggest benefit is in preventing the more severe complications or aspects of infection, so death, hospitalization, mechanical ventilation. They are much less effective in preventing mild to moderate disease, asymptomatic infection and even transmission of the virus. I think that message did not go through well and was not well discussed when the COVID-19 vaccines came out. The result is people thought "Well, it's going to be one and done." "Oh, oh, okay, I need a second... oh wait, I need three doses for a primary series." And then in rapid order, one booster after another.

So, people did not realize, particularly once they got their vaccines and then of course when exposed, got COVID-19 they began to think "Well these vaccines aren't effective." When quite the opposite, they were very effective in preventing what they're designed to do, which is to prevent, in a normal host, the severe complications of that infection. Even, as you and I were talking about Steve, even with long COVID, an entity we do not understand and have not defined very well. Nonetheless, in the studies that have been done, getting your COVID vaccine reduces the risk of long COVID by about 50%. Now that is stunning when you think about it.

Dr. Steven Gordon:

Well, that is a great point and maybe nuanced because we all have patients who say, "I got the vaccine, a vaccine for an illness." And then maybe they had a positive test for it, but I think to your point, you probably mitigated or it's your best change of mitigating a severe effect of that infection.

Dr. Greg Poland:

Absolutely. You know, you and I have heard it all in our careers. I will hear something, even from other physicians, "I got my flu shot." They always feel obligated to tell me when they see me. "Greg, I got my flu shot, but you know what? I got the flu anyway. So, I guess it didn't work." And I said "No. No. You don't have that right." Even when we have vaccines that are about 20, 30% effective in preventing infection, they are about 70% effective in preventing hospitalization. You know, John Smith, it worked, you did not end up in the hospital, you did not have an MI, you did not have a stroke from the inflammatory milieu of that infection, you didn’t die. This was a success. And in fact, what happened is a potentially very dangerous infection was converted into an interruption, an annoyance in your life.

Dr. Steven Gordon:

Thank you. And moving back to RSV, we have seen the numbers which have been presented, three and a half million infections, hundreds of thousands of hospitalizations, maybe 14,000 deaths a year in adults. So, we will focus on adults here. I wonder if you can run through some of the data that supports utilization of the two FDA-licensed vaccines we have for adults.

Dr. Greg Poland:

So, there are two of them. The RSVPREF3 (AREXVY) vaccine, which is trimeric, pre-fusion, stabilized F protein of the A-lineage of RSV, coupled with their proprietary adjuvant called ASO1E, sub-E. Well, what did it show? Well against severe disease, the efficacy in the first season was about 94%. When you looked at RSV-associated infection around 60%. Those numbers are generally plus or minus 10 percentage points true for both vaccines which have been licensed and the Moderna MRNA-based RSV vaccine which will probably be licensed pretty soon. A couple of interesting things. That efficacy fell by some 20 percentage points in year two, so they tried in one of the studies, to give them a second dose prior to season two. It did not boost immunity in the sense of vaccine efficacy in preventing infection and lower respiratory tract disease.

In some of the studies, they looked at protection against RSV-A and RSV-B. Well the RSVpreF (Abrysvo) vaccine is a little different, it is not adjuvanted but it contains 60 micrograms of A, 60 micrograms of B. Same basic efficacy results but in the RSVPREF3 (AREXVY) trial which was just A, there was a difference in efficacy against A versus B, not terribly important but some hints that were interesting to me as an immunologist so why can't we boost, after getting one dose? How long will efficacy last? To see something go from 80 to 90% in season one to 50 to 60% in season two implies that this is not going to be durable immunity, so when do we give a booster? We do not know. We are literally building the plane while we are flying it here. You can't really avoid that, it is not a criticism, it's an observation to say, "We are going to have to follow people and when do we start seeing an excess in cases and are we going to be able to boost them?"

But there were some things that perturbed these trials. We have no data on prevention against hospitalization or death. We have essentially no data in the most vulnerable, people over the age of 80, or complex co-morbidities, or people who are immunocompromised. Both seasons where these vaccines were studied were perturbed by starting very early and unusually enough, were RSV-B years. Now remember, one of the vaccines is A, one of them A and B. Now that probably works because the neutralizing epitopes that we're interested, or the epitopes that were against which were neutralizing antibodies directed are highly conserved across A-B and in F protein, so it's just interesting, as an immunologist and a vaccinologist, to speculate what is this going to mean? And there is a lot more data to be gathered. So that is the plus side. These vaccines provide really high to high-moderate protection against serious things like hospitalization and lower respiratory tract involvement. Less so with RSV-associated infection, but it is a moderated infection, people recover quickly from it.

What about the downside right? There are always risks and there's benefits. In both trials, there was a numerical imbalance in neuroinflammatory diseases, basically GBS, Gillain-Barre Syndrome. Why is that? We don't know and in the phase four so-called post-licensure studies, that’s a focus of concern is to look at this numerical imbalance in neuroinflammatory disease and to some degree, there was concern about a potential increased number of atrial fibrillation cases in vaccine recipients. I don't think that one's going to turn out to hold. I am concerned about GBS. Concerned in the sense of I would like to know the basis of it, but you are talking about 10 excess cases per million doses versus saving hundreds of thousands of hospitalizations and tens of thousands of deaths. So, it is a trade-off, and physicians need to know those data, talk to their patient about those data and let them know that we don't know when and if a booster is going to be needed and if so, what that will look like.

Dr. Steven Gordon:

You raise such interesting points and as you can look at this data probably more nuanced than many, right? It is fair to say you are still optimistic about these vaccines but always look for limitations. I wonder if you can then discuss this shared medical decision asterisk and in good intention and from an execution point of view, something that is still maybe trouble.

Dr. Greg Poland:

I like the term shared clinical decision making just broadly. I mean I think that is what we should be doing as physicians for everything. Where we interact with a patient, is to talk to them about here is what I think the best thing to do is, here is where we have some uncertainty, here is where risk lies, and here is what the benefits are. Let the patient be as educated as we can and give them a chance to ask questions. So why did the advisory committee on immunization practices of the CDC, the ACIP, a committee I've served on, why did they put an asterisk, as you said, and made this shared clinical decision making. The underlying reason is not knowing the true extent or how this would pan out in regards to neuroinflammatory disease and not knowing how long the effectiveness of the vaccine would last but it was particularly the former point.

I think we are going to see this coming year a movement in the RSV recommendations. One, I think that at least one of the manufacturers will get an indication to administer the vaccine down to age 50 in people who are at high risk, and we certainly see those patients, multi-comorbidities, they're at risk particularly with lung and heart disease. Two, we are going to see a recommendation, now that the seasonality of RSV has corrected itself after two years of mass and physical distancing to administer the vaccine in late summer, early fall. The other thing is that we will move away from shared clinical decision making to a universal recommendation. That does not mean we don't talk to our patients about it, we still do.

The other thing that is really interesting and I know we are talking about adults here but maternal immunization in regard to giving RSV. The only one currently approved is the Pfizer [RSVpreF (Abrysvo)] vaccine to pregnant women in the latter stages of pregnancy, and the concern there is that there has been a signal, I will call it, a numerical imbalance in pre-term births. Why would that be? No clear idea. A lot of hypotheses but no data yet to try to understand is it real and if it is real, why is it happening?

Dr. Steven Gordon:

Thank you for that. If we are talking about the maternal immunization which is a nice pivot. The active immunization is one strategy but then there is a new passive immunization also available.

Dr. Greg Poland:

Yes, nirsevimab is available to give infants in their first RSV season. The problem has been availability of it. Very effective, I mean high 80s in preventing hospitalization and that is truly where you see the highest risk of hospitalization and complications from RSV. It is kind of a U-shaped curve with a long arm in the infants, a shorter arm in the elderly people and people in their 20s, 30s, 40s, 50s still get infected but they tend not to get hospitalized or die if they are normal immune host. So, the options to protect infants in that first year are nirsevimab, a monoclonal antibody, hard to get and they've kind of rationed it to highest risk infants or immunize the mother against RSV so you get placental transfer of maternal antibody to the child and that works. In fact, the studies that have been done show about 70 to 80% efficacy in protecting that infant through the first season. Now I said through the first season, I should be even clearer. Through about 90 to 180 days at best.

Dr. Steven Gordon:

The question sometimes comes up and this came up when my niece was pregnant, should I get the active vaccine or maybe due to monoclonal. My understanding is there is not a head-to-head trial of that.

Dr. Greg Poland:

There is not.

Dr. Steven Gordon:

I advised her actually at that time to get the vaccine because I was not certain about supply and you take a jab for the baby, but I don't know if you have thoughts on that.

Dr. Greg Poland:

Like you said, there has not been a head-to-head trial. What I can say is that the safety data in the monoclonal antibody was excellent. I mean they did not see any numerical imbalances of signals of concern, so I probably have a soft lean that way. Full disclosure, I am not a pediatrician, but I would have a soft lean in that way if you could get your hands on it. If you could not get your hands on it, absolutely a proponent of immunizing the mother. Now, a nuance, immunizing the mother after 32 weeks of gestation so that if there is any signal there of pre-term birth, you are past the high-risk point. You do not want to get it in the first or second trimester, if there is a signal there, you run the risk of very premature birth and the outcomes attendant to that. But in the late stages, and I would probably only do it during RSV or pre-RSV season, so in other words, if a woman was going to deliver let's say in spring or summer, I probably would not give RSV vaccine because there's really no risk there that you are preventing. If it is late summer, fall, wintertime, absolutely just because of what we know, clearly know about the risks of RSV in those infants and neonates.

Dr. Steven Gordon:

Thank you. Why do not we pivot back, you mention the mRNA product that you are forecasting. Can you just tell our audience your thoughts on that product compared to the other two vaccines that are pre-fusion?

Dr. Greg Poland:

Yes, I think what Moderna is doing in this case, is adapting their mRNA in a lipid nanoparticle platform to the mRNA of the pre-F trimeric fusion protein, a very valid idea to do. They have done it, they have done phase two, three study. They have published those results, and it showed high efficacy, just like the other vaccines. Now, to my way of thinking as a vaccinologist, mRNA vaccines are pretty reactogenic, less so the more doses that you have gotten, but think back to your first dose and your second dose of the mRNA COVID vaccines. Pretty reactogenic, you know, I was down and out for 18 hours or something like that all transitory, self-resolving type thing. There were some cases, of course, with COVID vaccine of myopericarditis, and some cases, we think of post-vaccine associated long COVID-like symptoms. I developed a side effect of tinnitus as a number of people have so, all these trade-offs and again, wisdom resides in that finding the fulcrum, where does benefit exceed risk? That is where I want to be. Where does risk exceed benefit? I do not want to be there, so we have to be wise. We have to collect data.

The other thing that I am a little concerned about in that phase 2-3 trial is while the efficacy of both the GSK and Pfizer [RSVPREF3 (AREXVY) and RSVpreF (Abrysvo)] vaccine dropped in season two, it dropped quicker and probably a little more in the Moderna mRNA trial, so that is something that bears watching. Does that mean that it can be boosted? Now with the GSK and Pfizer [RSVpreF (Abrysvo) and RSVPREF3 (AREXVY)] vaccine, as I mentioned, giving a second dose prior to season two did not boost efficacy. Now that is a mystery to me as a vaccinologist. Will that turn out to be true for the mRNA-based vaccine? Do not know yet.

Dr. Steven Gordon:

Interesting. Very interesting. In terms of the clinicians now, they are faced with respiratory viruses possibly three products that may be given during respiratory viral season. Do you have any preferences in terms of sequencing in co-administration? Can you talk about some of those decision making that goes on that?

Dr. Greg Poland:

The co-administration is an interesting point, Steve, thank you for bringing that up, I neglected to mention it. There has been only one study of co-administration of influenza and RSV vaccine and what it showed is a decrease in the height of the antibody titer to all four strains of what was in the influenza vaccine. Not by very much, three to five percentage points, something like that so probably not clinically significant but other than that, with the RSV vaccines, we have no idea. There have been no studies looking at antibody titers and zero on cellular immunity with co-administration.

Co-administration is really sort of a public health measure. As you know, it is difficult. We are in a culture right now of, I will call it vaccine hesitancy or questioning. I know the vaccine rejectors get a lot of press, but they are a relatively small number. I think the others are people who are just wanting to make good decisions, but want good data from sources that they can trust. That is how I take it, that is how I communicate with them, that is what I publish about. I mention that my daughter and I developed a tool called the Empathy Tool, we published in the journal Vaccine, which helps clinicians talk to their patients who have questions or are hesitant about vaccines to try to help them to move towards vaccine acceptance if it is appropriate in their case. I am not sure I answered your second question related to that though.

Dr. Steven Gordon:

So, there is no contra-indications to sequencing of it.

Dr. Greg Poland:

Sequencing of it, yes.

Dr. Steven Gordon:

Yes, but you might have a different preference if you think the patient is going to come back or for availability.

Dr. Greg Poland:

So, I know I am about to construct a complex matrix here, but if they do not want to get them all at the same time. What I can say is, if you get COVID, I got a way to treat it. If you get influenza, I have a way to treat it. If you get RSV, I have no way to treat it. So, if they say to me, "Doc, I can't miss work. I'll get them, but I want to separate them by a couple of weeks." Okay, fine. You know, let us start early, in late summer. Let's not wait until November and I would probably, in a scenario like that, give them RSV vaccine first. Then I would look at what is the patient I am dealing with? Do they have a lot of morbidities that put them at high risk, or are they pretty healthy? Have they gotten COVID? Have they gotten COVID vaccines? If they have, and there is no new variant circulating, I would probably go with influenza next and then COVID.

If there is a new variant circulating, I would change that order. I would give them COVID first and then influenza second. One of the things that has not been well recognized is that data on the efficacy of Tamiflu is or oseltamivir is a little shaky actually and a very nice paper was published demonstrating this. Baloxavir, on the other hand, an anti-viral, one time, one dose. There is an expense associated with it, probably shortens symptoms by maybe up to 48 hours, more like 36 hours or something, but probably helpful in decreasing complications. So, I would use all that knowledge in constructing an individualized or personalized plan for that patient based on the realities of who that patient is and what their concerns are.

Dr. Steven Gordon:

Well, thank you. I know you feel very strongly about healthcare workers and vaccination, I wonder if there is any data looking at the household of the patient. Sometimes we try to say, "Look do it for your sick mother-in-law-or your kids," so the issue about thinking beyond oneself in terms of protection with vaccines.

Dr. Greg Poland:

You know when you raised that, and you are right, I raised that issue a lot, I am usually met with somewhat of a startled stare and that speaks to the very highly individualized, I would actually say it tips into narcissism of our culture. We worry about us. We saw that during COVID, didn't we? Where people that were not particularly high-risk did not want to wear masks to protect the elderly people that were at high-risk especially prior to the advent and development and distribution of the vaccines. So, it is a very keen point, Steve, and it is something in all of medicine. We should not just be looking at the acute episode of the individual patient, as important as that is. We should really be understanding the context in which that patient lives and works, right? I mean, you and I do it if somebody says, "Well I've got travel plans." "Oh where?" Because our minds are already racing towards what kinds of risks are there.

But what if you have your grandmother who is getting chemotherapy in the home, or you are helping to take care of them? What if you have a kid, and I helped a lot of people through this, kids with congenital heart defects or post-transplant, initially vaccine wasn't available so how are you going to protect those kids? Well, it is kind of back to the strategy that's been a little bit abandoned vis-a-vis pertussis, but it's the idea of cocooning, right? Surround people, it is the same ideas of, we talk about macro and microeconomics, let us use that same concept of family cocooning, community cocooning, population level cocooning, i.e., herd immunity, to protect people who we otherwise can't protect well.

Dr. Steven Gordon:

You know I enjoy that discussion and your approach. If I am a patient, I want to know if somebody is going to stick something in my arm. I think you should be curious, and it is okay to be curious and questioning.

Dr. Greg Poland:

Absolutely.

Dr. Steven Gordon:

The hesitancy versus resistance, as you said, you want to meet people, educate them, hopefully a bridge to decision, whatever that decision is, and keep going back. Now that requires time and some expertise, but I do think that these motivational interviewing techniques you talk about, the empathy, meeting your patients where you are. Because in the end, the healthcare provider is still the trusted person that can persuade patients to make the best decision for themselves.

Dr. Greg Poland:

Right. I agree with you, Steve, wholeheartedly. I think the nature of being a professional and in the particular situation where we deal with people and highly emotionally vulnerable situations. There is a power differential that the patient feels. I think it is incumbent and the price is ours, not on the patient, to care for this patient, that is the highest calling that we have. I always say to people, it is a privilege that we get to take care of patients as we do and so you always try to do as best you can the right thing and where you feel uncertain, call in somebody whose content expertise is such that they can help. I get a lot of vaccine consults and I love those. It is an opportunity to educate the provider and the patient and often the patient's family who accompanies them.

Dr. Steven Gordon:

I would like to flip back; you have had such a distinguished career. One of the highlights, and correct me, was in 2002 is when the ACIP, which you were on, had the recommendation for universal vaccine for everyone greater than six months and above.

Dr. Greg Poland:

Yes.

Dr. Steven Gordon:

I wonder if you can tell us a little bit about how that sausage was made.

Dr. Greg Poland:

That was a tough one in my career, Steve, I mean I was looking at the data, you know 20 some years' ago, I would have been considered more junior right? And here is this junior vaccinologist in a room full of senior vaccinologists and public health people saying "Look, this doesn't make any sense. By my count, there are 16 separate indications for influenza vaccine. Nobody knows them, they are not applied well. Immunization coverage of the population level is low. What are we going to do about it?" The easiest thing to do is recognize that everybody is at risk for influenza immunization and even if young, healthy teenager, for example. Now I have seen a death due to myocarditis and we all probably have, and I've seen complications, but it also helps protect the rest of the family, the school mates, people at church, synagogue, whatever it would be, protects the workplace even. So, I introduced, put in a resolution for let us just make this simple. Let's just recommend influenza vaccine for everybody age six months and older, roundly defeated.

"Show us the data, Poland." So, I did. I published a paper called The Seven Truths that we must accept in regard to influenza vaccine and the chair of the ACIP at that time when I reintroduced it, was Carol Baker. I love her. She is pediatric vaccinologist and ID person. Carol, if you are listening, blessings to you. But Carol called it, when it passed, a Poland Moment. I have always remembered that and thank her for that, and we actually got that introduced. I will tell you the hardest one though. I was the architect of the plan to implement mandatory influenza immunization among all healthcare providers. That went even less well. And it turned out that hospitals were more often, and medical centers, more often concerned and I say this with a degree of sadness in my heart, with the pushback that they might get rather than the highest welfare of the patient. That has thankfully reversed, certainly my own institution for example. There is required participation, mandatory participation. Same here at Cleveland Clinic. That is the right thing to do. The moral imperative is that healthcare providers who are seeing highly vulnerable patients, should not be transmitting respiratory diseases that we can prevent with safe and effective vaccines and that is my stance on it, similar to the military. Do I carry that over into mandatory immunization in all cases? No, I have concerns there. We live in a society where choice is still valued and it should be but when you are a military professional, when you're a first responder, when you are dealing with highly vulnerable patients, you so to speak, give up that individualism for the better of your patient. Guess what happens when you do that? You grow trust tremendously.

Dr. Steven Gordon:

Well, thank you for that.

Dr. Greg Poland:

Yes.

Dr. Steven Gordon:

Thank you for those efforts. As we wrap here, I wonder, not to end this topic but what keeps you up at night, Greg? And what do you fear will be the next thing that kind of keeps you up right now?

Dr. Greg Poland:

Yes, I have a couple of concerns. We are watching, nobody seems to be aware of it, a tremendously lethal pandemic that is happening right now among birds. A highly pathogenic avian influenza that now has been amply demonstrated, is crossing over into mammalian species including sea mammals and land mammals. The question is, is the shoe going to drop and we see that virus now become highly transmissible in humans? If so, like all pandemics, even after having been through COVID-19, I do not think we are as prepared as we should be. So, preparedness is something that is so hard in the human psyche, I mean already people do not want to talk about COVID-19, they want to put it behind them. It is a little bit like looking, I did a deep dive, into what happened in 1918 and 1919 and the great influenza pandemic. You can find almost nothing written about it immediately post pandemic. People just wanted to put it out of their minds.

So, I am worried about preparedness. I am worried about what is now obvious is the political interference into what should be a public health and medical concern. That does not mean you do not need politicians to fund programs, but you need them to not be making medical recommendations and not interfering at a public health. Public health cannot allow that kind of political interference because again, if we want to be trusted, our only concern has to be the welfare of the patient and the community we serve.

Dr. Steven Gordon:

Well, thank you for highlighting that. I think there has been a lot of good things come out of the pandemic, right?

Dr. Greg Poland:

Yes, yes.

Dr. Steven Gordon:

The wastewater surveillance is, as you said, the technology. Learning what we don't know, the testing, the telehealth.

Dr. Greg Poland:

Yes.

Dr. Steven Gordon:

So can you leave us with a positive note too.

Dr. Greg Poland:

You just said some really important ones. I mean the ability to utilize lateral flow antigen or so-called rapid testing in the home, I think is great. I think we will see it; we are seeing it with influenza, with RSV. That is fantastic. The development of telemedicine and telehealth, I think is actually a good idea, used appropriately, caveat there. Certainly, the wastewater surveillance is something that needs to continue to be funded, that is an issue. I think we cannot give up on, at the population level, educating them about vaccines and about prevention. That really needs to start in the schools, in the grade school level, just like we do with smoking, seatbelt use, etc.

We also learned that in the wealthiest most educated nation in the history of the world, despite having had two warnings in regard to coronaviruses, right? MERS and SARS-CoV-1. We were caught pretty flatfooted. Clinics didn't have the material they needed, N95 masks, they didn't have enough ventilators, all of our inventory is just in time inventory, so a lot of things have, at least, been recognized that we have to change. Similarly, and again, you and I know this well, we need to invest in the development of monoclonal antibodies, antivirals, and antibiotics. That is another thing that keeps me up at night is what we are seeing, and this has been a drum roll of highly drug-resistant bacteria and viruses and fungi that we need to be developing counter measures against and it is just hard.

Those are not sexy right? It's hard to put money into those things. Talk about regenerative medicine? Talk about a weight loss pill? as good as those are, I'm not saying that we shouldn't be doing those things, but a lot of enthusiasm for that and yet here we've just been through a pandemic and I think this stuns people to realize that one out of every 269 Americans that was alive in 2020 is now dead of COVID-19.

Dr. Steven Gordon:

Oh, very humbling. To end, I wonder if there is a book recommendation, medical or nonmedical that you might want to throw out for our audience here?

Dr. Greg Poland:

Well, I would say, a colleague of ours, Paul Offit, has written a number of books that I think are very helpful, written at the lay level, my kids have read them and found them fascinating. Peter Hotez, down in Texas wrote a book called Rachel's Autism Was Not Caused by MMR Vaccine. Another vaccinologist who really has a good way of communicating with the public, the other one that I think is really interesting from, you and I share a love of history, is John Barry's book, it's a little bit older now, but called The Great Influenza. I loved that book. I am really learning about the history and how the same issues of politics played out in different cities and there was, even in California of all places, can you imagine, an anti-masking league that developed in 1919.

Dr. Steven Gordon:

Well, thank you for that. I was just checking Dr. Offit's book, his newest one, Tell Me When It's Over, An Insider's Guide to Deciphering COVID is on my bed stand.

Dr. Greg Poland:

Paul has a wonderful way of writing, and he is fair with the data. I mean he talks about where we know, where we do not know, and he is talked about what has not gone well in vaccinology over the years, all the way back to the RSV trials, to the so-called Cutter incident when they were looking at live, attenuated polio vaccine. Something happened where a particular batch did not get inactivated and some of the kids in that trial developed polio.

Dr. Steven Gordon:

Well, you are also very transparent with the data. Again, my name is Steve Gordon, and it has been a pleasure to have Dr. Gregory Poland here on this podcast. Thank you for all you do and all you have done.

Dr. Greg Poland:

Thank you, Steve.

Dr. Greg Poland:

Well, you are a great champion for all this, so thank you.

Dr. Steven Gordon:

Thank you so much.

Raed Dweik:

Thank you for listening to this episode of The Respiratory Exchange Podcast. For more stories and information from the Cleveland Clinic Respiratory Institute, you can follow me on Twitter @RaedDweikMD.