Flu, COVID, RSV, & Shingles Vaccines in Older Adults: Ken Schmader and Sharon Brangman

Eric 00:12

Welcome to the GeriPal Podcast. This is Eric Widera.

Alex 00:17

This is Alex Smith.

Eric 00:19

And Alex, we’re going to be talking about vaccinations just in time for respiratory virus season. I was going to say flu season, but there’s more than flu going around. So who do we have with us to talk about this?

Alex 00:31

We are delighted to welcome Ken Schmader, who’s a geriatrician and researcher who studies zoster, influenza, and other infections. He’s director of the Duke Pepper Center and past chief of the Division of Geriatrics at Duke. Ken, welcome to the GeriPal Podcast.

Ken 00:46

Thanks, Alex. An honor to be on.

Alex 00:48

And we’re delighted to welcome back Sharon Brangman, I think for the 3rd time or so. She’s almost approached that jacket level that they have on SNL, a frequent guest. Sharon is a geriatrician researcher, a SUNY Distinguished Service Professor Emeritus and Emeritus Chair of the Department of Geriatrics at SUNY Upstate Medical University, and is co-author of a paper in JAGS that’s forthcoming about the AGS Older Adults Vaccine Initiative. Sharon, welcome back to GeriPal.

Sharon 01:18

Hi, nice to see you again.

Alex 01:19

Good to see you.

Eric 01:20

So we got a lot to talk about. We’re going to be talking about flu, COVID, RSV, I want to build in some time. I know it’s not about the respiratory virus season, but shingles too. So we got a lot to talk about, but before we jump into that and the AGS Vaccine Initiative, Sharon, I think you have a song request.

Sharon 01:37

Well, seeing as how I just got my COVID and flu shot last week, why don’t we talk about Hit Me with My Best Shot?

Ken 01:46

That’s great.

Eric 01:48

I won’t ask you why you chose that.

Ken 01:49

That’s a perfect song.

Alex 01:50

I think it’s pretty evident. All right, here’s a little bit. (singing)

Eric 02:26

Perfect song.

Alex 02:28

Perfect. That’s great. I think at AGS I did, uh, I’m Not Throwing Away My Shot. Oh, we’ll get to that. It was in relation to the RSV. I think I disagreed with Eric and Ken about their conclusions on that one. I was much more pro-vaccination. Yeah.

Ken 02:43

Yeah.

Eric 02:43

We’ll talk about that cuz that was an initial study. We can talk about the, there was one concern that Ken brought up with that. But we’ll talk about that when we get to RSV. Can I just ask before we dive into flu, COVID, RSV, and shingles, Sharon, I’m going to start off with you. You know, we’ve had you on for other things like Alzheimer’s and dementia.

You’re helping be part of this initiative around increasing vaccinations in older adults. Like, has this been a longstanding focus of your career? Like what, why, how did you kind of get involved in this and why?

Sharon 03:16

Well, like most geriatricians, I have seen older adults have very bad outcomes who didn’t get vaccines. So I have been very pro-vaccine for a long time. And the emerging information, which I know we’re going to talk about, that shows that it may reduce your risk of dementia is just an added bonus. But I used to feel kind of like Dr. Death in December and January every year because I had all these patients dying from flu.

And, you know, getting a flu shot can really reduce that from happening. So I was very happy and excited to be a part of this project, along with Tim Atzef. We were the co-PIs to help geriatricians increase the amount of immunizations that our older adults are getting, the amounts and types. We focus primarily on flu and COVID.

Eric 04:05

All right. And Ken, this has been a longstanding focus of yours. What got you interested in vaccines?

Ken 04:11

Well, I had a strong interest in infections from the beginning of my career, and it really came about for a clinical need, and that is improving care of older people with herpes zoster and postherpetic neuralgia. Believe it or not, when I got in the game, there was no treatment or prevention for it. Shows you how old I am. And during my geriatrics fellowship, I also got additional training in virology and vaccinology, which led me to become a lead investigator on the Shingles Prevention Study. This is the landmark study of Zostavax, the live attenuated virus vaccine.

And it showed that we could actually prevent zoster, which was a mind bullet, you know, at the time. And, uh, that led to further work on the recombinant zoster vaccine, flu, et cetera, and a long career in, you know, clinical care, education, and researching vaccines. And the other thing in doing that, uh, particularly when I was presenting on these things at the CDC, I started working on national policy and vaccine past 20 years with AGS and with the CDC. I’ve been the AGS liaison to the ACIP for 20 years.

Eric 05:13

Well, thank you for both of you, all of the work that you do in this. Let’s jump into this topic. And again, at the end, we’ll talk more about the AGS initiative and we’re going to definitely save some time for shingles. All right. Flu. I got my flu shot coming up on Monday.

And again, I think There’s so many populations we can talk about in this podcast. I’d like us to focus mostly on the most of the patients that we see, patients, older adults who may be living in the community or nursing homes, who may have very few or multiple medical problems. How should we think about for each one of these, whom we should be vaccinating, when we should be doing it during the course of the year and our choice of options? And let’s start off with flu, because when I think about flu, I think the vast majority, over 90% of flu deaths are in older adults. Like this is a big one.

Ken 06:03

Yeah, you’re absolutely right. What did you get, Eric?

Eric 06:07

Oh, I’m getting it on Monday.

Ken 06:09

Oh, you’re getting it on Monday? Okay.

Eric 06:10

Yeah, we, at my institution, they just started offering it this coming Monday. So it’s the very first day they’re offering flu shots. So I’m going to try it.

Ken 06:20

Yeah. So the recommendation is, you know, one dose annually with either high dose adjuvanted or recombinant influenza. influenza vaccine, and most of the doses that go to— for people over the age of 65, most of the market is high dose. Some, that’s Fluzone high dose, some adjuvanted, that’s Fluad. And the reason for that is those vaccines have enhanced protection against just the things you’re talking about, hospitalization, serious flu illness, death, compared to standard dose vaccines.

But the interesting thing is we’ve got a new player. that you guys have probably heard about, and that’s an mRNA flu vaccine. The FDA just recently approved this vaccine, and it’s an interesting story. Should I keep going?

Eric 07:07

Yeah. Sure.

Ken 07:08

Yeah, please.

Alex 07:08

All right.

Ken 07:09

So, you know, why would we want an mRNA flu vaccine? Well, the hope was that with an mRNA formulation, you could make a vaccine within weeks’ time to match new season or pandemic strains. High-dose adjuvanted vaccine, standard dose, they’re egg-based platforms. They take months to make. With an mRNA, it’s very nimble. You can make it quickly.

And this is coming from Moderna. And of course, they were hoping it would have enhanced protection too. So what they did was a large randomized controlled trial comparing the mRNA flu vaccine to the standard dose vaccine. Oh, what they found in the trial is it reduced flu illness by 27% compared to the standard dose vaccine. But that’s not what we prescribe for older adults, right?

Alex 07:59

Yeah.

Ken 08:00

So this left the FDA in quite a conundrum. Yeah. So what they did was they gave traditional approval for 50 to 64-year-olds, and for 65+, they gave a conditional approval. It’s called accelerated approval. based on some immune studies that said, you know what, you can have it on the market, but you have to go out and do a randomized controlled trial comparing mRNA flu vaccine against high-dose vaccine to confirm clinical benefit and keep your approval. And that trial started a few weeks ago.

Alex 08:33

Yeah.

Eric 08:34

So I can see both sides. Um, I can certainly see, I mean, we don’t, we see this outside of vaccine studies, people using suboptimal controls. To try to show that their drug is equivalent or better. Is that the concern here, why they did that? Or, and do you agree with it?

Ken 08:52

Yeah, I, I think their concern was that it wasn’t compared against standard of care. And so we do not know whether the mRNA flu vaccine is better than high-dose or adjuvanted flu vaccine. And by the way, speaking of hospitalizations, uh, we were talking about, uh, with RSV vaccine, there’s no hospitalization data in that trial. So it’s just influenza illness, whereas with the other one, high dose, we know it reduces hospitalization. Adjuvanted vaccine also reduces hospitalization during influenza.

Eric 09:19

All right, Ken and Sharon, if I’m talking to my dad tonight, Alex and I were just at a conference where we literally were talking about my dad about another issue, but if I’m talking to him, which one should I tell him to get? He’s over 65. Should I get him standard, high dose, or the new mRNA? Those are our options.

Ken 09:38

Yeah, it could be adjuvanted too, but…

Eric 09:39

All right.

Ken 09:40

You wanna start or…

Eric 09:41

Sharon, what would you choose?

Sharon 09:43

I’d say the high dose, uh, for now. I would not do the standard. The mRNA is very interesting though, and if it turns out in the flu season that, um, there is a new strain, I don’t know, Ken, would it be okay to get an mRNA at that point?

Ken 10:00

Only if they, uh, redo the formulation.

Sharon 10:03

Right. If they redo the formulation because a new strain comes out, I guess that’s always an option to consider, but I would definitely go for the high dose.

Ken 10:12

Yeah, myself as well. The best evidence is there.

Eric 10:14

High dose.

Alex 10:15

Yeah.

Ken 10:15

By the way, this flu season, there, there are 3 strains in the flu vaccine and all 3 strains are new this year. That hardly ever happens.

Eric 10:25

So, and they all have the same strain. They’re all targeted at the same strains. All 3 vaccines?

Ken 10:31

Yes, they do. Okay.

Alex 10:32

And this is kind of unequivocal. Older adults should get a flu vaccine. Yes, in my period.

Ken 10:40

They should.

Sharon 10:41

Absolutely. Yes.

Ken 10:43

Yeah. Alex, you’re, I think you’re asking a very interesting question here because let’s face it, flu vaccine effectiveness isn’t as what we’d like it to be in older adults. Last year, the vaccine effectiveness against hospitalization in older adults was 30%. You know, we, we want it a lot higher, don’t we? Yeah. And against outpatient flu, it was, it was about 30 to 40%. It’s a tricky organism. You know, there’s a lot of work going on in the area, but even so, there’s still some protection.

Sharon 11:14

So we get patients who say, oh, I’m so sick of all these shots. You know, we’ve, we found this in our, in our study. that there was some hesitancy and, or they say, oh, you know, the last time I got the flu shot, I got sick. And so you have to be very patient, nonjudgmental, and just kind of gently educate over and over again and explain that you can’t get sick from the flu shot and that it could keep you from being very sick and going to the hospital. And it’s just kind of Ongoing patient education.

Ken 11:50

Yeah. Yeah. Sharon, to your point, I think we’ve all heard this, the shot gave me the flu. Yeah. And of course we know that’s not true. However, it can give you local and systemic side effects that feel exactly like the flu.

Eric 12:05

Yeah.

Ken 12:06

It’s good to tell people that, yeah, I hear what you’re saying, but it’s a reaction. And, you know, taking some Tylenol or an NSAID before and after is a good way to help with that.

Eric 12:15

Okay, Sharon, I got a question for you then. Let’s say you have a patient who says, you know what, when I get the flu shot, I always feel miserable for 2 days. And then when I get the flu, I feel miserable. Why, like, why should I, why should I make sure I feel miserable for 2 days by getting the shot versus trying to maybe prevent feeling miserable for 2 days with the flu?

Sharon 12:38

So if you don’t get the flu shot, you may be miserable for longer than 2 days and you could end up in the hospital.

Eric 12:46

Yeah.

Sharon 12:46

So yeah, you might have some temporary discomfort after the flu shot, but overall it gives you better protection down the road.

Eric 12:54

Yeah.

Sharon 12:54

So that’s why I would say take some Tylenol, drink a lot of fluids, don’t have a lot of heavy activities that day if you’re really sensitive. Most of my patients though just get a sore arm.

Ken 13:07

Yeah.

Sharon 13:07

Local inflammation and discomfort.

Eric 13:09

So that’s the, that’s the only thing I ever get.

Sharon 13:12

Yeah. So I try to reassure them that it’s better to get the flu shot because it may prevent you from getting an even worse infection down the road.

Eric 13:23

And Ken, is there any data with flu? Like, does it— I know we’re going to be talking about shingles. That’s been a hot topic with dementia. But flu, does it help prevent other downstream consequences?

Ken 13:34

Yeah, it absolutely does. And I mean, while we’re talking about respiratory viruses, this is true not only for influenza, but also COVID-19 and respiratory syncytial virus. That all 3 of those vaccines acutely increase the risk for heart attacks and strokes. Now, this is mostly in people with cardiovascular disease, right? But the risk is spectacular.

It’s 5 to 6-fold, usually during the first few weeks after the infection, then attenuates over time. And it turns out there’s a lot of good data that shows that influenza vaccination, RSV vaccination, COVID-19 vaccination reduced that risk for major adverse cardiovascular events by about 35 to 40%.

Eric 14:13

Did they see that in the randomized controlled trials or is that mostly observational?

Ken 14:17

Yeah, both. That’s a really good question. There is a randomized controlled trial where people got vaccine and did not get the vaccine. That’s influenza.

Eric 14:26

Yeah.

Ken 14:27

Sure about RSV, COVID-19 there.

Sharon 14:28

Okay.

Ken 14:29

And the reduction in risks was pretty remarkable. Can I just point out, I, the American Heart Association has finally woken up to this and I’ve been on their scientific panels recently and they are really hot on letting cardiologists know this because they said, if I gave you a cardiac intervention that reduced the risk for heart attack by 20 to 30%, like aspirin or beta blockers, would you prescribe it? Yeah. And obviously they should.

Alex 14:57

Right.

Ken 14:57

Obviously.

Alex 14:58

Yeah, that makes a lot of sense. And then the mechanism here is likely something inflammation related. Is there any thoughts about what, why that is?

Sharon 15:04

Yeah, so we underestimate the role that inflammation plays in a lot of these diseases, including dementia. You know, especially in dementia, we’ve had a lot of focus on amyloid and tau, but there’s studies that show that inflammation over time is, is just as damaging and can really start that cascade that leads to dementia. So we don’t want to have an inflammatory response in our heart, in our blood vessels, in our brain. So that’s another reason why to get immunized.

Eric 15:35

But I can also imagine that like just caring for people with flu who get hospitalized, like they become really sick. They may have troponin leaks, they may have worsening of their heart disease. Like that hospitalization is, if they get hospitalized with flu, it’s a hard hospitalization. Same thing with COVID Yeah.

Ken 15:52

I’ll just add that even at the molecular level, Alex, that that inflammation causes plaque destabilization and prothrombotics. So it’s, yeah. But Eric, what you mentioned is a good one. You know, hospital-associated disability, you guys know about that. Yeah. So if you don’t go in the hospital because of these vaccines, you don’t get disabled.

Eric 16:11

Yeah. I think of Ken Kavinsky, 2/3 of older adults get hospital-associated disability. A third don’t recover from it. Great, great study from the archives. Okay. One last question about flu for me. Let’s say you happen to be a 51-year-old healthcare provider who goes in and out of the nursing home.

Alex 16:28

That sounds like you, Eric.

Eric 16:30

They have a podcast and it’s going to get a flu shot on Monday. Uh, what vaccine should I get?

Ken 16:35

For a 51-year-old?

Eric 16:36

Yeah.

Ken 16:37

Yeah.

Eric 16:37

Healthcare provider, like which of those options?

Ken 16:41

Uh, yeah, I’ve, the high-dose, uh, recombinant and adjuvanted vaccines are enhanced vaccines for people over the age of 65. So generally it’s standard dose.

Eric 16:50

Standard dose.

Ken 16:51

Yeah.

Eric 16:52

Okay.

Ken 16:52

But good on you because there’s a big problem with healthcare workers, uh, healthcare personnel, as Shay would call it, for not getting vaccinated. Particularly for nursing home residents.

Sharon 17:03

And so the more workers that are vaccinated actually help protect the patients too, because we know that especially frail older adults may not get a robust immune response, but if all of the workers and caregivers around them are vaccinated, then you’re also giving them extra protection.

Eric 17:20

Okay. Well, I swear I said last question, but I swear this is going to be my last question about flu timing. When should I get it? Like, Right. You want to kind of time it a little bit with flu season. Is that right?

Ken 17:31

Yeah. Can I just say one thing? I can tell you when not to get it. You know, the vaccine comes out in the pharmacies in August, for God’s sakes, do not get it then if you’re 60. And the reason is the immunological response wanes over 4 to 6 months. So you want it later in the season when the influenza season starts and October’s a good time.

Eric 17:51

So am I getting it too early?

Alex 17:53

Well, except we’re having an outbreak here in San Francisco.

Ken 17:55

There is a flu going around.

Alex 17:58

It’s also local, right?

Eric 18:00

So, so it depends on your local environment.

Ken 18:02

Okay.

Eric 18:03

Alex, any other questions?

Alex 18:05

No.

Eric 18:06

Let’s move on to COVID.

Alex 18:07

All right.

Eric 18:08

All right. COVID, when we’re thinking about this for older adults, again, COVID feels very different than it did, you know, when, uh, was it 5 years? I’m losing track of 5 years ago. Um, 6 years ago. Especially for younger adults, but we still see like older adults being admitted for COVID in the hospital right now who get really sick and they develop disability. When we think about COVID vaccines, who, who do you think should get it?

Ken 18:37

Yeah, I’ll start. I mean, anyone over the age of 65 should get 2 doses of the COVID-19 vaccine separated by 6 months. The minimum interval is 2 months. Sometimes people want it, they’re about to go on a trip and, you know, maybe 5 months after their first, they want to get it again. And that’s okay. And I know what you’re saying, you know, it’s COVID infections aren’t as prevalent, but the hospitalization rates are still by far the highest in 65 and 75.

Alex 19:01

Yeah.

Ken 19:02

75-year-olds. And, uh, the, uh, 2-dose regimen is because it loses effectiveness by, by 6 months. But here’s a really important point here that I don’t think a lot of people realize. Last year, the 25/26 COVID-19 vaccine reduced hospitalizations of people over the age of 65 by 53%. And emergency room visits by 48%. That is an added benefit on top of a population that already has a high level of immunity to SARS-CoV-2 because of vaccination, natural infection, or both.

Eric 19:38

Yeah.

Ken 19:38

It’s incredible. It’s still having some benefit on top of that.

Eric 19:42

Sharon, any additional comments on who should get COVID?

Sharon 19:45

No, I agree with Ken and it should be twice a year. I usually say spring and fall, you know, 6 months apart. And again, it’s a matter of giving people information and gentle encouragement because there’s been so much misinformation about vaccines and so many people are hesitant about it.

Eric 20:06

Can I clarify? Are we recom— is it the recommendation older adults get twice a year, every year COVID vaccines?

Ken 20:13

Yeah. So far, I mean, Who knows what’s going to happen in the future, but that’s just—

Eric 20:19

Do we know what, how many older adults actually get 2 shots?

Sharon 20:22

Yeah.

Eric 20:22

How many?

Ken 20:23

Well, last year, about 33% of people over the age of 65 got one or more COVID vaccines.

Eric 20:30

Yeah. Do we know how many got 2?

Ken 20:32

2024, it was 42%.

Eric 20:33

Do we know how many got actually 2 shots a year?

Ken 20:36

Yeah. I’m not sure about that. Not sure.

Sharon 20:38

All right.

Ken 20:39

Yeah, but it’s, it’s definitely less than 33%. Yeah. So there’s this COVID fatigue, no question about it.

Eric 20:44

Yeah. I mean, I think this is the hard part of coronaviruses in general, right? Like, yes, your immunity wanes pretty quickly after a vaccination, probably to some level, right? Like we’re all still somewhat immune. That’s probably why we’re not reacting so badly to most of us for COVID. Is that right?

Ken 21:03

Yes.

Eric 21:04

Yeah.

Sharon 21:04

Right. And it takes about 2 weeks. That’s the other thing for people to understand. I’ve had some patients who were going to go travel. And I say, well, you know, it takes about 2 weeks to build up that immunity, so you have to plan it carefully.

Eric 21:20

And what are our vaccine options?

Ken 21:23

Yeah, there are basically 4. A lot of people don’t realize that. They’re all familiar with the Pfizer mRNA product, Comirnaty, and the Moderna mRNA Spikevax. And we have the protein adjuvanted product, Nuvaxovid, which by the way is being handled by Sanofi now. Novartis is not doing anything.

Eric 21:38

Oh, really?

Ken 21:39

Yeah. But last year there was a new product introduced, an mRNA vaccine called mNex spike that Moderna makes. Uh, and it’s different than the other 3 I mentioned use the full-length spike protein as the antigen, but this one uses just part of the spike protein, couple of domains, and it induced neutralizing antibody. But all of those induced neutralizing antibody. Now the company did a head-to-head trial. of Spikevax versus NXPike, and there was no difference clinically in the instance of COVID So they’re all okay.

Eric 22:12

If you had to pick one for yourself, do you have one that you would pick or is it just whatever is being offered? Let’s say for an older adult.

Ken 22:20

Yeah. What do you think, Sharon?

Sharon 22:23

I would take whatever’s being offered.

Eric 22:25

Whatever’s being offered.

Sharon 22:26

I think the latest one is getting a lot of press though.

Ken 22:30

Yeah, the index spike. You know, the CDC for a while said, you know what, if you got, I don’t know, the Moderna product, you know, it’s good to keep getting that over the years.

Eric 22:39

Yeah.

Ken 22:40

Vice versa. But then they backtracked and said, well, sometimes a pharmacy doesn’t get the Moderna product, they get Pfizer instead. Just get whatever they have.

Eric 22:48

Okay. And then let’s talk about those younger than 65. Let’s say they’re 50 to 65. What’s the recommendation there?

Ken 22:59

Yeah, that’s a really interesting point. You know, the FDA just a few weeks ago approved a new formulation of the COVID-19 vaccine to match the dominating circulating strain. I won’t mention all the initials for that, but at the same time, they approved it for use in people over the age of 65 and any adult over 19 that’s at high risk. for developing severe COVID illness.

So the kinds of patients we are very familiar with in geriatrics, and happens in middle-aged adults too, chronic cardiovascular, lung disease, immunocompromising conditions, et cetera.

Sharon 23:35

Yeah. So the one, the one challenge though, is if you’re over 65, there’s no copay and the vaccine’s essentially free. But if you’re younger, maybe if you are out of those categories that are high risk, you have to pay for it. And that is a big barrier for a lot of people. So I don’t think a lot of younger people are going to get the vaccine unless they have good insurance coverage.

Eric 24:04

And then I guess for healthcare providers. So I remember in the beginning of the pandemic, we’re all, everybody get your shot. It helps prevent transmission. And then a couple of years into the pandemic, oh wait, it doesn’t prevent transmission. Where are we with COVID and healthcare providers? Like, should we take it not just to protect ourselves, but from a transmission standpoint, or is it just too hard to tell? Where are we with that?

Ken 24:29

Yeah, I think, you know, we’re not doing mandates anymore and it’s individual clinical decision-making. Some people use the word shared decision-making in this context. Personally, I think it’s useful to get vaccinated and for the reasons you mentioned, but a lot of individuals who aren’t interested in doing it. Great.

Eric 24:47

Sharon, any additional thoughts?

Ken 24:49

Yeah.

Sharon 24:49

So that’s again, the big challenge is that there are no mandates and a lot of people have very strong feelings about this vaccine in particular.

Eric 25:00

Yeah. Well, let’s move on. We got a couple more. I wanna make sure we have time for everything. RSV. So who should get the RSV shot?

Ken 25:11

Now, this is interesting in that there’s a kind of a bifurcated recommendation. Any person 75 and older should get the RSV vaccine. There are 3 of them. And the reason for that is the hospitalization rates for RSV is by far the highest in people 75 and older. So when we were coming up with the recommendations, this is when the ACIP was functioning well, he said, you know, let’s not make this complicated.

But the data weren’t as strong in people between the ages of 50 and 74 for that. So that became a risk-based recommendation. So people are at high risk for severe lower respiratory tract disease from RSV should get the vaccine. And again, it’s the usual suspects like we’ve been talking about: chronic heart disease, chronic lung disease, kidney, liver, diabetes, obesity, immunocompromising conditions. And the great thing is we fought hard to have frailty and nursing home residents in that recommendation. Great.

Eric 26:09

Sharon, any additional thoughts?

Sharon 26:11

So it’s 75, one and done is what I tell my patients is that if you’re 75 and over, you want to avoid getting RSV. It’s very debilitating and it’s a one-shot deal.

Eric 26:26

Is it one and done or is… do we think that we’ll learn more if it’s one and done? What do you think, Ken?

Ken 26:33

We’re learning more.

Sharon 26:35

We always learn more.

Ken 26:39

That’s right. It’s not an annual revaccination because right now the, the data indicates that there’s some protection out to 2 years, 2 seasons, and it’s under investigation. The other thing is whether we should get revaccinated, and there’s no data to support revaccination right now. Let me just, there’s one outstanding clinical trial that basically looked at this over 3 years.

They gave everyone a vaccine before season 1 or a placebo. And, uh, in that group at season 1, it was about 81% protective against, uh, lower respiratory tract disease, 54% by season 2, 48% by season 3. And they did an interesting thing. They re-randomized the people that got a vaccine, a group of them in season 1, they get vaccinated again and kept a placebo group. In that revaccination group, the efficacy at season 2 was the same as in season 1. Oh, it was 58. Yeah. So no revaccination at the present time.

Eric 27:41

Okay.

Alex 27:42

So Eric, I mentioned this at the beginning at AGS. I forget what year. Oh, 2024. We did the literature update plenary, and my song for this article about RSV was Not, Not Throwing Away This Shot. it’s a golden opportunity to have some immunity and you’re not throwing away the shot, you know, parody of Hamilton. But you and Ken sort of disagreed and you came to a different conclusion. How was that?

Ken 28:08

Yeah.

Eric 28:08

So this was a 2023 article. It was, I think it was the first RSV article, a vaccine article that came out, and it did not have outcomes of hospitalization, ICU, but it did reduce RSV symptoms. So lower respiratory tract symptoms. A very small reduction in that, I would say. And there were 30,000 people in the trial, 15,000 in one arm, 15,000 in another arm. There were 2 cases in the study of Guillain-Barr.

Like, and it wasn’t even talked about in the article, but it made me like, I don’t see that disease that much. And if you’re inject, like, giving 15,000 people RSV and you’re seeing this disease and the best thing we can tell from that article was it just prevented lower respiratory tract infections, but not hospitalizations, mortality, or anything else. We really questioned that. Since then, I think, Ken, am I right? We have some better data.

Ken 29:06

Yeah. And I share your— I think all of us at ACIP and that workgroup shared the same concerns. Not only did they not have hospitalization, they had very few people over the age of 75. So we just didn’t know.

Eric 29:16

Yeah.

Ken 29:17

High-risk group, whether it worked or not. Now, for all 3 vaccines, within the randomized controlled trials, it was pretty effective, 65 to 88%. But what’s happened since it’s been licensed is post-licensure observational studies, and there have been pretty robust ones, very large studies, including lots of people over the age of 75 and 80, and hospitalization outcomes have shown that it reduces hospitalization by about 75, 77%. And ED visits too.

Now you could, you could argue these are cohort and case control studies. They have their weaknesses. They’re not randomized controlled trials, but I think there’s enough data there to suggest that that’s probably pretty important.

Eric 30:00

How many RSV vaccines do we have out there?

Ken 30:03

Yeah, we, we have 3. There’s, they, they all use the, what’s called the, the RSV prefusion F protein. Yeah. They all use protein, but GSK’s product. puts an adjuvant onto that. Fun fact, that’s the AS-01E adjuvant. That’s half the dose of the Shingrix adjuvant. The Pfizer product, uh, ABRISCO, just uses the RSV protein alone. And then the Moderna product, of course, uses mRNA to make that protein. Now, the concern about the Guillain-Barr is a big one.

Alex 30:35

Yeah.

Ken 30:35

Another concern at, uh, the ACIP workgroup. So over time, the FDA has collected a lot of data, and this is mostly from Medicare databases and other large health systems to estimate the risk, and there is not a risk with the mRNA vaccine, interesting enough. No signal happened in that clinical trial and in the observational studies. So this is just the GSK and Pfizer products. And what they found basically is it’s about 7 to 9 cases of TBS per million doses. That’s the best data we have now. To make a comparison for flu, it’s about 1 to 2 per million. And, uh, Zostavax vaccine is about 3 per million.

Eric 31:13

So if you were to choose a vaccine for RSV, would that influence the choice you recommend?

Ken 31:20

Yeah, great question. I think this is patient preference and value.

Eric 31:25

Patient preference. Okay.

Ken 31:26

Yeah, I, I, I, I’d be okay with getting any of ’em myself, but I can tell you there are some people would say, you know what, I want the mRNA vaccine.

Eric 31:34

Yeah. Sharon, how about you?

Sharon 31:36

Well, I, I like the, the data for the mRNA. mRNA vaccine myself. I just don’t know how easy it is to get it. So I know the Pfizer is very available. So Ken, have you seen any problems with access for the mRNA?

Ken 31:54

You’re exactly right that the GSK and Pfizer products dominate the marketplace by far.

Sharon 31:59

So—

Alex 32:00

Yeah.

Eric 32:00

And that’s the pre-fusion F vaccine.

Ken 32:03

So that, yeah, they don’t use an mRNA formulation.

Eric 32:06

Does it matter when we give it?

Ken 32:08

Oh, that’s a really good question too. I, you know, ideally it should be before the RSV season starts, you know, maybe September, October.

Eric 32:15

So about the same time for all of them.

Alex 32:17

Yeah.

Eric 32:17

Is there concern about giving all 3 at the same time?

Ken 32:21

Sharon, have you had any patients do that?

Sharon 32:23

Um, I’ve had some patients who wanna space it.

Eric 32:26

Yeah.

Sharon 32:27

But, um, I’ve, I also have patients who get, uh, COVID and flu at the same time without any problem.

Ken 32:33

Okay.

Sharon 32:34

But I just think if that helps someone feel better, you can space it out a couple of weeks. I’m not sure it really makes a difference though.

Ken 32:42

Yeah. So there’s a lot of data on co-administration of 2 vaccines, you know, influenza and COVID, influenza and RSV, RSV, and people tolerate ’em pretty well. Yeah. There’s no difference in the immune response really. Uh, and I’ve, I’ve led some of those studies. The 3 The 3-peat is not as well studied and it makes me a little worried, but the CDC party line is you can get all 3 at the same time. Okay.

Sharon 33:10

Okay.

Eric 33:10

Okay. I’m going to move. Alex, any other questions before we move on?

Alex 33:12

Last question. How are we doing with the RSV vaccine? Like, what’s the uptake?

Ken 33:16

Yeah, the uptake’s okay. Last year, I think we’re up to 35 or 40% of the population, but it’s relatively new. So I think it’s going this way. Okay. Good. That, that was going on.

Eric 33:27

And currently RSV, one and done.

Ken 33:29

That’s right.

Alex 33:31

One and done.

Eric 33:32

All right, let’s move on to shingles. Um, uh, ’cause this is interesting. This is probably one I wouldn’t do at the same time as those others because I have my shingles shot and man, it was like the worst flu for like 3 days. Still don’t regret it at all. I still need to get my second shot. I’m a little bit wary of that, trying to time it correctly. But it hit me hard, but I still want to get it because I haven’t cared for a lot of people with shingles. That looks miserable.

Alex 34:00

And my doc said, you know, maybe wait until you’re older. I’m 52 and the risk is higher because there is some waning of immunity. I wonder what to think about that.

Eric 34:13

So who, who should get shingles shot? Not, not shingles, but the shingles vaccine.

Ken 34:18

No one should get shingles. Yeah, to your point, Alex, it’s a really interesting point. And, um, the risk for zoster goes up exponentially and postherpetic neuralgia as you get older. The risk for zoster and PHN is much lower in 50-year-olds than it is, say, in 75-year-olds. So it’s not unreasonable to suggest to get it later. You know, when we did the Shingles Prevention Study, we designed it at 60 and above specifically for that reason.

Whereas the ZOE-50 and ZOE-70 studies, the, for Shingrix, were done at 50 and above. to try to enhance the marketplace. And there are some people who get— so I don’t think it’s unreasonable to wait. Different patients have different anxieties about this. And, you know, they may have that family member that had SOSTER and PHN and they want it the second they turn 50, you know, for God’s sakes. But getting it later is not unreasonable. By the way, this gets back to how long is— what’s the duration of protection?

Eric 35:12

Yeah.

Alex 35:13

Yeah.

Ken 35:13

Yeah. And so what’s very interesting here is that the original Shingrix trials, ZOE-50 and ZOE-70 trials, have had follow-up out to about 10 to 11 years now. Okay. And the vaccine effectiveness has stayed about 80% out that far. And the immunological response has stayed a decade later. That’s pretty good. So it looks like it’s pretty prolonged so far. Uh, so that, that’s, that’s a good thing. Yeah. But the bad thing is, oh my God, it’s so reactogenic, right?

Sharon 35:46

Yeah.

Eric 35:46

Are, so what are our choices for For shingles shots?

Ken 35:49

It’s just the Shingrix. That’s the only thing on the market now. Yeah.

Eric 35:53

Shingrix. Yeah. And how many people got the, how many people get the same thing I got? Like this feeling of like, really, it felt like flu for 3 days.

Ken 36:03

Yeah. Let’s talk about that some more. You know, the FDA and pharmaceutical industry uses a categorization of severity of reaction that we would never accept in geriatrics. Let me explain why. They use a grading system. Grade 1 is mild.

Sharon 36:20

Yeah.

Ken 36:21

You can, you can do your activities. Grade 2 is moderate. You can, your activities aren’t quite as good. Grade 3 is prevents normal everyday activities. That’s that.

Eric 36:31

I had grade 3.

Ken 36:32

So you got a grade 3. Now what happens with grade 3s is that 16% of people, about 1 in 6 over the age of 50, got grade 3s. in the clinical trials. And that’s what I tell the patients. You know, there’s about 1 in 6 chance you’re going to be not wanting to do much over the weekend. I tell people to get it on a Friday.

Alex 36:51

Yeah.

Ken 36:53

But on the other hand, I’ve talked to large numbers of older adults about this. I go and tell you, give a zoster talk. How many of you had Shingrix here? 75% of the hands go up. How many of you had bad reactions? You know, you know, a certain percentage. How many had no reactions? 10%, no reactions. So there’s this huge heterogeneity.

Sharon 37:12

Yeah.

Ken 37:12

It’s hard to predict. By the way, reactions to the first dose don’t predict reactions to the second dose.

Eric 37:17

Oh, good. So I, I can fall into any of those categories.

Ken 37:22

Yeah. But it, but it is useful to tell people to avoid strenuous activities for the first few days after the, uh, the vaccine. My, my best anecdote, if I can give one, is when we were we also did studies of the impact of reactogenicity on quality of life and functional status in older adults. And it turns out the grade 3 reactions do affect ADLs and do affect mobility for a couple of days.

You have those grade 3s. But I had a tough physician in this study that came in on a Friday and I said, look, you better just take it easy over the weekend. He said, I’m going for a 100-mile bike ride on Saturday after he got in on Friday. I said, okay. Monday he calls me up. There’s no way I could have made that bike ride.

Sharon 38:05

I was so tired. All right.

Eric 38:09

Um, since we talked about it before, shingles vaccine and dementia, which was a hot topic, what, 6 months ago, largely, again, this is all coming, I think, from observational studies, which again, I, there’s, there’s always a difference between people who get these shots and people who don’t. So having some type of just caution, where do you both fall of, A, does it matter? Because like for me, it didn’t really matter because I just don’t want shingles versus like, no, the evidence is actually pretty good that it helps prevent dementia. Sharon, what do you think about that?

Sharon 38:45

Well, I think it does reduce risk according to the data, and I’d be interested to see what Ken says. It’s an added bonus. It’s not the main reason why you get it, but it might be an added bonus. And again, it may be related to long-term Reduction in inflammation. And, you know, they have found herpes in the brains of some people with dementia. And so the concern is that maybe the virus settles into the brain, which then can trigger all that cascade of changes that we see with Alzheimer’s disease.

Ken 39:20

Yeah. Well said, Sharon. I mean, it’s biologically plausible, right? Because of, you know, varicella-zoster virus is a neurotropic virus and it does establish latency in the brain, cranial nerve ganglia. So either direct viral toxicity or the inflammation, like we talked about, and then, and also, by the way, zoster increases the risk for dementia. So giving a vaccine to prevent all that kind of makes sense. Yeah, the observational studies have been pretty consistent showing about a 20 to 25% reduction in dementia risk.

But like you said, Eric, they’re observational studies. I have to say the most recent ones have had very sophisticated designs to try to get around those biases. But they still can’t completely control for residual confounding, healthy vaccinee bias. And the other thing I think we are concerned about is the actual measurement of dementia in the studies. It’s all codes, you know, administrative databases, which is terrible. Yeah, exactly.

Eric 40:14

That’s terrible.

Alex 40:15

Well, it’s very specific, but well, is it very specific? It’s probably more specific than sensitive, most likely.

Ken 40:21

So, yeah. Yeah. So there was an NIH workshop on this that I attended just a few weeks ago. So Talk about time late. And I’m going to sum up 2 days of a lot of interesting discussions. So at the end of the day, everyone said, you know what? We need randomized controlled trials to solve this conundrum. And guess what? There are 2 going on right now, one in Finland and the other in Denmark.

Eric 40:44

That’s fabulous.

Ken 40:46

Yeah.

Sharon 40:47

Yeah.

Eric 40:48

That’s the point of observational study, right? You find something of interest and then you do a randomized controlled trial to confirm it. And if the effect size is as big as those observational studies are showing, like, hey, we should be able to see it in a randomized controlled trial. That’s great news. Okay, Sharon, I’m going to ask, last question is, can you tell me what the AGS Vaccine Initiative is and what’s it doing now?

Sharon 41:14

So it was a grant that the AGS got in 2021 to increase immunizations in older adults. Unfortunately, it got cut a little early. So right now we’re just kind of wrapping up looking at data and we have a paper pending in JAGS. But the interesting thing we found, and we’re generally working with geriatricians who we don’t have to convince about the importance of vaccinations, but there’s a lot of kind of structural things in our healthcare system that can make it a challenge.

And so what we did was we picked 7 health centers, health systems across the country, and they all tackled it to see how they can improve immunizations in their institutions. And it looks like it was pretty consistent is, you know, the team approach, which we all know in geriatrics is getting the medical assistants and the nurses on board. And, you know, some of them may be ambivalent about vaccines, but after a lot of in-services and staff education, they got on board. And making it part of the rooming process was a big plus. Many of us have an electronic health record, but the rooming process does not have a platform for vaccines.

Eric 42:27

What’s rooming?

Sharon 42:29

You know, when you’re getting someone ready to be seen and they get their blood pressure checked and, you know, you check their meds? Well, there weren’t any platforms in electronic health records for checking on vaccine status.

Ken 42:43

Oh.

Sharon 42:43

So a number of the health systems got with their IT people and added another piece into their rooming process so that the medical assistants could ask about vaccines. And if the patient was interested, they could put a pending order in there. Or if they declined, they could put that in there and that would give the provider a chance to talk about it with the patient. So we found that just by bringing it up and asking, that helped to improve awareness and to get people on board for getting vaccinated.

So those are some of the things that you can think about out there if you want to improve immunizations in older adults. And then there were things like putting messages in the after-visit summary, sending out letters, especially during the flu season, seemed to help. We created a real-time learning network for healthcare providers who could share information and get tips on how to increase immunizations in their patients, putting flyers and brochures in the exam room while they’re waiting so that they could ask questions. Anything that keeps the conversation going was actually very beneficial.

Alex 44:00

I like that framing. Anything that can keep the conversation going. Let’s keep talking about it. Keep talking about it.

Sharon 44:07

Right. And even if they’re hesitant or they’re so sick of vaccines, don’t write ’em off. Just gentle conversation and you’d be surprised at the results.

Eric 44:18

And when that paper comes out, we’ll add it to our show notes for this podcast. Uh, should, I think it should be coming out soon. Is that right?

Alex 44:25

Soon. Soon.

Eric 44:27

Okay. Well, uh, before we end though, how about we give a little bit more of Hit me with your best shot.

Alex 44:37

Hit me with your best shot. Why don’t you hit me with your best shot? Hit me with your best shot. Fire away.

Eric 44:53

Ken, Sharon, thanks for being on this podcast. Learned a ton.

Sharon 44:56

Thanks for having us.

Ken 44:58

Yeah, it’s so great. Great talking to you guys.

Eric 45:01

Great timing too. And thank you to all of our listeners for your continued support.

This episode is not CME eligible.

For more info on the CME credit, go to https://geripal.org/cme/