The official podcast of the International Parkinson and Movement Disorder Society. I'm your host, Sara Schaefer from the Yale School of Medicine. And today we will be speaking to Dr. Richard Smeyne, a chair and professor of the department of neuroscience and director of the Jefferson Comprehensive Parkinson's Disease Center and Vickie & Jack Farber Institute for Neuroscience.
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[00:00:29] Sara Schaefer: So today we have a very interesting topic. We're gonna be talking about a recent paper in the Movement Disorders journal entitled, "COVID-19 Infection Enhances Susceptibility to Oxidative Stress–Induced Parkinsonism" — obviously a hot topic. And I really appreciate you taking your time to talk to us about it today.
Can we start with a background for the concern for a link between COVID and parkinsonism, and what are the proposed mechanisms for this link?
[00:00:59] Dr. Richard Smeyne: Sure. [00:01:00] So our laboratory has been studying the role of viruses in Parkinson's disease for the past 10 or 15 years, starting with looking at influenza viruses and then with other collaborators such named Ron Tjalkens at, at Colorado state looking at Western Equine Encephalitic Virus, always looking at the idea that viruses could be a part of the initiating factors for inducing Parkinson's disease. Our initial interest in viruses really arose from literature of the 1918 Spanish flu, subsequent to that flu. There was a, number of cases of parkinsonism that seemed to be linked back to years before, to the infection with the 1918 flu.
This is often called Von Economos encephalopathy or sleeping sickness or postencephalic parkinsonism. [00:02:00] And really was made famous by the book by Oliver Sacks called Awakenings. So we, got interested in studying those flus back then. And we found that animals that had been infected with the influenza virus had an increased susceptibility to other chemicals that we've used to model Parkinson's disease in animals.
And so with that background, knowing that several different strains of influenza could make animals more susceptible to these agents. We were interested to see if COVID, being that it infected so many people across the world would act in a similar manner to what we had previously seen with influenza.
[00:02:48] Sara Schaefer: And what are the proposed mechanisms for this link between viruses and the development of Parkinson's disease?
[00:02:54] Dr. Richard Smeyne: Well, as I said, you know, earlier we have a link that's really [00:03:00] just a correlational statistical link, between the 1918 flu and the development of a very large and significant number of people who developed a postencephalic parkinsonism, years after they had recovered from the 1918 flu. So that's our human link.
There's no definitive proof of that link, but it is a very clear statistical link in that you know, about 10 to 15 years after people had recovered from the 1918 flu There was just such a large number of these cases of postencephalic parkinsonism, all of them having recovered from the Spanish flu.
And in fact, it's one of the few times, in fact, it maybe the only time in history where the actual rate of Parkinson's disease increased from what we generally say from one and a half to 2% of a population getting Parkinson's disease. Over that period of time, it went up an extra percent to 2 and a half to 3 percent of people generating Parkinson's disease. Again on an individual basis, [00:04:00] not a great amount, but it added several million people worldwide to, having some form of parkinsonism.
[00:04:08] Sara Schaefer: And what about the substantia nigra pars compacta increases its susceptibility to post infection, inflammation, and neuronal damage.
[00:04:18] Dr. Richard Smeyne: Right. So that's very clear, at least in our preclinical studies. So in some of the earlier studies that we had looked at looking at both the H5N1 bird flu, as well as the H1N1 2009 pandemic flu we found that infection with these viruses, whether they got into the brain or not, induced inflammation in the substantia nigra.
And in this case, what we were talking about is a statistically significant increase in the number of microglial that were activated both morphologically as well as us seeing that they were secreting pro-inflammatory cytokines after the virus. So in terms of COVID we can get into the [00:05:00] results of this particular paper we're talking about.
But one of the things that we found similar to the 1918 flu. The H5N1 flu and the 2009 H1N1 flu also was this increase in inflammation in the brain, in the substantia nigra. That was secondary to infection with COVID.
[00:05:23] Sara Schaefer: And is there any. Reason that it's this particular part of the brain that seems to be susceptible in terms of, you know, vascular supply or metabolic demand or any other factors that you think play a role.
[00:05:37] Dr. Richard Smeyne: It's a very interesting question. I often joke about the substantia nigra that, you know, that the cells in there were born to hang. And when I say that, what I mean is there was some really classic work done by a scientist at the NIEHS named John Hong who showed that in the C57 black six mass, [00:06:00] which is the typical strain that we use for many of these studies, the proportion of microglial cells to astrocytes to neurons was particularly large.
And in fact, compared to many other regions of the brain, it was three to five times more microglia per astrocyte and neuron in that region than any other region of the brain. And we think for that reason that this area of the brain is particularly sensitive to agents that induce inflammation, because there's so many microglia in that particular small area of the brain.
[00:06:38] Sara Schaefer: How did your lab go about testing this link between COVID and parkinsonism?
[00:06:43] Dr. Richard Smeyne: So this was a collaboration that initiated at East Carolina University By a colleague named Pete Schmidt, who at the time was the associate Dean there. They had gotten some funds from the United States government and from the state of, [00:07:00] North Carolina to look at COVID and given my previous experience studying different viruses in the brain, they contacted me to see if we wanted to do a collaboration.
So with two scientists there, Jeff Eells and Dorcas O'Rourke we went about testing the question of whether COVID could, induce the same sensitivity that we had previously seen with other forms of influenza. So they started this study by looking at the effect of different titers of COVID and I should say, you know, one thing to be made clear here is the COVID that we are reporting in this paper was the initial strain, which we call USA-1.
Some people call it Alpha. And so all of our results are particular to this particular strain of COVID. And while we're interested in studying, it cannot be generalized to the later Delta variant or our current Omicron variants Those [00:08:00] have to be studied individually. We just can't make that assumption. So, the alpha variant infected about 5 million people worldwide.
So it's still a significant issue to study that particular strain. Anyway, we had devised three different titers to test in there. And we gave these three different titers one that would've been a remarkably high dose. One that would've been probably enough an equivalent to what would've put someone into the hospital to be intubated in the ICU and likely could have induced death.
And what we saw with that particular titer was a mimicking, the animals got very sick and almost all of them died. We then used two lower dose titers. One of the titers we used caused animals to get sick and by that, you know, judged by, they lost weight a little bit. we had a very small number of the animals die, but most of them recovered quite well and went on and we called that sort of the mild COVID. And then we used a very low dose where the animals seemed to have no [00:09:00] effect at all. We saw no animal sickness, we saw no animal death. So we decided of those three titers to use the intermediate titer. So we called that sort of mild, the equivalent of mild, COVID both by the surviving number of animals and their response in terms of cytokines in the body. So, the animals clearly were infected. They clearly got sick. But they all pretty much recovered. So we called that mild disease. And so we used that middle titer to examine the effects of the brains. And then, we infected these animals and this was all done at East Carolina University.
And we let them go till they had completely recovered. And this was, you know, about a month. And as we know from, the human studies the virus doesn't last that long inside the body. And in fact, you know, most people recover within a week or two. We see the same recovery period in animals.
So we allow those animals to recover. And then [00:10:00] after about a little bit more than a month, we gave them a very low dose of a chemical called MPTP. MPTP is a drug that was discovered actually in the 1980s, as a byproduct in a synthetic heroin synthesis that was being made actually as a designer drug made famous in the book called The Case of the Frozen Addicts by Will Langston.
And we used a very low dose of that, that in a normal animal that had not been given, COVID had really no effect at all. It caused a little bit of an inflammation in the brain, but no loss of neurons. And then when we used that same, very low dose of MPTP, which is a mitochondrial toxin I should add that it's a mitochondrial toxin.
When we used that very small dose in animals that had previously been infected with COVID rather than having no effect, we saw a very large amount of inflammation in the substantia nigra, and about a 25 or 30% [00:11:00] loss of dopamine neurons. So what normally would not have had any effect because these animals were now infected with COVID. We saw a significant loss of these dopamine neurons.
[00:11:12] Sara Schaefer: All right. Well, so one thing that struck me when I was reading the study, is the mice in the study were genetically modified to have increased ACE2 receptor expression in order to be more susceptible to COVID.
The ACE2 receptor differences across ages has been implicated as one reason children might be less affected than adults. And as one explanation for differences in disease severity in general as far as I know. Knowing that humans have variable levels of expression, how do you translate your findings to the human population?
[00:11:47] Dr. Richard Smeyne: Well, it's a very tricky question and this is one of the issues that we have to deal with and to keep in mind when we are modeling human disease in animals. So the C57 black [00:12:00] 6 mice that we have do not have the human ACE2 receptor. So therefore, if you were to take the COVID virus, the human virus that infects people and give it to animals, just a normal, wild type animal, there would be no effect because the receptor for this particular virus is not present.
So in order to now study some of the longer term effects and other effects, you know, not just in the brain, but in the body of COVID in mice. We generated transgenic animals, where we introduced the human ACE2 receptor driven by a promoter called the K18 promoter. So, which is the current promoter.
So in all of epithelial cell lineage which of neurons are we'll express this ACE2 receptor. So we made an animal that is now susceptible to human COVID. It is expressed at high levels. So this would be the equivalent of really an adult fully [00:13:00] formed animal.
So we can't judge using this model, whether there would be a difference in ACE2 levels as being responsible for why children might be less affected than people. But just even without that, you know, there's many other variables that are involved in generating illness here. One thing that we often see is that the immune system of children is less developed than adults.
And so one possibility for why children could be less affected than adults, independent of ACE2 levels, would be that they just don't generate as much of an immune response to the sickness. And, there would be a multitude of other reasons that there could be, it could have to do with the epithelial passage from the nose or the eyes, which is how we normally get infected by COVID, it's a respiratory virus into the lungs.
So there's many other pathways and [00:14:00] variables that you have to think about with age related to the induction of sickness and the degree of illness following infection. So that's something with this particular animal that we can't judge.
[00:14:15] Sara Schaefer: Well, it sounds like what you're saying is. If you had to guess that this would be more appropriately comparable to an adult human than a child for a number of reasons, including the degree of inflammatory response and the degree of ACE2 receptor expression, would you say that that's correct.
[00:14:37] Dr. Richard Smeyne: I think that's a fair interpretation of how we would judge the results from this animal. That being said, since we were studying really the induction of experimental parkinsonism or the induction of parkinsonism in these animals. That's also not traditionally a disease that we see [00:15:00] in younger people.
Okay. Parkinson's disease, even in young onset, we're seeing people in their twenties to forties, but the traditional population that would be getting Parkinson's disease are in the 50 to 60 years. So in any case, all of them being adults.
[00:15:18] Sara Schaefer: So let's get to the timing. You injected mice with the MPTP 38 days after infection, which yielded the results you discussed, where those that had been infected with COVID-19 had increased inflammation and neuronal cell loss. How do you think timing of a second inflammatory or toxic stressor like MPTP or whatever infectious or, inflammatory or toxic stressor we might find in our own environments may alter the results. Do you think that this post-infection sensitization persists indefinitely or is time limited? Is there any data in other studies of other [00:16:00] viruses to support one or the other.
[00:16:02] Dr. Richard Smeyne: It's a fabulous question. In none of the studies that have been done with influenza. Nor in this current study with COVID. Did we ask that question? But it's a very, very important one. To know, you know, there's a multitude of theories of what causes Parkinson's disease in people. We have a few genes that seem to act as significant risk factors.
Mutations in the GBA1 gene or the PARK2 gene dramatically increase your risk of developing Parkinson's disease. But what's clear with that is even just having those mutations alone is not a guarantee that you will develop Parkinson's disease. So with that, we have a pretty well accepted hypothesis, which we call the multi hit hypothesis of Parkinson's disease.
The idea that small insults over time synergize with one another. And if you [00:17:00] get enough of these damaging hits and kill enough cells, in the substantia nigra or other parts of the body that are affected by Parkinson's disease, that's when you'll see symptoms. And so in this particular study, we were using two hits, the first hit being infection with COVID and the second hit being a exposure to a very low dose of the mitochondrial toxin MPTP. But your question is, you know, we did this 38 days apart. What would happen if we gave MPTP 90 days after COVID? Would we see the same effect? It's an important question to ask and one that we're proposing to follow up and do, but, you know, I can't speculate now. The only thing I can say is that with influenza, as well as what we've seen with COVID, the inflammation seen within the [00:18:00] substantia nigra appears to be permanent. So we did look at that specifically in our studies that had looked at influenza and we found that the microglia inflammation in the substantia nigra persisted as long as at the latest point we ever looked, which was three months after the infection.
So that would suggest that at least the priming event here, the increase in inflammation, in substantia nigra with that particular virus lasted for three months or three times longer than the period that we looked at with COVID. I do not have any information on COVID because we've not done that, So it would not surprise me to see an extended period of inflammation following COVID that is similar to what we had previously, already experimentally shown following influenza.
[00:18:57] Sara Schaefer: So this brings up the next [00:19:00] question, which is, I think an important one. You know, with a toxic exposure or with a virus, you might think this is one moment in time. This is a static situation. So whatever effect happens the one time and then it's over. But at some point along the way, this becomes degenerative in the development of Parkinson's disease and your study since the animals were sacrificed after the MPTP doesn't really help figure that out.
But I'm wondering also, you know, thinking back to the 1918 influenza epidemic. Was the parkinsonism there, static or degenerative and it's interesting that you mentioned that the symptoms occurred 10 to 15 years later, and we know that in Parkinson's disease, idiopathic Parkinson's disease, there are all these prodromal symptoms like REM sleep behavior disorder that can happen 10 or 15 years beforehand. So clearly something's going on for a long time before the motor symptoms [00:20:00] develop. I'm kind of thinking out loud here. What are your thoughts on all of this in terms of degenerative versus static, multi hit types of situations leading to parkinsonism.
[00:20:12] Dr. Richard Smeyne: Yeah, it's a fascinating question. So we do know in the small number of people who became intoxicated by MPTP, as I had discussed in the book, The Case of the Frozen Addicts, these heroin users in California, that was a very acute effect. So they had injected themselves with this synthetic heroin that was contaminated by MPTP and over a very short period of time developed the parkinsonism that was secondary to MPTP.
They did not progress. It was an acute event. And so we do know at least with MPTP it causes an acute event that does not get progressively worse. Now, your question is a slightly different question. Your question is, you know, because [00:21:00] we see this long time period between the onset of the infection and the induction of secondary parkinsonism. Will it get longer.
Our guess is that it will depend on what the secondary hits are. It's how fast it will come on and how long it will last. I should say the first description of the encephalitis lethargica that followed the Spanish flu. There was a German neurologist named Felix stern who really followed this closely. And, you know, when we talk about, it was you know, 15 to 20 years later that they got this encephalitis lethargic and the parkinsonism, he really described it as three waves.
He had said there was an acute phase where there was drowsiness. Then there was a secondary phase, a little bit longer after that, where they developed eye and motor problems, then they seemed to recover. And then following this period of [00:22:00] recovery, all of a sudden they developed parkinsonism. So it was like this multi wave induction of this encephalitis lethargica secondary to the 1918 flu.
We don't know what to think of in terms of the time period for our results and what we think. My guess is that COVID has set up a inflammatory environment within the substantia nigra that now will make it have a heightened sensitivity to many other agents that in and of themselves would not have induced any loss in the nigra.
So, you know, sort of to show this in a mathematical formula, if you had one hit on top of the COVID, maybe it would take you 25, 30, 40 years to develop, you know, enough of that combined effect to start to see [00:23:00] symptoms. But what now, if you have another small hit such as, maybe you get the flu a few years later after COVID, or you're exposed to a number of industrial and agricultural products that have been shown to be linked to Parkinson's disease. So now maybe you have two hits on top of that, so that changes the slope of your decline even faster. So I think each person's gonna be individual, but I do think that if the initiating event such as COVID is going to be the initiating and key factor, that this will all happen over a period of maybe, a few years.
Because the initiating factor at least for the alpha variant only lasted about a year. All those people infected with that only happened over one year. So I think that you're gonna see if this does induce a secondary parkinsonism. It will happen in the future and I can't predict how many, you [00:24:00] know but it will happen over a very short period of time.
One thing that actually helps us make a judgment is a study that was just published within the last few months out of Denmark, looked at the medical records of people who had been infected by the 2009 H1N1 influenza virus. And they had been infected and gotten sick enough to have to be hospitalized.
But what they found has followed them out and they found that of that population who was sick enough to be hospitalized from the 2019 flu, there was a significant increase in the number of patients who developed Parkinson's disease. This was just reported this year and that virus happened in 2009.
So right now we're talking about 13 years after the initiating event. That they're starting to see this significant increase in the number of people that are developing Parkinson's disease. After that infection. That's [00:25:00] about the same time period till we saw the increase in parkinsonism following the 1918 flu.
So that's two different influenza viruses. And if the mechanism of COVID is similar to that of influenza, maybe we're looking at 10 years from 2 years ago. So 8 another, you know, maybe 20, 30, 20, 32, sometime in that period, when we should be aiming to examine, if what we have seen in animals is replicated in people.
[00:25:33] Sara Schaefer: It's just so interesting to think about this because you know, idiopathic Parkinson's disease, as you mentioned, has a lot of risk factors, right? And a number of those risk factors are toxic exposures and chemicals and things like that. And presumably at some point, it turns into a self-propelling degenerative condition as opposed [00:26:00] to acute inflammation from that exposure, unless we're presuming that these patients are continuously exposed to hit after hit, after hit throughout their disease process.
And I just wonder if you have any thoughts, really all this is speculation. Of course. About how that shift might occur. Flipping the switch from a static hit after a static hit, after a static, hit to a self propelling degenerative condition.
[00:26:29] Dr. Richard Smeyne: And, and I think this is important in what we understand about the ideology of Parkinson's disease. As you mentioned earlier, there is significant prodromal what we call prodromal Parkinson's disease. Oftentimes almost, even up to a decade prior to the onset of what we traditionally think of as Parkinson's disease with its classical motor symptoms.
We do know that a significant number of those patients had developed probably one of the first signs would be constipation. And then later you start to see [00:27:00] sympathetic nervous system changes, heart changes. Then we see as you move higher up in the body, we start to see sleep disorder, REM sleep disorder, and then eventually you get to what we see as the classical signs of tremor bradykinesia you know, loss of balance that we just typically associate with you know, the visible signs of Parkinson's disease. So that's all based on a progressive misfolding of a protein called alpha-synuclein, as well as other other factors and inflammation.
And it does seem to progress up what we call the neuraxis. This was you know, a progression first described by German neuropathologist, Heiko Braak and his wife Kelly Del Tredici. So that seems to be the case and you know, it's very possible. COVID being a respiratory virus.
One of the things that we know about respiratory viruses is, you know, since it's in the lung, we often cough. We develop mucus. The virus lives in [00:28:00] those secretions that come out of our lungs and then we swallow them. So it's very possible that the virus in addition to infecting the lung could infect the cells within the gut.
They also have ACE2 receptors, so you can get gut infection, the cells in the gut infected. And it is possible that the infection in the gut is actually the predisposing factor. And that might be also, you know, one simple reason why it takes 10 years for us to develop this postencephalic parkinsonism, because that's the normal prodromal period that some people think about, you know, the the progression of PD from what we think of, you know, sort of the early symptoms in the gut till we see the central nervous systems due to loss of dopamine neurons in the substantia nigra.
That's just another possible explanation on why we see this very large, you know, decade interval [00:29:00] between the initiating hit and the development of fulminant Parkinson's disease.
[00:29:07] Sara Schaefer: That is so interesting. So one final question about these previous virally infected patients who developed parkinsonism later from the 1918 flu influenza epidemic and H1N1, did these patients present as well with these non-motor symptoms and sleep disruption and things that we mentioned as we see in idiopathic Parkinson's disease.
[00:29:30] Dr. Richard Smeyne: It's a great question. It was not described in the paper that I referenced regarding this Danish cohort. That was not described what it really was just a review of the medical records for coding for Parkinson's disease. So I don't know the answer to that, but it's a fabulous question to ask because I think that would get at, the mechanism of explaining this large decade interval.
It is just as possible that, this is not what we're [00:30:00] seeing in postencephalic parkinsonism. And that's where we use the term parkinsonism rather than Parkinson's disease. It's because a lot of these patients don't have all of the symptoms that are traditionally seen in the full spectrum of Parkinson's, so they may just only have the motor symptoms, or they may only have maybe some of the sympathetic, the REM sleep disorder, but they don't have constipation.
And so we call that parkinsonism because it's just part of the spectrum. That's more what we saw with von Economo's encephalopathy the postencephalic parkinsonism from the 1918 flu. It wasn't described that way in the Danish paper. It was just, coded as Parkinson's disease.
So, you know, I, can't answer that question for the Danish study, but it's likely that with these virally induced hits that lead to parkinsonism, that it is not actually the full blown spectrum of Parkinson's disease. And we may [00:31:00] actually see this as a direct effect in the brain, and so instead of it being the progression of the misfolded synuclein of the neuraxis taking 10 years, it might be that that's not involved at all.
It's a direct effect of the brain but then it takes years and years to develop these other hits to then cause enough cell death and enough damage to induce the symptoms. One of the good things of Parkinson's disease and one of the bad things of Parkinson's disease related to the motor symptoms is that you have to have almost about 60 to 70% of the neurons that are in the substantia nigra die or become dysfunctional until you see symptoms that we traditionally think of as Parkinson's disease. So there's a lot of redundancy in that system. And so if we were to, because of the infection, then sensitize cells, so that maybe 10% more died over a [00:32:00] year than normally. It would take you five decades or many years in a normal case, but let's say we've increased it now to 20 or 30%. It would take maybe an extra 10 years now till you killed enough of those cells or damaged enough of those cells, that you would start to see the effects. So it's clearly not a hammer hitting the substantia nigra at one time, like that giant dose of intoxicating MPTP that was present in that small group of individuals in California. Here it's a slower hit and it takes time. Of course, the downside of Parkinson's disease. And, this has to do with our treatment after the fact is that there's only 30% of the neurons left to work with to try to repair the symptomology.
[00:32:49] Sara Schaefer: So moving on to brighter topics. Can you discuss various ways that the susceptibility to parkinsonism after COVID infection [00:33:00] might be altered? You mentioned in your paper, vaccination, antivirals, perhaps steroids to decrease the you know, the inflammatory response crossing the blood brain barrier or any other things that you can think of.
[00:33:15] Dr. Richard Smeyne: Yeah, this is something we're, actually very excited about. We're actively starting studies to look at this, but one of our great hopes with this is based on a study that we had done with the 2009 pandemic flu. So those animals should basically almost an identical finding when we gave animals the flu we waited 30 days, we gave them the same low dose of am MPTP and we sold the same effect. So the virus induced this increased sensitivity. What was exciting about that study was we, tested a flu vaccine because we've had flu vaccines. And so what we found was that animals that had been given a flu vaccine prior to us infecting the animal with flu [00:34:00] as well as interestingly animals that had been infected with flu, we let them get sick. But then we gave them a dose of Tamiflu, which is a, you know, a drug that stops the flu virus from replicating. And it's a human treatment. If you get the flu, you can call your doctor. And go into the pharmacy and get Tamiflu and it reduces the severity and the length of the influenza infection. So we did both of those. And we found out that if you had taken either the vaccine or the Tamiflu, you know, right after the infection, if the animals were given that we never saw this increased sensitivity. So we were able to rescue basically the effect.
Now, was it due to decreased inflammation? Was it due to other chemicals being lessened, such as cytokines. We talk about cytokines as one sort of inflammatory chemical being the case. There are numerous reasons why we could have [00:35:00] seen this protection, but it was irrelevant. We didn't see any extra loss in those neurons. That actually gives us great hope for COVID. Unfortunately not for that first cohort of people who were infected prior to vaccines you know, for them based on our predictions, we're just waiting to see and hope that our animal modeling isn't replicated in people, although, you know, based on previous flus and the cytokine profile, basically the amount of inflammation that we saw following COVID. I would predict a very similar effect with COVID as we saw with flu. However, there were a lot of people that were able to get that first set of infections while the alpha variant was still circulating. And it is those people that will be, you know, very informative to see whether there's a differential response. Again, [00:36:00] we have not done the study in animals. We've proposed doing it in a grant proposal, and we're starting some of those studies now but I have great hope that the use of the vaccine will prevent this increased risk for developing Parkinson's disease. We know the vaccines still allow you to get the virus, but, you know, they say, well, it will prevent you from being hospitalized. It will prevent you from dying. And that seems to be the case medically. And probably because it has lowered this severe inflammatory reaction that occurs across the body, which is what causes, you know, people to get sick and die.
So the brain we don't think will be any different. And we have great hope that the people that were vaccinated will be excluded from this cohort of individuals that we think will be at increased risk for Parkinson's disease. Now, we're only talking about Alpha We have to repeat all of these studies with the Delta, [00:37:00] with Omicron, with the different types of vaccines, you know, whether are we going to use the Johnson and Johnson vaccine which is more of a traditional vaccine or an RNA vaccine. We're going to have to test them individually, to ask these questions.
[00:37:17] Sara Schaefer: Well there, you have it. The most complicated public service announcement for vaccination against COVID-19 and influenza.
[00:37:26] Dr. Richard Smeyne: Get your vaccine. You know, after our study with the flu vaccine. That was one of the reasons at the institution I was at at the time that people were saying, well, not only does it protect you from the flu, but it might protect you from getting Parkinson's disease. And I would say, you know, as a public health service, I guess, announcement.
I would suggest that the COVID vaccine likely will have similar effects. Again, we have to prove it experimentally, but, it's as good a reason as any other than preventing long COVID, preventing death, [00:38:00] preventing illness. It's another reason to get your COVID vaccine.
[00:38:04] Sara Schaefer: Well, thank you so much for this enlightening conversation, Dr. Smeyne. I certainly learned a lot and have a better understanding of all this, and I'll be getting my flu vaccine here in the next couple of months.
[00:38:14] Dr. Richard Smeyne: Yeah, flu and COVID they're always good to get for general health as well as, you know, hopefully will be at least one less risk factor for developing Parkinson's disease.
[00:38:25] Sara Schaefer: And thank you to all of our listeners. Have a great day.
[00:38:28] Dr. Richard Smeyne: Thank you.