Influenza, long COVID & co: What impact do infections have on our brain and how can we protect ourselves

00:00:00: An infection that never ends. First you suffer from the coronavirus.

00:00:07: And then, the body, especially the nervous system, the brain, everything stops working.

00:00:16: Brain fog, a symptom of long COVID, the illness after the illness.

00:00:28: But it hasn't just been around since the coronavirus pandemic.

00:00:32: MECFS, myelgic encephalomyelitis with chronic fatigue syndrome, has been known as a medical phenomenon since the 1950s.

00:00:42: Hardly anyone in the population knows about it. Except those affected. And there is no help.

00:00:51: Professor Martin Korter is researching how diseases triggered by infections with viruses or bacteria, which are not actually intended for the brain,

00:01:00: can affect it, what role infections play in neurodegenerative processes, and how Alzheimer's and dementia actually develop.

00:01:09: He heads the Neuroinflammation and Neurodegeneration Research Group at the HZI in Braunschweig.

00:01:16: In this episode of InFact, we talk about these two important and exciting things.

00:01:22: And at the end, you will find out what we can do to keep as much of our brain for as long as possible.

00:01:28: Yeah, we are here in the library of the HZI. And joining me today is Professor Martin Korter.

00:01:34: He leads the Neuroinflammation and Neurodegeneration Research Group at the HZI.

00:01:40: Thank you for talking to me and take your time to speak with me.

00:01:44: Among other things, you're studying infections and memory. How can infection outside the brain affect cognitive function at all?

00:01:55: I think it's not a surprise to everybody that when you are ill, your brain is also not functioning normally.

00:02:01: You cannot learn when you are seriously ill. You have a hard time to memorize something.

00:02:05: You try even to stay out of social contact. You prefer to be in bed and you do not prefer to think.

00:02:12: You are seriously ill from an influenza infection, as an example.

00:02:16: And the thing that shows already that an infection, of course, affects the brain.

00:02:21: It's probably even an evolutionary function that the brain reacts to an infection because it also keeps you away from other people.

00:02:28: And also, it helps you to save energy, which the immune system at that time actually is needed.

00:02:35: But what we discovered is that the brain is longer affected by an infection than, for example, the lung,

00:02:43: which means that 60, 90, even sometimes 120 days after an infection, we can still learn less good than we could before.

00:02:53: We could think less good than before.

00:02:56: And that's due to the fact that the inflammatory response in the brain is still going on.

00:03:02: Whereas the rest of the body is already completely normal again.

00:03:05: The immune system is silent.

00:03:07: And in the brain, the immune cells of the brain, the so-called microglial cells, are still active.

00:03:13: And it's not clear why.

00:03:15: But even in young age, it can last for longer times than the infection itself.

00:03:22: But does the brain recover from such effects or can the consequences be even long-term?

00:03:29: It's an important point you are raising.

00:03:31: When we are young, let's say below 40, it usually recovers very quickly.

00:03:37: There's an exception, which we all know is long COVID.

00:03:40: But let's leave that aside for the moment.

00:03:42: Normally, the brain recovers completely in 60, 90, probably 100 days.

00:03:48: When we get older, it's different.

00:03:50: When we get older, the brain might not recover at all.

00:03:54: And after a serious influenza infection, it could be that our memory is less good

00:04:00: than we were before the infection when we are of old age, let's say 60, 70, 80.

00:04:05: That's why I always emphasize when we get older, we need a vaccination against influenza.

00:04:11: And now one can also say we need a vaccination against the coronavirus.

00:04:15: And we might even need it every year.

00:04:18: The beginning of the vaccination against the SARS-CoV-2 virus people thought probably once is good

00:04:24: because the virus is not mutating so much.

00:04:27: But the virus proved us wrong, our scientific assumptions.

00:04:32: It actually has lots of variants.

00:04:35: And we need, when we get older, definitely an upgrade of the vaccination process.

00:04:41: And there's a nice thing you can do it at once.

00:04:43: In the left arm against influenza, in the right arm SARS-CoV-2, the next year you do it the other way around.

00:04:49: And that actually helps against not the infection itself, but that the infection gets serious.

00:04:56: And this is the problem for the brain.

00:04:58: It's not the infection itself.

00:04:59: It's when it is a strong response of the immune system, then our brain might be affected

00:05:06: and it might be affected for a long time.

00:05:08: Okay, but as we age, memory naturally declines and learning becomes difficult and stuff like this.

00:05:16: I would have said this is simply a normal part of aging.

00:05:20: But how often this happens due to infections?

00:05:23: Yeah, what you say is what people even in the scientific literature thought for a long time,

00:05:28: we just age, the brain gets older and the memory is deteriorating.

00:05:32: And that's just a genetic fact of life, of aging.

00:05:35: And actually it turned out not to be true.

00:05:37: 80% of our brain power is determined by how we live, how much we learn, how much we do exercise, what we eat.

00:05:45: And indeed, how many serious infections in our lifetime we had, how often the immune system was stimulated in a strong way.

00:05:54: So in that sense also infections do not determine, but do influence how fast our brain is aging.

00:06:03: So this deterioration of memory, the decline of memory is not a natural giving.

00:06:09: So if we do learning even at older age, if we exercise at older age, if we get our vaccination every year,

00:06:18: the deterioration of memory is a lot slower than it is in people who sit, don't get a vaccination, probably even smoke, drink alcohol.

00:06:28: Then the brain is aging a lot faster and also the risk factor for neurodegenerative diseases like Alzheimer and Parkinson's is increasing.

00:06:39: So basically whatever protects us from aging, but whatever is good in order to have a brain that ages slower,

00:06:50: is also something that reduces the risk of becoming seriously ill.

00:06:54: So actually in a double sense we do as good.

00:06:56: So we have a better functioning brain when we age and we avoid diseases or at least we get diseases many, many years later.

00:07:06: The diseases you called Alzheimer's for example, this is also a field that you are researching, but what exactly happens in the brain in these diseases?

00:07:19: Let's take Alzheimer as an example.

00:07:22: During the Alzheimer disease we have extracellular plugs, they are called beta plugs, small proteins that clump together and that trigger process that leads to, we call it, hyperphosphorylation,

00:07:37: which means the changes in the molecular composition of molecules that are inside neurons and they are very important for the infrastructure of neurons, for the mobility inside neurons of organelles and of molecules.

00:07:52: These are the so-called microtubules, they get stabilized by a molecule that is called tau and this tau molecule can also clump.

00:08:01: So we have extracellular clumps of proteins and intracellular and that kills neurons.

00:08:06: This is what we observe.

00:08:08: We're just wondering why do they exist at all and why do some people have them and some people don't.

00:08:14: And it seems to be the case that the occurrence of the plugs and how toxic they are is also influenced by inflammatory processes.

00:08:23: And we do have our own immune system in the brain, they are called microglia cells and these microglia cells can actually also do something to the molecular composition of the plugs and makes them more toxic if they react for a long time.

00:08:39: And the older we get, if the microglia cells are stimulated, the harder it is to turn them off again.

00:08:47: One thing that happens during aging is the inflammatory response in the brain is starting but it's not stopping anymore.

00:08:55: This is called the nest sense of the microglia cells, they become older and they are less good to regulate.

00:09:01: It would be like if we turn up our smartphone, if we turn up the music and we cannot turn it down again, that's a serious problem.

00:09:10: It's the same in the brain for the inflammatory response, it would be like an inflammatory response in the skin, the skin is getting red after some days, it's normal again.

00:09:19: But if that is not turned off again, the skin is damaged in a way that it cannot be repaired anymore and the same is happening in the brain.

00:09:29: But how do you study the impact of infections of our brain function?

00:09:35: In order to study that we need animal models, in this case we need the mouse. Why?

00:09:41: We have very standardized conditions, we know precisely the genetic composition of these mice, they get precisely something to eat, we give them, they have 24-hour days, they have enough fluid to drink.

00:09:56: We can determine everything very precisely and then we can look at a so-called model for the Alzheimer disease.

00:10:03: These mice are genetically altered so that they have a high likelihood of becoming Alzheimer's disease and then we can compare them to control later mates.

00:10:12: Same conditions, just they don't get Alzheimer's.

00:10:15: Then we can infect the Alzheimer model mice with influenza virus and can see, and actually that's actually what we saw, that there is an increase in mice who get Alzheimer at a younger age, more serious.

00:10:31: They even react to the infection in a much more serious way in comparison to the control groups and that's how we study this.

00:10:38: And then we make assumptions, we make new experiments, what can we do to prevent that?

00:10:44: For example, if we vaccinate the mice, the Alzheimer model mice, the risk of becoming Alzheimer at even younger age than they would get it anyway is reduced.

00:10:56: So we can look for certain biomarkers that are available in the blood that actually are a sign of getting the disease earlier.

00:11:05: And this usage or this knowledge we can use for humans, for human studies because an animal model is an animal model, so it's still a model.

00:11:14: So in the end we need to prove our data in the real world, in our body and for that this animal research is of tremendous importance.

00:11:24: Okay, when I look into our society we are getting older and older, we also have a growing number of people vulnerable to infections and neurodegenerative diseases.

00:11:40: mean for us as a society?

00:11:43: - For us as a society, we need to be aware

00:11:47: of that the aging society also has costs.

00:11:50: It's not only good.

00:11:51: And one of the costs that we need to keep in mind

00:11:53: is that the number of people

00:11:55: with Alzheimer's disease is increasing.

00:11:57: We know worldwide we have in the moment 27 million people

00:12:02: affected by Alzheimer's.

00:12:03: This number will increase by 2050

00:12:06: to more than 150 million.

00:12:09: So that also means we have the same problem in Germany.

00:12:12: The society is aging.

00:12:13: So if we don't do anything,

00:12:15: we have more people with Alzheimer's disease

00:12:17: which is a huge burden everybody else for the family,

00:12:20: but also for us as a society

00:12:22: because Alzheimer's disease is a very expensive disease.

00:12:25: It takes six to 12 years where people need care.

00:12:30: Very expensive care, 24-hour care.

00:12:33: So we need to do something to avoid that

00:12:35: or to delay the disease onset

00:12:39: either with better research,

00:12:41: leading to new medication to therapy.

00:12:45: But the good thing for us as a society

00:12:47: is at least in principle, it would be,

00:12:49: or it is a good thing, or it could be a good thing

00:12:52: that actually we can do something ourselves.

00:12:54: For example, exercise reduces the risk.

00:12:57: To learn something interestingly reduces the risk

00:13:00: because the brain when we learn something

00:13:03: builds new neurons, new synaptic connections,

00:13:06: and all this can be used as a compensatory power.

00:13:10: If something, the brain dies,

00:13:12: if we have a higher level of neurons

00:13:14: or synaptic connections,

00:13:16: then we see the effects, the cognitive effects

00:13:20: of this disease a lot later, up to seven years later.

00:13:23: That's a huge difference.

00:13:25: So exercise, learning, also eating healthy.

00:13:29: Best is to avoid obesity.

00:13:32: Obesity is a huge risk factor for Alzheimer's disease.

00:13:35: Also what people always underestimate

00:13:38: is to have a functioning hearing system.

00:13:41: So if you lose part of your hearing,

00:13:43: it's actually a risk factor for Alzheimer's

00:13:44: because in the social sense, you become isolated.

00:13:48: And social contact is a huge stimulus for the brain

00:13:51: and whatever stimulates the brain leads to the release

00:13:55: of neuroprotective factors of so-called neurotrophins,

00:13:59: which we also study.

00:14:01: And they protect neurons, they protect the brain

00:14:05: to function for a longer time period.

00:14:07: So this is what we as a society need to keep in mind.

00:14:11: We can do something ourselves

00:14:12: and we need more, more, more research

00:14:15: for the origin of the disease, for the therapies,

00:14:18: because in particular for Alzheimer's disease,

00:14:22: our therapy is almost absent.

00:14:24: We have now three antibodies that delay the disease

00:14:28: for a couple of months and which have side effects.

00:14:31: So we need to get much, much better.

00:14:32: We need more research in order to get better therapies.

00:14:36: - Yeah, because you can't, or actually in this moment,

00:14:41: it's not possible to cure these diseases.

00:14:47: So could better treatment and prevention

00:14:49: of infectious diseases also reduce the burden

00:14:52: of neurodegenerative diseases?

00:14:55: - That's at least the hypothesis

00:14:57: that comes out of our research.

00:14:58: So we think one of the risk factors for Alzheimer's disease

00:15:01: is the huge immune response.

00:15:03: And the huge immune response you get

00:15:05: when you get a viral infection,

00:15:07: or at least for some viral infection.

00:15:09: So whenever we can prevent them, either avoiding them,

00:15:12: but better filtering the air, making sure

00:15:15: that people with a viral infection stay at home

00:15:18: and work from home if possible, or they're simply sick

00:15:21: and should stay at home and not go to work.

00:15:23: And we need vaccination against every virus one can think of.

00:15:28: And if there's a vaccination available,

00:15:30: we need a society who's willing actually

00:15:33: to take the vaccination, for example, against influenza,

00:15:36: or also now against SARS-CoV-2.

00:15:39: And the older we get, the more important it is

00:15:42: to get these vaccinations, because in my opinion,

00:15:46: serious infection is also a risk factor for the brain.

00:15:49: Yeah, so we talked a lot about older people

00:15:54: and their risk with infections for the brain.

00:15:57: But what about younger people as we think about long COVID

00:16:02: or something like this?

00:16:03: - If people have a SARS-CoV-2 infection called COVID-19,

00:16:07: very often in these days, it is very mild.

00:16:10: You have a headache, you are ill for a week,

00:16:12: and then basically you go back to work.

00:16:15: But in three to 6% of these people,

00:16:18: two weeks later, it kind of hits them again.

00:16:20: They kind of get in a brain fog.

00:16:23: Memory is working less good.

00:16:25: They might even get a fatigue syndrome

00:16:27: and they cannot move at all.

00:16:28: They need to stay in bed.

00:16:30: Everything is extremely exhausting,

00:16:32: even thinking, not only walking.

00:16:35: And as this is called long COVID,

00:16:37: I prefer to call it long virus

00:16:39: because it can also happen after an influenza infection.

00:16:42: It just needs to be a strong stimulation of the immune system

00:16:45: which might affect the brain for months,

00:16:47: sometimes years.

00:16:49: And even if you lose your sense of smell,

00:16:52: that's quite a burden of people.

00:16:54: If you can't taste the food you are eating,

00:16:58: so it's very distressing.

00:16:59: - Yeah, and it's even a little bit of a little danger, yeah?

00:17:04: If you can't smell, if food is good.

00:17:09: - Yeah, one thing.

00:17:10: And another thing is memory is affected.

00:17:12: So viral infection can lead to a long lasting activation

00:17:16: of the immune system in the brain.

00:17:18: And that then can affect neurons

00:17:20: in different parts of the brain in the way

00:17:22: that our sensory systems is deteriorating,

00:17:27: our memory is not as good.

00:17:29: We cannot work as efficiently as we could before.

00:17:32: And in particular, for my students,

00:17:34: they cannot learn as good as they would be.

00:17:36: And this affects also young people.

00:17:39: And you might also be affected

00:17:41: if the original infection with the SARS-CoV-2 virus

00:17:44: is razor mild.

00:17:46: And that's why for my people,

00:17:48: it's clear at my working space,

00:17:51: if people have a SARS-CoV-2 infection,

00:17:53: they stay home, they work from home,

00:17:55: even if they don't feel seriously ill,

00:17:57: in order to avoid affecting other people

00:17:59: who might then be affected by long COVID.

00:18:02: - Which role does long COVID research play in your research?

00:18:06: - We do research here at the HZI

00:18:09: with different viral strains in different mouse models

00:18:12: in order to understand why the SARS-CoV-2

00:18:16: virus is so much more dangerous for long-term effects.

00:18:20: And of course, then how can we prevent it?

00:18:22: Would a vaccination prevent it?

00:18:24: We have preliminary results that actually does help

00:18:27: to reduce the risk of getting long COVID.

00:18:30: Might also be that other seropoietical interventions

00:18:33: might help anti-inflammatory agents in the brain.

00:18:37: Also, some auto-antibodies might play a role.

00:18:40: So it seems to be also partly in autoimmune response.

00:18:43: And then the nice thing is the SARS-CoV-2 research

00:18:47: that we are doing could actually help

00:18:50: to understand autoimmune diseases in a much better way

00:18:53: because there seemed to be a link

00:18:55: between long COVID and autoimmune diseases.

00:18:57: So it might also be of advantage for other research areas

00:19:01: because until a couple of years ago,

00:19:03: autoimmune research was not very well developed,

00:19:08: was not very well understood.

00:19:09: And we now we get a huge boost from one research area

00:19:12: to another.

00:19:13: We are working together with people

00:19:15: we have never imagined before.

00:19:17: So that's one of the stimulus

00:19:18: and one of the interesting thing of doing science

00:19:21: of always connecting new things to one another.

00:19:25: - Yeah, I think you love your work, you love your job,

00:19:30: but you're also a human being.

00:19:31: So you have to sleep, you have to do some,

00:19:35: maybe you want your private life.

00:19:38: What do you do to calm down, to relax?

00:19:41: What do you do in your private life?

00:19:43: - Yeah, I like traveling.

00:19:45: Luckily, my whole family, my wife and my two sons

00:19:47: do as well.

00:19:49: I like reading and also I like to do sports.

00:19:54: My whole life I was a sports person.

00:19:56: First I played soccer and after I ruined my knees,

00:19:59: I switched to a bicycle.

00:20:01: So a bicycle to work.

00:20:03: When I go upstairs, I don't use the elevator,

00:20:06: I use my legs.

00:20:08: So I try to not relax,

00:20:12: but I try to live a healthy life also in terms of

00:20:15: what I eat or actually what I don't eat.

00:20:18: On the other hand, I must also say,

00:20:20: I also like good food.

00:20:22: I like to enjoy things.

00:20:24: So I think it's always a balance between staying healthy,

00:20:28: but still love, play and eat well.

00:20:32: I think that needs all come together

00:20:34: and that's also the kind of balance I try to do.

00:20:37: For example, on the downside, I don't sleep enough.

00:20:40: That's one of the burdens of trying to have a private life

00:20:43: and work a lot at a certain stage.

00:20:45: Also my day is only 24 hours.

00:20:48: And actually not getting enough sleep is also a risk factor

00:20:51: of getting a neurodegenerative disease.

00:20:54: So this is something I need to work on,

00:20:56: but in the moment, that's one of the downsides

00:20:59: of being a scientist and having a trying to have

00:21:03: a private life.

00:21:04: - Yeah, but you can have all.

00:21:05: So as a take home method,

00:21:09: what can we all do to keep our brains fit

00:21:12: for as long as possible?

00:21:14: - I think it's just a reminder of what people already know.

00:21:18: Exercise, exercise, exercise,

00:21:21: and build the exercise in your life

00:21:23: because we all knew it's good to exercise

00:21:25: and normally we do it for a day

00:21:27: and then on the second of January, we start to forget.

00:21:30: So we need to implement exercise in our life.

00:21:34: Put your jogging shoes in front of your door.

00:21:36: Put your bicycle in front of your car.

00:21:39: If you are in a building, don't use the elevator

00:21:41: and always try to have friends who do the same

00:21:44: because we are much better to do things in groups

00:21:47: and exercise it.

00:21:48: Play with other people, games, cook with them,

00:21:52: meet other people because that's meeting other people,

00:21:55: having a social life is demanding for the brain

00:21:58: and everything that is demanding for the brain

00:22:00: is actually good for the brain.

00:22:02: And learn something.

00:22:04: And learning does not mean you learn something you hate.

00:22:07: If you travel, you learn actually a lot.

00:22:09: So do something that you like to do but learn.

00:22:12: Eat well, but eat healthy

00:22:15: and try to avoid unnecessary calories.

00:22:19: For example, when you drink something, drink water,

00:22:24: or at least be aware if there's sugar

00:22:27: in what you are drinking.

00:22:28: Many people when they buy an orange juice

00:22:30: in the supermarket don't realize that the sugar

00:22:33: in that orange juice is as high as it would be

00:22:36: in a Coca-Cola.

00:22:37: That's what I mean.

00:22:38: So eat healthy and try to meet other people exercises

00:22:42: would be my take home message.

00:22:44: - Thank you very much.

00:22:45: And thank you for telling me what happens

00:22:47: in new root day generations as a whole.

00:22:49: It was very, very interesting.

00:22:51: Thank you.

00:22:51: - Thanks for having me.

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00:23:18: Come back again on Sunday and don't miss it.