Instant Genius - Dr Rachel Brown: Why are some COVID-19 patients suffering from neurological complications?

Episode Date: August 10, 2020

A recent study carried out at the National Hospital for Neurology and Neurosurgery, UCLH, on confirmed or suspected COVID-19 patients has found neurological complications of the virus can, in some rare cases include delirium, brain inflammation, stroke and nerve damage. We spoke to Dr Rachel Brown, an MRC Clinical Research Training Fellow involved with the study to find out more. Subscribe to the Science Focus Podcast on these services: Acast, iTunes, Stitcher, RSS, Overcast Read an edited version of the interview below This podcast was supported by brilliant.org, helping people build quantitative skills in maths, science, and computer science with fun and challenging interactive explorations. Listen to more episodes of the Science Focus Podcast: Project Discovery: Could computer games help find a cure for COVID-19? Elisa Raffaella Ferrè: What happens to the brain in space? Sandro Galea: What is the difference between health and medicine? Nessa Carey: Is gene editing inspiring or terrifying? Dean Burnett: What’s going on in the teenage brain? Bill Bryson: What should we know about how our bodies work? COVID-19 could cause delirium, brain inflammation and stroke A study carried out on a small number of confirmed or suspected Covid-19 patients at the National Hospital for Neurology and Neurosurgery has linked the coronavirus to a number of neurological conditions. Can you tell us about your research? COVID-19 is still predominantly a respiratory illness, but in a small subset of patients we’ve been seeing neurological symptoms and syndromes. Some of the early studies from Wuhan showed that around a third of patients were having neurological symptoms. In those early descriptions a lot of the symptoms that people were describing included things like headache and dizziness, loss of smell and things that could just really be attributed to viral illness. As we gained more experience, we noticed other cases appearing that looked a little bit different. We have information from... Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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So you can experience exceptional sound at home. Music just as the artist intended. Visit name audio.com to learn more. Yeah, so in our study, we had a number of patients who actually only had mild respiratory symptoms from COVID-19. And in some of those cases, the reason they came to hospital was not because of their respiratory symptoms, but actually because of their neurological symptoms. And we saw that across the different routes that we had. You're listening to the Science Focus podcast from the BBC Science Focus magazine team.

With the UK's best-selling science and technology monthly, available in print and in several digital formats throughout the world. Find out more at ScienceFocus.com or look out for us in your app store. Hello, I'm Alexander McNamara, online editor at BBC Science Focus. A recent study carried out at the National Hospital for Neurology neurosurgery, UCLA, on confirmed or suspected COVID-19 patients, has found neurological complications of the virus can in some rare cases include delirium, brain inflammation, stroke and nerve damage. Jason Goodyear, commissioning editor of BBC Science Focus magazine, spoke to Dr Rachel Brown,

an MRC clinical research training fellow involved with the study to find out more. I saw the study on the press newswise and thought it was really interesting because we're, Obviously, we've been covering COVID-19 lots. This was stuck out because it was something that we hadn't seen anything about before. Obviously, everyone thinks, or most people think of it as a problem that's in the respiratory system. But then your study was saying that there's some neurological conditions have been potentially linked too. So could you tell me a bit about that, please? Sure.

So I think that's still true. COVID-19 is still predominantly a respiratory illness. but we know that in a small subset of patients, we've been seeing neurological symptoms and syndromes. And that first came out of China, actually, some of the earliest studies from Wuhan showed that around a third of patients were having neurological symptoms. Now, in those early descriptions, a lot of the symptoms that people were describing, included things like headache and dizziness and loss of smell, and things that could just really be attributed to,

viral illness. But as we saw more and more cases, there are also these other ones popping up that look a little bit different. And we have, we have sort of previous information from other viral illnesses and SARS and MERS and things like that in the past. It wasn't unexpected that neurological symptoms or syndromes might come out of COVID-19 as well. And what we did here in London is we have a specialist neuroscience centre. We're tied up with lots of different hospitals and centres across London and across the UK. And we already had a platform, a sort of multidisciplinary plenary platform where we would discuss on monthly basis, interesting to neuroinflammatory conditions, including things like

encephalitis, which is inflammation in the brain. And so that's a multidisciplinary meeting where we'd have a mix of professionals in the rooms, we'd have neurologists, infectious diseases, physicians, virologists, scientists, and radiologists. So we already had this sort of platform for discussing sort of neuroinfluensurate diseases. And so when COVID-19 came and when we started getting sort of information from China and Italy, we made that a weekly meeting, which while usually would be predominantly at our centre, we sort of open that up to colleagues across London as well. And by doing that, we were able to pool experience as it was coming through

as the sorts of neurological problems that we were seeing. And that was really, really important, that sort of collaborative effort because these conditions are on the rare end of the spectrum in terms of complications of COVID-19. But by pulling all that experience, we were able to spot different patterns of problems that were coming through. And the sorts of things we were seeing were encephalopathy, which is a transient brain dysfunction, sort of delirium type of picture, which can be very common in infections, can be common in people

with hospital admission generally. We often see it in the intensive care. We were seeing it quite often with patients with COVID-19 infection. We were also seeing patients with paramefectious or post-infectious problem with the brain or the nerves. So this adem like illness and we also had some patients who had this Guillem Barry syndrome as well. And we're also seeing some unusual strokes. We now know that COVID-19 can cause a pro-phrombotic. So it can make your blood very sticky.

And in some patients that can lead to development of stroke, even in some patients where there aren't those traditional stroke risk factors. So those were the sorts of patterns that we were seeing. And through that platform that we had, we were able to put those cases together into the study in the paper that you've seen. So you mentioned there two conditions that I've previously never heard of, A-DEM, and Guillain-Berry Syndrome. Could you tell me a bit about what they are,

what the symptoms of those are, what's going on in your body when you have them? Yeah, sure. So they're both what we call parol, post-infectious inflammatory syndromes affecting the nervous system. A-DEM affects the brain and the spinal cord. So it's an inflammation of brain and spinal cord, usually after infection. Aden's actually most common in children and adolescents.

And in about half of them, they have an antibody against one of the proteins on the myelin sheath, so that's the sort of protective sheath around the nerves and the brain. And that tends to be a one-off infection. Patients can be very unwell with that syndrome. They can get headaches. They can become very drowsy. They can have weakness, sometimes seizures as well. But it tends to say it tends to be a one-off, one-off illness and with recovery afterwards. Giamber is similar in that is it's also a sort of post-infectious inflammatory syndrome, but it affects the nerves. So the nerves supplying movement and sensation to the muscles in their arms and legs. So it's sort of a cross-reaction most likely of the immune system that's trying to fight off the virus.

Maybe it sort of mistakes certain proteins or cells in our body for those viruses and then can lead to inflammation. So you mentioned the immune response there. Can we just sort of go sort of on a very basic level and say, what actually happens in the bodies when we catch a virus? What is the immune response? And how can that, in cases like this, sort of go a bit wrong? So that's a very complicated question, quite a broad question. So we have some natural defenses against bugs, viruses, bacteria. We have our sort of innate immune system, which is the sort of front line immune cells, which can try and fight off viruses and bugs.

But we also have our adaptive immune system, which is a more sort of specialized part of the immune system. That is able to generate memory. And that part of the immune system can fight off more specific cells. So ones that are virally infected, the antibodies can have. help neutralise viruses. And as said, that part of the immune system can generate immune memory. So that if you were to sort of face that same virus or bug again, you would already have cells, so immune cells that could rapidly expand and rapidly fight off a virus. That's how things like vaccination work. So you sort of show the immune system.

a particular bug or proteins from a bug. And so the immune system generates that memory so that next time you encounter it, you don't become unwell from it. So you mentioned that other viruses do have quite often have this kind of effect. It's not sort of a unique thing to this virus and it's like a super virus and it's got some special properties. So we know that viruses can affect the body and the nervous system. in lots of different ways.

Some viruses can affect the brain itself, some and cause the encephalitis, which is inflammation in the brain. Some can affect the meninges, so the lining of the brain. We know that some can affect the blood vessels and cause inflammation of the blood vessels and strokes. And we know that others can cause

sort of inflammatory responses. So we know that other viruses can cause a post-infectious syndrome so they can trigger sort of immune responses, which, as we said before, can mistake parts of our own body or parts of our own nervous system and cause that sort of auto-inflammatory attack. So it wasn't, as I said, it wasn't unexpected

that we were going to see some things from COVID-19. I think what we're seeing is, obviously we're seeing a viral infection on pandemic levels, So we're obviously seeing a lot more people affected than, for example, with SARS and MERS. I think SARS in 2002 affected around 8,000 people. And MERS was around just over 2,000 people compared to, I think, we're on about 13 million across the world. So I think the numbers are obviously much, much greater, much different. So perhaps that's why we're seeing these things more frequently.

So is it possible that some of the patients, they weren't seriously ill, they had only mild symptoms, but then they later found out that they had these additional neurological complications? Yeah, so in our study, we had a number of patients who actually only had mild respiratory symptoms from COVID-19. And in some of those cases, the reason they came to hospital was not because of their respiratory symptoms, but actually because of their neurological symptoms. And we saw that across the different groups that we had. So yes, absolutely. That was a little bit of a surprise to some degrees,

but actually if you look at the syndromes that can cause things like Adam and Guillemberry, usually they're not always sort of infections that hospitalized people because of the infection. Guillem Barry is typical after a respiratory or gastrointestine dynal illness that's about a few poisoning with the second bacteria and viruses. So could it even possibly affect those who don't display any symptoms whatsoever? You mean no respiratory symptoms?

Yeah, yeah, yeah. So they don't realize that they've caught the virus at all, but then they later have some one of these neurological effects. Is that a possibility? Yes, there is a possibility. in a couple of the patients we saw, they only had really very mild, if minimal respiratory symptoms. So I suppose the most likely ones would be the ones that, as I said, do sort of interfere with the immune response

and cause that sort of abnormal auto-inflammatory reaction. But those people would know about their neurological symptoms, so it wouldn't sort of go. and recognise. Are we seeing these type of neurological problems in even younger people? Yeah, so we saw a range of ages affected in our study. I think our youngest patient was 16, but we know that neurological complications can happen in children younger than that. It's pretty rare for young children to be seriously affected by COVID. Our colleague at Great Ormond Street have recently written a study as well looking at neurological complications and children,

but really very small numbers. We, as I said, we saw people in their 20s and 30s. But so our study is a retrospective observational study. So it's not a, so we can't extrapolate from it in terms of talking about relative risk, if that makes any sense. So what we need for that is our larger, population studies and those those are ongoing. We've got colleagues and collaborators who are doing more nationwide surveillance studies looking at how frequent each of these types of conditions

are and are looking at things like demographic data to see if there are any clues as to what might, you know, whether there are trends in terms of age groups affected, men and women affected, people with underlying health conditions, for example. And that's largely through a reporting system that's through a number of the large medical organizations, including the Association of British Neurologists, the British Association of stroke physicians, and Royal College of Psychiatrists.

And that's being led by a team, the coroner study, So that's where information like that in terms of more sort of population-based, in terms of the frequencies, the types of people affected. That's where that sort of information will probably come from. I mean, you mentioned their sort of pre-existing conditions. I mean, how does that play into your study? Was it people who already had some sort of neurological issue previously and it was exacerbated after they caught the virus? or was it completely fresh?

So the neurological symptoms were largely new things. So, for example, the patients with inflammation in the brain or in the nerves, that's not something that they had before. That was something that was described them having acutely. It's possible that certain underlying health conditions might make people are more prone to things like stroke or encephalopathy. We know that encephalopathy, for example, as I said before, is common in patients who have federal illnesses or who have hospital admission, particularly with advancing age.

So there's probably some sort of underlying factors there. But it's not really not so much an exacerbation of things that were already there, but maybe that there are some certain. predisposing factors that make people a little bit more prone, but we don't really know what they are yet. And actually, you know, a number of patients that we described were previously fit and well, and certainly didn't have any no neurological or psychiatric comorbidities.

So might there be other similar effects like this that emerge as we study and more about the virus? I think it's possible that we'll see other things come through. I think what we were able to do was, as I said, to describe these different patterns. And so I think most of the things we're seeing will fall somewhere into one of these categories. But it may be that there are, you know, other more sort of unusual things that we see in certain patients. We had a little miscellaneous group of a small number of patients that we couldn't, fit into any one of those groups. So it may be, it may be that we see other things that are a bit

more unusual, perhaps if, you know, they're underlying immune factors or patient factors that make those more likely to happen. But certainly that these are the sorts of trends that we're seeing in terms of, in terms of the sorts of presentations that people are having. And that fits also in with other studies that have also reported on the neurological and psychiatric complications of of COVID-19. I mean, is there anything we could do to sort of factor in treatments sort of that correspond with the respiratory intubation or etc? To try and lower the risk of these neurological complications from emerging in patients who are

hospitalized with COVID? I think that's an interesting question. I think what we don't know at the moment is exactly what is driving each of the, each of the conditions that we described. So we know that sort of ADEM and Guillem are usually post or para infectious, auto-inflammatory things. But some of the cases were a bit more unusual. We described as some of the ADM cases described as ADEM-like. The delirium cases could have a whole host of underlying causes, stroke cases, as we said, you know, that COVID-19 can trigger a sort of cryopathic or sort of.

prerombotic effect which might be feeding into that. So there's probably a number of different mechanisms underlying the different neurological syndrains that we're seeing. And some of the ones that we suggested in the paper and that other people have suggested. So there's a possibility that the virus itself is doing some of this. We don't actually have a lot of good evidence that not many people have actually found the virus in the brain or in the spinal fluid. So that's So either that's the sort of factor of related to the ways we're looking for it and testing for it, maybe our tests are sensitive enough, or maybe it's actually that there are the things that are underlying these conditions.

So the immune system is probably going to be a major factor for a number of these, either in terms of, as I said, that sort of cross-reactive effect, or we know that some people have a sort of very hyper-inflammatory response to the COVID-involve. COVID virus and whether or not that is contributing. But there also might be other factors, for example, a lot of these patients become very hypoxic and we know that low oxygen levels and we know that that can affect the brain and the nerves sometimes. And generally the effects of being very unwell on intensive care unit for several weeks

you know, also also has its effect. So it's probably a combination of those things. And what we need to do now is really interrogate the different groups that we've found to try and understand all those different mechanisms, what's at play in each one, and then how we can try and reduce risk or identify people at risk and try and prevent these neurological things from happening. So that's almost covered everything. And so I'd just like to know now what the sort of next steps are for you and your research,

what you'd like to do next, what you'd like to find out, you know, what your goals are and your targets in the next 12 months. So there's sorts of things that we need to do. We need to look at each category. We need to see how frequently these are actually occurring, how many people they're affecting. We need to see, are they definitely associated with the coronavirus? And, you know, is it the virus itself or the illness?

that's triggering it. What are the underlying mechanisms? Said is it, is it the virus itself, is it the immune system, is the effects of the sort of experience of being very unwell? We need to identify which patients are most at risk so that we can try and reduce the risk of these neurological complications happening. And then we need to look at how we're going to, how we're going to treat each one. There's lots of questions about, for example, best management a stroke and how we manage these prothrombotic conditions. We need to have a look at how we best manage all the inflammatory conditions. Are they similar to the, you know, the Guillenberry and the Aden that we know and are very

familiar with or are there other things that we need to think about? I think we need to really focus also on our patients in intensive care unit. They're very difficult patients to investigate and manage, not just because of how unwell they are and often being needed. needing very specialist nursing and respiratory care, making it difficult to sort of get them into a scanner, for example, but also there's all the infection control things related to that. So I think we need to have a look at those patients in more detail,

try to understand exactly what is causing the sort of neurological problems that they experience because we know that some of those patients can be very sort of neurologically and well afterwards. And then the final thing would be about rehabilitation and how we best support and rehabilitate our patients. We're very used to rehabilitating people with things like stroke and edem and gear and Bari. COVID brings another level of complication. And also a lot of these patients have been very unwell, are very deconditioned. We might have residual breathing problems, respiratory problems as a result of this virus.

So there's lots of sort of things that we need to. to do to try and optimize care for patients. And then perhaps the other thing would be to sort of look at people who've had a milder syndrome. We know, we're hearing about people who've had, you know, mild memory problems or things like that afterwards and maybe looking at those patients as well. Not everyone with the sort of post-COVID syndrome will have neurological problems, but there may be a subset in whom, you know, that we might need to sort of have a look at them

and see if there's anything affecting them as well. That was Dr Rachel Brown, an MRC Clinical Research Training Fellow affiliated to the UCL Queen Square Institute of Neurology and the UCL Institute for Immunity and Transplantation. You can find out more about the latest on the COVID-19 pandemic at ScienceFocus.com and pick up the latest issue of BBC Science Focus magazine

for more amazing science and tech. This month, we're looking into the radical new theory that suggests that some planets orbiting supermassive black holes may have the perfect condition. conditions to harbour life. As always, let us know what you think of the show with a rating and a review wherever you listen to your podcasts. Goodbye. Thank you for listening to the Science Focus podcast from the BBC Science Focus magazine team. With the UK's best-selling science and technology monthly, available in print and in several digital formats throughout the world. Find out more

at sciencefocus.com or look out for us in your app store. This podcast is sponsored by name, audio and focal. The texture and emotional depth of music can be lost through digital sources or poor signal. Name Audio believes you can have digital precision with analogue warmth. Alongside French acoustic specialist focal, name creates high-end audio systems combining innovation with craftsmanship, so you can listen to music, just as the artist intended. Discover more at name audio.com.