Applying genomic research to accelerate our understanding of COVID-19
Professor Ross McManus, Professor in molecular medicine at Trinity College Dublin, discusses the power of genomic research in the context of COVID-19. He talks about how genomic research is accelerating our understanding of the virus so that we have clearer insights into how our immune system responds to the virus and how we might develop effective treatments beyond vaccines in the future. We also hear from Britta Wyatt who shares her experience with Long COVID; how it has impacted her life over the past 9 months, and her trust in research to find answers.
Part 1 – An interview with Professor Ross McManus, Professor in molecular medicine at Trinity College Dublin
With the global spotlight on COVID-19, one of the biggest questions being explored by researchers around the world is why the immune response to the coronavirus infection varies so much from person to person. Why are some people reporting little or no symptoms, while others require oxygen, hospitalisation, or potential ventilator support? Genomic research and technologies are being used to better understand the link between our genomics and how our immune system responds to the virus. These insights will deepen our understanding of the virus, help to identify those higher risk groups, and better inform the development of treatments such as vaccines and other therapies.
Professor McManus completed his doctorate in genetics at Trinity College, Dublin before going on to study the genetics of complex diseases. His research career has largely focused on the genomic basis of conditions such as coeliac disease, inflammatory bowel disease, oesophageal disease, psoriasis, and sepsis, among others, contributing to the discovery of many susceptibility genes and alterations in gene expression. Involved in the ground-breaking discovery of the BRCA2 breast cancer susceptibility gene published in the journal Science in 1994, Professor McManus has more recently been contributing to the research efforts to unravel the complexities of COVID-19. His research is focused on the host genetics and the significance of our genomics when it comes to understanding our immune response.
Ross, you’re very welcome to this episode of In Sequence.
Thank you, Elaine. It’s a pleasure to be here.
So, the discovery of the BRCA2 breast cancer susceptibility gene was obviously such a milestone discovery for genomic research and for medicine. Can you tell us about your involvement in that achievement and why it was such a turning point for genomic research, in the context of disease?
Thanks Elaine. It was a really interesting time in genetics. I actually had done my PhD and at that time human genetics was really exploding, and it was obvious that we could take some of the recently developed technologies such as gene mapping into these more complex diseases and cancer was a really big interest because we knew very, very little about it. At that time, we understood things about lung cancer, for example, but very little about breast cancer. Lung cancer, you know, we knew that obviously smoking could cause it but we didn’t know what was causing such a big toll of breast cancer, particularly because there were definitely environmental aspects to it but we didn’t know what they were. So, to be able to get involved in breast cancer was very, very exciting thing to do and BRCA1 had just recently been discovered. We got involved in a consortium in the UK to try and map other families that were clearly not related to BRCA1. So, that allowed an opening and we had observed a number of families that were really terribly affected by breast cancer, including one which was named 186 and that ultimately is the family that gave rise to the mapping of BRCA2 onto chromosome 13. It was a huge effort to try and accumulate that family or assemble that pedigree and we really have to thank the members of the family involved. They really put their shoulder to the wheel to try and gather as many members – up to 500 members I think, we eventually had on the pedigree. It was about 30 pages long; we could never look at just one part of it because it was so big. Over three continents and that really was the defining I think moment in the discovery of BRCA2. So that was really all our effort.
Wow, fantastic. And so, in thinking about how genomic research has already helped us to better understand breast and other types of cancers, what does this mean for other complex diseases and what exactly do we mean when we talk about COMPLEX diseases?
Yeah, so I mean when we’re looking at genetic diseases, we’re thinking about two different types. One are the so-called mendelian ones which are caused by a single gene, which has a big impact. And if you get the gene, you’re very likely to get the disease. So, there’s a lot of those out there if anybody’s interested, they can look up this thing called OMIM on the web Online Mendelian Inheritance in Man’s a database of this. I think there’s something like seven or nine thousand different diseases associated with more or less single gene defects. That’s a big impact but the large toll or morbidity on human health are more of things that are like rheumatism, coeliac disease, inflammatory bowel disease and asthma and coronary artery disease. And all of them have a genetic component, but they’re quite different from the mendelian diseases, insofar as there’s usually a cocktail of susceptibility genes involved. So, you need to have more than one gene. You need a bunch of them probably we don’t know how many and all of them have very low impact on the disease. So, they help you get the disease, but they’re not necessary. So, there’s probably lots of combinations of these things. There’s lots of them. Some of them are beneficial in other contexts, but damaging in different types of contexts, especially if there’s a network of them involved. And that’s been the challenge for genetics is to try and move into that phase to understand those diseases. Understand what combinations of genes are involved and how they’re working to promote a disease. And I should also add that they have a big environmental impact on these diseases. So, it’s always a case of genetics and environments, it’s not just one thing. So, that’s why they’re called complex diseases. They have a complex genetic basis and it’s hard to work out what they are. And that’s really where the field has a huge capacity, I think, to ameliorate human health.
And what kinds of changes have you seen over the past 25 years? Would you say there have been significant advances in how genomic research has been applied to improve treatments of these complex diseases?
Well, you know, it is a long time, 25 years as you can just tell from the sort of changes in the technology. And the capacity to do things is absolutely mind blowing. I would never ever have imagined that 25 years ago, we’d end up where we are today. High technology in those days was to sequence 600 bases of a genome. Now you can do a whole genome, you know, thousands of millions of bases in 24 hours or 48 hours, whatever it is. So, the technology has moved in a huge way. But also, other things have had to happen and that is we’ve had to understand the field. We didn’t really understand it back in the late 80s to the 90s. We didn’t understand issues of power. We didn’t understand the fact that we need massive sample sizes in order to tackle these questions. We didn’t really know much about what the genetic basis of the disease were like, as I say, cancer really just developed from the late 80s to where we understand now so much more. And it’s been the same with these other diseases. So, I think there’s been a huge process of learning, a huge focus on developing statistical analysis and proper computational means, as well as the technology to allow us to tackle the genomic aspect as well which is sequence large amounts of DNA. Up to now, we’ve been using chips and stuff, you know, more recently, it’s moving on to sequencing, but it just means that the human genome project had to happen. That was a colossal effort. And then after that it allowed mapping to happen and it’s really, you know, only in the last 15 years we’ve done any meaningful mapping in these diseases and still we’ve gotten really a long way.
And so obviously you have continued working on the health side of genomics, but your current research is more focused on COVID-19. Obviously, this topic is of huge interest as the world continues to be so impacted. And we are going through a particularly worrying time just now with a new variant causing high transmissibility rates. Can you talk to us about the role of genomic research when it comes to COVID 19? And maybe explain little about the virus itself?
Yeah, so I’m not virologist, I have to say but basically the virus is one of the coronavirus family, obviously, and that is a big family of viruses. There are many of them in the wild. Obviously, we believe that there’s a big reservoir of them in bats for example but also in other animals. But there are also coronaviruses that are common in humans. So upper airway tract infections are commonly caused by coronavirus and maybe 10 to 30% on average of your common colds and things like that are caused by these types of four common types of corona viruses that are already circulating the human population and have been for a long time. They’re all part of the beta sub-group of the corona viruses as are SARS actually; the new SARS and the MERS viruses that went before it. And I think, first of all, as an aside, we should say we should count ourselves lucky that SARS, the original SARS happened because it did strike a note of fear into the research population, indeed also into health epidemiologists. And there was a lot of work done in that which has really stood us in good stead for this particular pandemic. Otherwise, I don’t think we’d be having vaccines so quickly. MERS also contributed to that. It’s an unusual virus, insofar as it’s rather a big virus for an RNA virus and it’s got a large genome for RNA viruses, maybe one of the largest. It’s about 30,000 bases long. And that’s about twice the size of the influenza virus, for example, and three times the size of the AIDS virus.
And both of those viruses are quite different. There’s huge complexity in these things. They’re all very different from each other and their strategies for invading the body are quite different as well. And coronavirus has 29 proteins, which again is very large for an RNA virus. It’s unusual insofar as it looks after its genome quite carefully when it’s replicating, again, HIV doesn’t do that. And that means that it’s less prone to mutating, although there’s been a lot of mutations recently that we’re getting concerned about, but it has these structural elements that make it quite different from other members of the RNA virus family.
And so, in terms of how the coronavirus is affecting those who contract it. What do we understand about their response to the virus because we know people are being affected differently? Some people have no symptoms at all. Some people are developing very serious symptoms, being hospitalized, and even more serious.
Yeah, so, if you just take the virus aside, this is pretty much a standard human genetics issue where we’re trying to look at our susceptibility factors to a disease. It doesn’t matter if it’s a virus or something else that just changes the paradigm a little bit but we’re still looking for the host factors that influence the growth and the transmissibility really of the virus – number one. Also, the factors that then cause the virus to have a more severe course in an individual person, and we know that obviously things like Body Mass Index is one issue that seems to make the virus worse so if people have got larger BMI are at greater susceptibility – increased age is another one. Sex is another one; males tend to get a more severe disease. And there are other ones. There are other kinds of conditions such as coronary artery disease. Asthma may also affect it. And a lot of these associations may not be obvious. It seems like in some cases, severe asthma is a bad prognosis, but mild asthma might be good because it reduces the ACE-2 expression. So, we really need to understand how the virus is interacting. What are the nuts and bolts of its lifestyle? How does it get into the cell? What does it do when it’s in there? How does it get back out again?
And there’s been some really fascinating developments, not by our group, but it’s been published recently, for example, where a number of groups have used CRISPR, another really nascent technology only developed seven years ago that has now overwhelmed the field with these exciting possibilities. One of which is that these groups have knocked out a lot of human genes. And infected, the cells with coronavirus and see which genes affect the rate at which the virus can manage to grow. And this has uncovered a whole wealth of data about what’s happening under the surface of the cells.
So, could you maybe go into a little bit on how the virus is actually getting into our cells and what’s involved in that process?
Yes, the main entry mechanism is this: the virus has got this Corona on the exterior of itself, which are these little spikes and they’re called a spike protein. And that is the key if you like, it’s like a lock and a key mechanism. This thing comes along to your cell and tries to insert its key into the cells lock. The cell’s lock effectively is this thing called ACE-2 – this is the primary attachment point for the virus. The spike protein goes up to the ACE-2 and attaches to it. And this is mediated by a secondary protein on the human cell surface which is called TMPRSS or TMPRSS-2 which we don’t talk about so much, but this is important because it modifies the spike protein and allows for very close contact with the ACE-2 Protein on the cell surface. So, it’s primarily infecting cells that express this angiotensin receptor molecule on its surface. And once it does that, then it’s able to start the whole process of being pulled into the cell, getting entry into the cell, and then releasing its genome in the cell.
Okay, what happens then is that that genome starts to be replicated by the cell’s machinery. First of all, it’s read into protein so the virus proteins. And then they take over; start making copies of themselves, start forming these mature viruses within the cells and then they eventually burst out usually causing cell death. Maybe, not always. But we know also, I think the intriguing thing is that that’s not the only way they can get into cells. They can get into cells that don’t have too much ACE-2 on them and so they’re very adaptable and they tend to change a little bit. And I think that whole process is one of the key issues that people are going to try and block I suppose. It offers a therapeutic possibility to block that interaction. If you can block the interaction with the spike, for example, with the ACE-2 then the virus isn’t going anywhere. And that’s primarily a source of a therapeutic opportunity for example.
So, you’ve mentioned some of the other research efforts that are going on across the globe on coronavirus. What about your own research on COVID? Can you tell us about the specific focus of your COVID research?
So, the research that we’re doing is to look at the genomes of Irish people. So we have really no information about Irish genomics in the context of COVID at all and Irish genomics are likely a little bit different from other people’s genomics, it may well have a bearing on the progress or the type of disease course that we see. And we really need to get down and try and understand what’s different about the Irish population that can contribute to the disease in our population and whether that’s any different from other types of populations. There’s only one way you can find that out and that’s by studying it and it’s being done right around the world. And there’s a huge benefit in that insofar as we can see. we already have a lot of these common variants in our populations that maybe change the expression of a gene more commonly in Irish people than say some other nationality. And we want to see what are those things in the Irish genome that either contribute to severity or contribute to lack of severity or, you know, what’s the relationship with other complex diseases such as body mass index or sex or whatever it is. And if there’s any differences there and it’s only by studying large populations and as diverse as possible – this is the thing – you need to understand what’s different about the Chinese and the Asian genomes. And I think there is differences in the Chinese and Asian genomes. I think that’s one of the reasons why it’s being, you know, probably less severe in Asia. Part of it is excellent management of course but there probably are genomic differences that may contribute to a different outcome as well and we just need to understand in any case. We can speculate but until we study it we don’t know, and I suppose, finally, the thing is that we contribute to large multinational studies by contributing our DNA to the other studies that are happening all around Europe and the US and right across the world. And by having that big data set we can get a much better handle on it.
So, we are working with a group in the North of Ireland, and we hope to sequence with Genuity, a thousand genomes and look at other parameters of the genetic environment such as gene expression and so on to try and understand the Irish genomic scenario and how that is interplaying with the viruses in Ireland.
That’s fantastic. And over what period of time are you looking at collecting samples?
Yeah so, we are course at the mercy of the vagaries of the different waves of the virus. So, while it’s never good news that there’s a lot of samples or a lot of people being infected, it does give us the opportunity to collect samples and this has gone up and down. In the summer there was very little, very few samples turning up. So, at the moment clearly, we hope to achieve our target of 500 samples. We’re going to look at severe and mild disease. So, we’re going to split it so we should have 500 of each when we combine the north and the south. And we want to then sequence those with Genuity who have very generously agreed to do that for free and give us all the data back. Not holding on to it themselves. This is really just as a public gesture. And that’s going to be very useful for us. We will then hopefully deposit that in the European archive and that’ll be part of, of what we can then look at.
So, we will be digging into that ourselves, looking for host factors that are associated with various things. So, you know, do we see some gene that’s more common in people who are male over 70, for example. Some variant in those genes that have more severe disease as opposed to the ones that are less disease and actually even more interestingly will be to look at people who are that age who don’t get the disease will be really interesting because it might show us that there are some variants that are protective. We’re also very interested in looking at single cells, so gene expression. Not only the genetics, but obviously the genetics is the core blueprint for how our bodies work and how our immune systems work. But we can look at what are the offshoots or the consequences of our different genetics by looking at the expression of individual genes. For example, in different types of cells. So, we have a nice technology which is a recent enough addition as well to the arsenal of techniques that are available. This is called Single Cell Analysis and allows us to take a single immune cell, say whatever type, we just take a sample of 5000 immune cells say and examine each and every one of them individually. Looking at their own gene expression, how they react, what sort of proteins they are producing and what abundance they have in different individuals at different stages of the disease. So, this is going to give us a very complex and rich data set that we can overlay on the genetics. So, we have the genetics there. Then we overlay this data on top of that. And then that shows us how the genetics is actually affecting how the cells work and we want to really understand that it’s the immune system really, we’re focusing on. That’s not the only story in town, but it is the key issue in terms of trying to beat the virus in the first instance. Obviously then these other issues such as how it’s affecting other parts of the body are clearly important as well. They’re less of our focus, we’re really focusing on the immune response at the moment.
Great. Well it sounds like an exciting collaboration, certainly and obviously there is so much to uncover. Another group that is interesting is those who are experiencing this Long COVID as it’s been referred to. People who continue to have symptoms or relapses beyond what might be considered the typical course of the illness caused by the virus. Is there much in the way of research telling us anything about why that is happening for some people?
Yeah. So again, I think, you know, we’re probably looking at a situation, maybe for the first time that we’ve really dug into the biological effects of a complex virus like this. A lot of the time we’re not too worried about the other corona viruses that are circulating in the population – we’re quite attenuated. So, we’ve been interacting, the viruses and ourselves for a long time and the tendency over time is that the virus has become less damaging. But once they emerge like this, they can be quite damaging and evolutionary process tend to reduce that. But right now, we’re suffering those, and we’ve never really looked into what the multi various types of impacts that a virus like this can have on our bodies. First of all, they have probably a very dramatic effect on the primary cells they affect which are known to be in the lung, but there are other cells scattered around the body. Maybe in the endothelial cells in the blood vessels and also there’s a clear association with the gastrointestinal tract. So, GI diarrhoea is a phenomenon that’s been often noted. With these there seems to be some interaction with nerve cells as well. So, we really are at the very start of this. We don’t know what it’s doing, to be quite honest with you. We do know the general dramatic effects that it has on the lungs, causing pneumonia and causing a huge inflammatory response. If that’s not managed correctly in the first stages it gets out of hand, then the body throws the whole kitchen sink at it to try and fix things only making things worse then. And that’s why when steroids come into play. But we really don’t know much about the other knock on effects and I think this whole long COVID syndrome is very, very fascinating. It’s not really understood. Certainly, I don’t understand it. But I don’t think anybody does right at the moment what’s going on with that, but there certainly seems to be a delayed reaction. I don’t think it’s an ongoing viral infection for the most part. It’s probably just some sort of consequences of the initial infection. Although saying that, it’s clear that some individuals do suffer long term infections and that may be the source for example of these new scary variants that have emerged in the population because the body isn’t able to clear it and it just bubbles away in these people for long periods of time and then generates all these new crazy variants that then can escape and cause a worsening of the pandemic, like we’ve seen with the new English variant.
Yeah, I imagine, there’ll be more research on long COVID as time goes on, and there’ll be bigger sample populations to work with.
Absolutely. And just to add to that Elaine that’s a big focus in St. James’s. There’s a convalescing clinic and there’s a lot of focus on taking samples from that and trying to understand the immunological outcomes in those patients, what’s happening in them at the later stages. So, it’s, it’s all, it’s all really happening right now.
So as a researcher working in this field and watching closely how all of this is unfolding and how we are progressing with vaccine development, how hopeful are you about our ability to control the virus in the near future?
Yeah, I’m certainly hopeful that the vaccines will make a big impact on this. You know that’s very, very important, but I think the other issue is, we really need to see some big advances in therapeutics. So, understanding what I was saying to you earlier, you know, understanding what’s going on once the virus gets into the cell, this might lead a lot of possibilities to interfering with viral replication, that’s going to be important. Like, let’s face it, HIV, there’s no vaccine but actually it’s very effectively treated now. So, we need to have that we need to have some sort of toolbox that prevents another virus that comes along in five years’ time or 10 years’ time, or whatever it is. We need some sort of a general anti corona virus therapeutic. So, we need to know an awful lot more about the biology of them, there’s no easy way about this. It just means more research, more hard slogging to try and figure out what’s going on. And that’s what gives the insights that will leave us better prepared for the next pandemic and there’s going to be more, of course. You know, in the field, everybody’s thinking or what if you had something that was damaging as Ebola, and as commonly or easy to transmit as coronavirus or a flu, for example. That would be extremely, extremely damaging. So, we really have to focus on getting therapeutics and that’s going to be hard because unless we find when we start digging through what’s happening in the cell that there are already compounds that have gone through regulatory processes. This commonly takes 10 years to go through regulatory processes so, slow. For looking for new therapeutics, it’s going to be harder than if we can get reposition drugs that are already out there that might in some way interfere with this. And I think there’s probably good possibilities of that once we start looking. There’s certainly some exciting things happening in terms of small compounds that might be able to interfere with viral interaction. Small proteins, for example, that will clog up the spike protein and this sort of thing. And maybe monoclonals will help as well. But that’s really what needs to be done, I suppose. I think, in the short term we’ll manage this virus, but in the longer term, we need to understand more about how they work and also what are the viral populations out in the wild.
I mean, it’s a big concern that that humans are invading the natural habitat of a lot of these animals. Bats in particular seem to be a real concern for coronavirus. I’m not sure if that extends to lots of other types of viruses. But certainly, you know, HIV came from wild animal populations of monkeys and of course has a completely different course in those animals because it’s been attenuated over time. So, there is always going to be this risk. Ebola is another one and I think actually that might be associated with fruit bats in West Africa if memory serves. Zika – what about that. That’s another one spread by mosquitoes. There’s a whole host of others, Chikungunya, the West Nile Virus. There’s lots of things and they’re coming our way of course, because of climate change. This is going to be increasingly a problem in northern European and other places that have been traditionally saved by the climate where you don’t have mosquitoes for example, as vectors. So, there are going to be more pandemics. I mean if you remember the swine flu. Everybody was really scared about the swine flu, you know, there was this kind of concern that you’re going to have a dramatic shift in the characteristics of the flu, for example, that could replicate something like the 1918 pandemic, which was absolutely devastating. Maybe 50 to 100 million people died in that and that could recur. So, we just don’t know. But I think being on top of it, you know, the fact that everything is being sequenced very very quickly and very significantly now, very comprehensively, really gives us an insight into what could be happening and kind of forewarns us in terms of how to prepare. I think this has been a real shock to the system. And people will invest more in viral research. It’s already happening. We’re going to get a good handle on the coronavirus, you know, over time, and this will stand us to good stead, but has to be extended and, you know, a note of caution, look what’s happening with antibiotic resistance. I don’t think there’s enough urgency there for example. And you know, people really need to, I suppose governments and just the general population need to demand that this area is researched properly so that we have effective therapeutics. Antibiotics, for example, is a scary sort of precedence. They’re becoming less effective and that means you might have just common infections killing people where that hasn’t happened for 50 years. So, there’s a whole lot to play for. We are so well equipped nowadays with new technology and new understanding of biology which has just exploded as I say over my research lifetime and is only going to get faster and faster. So, we will be better equipped I think to deal with these things. But it does require that the public wants to do it and invests accordingly.
Well it’s great to hear about your work on COVID-19. As you say, there seems to be a good appreciation for the importance of this kind of research, the need to better understand our own responses, find therapeutic solutions beyond vaccines and also be better equipped to handle other pandemics that may arise in the future. So, there’s no doubt that you’re once again at the cutting edge of research with the work that you’re doing on COVID and it’s been absolutely fascinating talking to you about it, Ross. Thank you so much for joining me today.
It’s been my pleasure Elaine. Thank you.
Part 2 – A personal story by Britta Wyatt, Managing Consultant, Oxentia Ltd.
So many of us have been impacted by illness – we wanted to take some time at the end of each episode to share a personal story that helps to exemplify the need for precision health. This episode we hear from Britta Wyatt who shares her story of how Long COVID has impacted her since she became ill 9 months ago.
My name is Britta Wyatt. I live in the UK in Oxford, England. I’m 42 years old and I started having coronavirus symptoms in March of 2020. I wasn’t really sure what was going on when I first started having symptoms – I had just gotten back from a holiday abroad. Was feeling really lethargic, aching, tired… kind of just out of it. And I thought maybe it was just jet lag.
When I first started feeling unwell, I called my GP. And at the time they didn’t really know what to do or what to advise for this. They just said, you know, if your lips aren’t turning blue, if you’re still kind of able to function just stay home. If things get really bad, then you need to call an ambulance. And that was really scary, pretty much, because they were basically telling you that when you get to that point where your lips are turning blue, okay, now it’s really bad.
So that first month – pretty scary. Didn’t really know what was going on and that was amplified by it not getting better.
So, when you are told that you should get better after two weeks and you don’t get better after two weeks that starts to get pretty scary. So, it wasn’t actually until a few months later, that we started to hear about something called long COVID or at the time they were calling it long haul COVID, which I first heard about when a colleague of mine shared with me an article from a journalist in the US who had been interviewing people that had been having similar experiences to me, where the symptoms just stick around and stick around and stick around.
And it was at that time that I also started to find out about some of the online support groups for long COVID. Particularly, in Facebook and Slack and some other channels that are out there. And when I joined those, that’s when I realized that there’s this whole other community of people that were having the same experiences as me where the COVID symptoms just weren’t going away.
My doctor has diagnosed me with long COVID but I say “diagnosed” in finger quotes I guess because there’s not necessarily a diagnosis, per se, it’s more that at this point in time, if you’ve been ill for a long period of time, they start to recognise that you might have this thing called long COVID. I’ve never tested positive and I, you know, don’t even have the antibodies. So, having been tested for the antibodies and the tests not showing any, the doctor was not surprised by that. The current view is that for some people it appears over time, the antibodies will dissipate, disappear. That doesn’t happen for everyone. I’m not sure why there’s a difference, but for a good number of people, they expect that you won’t see them over a period of time after the initial infection.
So, what actually is long COVID? There’s a couple different names for it. They call it long COVID, chronic COVID, post-acute COVID, long haul COVID. It’s basically when you have the initial infection and symptoms and it lasts for more than a certain amount of time. I’m not sure if there’s an official amount of time yet, but I think it’s anywhere from, you know, four to six to eight to 12 weeks is what they’re looking at right now.
I, you know, used to be a runner. I was training, weight training, lifting, running, exercising – couldn’t do any of that. Really just could barely, you know, go for a walk around the block when I was feeling really unwell. Couldn’t go up the stairs without getting winded. Was having to sleep a lot. Had insomnia on top of that, which doesn’t help. And so, when I had started to kind of turn a corner a little bit. I thought ah well, I’m out of it, this is it! This is great! And that lasted for about a month and then I started to get sick again. And what I’ve since learned is that people who have long COVID go through these waves or cycles of symptoms, where they get well and then they get worse again and it really fluctuates. For some people it can fluctuate from day to day or hour to hour. For other people like me, it fluctuates over periods of weeks.
They did a chest X-ray and they ran a whole bunch of blood tests which all came back clear, which, in many ways is good news because it means there’s nothing underlying that, there’s no underlying condition. There are a lot of people with long COVID who have damage from the initial injury. So, in that way, it’s fortunate. But the flip side of that is you just really want an answer and you don’t know what’s going on. So, it’s also frustrating at the same time.
The people who have long COVID sometimes have slightly different symptoms than the traditional short COVID if I can call it that. It really is a grab bag of symptoms. And I think the kind of the breadth of symptoms and the variety of different ways that people experience this is really important to consider because it means that you know there’s not a one size fits all necessarily diagnosis or treatment for everyone.
There was a study that I found that was done in collaboration with a group of long COVID sufferers and a university in the US where they did an online survey asking them to report their symptoms, to report their experience and they came up with a list of over 50 different symptoms. A lot of people with long COVID report shortness of breath, chest pain, palpitations, or some sort of blood pressure issues. Headaches are quite common. Body aches, really strange body aches in parts of your body you wouldn’t imagine. You know mine is in the sides of my neck when I’m feeling unwell. It’s just in my shoulder. It’s extremely strange. All of the recommendations are really about symptom management at this point for many people who aren’t you know very very ill with long COVID and aren’t hospitalized.
How am I feeling right now? I’ve been able to go for walks again. You know, that’s very encouraging. I feel optimistic about fact that I’m not always sick. I know that sounds crazy, but the fact that even that there are these windows, where I start to feel better makes me have confidence that eventually you know if we can find the reason or the source that those windows can maybe become permanent.
I think that that’s probably where the importance of having more research comes in so that we can actually understand why people are having these experiences; what’s going on; what the symptoms are being caused by and really get to the root of it, rather than just trying to make our daily lives manageable for people who have long COVID.
Some people with long COVID have been in and out of hospital. And it really does affect people of any age and gender and in fact there’s a study here that’s showing it seems to affect women slightly more than men – long COVID does, which is interesting. So average age, being a 45-year-old woman is the most likely person to get long COVID, Wahoo, that’s me. But no, it does affect people of any age. it just makes you realize you know it’s not always the, the older frailer population that they talked about in the news – it really can affect anybody.
I’m involved in a couple of studies at the moment, just, you know, filling in surveys and data online, that kind of thing. One of the things that I’ve been involved in from the very beginning is an app that is run by a spin out company and a university in the UK where they have been asking members of the UK public to report their symptoms on a daily basis.
They’ve been doing some really great research with that and they’ve identified that potentially one in 20 people is likely to be suffering from long COVID even though we don’t have that data in the official testing. They’re doing it looking at big data sets and seeing who’s matching these symptom profiles. And that sort of data has been great because, you know, it helps to make the case and the evidence to fund further research on this.
So, there’s a couple of big nationwide studies in the UK that are looking at the effects of long COVID for people that had been hospitalized and recently they announced another 20 million in funding for the study of non-hospitalised COVID patients, which is absolutely huge. It’s been a kind of a long slog for many long haul COVID patients because for a long time, they weren’t really being recognized by the health care system because they hadn’t been hospitalized because they didn’t fit the initial profile. And finally, to get that recognition and that appreciation in that slot of funding for that is really a big important next step, I think.
So, you know my background, I work in the world of innovation, you could say. I work with a lot of academics and scientists and so I’m familiar with, with the research process and I’m familiar with, you know, the benefits that it can bring in terms of, not just new discoveries and knowledge but also translating those discoveries into products and service and better health and better care. And so, I’m a real advocate for supporting research and I have tried to participate however I can. So, although I’m not totally well yet I’m feeling positive and optimistic that, you know, eventually, this could go away and I’m hopeful that the research that’s being funded will help to find out the reasons and also the solutions to help myself and others who are, you know there’s a lot of people that are suffering much worse than I am. So, I’m hopeful that we can help them and help myself as well.
Thank you for listening to this episode of In Sequence, a podcast by Genuity Science. Be sure to subscribe on Spotify, Apple Podcasts and Google Podcasts and turn on your notifications so that you get alerts when there’s a new episode! While we know a lot about the human genome, there is still a lot we don’t understand so keep tuning in to learn about what we do know and be inspired to be part of the discovery of what we don’t.
Senior Education Specialist
Professor Ross McManus
Professor in molecular medicine
Trinity College Dublin