Professor Danny Altman: Am I going to be the one who kind of lies on the duvet for a week feeling like death and then carries on with my life? Am I going to be the one where I've got such an intense pneumonia that within seven or eight days my oxygen saturation has fallen from 98, 99% to 80, 82% and I feel like I can't breathe and I'm turning blue and I'm ambulance to hospital where I either make it or I don't? Or am I going to be one of the ones who gets through and survives but comes out with long COVID and wondering when am I going to feel normal again? How could there be this incredibly diverse array of outcomes? And a lot of that is diversity of immune response.
Voiceover: Welcome to the Doctor's Kitchen podcast. The show about food, lifestyle, medicine and how to improve your health today.
Dr Rupy: I'm Dr Rupy, your host. I'm a medical doctor, I study nutrition and I'm a firm believer in the power of food and lifestyle as medicine. Join me and my expert guests where we discuss the multiple determinants of what allows you to lead your best life.
Dr Rupy: Today I'm speaking with Professor Danny Altman from Imperial College about COVID-19 and the post-viral syndrome associated with its infection, currently referred to as long COVID. It's part of our long COVID series and not a lot is known about this chronic condition which for some people is absolutely debilitating. And it could also affect up to 500,000 people in the UK or more. And we really need to further research this condition and build the infrastructure to tackle it. Professor Altman heads a lab at the Hammersmith Hospital campus of Imperial. Key research interests are the immunology of infectious disease including severe bacterial infections, Zika virus and Chikungunya virus, something that we refer to in the podcast where he can pronounce it better than me. Other projects focus on autoimmune disease including the role of the microbiota in rheumatoid arthritis and autoimmune immunotoxicity in cancer immunotherapy. Today you're going to learn a lot. We refresh our memories about what we know about COVID. Danny gives us a quick recap about the parts of the immune system, how the virus enters cells via the ACE2 receptor which is found on multiple sites of the body, hence why we have a plethora of different symptoms associated with COVID-19 infection. We talk about the inflammasome, what it is, why it's useful and what goes wrong with the virus. The over 50 symptoms documented to do with long COVID including most popularly fatigue, headache, loss of attention and shortness of breath. We talk about the theoretical mechanisms of long COVID, multi-organ fibrosis, persistent undetected infection that needs to be cleared, as well as the similarity between autoimmune and inflammatory conditions as well. There isn't a clear correlation between the severity of acute disease if you are unlucky enough to contract COVID and the long-term issues associated with what we call currently long COVID syndrome. But the cyclical nature could point to an autoimmune-like picture. We go into this in a bit more detail as well. We also look at parallels between other post-viral syndromes such as EBV and post-Ebola. And we have a slight digressed conversation about diagnostic uncertainty in medicine and how we actually approach that. And perhaps we really need to be thinking about the ways in which we see patients where investigations are all normal, there isn't anything to point to a clear diagnosis, and instead of thinking, well, this is a psychogenic, it's psychogenic in its foundation, we need to be thinking about the other possibilities and what we do not know and how we how we deal with that in medicine as well. And we round off our conversation talking about the vaccine, variants to coronavirus and why Danny doesn't believe that it's going to be a cyclical vaccine schedule and it could behave slightly different. But everything is up for discussion here and I'm sure that many of us are going to be proven wrong during this period of time. I really hope this clarifies some understanding about long COVID and we will be doing some other episodes on this really important topic as it pertains to how we treat other systemic inflammatory diseases as well. And there are certainly going to be some nutritional and lifestyle changes that perhaps are going to be useful for this and other conditions, although Danny wasn't able to offer any on this occasion and I understand his reservation for doing so because a lot of it is anecdotal at this point. But we will see for now and watch the space. But for now, I really hope you enjoy this conversation with Professor Danny Altman. Danny, thank you so much for joining me on the podcast today. It's a pleasure to have you here.
Professor Danny Altman: Pleasure to be here.
Dr Rupy: Great. I thought before we go into the main focus of our conversation, I would love to know what drew you to immunology and a bit about your your career thus far.
Professor Danny Altman: Well, it's hard to say. So I've been an immunologist for a frighteningly long time that would make me sound very very old. There's I've just loved it and lived and breathed it seven days a week. I mean if it's possible since since I turned up to start my my PhD September 1980 at at Bristol University. The sort of big chief was called Tony Epstein, who was the person, one of the people who discovered Epstein-Barr virus, which was the first virus that we knew of that causes human cancers. And so I turned up on day one and they said, why don't you seem to like T cells and immunology, why don't you spend three years doing something on that? And I've I've never really stopped since. And, and I absolutely love it and, live it and breathe it.
Dr Rupy: Wow. I mean, it must be quite amazing having had such an eminent immunologist, someone to look up to.
Professor Danny Altman: Well, there were there were, you know, lots of of great great people there that I could talk about for for for many many hours. It was just a very exciting place and somehow academia somehow appealed to me, the idea that there was all this exciting knowledge out there and all this stuff being discovered. So around that time, it was one of the many times that the Nobel Prize in medicine had been awarded to immunologists. So somebody called Rolf Zinkernagel won the Nobel Prize around then for discovering how T cells recognise antigens. And it just felt like a very exciting world somehow.
Dr Rupy: Well, I mean, it is a really exciting world. I mean, we've spoken on the podcast before about immunology and the system and how it pertains to things like cancer, but also obviously with what's going on right now. I wonder before we go into the main focus of our conversation, we could do almost a bit of a primer around immunology for the folks listening at home. So what do we mean by the immune system and how would we partition it into the various cell types?
Professor Danny Altman: We've all got some grasp of of human biology and especially this year, I think we've all kind of come on in leaps and bounds. But I think one of the things that's perplexing to people is that if I spoke to you about your respiratory system, you'd kind of know I meant lungs. And if I said cardiac, you'd know I meant heart. And if I said central nervous system, you'd know I meant brain. But where does the immune system live? So that that's the first kind of confounder because what are we talking about? We're talking about the things that white blood cells do to protect you against the outside world, which if you want to be a complex animal living on this planet is an enormous challenge. And so obviously those white blood cells, the clue is in the name, are whizzing about in your blood, but they're also doing things in quite a kind of complex choreographed way in particular bits of your body. So there's your spleen and your thymus and your lymph nodes and your tonsils and all these kind of lymphoid organs where they actually have to kind of get together and talk to each other and make things happen. So that's the first thing to know that it's, you know, it's kind of bustling around your body, but sometimes localising to particular places to do fancy things. And the other thing that gets us really excited is just, you know, the sheer complexity of it that, you know, if I got you to look down a microscope at some blood and we separated out the white blood cells, it possibly wouldn't look that exciting because they'd look like little tiny white round blobs of of, you know, slightly different shapes and sizes. And yet we could then do fancy things to them to identify them and and light them up with different coloured antibodies. And I'd be able to show you that those things that look like one type of white blob actually contained populations of tens of thousands of different cells protecting you in different ways with totally different genetic programs. And, you know, we'd be off.
Dr Rupy: And and broadly speaking, if we if you look at the immune system, which you've you've described there, just to give an idea of the the magnitude of it to to the listeners, what what are the the main parts of the immune system?
Professor Danny Altman: So so so, you know, if you were to sort of rewind from my tens of thousands of of different types and, you know, go go go back a little way, there's there's lots of ways that immunologists like to kind of cut and slice this. But for me, one of the most useful starting points is to talk about some of the cells that look the simplest, the lymphocytes, which are the little sort of white round ones. And they especially for immunologists come in two different flavours. So since the 1970s, they've been called B cells and T cells. And the B cells are the ones that make your antibodies. And the T cells make lots of other kind of chemicals, lots of other cytokines, and also are sometimes known as killer cells because if a virus or for that matter cancer is is is in your cells, they'll recognise it and they'll kill it and and stop it stop it spreading. We we mainly get excited about B cells and T cells when we're not getting excited about all the other types of of of of white blood cells because B cells and T cells are kind of, as we've seen in all the discussion over COVID, are kind of solving the problem in different ways because a B cell can make this kind of soluble molecule, an antibody that whizzes around and soaks up bits of virus, hopefully before they can get into your cells and infect you or kill you. And the T cell is doing something slightly different. It's both recognising the viruses got in and making lots of of stuff to kind of boost the immune response and boost the B cells and get them activated. And it's also saying, help, I've spotted some viruses actually made it into some cells, it's actually penetrated the defences, let's kill those cells before it spreads. So it's both of those halves. And, you know, like I said, that's that's been my life really for the last several decades.
Dr Rupy: Yeah, yeah. I mean, it's fantastically complex as well. I mean, I I I know you're pretty prolific on Twitter and I've I've gone through some of the articles that you've retweeted and stuff. And I'll be honest, I get I get a couple of pages in and I'm I'm having to look up a lot of the definitions. But I think that's great to sort of, um, even pictorially represent in people's minds exactly how the immune system is and what the different types of cells are. And and also, you know, we've heard a lot about the immune system and the gut. Um, and a lot of people have heard various proportions of the number of immune cells that are located in your gut. Can you talk a bit more towards that concept?
Professor Danny Altman: It's a subject I I love talking about. So in non-COVID times, a big part of the the day job in our lab is people looking at the interaction between, um, the, well, you know, let's put it this way, between, um, diet, gut microbiota, education of immune cell populations, things made by those gut microbiota and by the immune cell populations and disease outcomes. And for me, disease outcomes in that sentence means for us anything from susceptibility to autoimmune and inflammatory diseases like rheumatoid arthritis, or, um, in another project in the lab, cancer patients being treated with antibodies to attack their cancers and how they they come out of it very differently depending on differences in their gut microbiota. We're we're sort of passionate advocates of of of that field. So so put simply, what it would say is that your microbiota is almost like another organ or another system in your body. It's part of who you are. It's almost, um, a bigger part of your body than the human cells, the the, um, the, um, sort of microbiological cells within you. And in the olden days when I was a student, we used to think that they were kind of there by accident or not noticed or not relevant. And now we think they're an absolutely intrinsic part of who you are and why you're different. And they're in constant dialogue with different parts of your body, but especially your immune system, kind of establishing a set point. Is it going to be pro-inflammatory? Is it going to be anti-inflammatory? Is it going to be good at immunity to cancers? Is it going to, you know, let the cancers fly by? What's it going to do? It couldn't be a more exciting time than it is at the moment for, um, decoding those interactions, um, not least for the obvious reason that, um, for so much of the medical research we do, the answer is something very complex and expensive and intractable and hard to deliver. Whereas when you do microbiota research, the answer might be to do with, um, dietary change or changes to use of antibiotics or quite, you know, quite tractable things. So, um, so we love it.
Dr Rupy: Yeah, yeah, absolutely. Can you speak to any, I'm not too sure if it's been looked into to, but if there are any differences in the response to COVID based on the microbial population of the patient at all? Is that has that been looked into?
Professor Danny Altman: The beginnings of a few studies and lots of people setting up to look at it. You know, there's so many things to look at in COVID and we've been very impatient, haven't we? Because we've gone in a year from a standing start to knowing almost more about infection and immunity in this infection than about, you know, any others on planet Earth. You know, why wouldn't you in in in in the current situation? So, yes, when there are so many immunologists who love sequencing and characterizing microbiota species, that's ongoing as well. And there've been a few reports and there will be more. You know, it wouldn't be very hard to, you know, to draw the diagram because, um, you know, as you know very well, people on planet Earth have very different species of microbiota in their bodies. And, um, you know, in very simplistic terms, there are goodies and baddies and ones that send your immune system in good protective directions and ones that don't. And that certainly will have implications amongst many other things in COVID.
Dr Rupy: Yeah, yeah, absolutely. Um, before we go into, um, the chronic aspects of COVID, I wonder if we could probably, um, we could touch on the acute side of the infection with with COVID-19, i.e. from how the virus infects a cell to its viral replication stage and then to the the acute effects of COVID.
Professor Danny Altman: If we all can think back to how we were thinking about COVID in February or March last year, it's been a steep learning curve for all of us, hasn't it? Because in February or March last year, people were saying to me, oh, it's a bit like SARS and we dealt with that one. It's a bit like flu and we deal with that every year. And, you know, we know how to treat pneumonias and it's just another pneumonia. And maybe it doesn't spread very seriously from person to person, so we'll probably be okay. And this is all a bit alarmist. And, you know, if you move on from there, we've all all had to learn an awful lot about it. You know, it really is a very, um, oh, kind of insidious, deceitful virus that does weird things when you least expect it. And every time we thought we had certainty about different aspects of it, we turned out to be wrong and had to rethink and regroup. Um, so, um, you know, it was far more transmissible than we thought. So we know that whenever it finds a cell in the human body that has this receptor on it, the ACE2 receptor, which is especially in your lungs, but also in your blood vessels and your kidneys and, you know, all all over the place in your body, it can get in and can do damage, which is why you see such a kind of diverse array of symptoms in in in in COVID. The bit that's been hard to narrate, um, has taken a bit of time, is how the range of symptoms could be so diverse. And, you know, if you catch it, you don't know which person you're going to be. You know, am I going to be one of the lucky ones who gets it more or less asymptomatically? Am I going to be the one who kind of lies on the duvet for a week feeling like death and then carries on with my life? Am I going to be the one where I've got such an intense pneumonia that within seven or eight days my oxygen saturation has fallen from 98, 99% to 80, 82% and I feel like I can't breathe and I'm turning blue and I'm ambulance to hospital where I either make it or I don't? Or am I going to be one of the ones who gets through and survives but comes out with long COVID and wondering when am I going to feel normal again? How could there be this incredibly diverse array of outcomes? Um, and, you know, a lot of that is diversity of immune response. Um, so, you know, for example, when we look at those severe events in the lung, some of that is is lots of inflammatory cells getting into the lung and, you know, doing you damage.
Dr Rupy: Yeah, exactly. I mean, it it's quite incredible how we have this vast response. And is that, um, is that in part because of the particular receptor site that this virus enters the cell via? So the ACE2 receptor that you just mentioned there that's present in the blood and in lungs and intestines. Is that the reason why we're seeing this multimodal, so this this plethora of different symptoms?
Professor Danny Altman: So one of the illuminating things quite early on, so when when, you know, if you go back to this time last year, when, um, papers were coming out thick and fast, particularly out of Wuhan and then out of Italy, I was absolutely obsessively reading them, you know, every every hour of every day because everything in it was surprising. And if you look at those early papers from Wuhan, there were people who didn't in ways that we would think of influenza and things like that, they didn't look explicitly at first glance ill yet. And yet when they did CT scans of their body, of their heart, of their lungs, there was immense damage going on. Um, you know, so this was a really, um, nasty virus for getting into, you know, getting into cells, getting into places and, you know, doing damage.
Dr Rupy: Yeah, yeah. I remember, um, during the first wave when I was working in ITU and helping out some of my colleagues there, exactly as I generally work in A&E, the CTs that we were looking at were just horrific. And there was a clear, before I think it permeated into public knowledge, there was definitely a clear recognition that this was, um, a disease that that was related to clots and sticky blood. We saw PEs, we saw strokes, we saw a lot of that. So there was definitely something like that going on. And and and we're going to get to long COVID in a second, but I wonder, um, if we could talk to this whole process of the inflammasome and the cytokine storm. What what do those terms actually mean from an immunological perspective?
Professor Danny Altman: Let's start with the the the inflammasome. So you can think of the inflammasome as a kind of innate activation cassette of all of the the early defences that need to be turned on to protect you against invasion. And, um, that's a big part of our of our antiviral immunity. I feel like sort of COVID kind of does a double whammy on us, doesn't it? Because on the one hand, there's this kind of hyperactivation of the inflammasome so that lots of inflammatory things are going wrong. On the other hand, like a lot of the viruses in its family, like the common cold viruses, the human coronaviruses, it's actually very subversive. It's very good at subverting and turning off bits of the innate immune response, what are called the type one interferons, that ought to stop it getting into cells. Um, so it's very sneaky. So you've got both too little and too much immunity all at the same time. Um, and then leading into that, cytokine just, obviously it's just the jargon for, um, the, um, the sort of molecular mediators that come out of white blood cells. Um, you can think about them almost like like like hormones that sort of travel around the body and make stuff happen. So obviously there if you've got too much of the very inflammatory ones coming out, um, that's not good news. So, you know, so one of the ones we heard about very early on was interleukin 6, um, thus leading into, um, tocilizumab, um, one of the antibodies that blocks it that's been sort of fairly successful. You know, this is a virus where, um, you know, some of us are dogged some of the time by too little immunity and sometimes by too much of the wrong sort.
Dr Rupy: It's quite interesting because a lot of people were drawing parallels between this pandemic and the Spanish influenza as well. Um, I mean, there were clear differences there, right? So the Spanish influenza, it seemed to impact those who had robust immune systems more. Is that am I right in saying that or?
Professor Danny Altman: If you go back and look at the ancient, um, you know, Lancet papers and things from the Spanish flu from from those days, they're, um, to some extent so similarly terrifying in terms of, you know, those incredibly kind of over exuberant, um, inflammatory responses they're showing in the lung that must have been, um, like I said, a slightly different but really horrific way to die. And there is some resonance there, isn't there? If you look at, you know, the kind of, you know, the kind of CT scans that you were talking about.
Dr Rupy: Yeah, yeah, absolutely. Let's talk about long COVID. So it's a it's a term I think that's being used quite often, uh, in in the media, certainly over the last couple of months. I keep on hearing it popping up and which is what's prompted me to do a podcast on this and actually discuss it in a bit more detail. What do we know about long COVID at the moment and what does that term actually mean?
Professor Danny Altman: It's an interesting situation, isn't it? That almost everything we know about long COVID has been patient-led. Um, so I feel like the medical profession has contributed surprisingly little to this, um, textbook chapter so far, apart from, you know, some colleagues actually sort of dragging their feet kicking and screaming against the very existence of the textbook chapter. Um, so, you know, all power to the long COVID groups, um, you know, all all over the world, particularly in in, um, in in in Italy and the UK, um, and then, you know, places like sort of body politic as as as well across across the across the US. And they were the ones, you know, using 21st century social media platforms and coming out and saying, we're all describing the same thing. We're all describing a phenomenon whereby we know we had COVID, even if we had COVID at a time when you couldn't access a PCR test or you couldn't access an antibody test, because we had the symptoms, and life has never been the same afterwards. And high on their list, they describe fatigue, you know, the fact that these very often were young or middle-aged active people who were walking and running and cycling and doing a full-time job, who who now feel, you know, that they're at sort of, you know, a quarter or a tenth of their their former speed. And they describe cognitive symptoms, um, brain fog and memory loss, and they describe, um, wheezing and breathlessness and chest pain and joint pain and rashes. And, um, you know, this this so isn't in people's imagination because it's, um, you know, convergent accounts from different countries around the world. It's very validated across very, you know, very, very large studies and surveys and publications now. It's it's it's a real thing.
Dr Rupy: To to define whether someone's got prolonged symptoms of, uh, COVID, i.e. post-viral infection, you have to sort of decide what what is defined as full recovery from from COVID. Um, so how do we know that you're fully recovered? I give you an example. I mean, I had COVID at the start of the year, most likely contracted from the hospital. Uh, after 10 days, I was fully recovered, but actually I probably had prolonged symptoms for a week thereafter, whether it's because I wasn't allowed to go out and exercise and I lost a bit of exercise tolerance, or whether it was genuine prolonged symptoms of COVID post-infection, I'm not too sure. But I feel absolutely fine now and I don't have any residual effects. But I haven't come across a a clear definition of full recovery from COVID that thus far.
Professor Danny Altman: I think the simple answer to your question is that we really, really need one. Um, and there's different, um, you know, there's some quite learned people who've, you know, written, um, you know, for example, pieces in the in the BMJ and in, um, in the in the NICE guidelines to try and put down some markers for, you know, number of symptoms at three weeks or more. Um, but, you know, we we really need it, um, for obviously for many reasons because, um, you know, we can't count the cases and treat the cases and refer the cases unless we know what we're counting and what what our kind of threshold is for for being alarmed. I think that's been a real issue and a real confounder, isn't it? Because, um, right at the beginning, many of my colleagues were very, um, skeptical and still are and dismissive and, um, you know, want everybody to be as you were and say, well, you know, you're bound to feel a bit dodgy after you've had a viral infection, you know, you'll get over it. How dodgy is dodgy and how dodgy do you have to be for how long to think, well, actually, I'm not getting over this. And I don't know about you, but many of the people I meet and talk to with long COVID, you know, are very kind of, you know, robust, hard-working individuals who aren't just putting it on and really feel devastated that they, um, you know, six, nine and 12 months out, they they they still feel bad, um, and, you know, completely underpowered and completely unwell and completely symptomatic. But I think it's very, um, it it's almost antagonistic to some people to try and count long COVID because how do you have a single diagnosis that lumps in somebody who's still can't exercise as well as they formally could three or four or five weeks after their acute attack with somebody who nine months after their acute attack feels like they can't go out without taking a wheelchair with them.
Dr Rupy: Yeah. It was very sobering for me. One of my interactions was with a researcher from Radio 4 and Radio 4 were doing a program on on long COVID and were very keen on the counting of it. And this chap got absolutely furious with me because I was, um, quoting the, um, Office for National Statistics data on at least 10% of all COVID sufferers having long COVID, which would put the UK, for example, at what, you know, half a million people with long COVID and would certainly have implications for NHS provision, expenditure, etc. He got absolutely furious with me and said, come off it, you're not telling me that 10 or 20% of the population are in wheelchairs, we'd have noticed that. Um, and I'm I'm not because it's much more complex than that because there's people coming into that disease space and there's people leaving that disease space and recovering and there's some of the three weekers and some of the three monther and some of the 12 monther. And it's a very, you know, it takes very complex maths to model and count that, but it's there.
Dr Rupy: Yeah, it really is. And I think this kind of brings me to the question which I know is going to be very hard to answer, but theoretically and and perhaps even lending on your experience and knowledge around the gut microbiota, are there any things that people can do today to mitigate against any potential post-viral syndromes, whether it be diet, lifestyle related or or otherwise?
Professor Danny Altman: I think that's really hard for me to to answer because I'd only be giving, um, you know, second-hand information that's come out of the groups themselves who really have done all of the running on this. So I know that, um, there's a lot of anecdote out there and some things more favoured and some things less favoured. And there are people looking at diet and there are people looking at, um, graded exercise and physiotherapy. Um, so, you know, I'm in no position to give any kind of critical judgment on any of those because I haven't haven't sort of tried them or or seen any of the data. But, um, you know, without kind of poo-pooing anybody's anecdotes or research, I just think those are kind of, um, slim pickings compared to just, you know, doing the peer-reviewed research, getting some mechanism, getting some answers and working from there because that's where the answers will come from.
Dr Rupy: Yeah, yeah, absolutely. Do do we have any, um, idea of the potential mechanisms behind this, um, post-viral syndrome with with long COVID?
Professor Danny Altman: Well, you know, there are there are hypotheses out there and, you know, like other people, we're kind of champing at the bit to to analyze them and try and get some answers. And I'm hoping that this week we'll have our final ethical approval through to start doing investigations with people in the community, um, not just with hospitalized cases, because if I was trying to list my favorite hypotheses in no particular order, I'd say, um, that this is a virus that likes getting into cells around the body that have ACE2 on them. And it's quite a damaging virus that causes, you know, scarring, fibrosis, and leaves damage in those organs that you can see on a CT scan. So if you've got a damaged heart or liver or lungs or kidney, why you why shouldn't you feel ill? Um, so I'm I'm interested in that one. For me, the only counter argument to that one is if if it was simply that one, you'd say there should be a very strong correlation between how ill you were and how hospitalized you were for how long and how much long COVID you have afterwards. And I'm not convinced that's the case at all. Um, or you could say, well, maybe it's a bit like other, um, viruses like, um, Epstein-Barr virus or cytomegalovirus or something, which kind of, um, completely, you know, disrupts and perturbs your immune system so that all your subsets go haywire and, you know, you just haven't got a normal immune system until it can reset to set point again some years later, you know, and that might be one or two or three years later depending on on how badly you do. Then, um, I'm quite interested in the idea that a lot of people in the community have that maybe it is a reservoir of lingering virus that's doing you harm. We know that people have found lingering SARS-CoV-2 both in in gut biopsies and in in stool samples. So why couldn't it be that? And that would speak to all the people out there doing surveys at this very moment saying, you know, did I get better or worse after my COVID vaccination? And I think the I got better people are kind of quite far in the lead at the moment. So that would be interesting to me that maybe it just took a really amazing vaccine to, you know, to to to boost up those antibody levels and clear that reservoir. So so that that's really fascinating. And as a kind of, you know, immunologist who spent most of my life also worrying about autoimmune diseases, I'm quite interested in the idea for which there's lots of evidence that it's one of those viruses that can set up a full-blown autoimmune disease, in other words, antibodies, you know, against bits of your of your body, a bit like, um, you know, Chikungunya virus does or Ebola virus does, that you actually start out with a full-blown, um, autoimmune attack. So all of those hypotheses, I think, are up for investigation. And we and other people are sort of dying to sort that out over the next, you know, three months, four months.
Dr Rupy: It's interesting to see if with whether there would be any parallels between other post-viral symptoms, um, syndromes like you've just mentioned there, like EBV and and Ebola as well. Do do we have is is there is there, um, evidence to suggest that there is that issue around autoimmune conditions being set off by the virus itself, like viral arthrologies, like rheumatoid arthritis, that kind of stuff?
Professor Danny Altman: One of the viral infections where we know the most about it is another one that, um, that my lab is very keen on and and works on in Brazil called, um, Chikungunya virus, or Chikungunya is one of the ones where the, um, the little mosquitoes there, they have the the Aedes aegypti, nip you and, you know, you either depending on the season and the year, you either get, um, Zika or dengue or Chikungunya or yellow fever virus. And if it's Chikungunya, you'll get one of those kind of, you know, sort of fevers and rashes and things and, um, sort of bad headaches. And if you're lucky, you might be better after seven or eight days. But if you're one of the 30 or 40%, you go on to get, you know, a full-blown disabling arthritis that could last three or four or five years, um, that, you know, that looks just like any arthritis. And, you know, and that becomes far more devastating to the sufferers and the economy and the healthcare system than the viral infection itself. So, you know, you can see why I bring it up quite quite quite a lot in in this context. And that's led us and other people to think about that kind of analysis in COVID. And there've been two or three pre-prints so far where people have screened people after COVID-19 infection for new repertoires of antibodies against their own tissues and found loads of them, just loads and loads of them.
Dr Rupy: Wow. That that's quite scary.
Professor Danny Altman: Scary and amazing and interesting. But, you know, um, you know, it is what it is. But, um, it's interesting for an immunologist because, um, obviously immunology has come on leaps and bounds in the clinic in the last 10 or 20 years. So when you see immunological problems, at least you have some immunological solutions because there's there's so many goodies in the larder of ways of of of treating autoimmune diseases now in terms of all the sort of biologics out there, that if we could only nail down what the problems are, I feel like we'd have, you know, good stuff to offer.
Dr Rupy: Yeah, yeah, absolutely. And and to do with the vaccine and and the variants. So we have a vaccine at the moment. It's an incredible, you know, feat of science and and collaboration across the world. How are we keeping up with, um, variants that are to be expected to occur over the next year or so? I think people are sort of, um, and I think this this feeds into vaccine hesitancy a lot from from what I hear on the front line from patients that I deal with as well. How do we how do we keep up with variants as as we progress through this, um, pandemic?
Professor Danny Altman: Yeah, um, well, let me do you kind of two or three minutes of sort of my, um, my current sort of state of play in my head about about about about the variants. So so sort of point number one to me is that, you know, we do across the world have this amazing vaccine program that's panned out so much better than I ever dreamt of. As in, as much as I describe it as, you know, a sort of ghastly and horrific and audacious virus and things, it's actually been, um, very tractable to some quite basic vaccinology. So anywhere in the world that they managed to find a way to express this spike antigen in a very stimulatory way, they've almost without exception come out with very potent vaccines that induce humongous levels of neutralizing antibodies and T cells that really do the trick in a glorious, glorious way. So, you know, so that's panned out so well. So, so, you know, so answer number one from me is that the vaccines are amazing and just grab any anyone you're offered. And because they're so amazing, um, so, um, in the jargon, sort of, you know, neutralizing antibody levels in the thousands and tens of thousands, you know, higher than we've ever seen before, what it means to me is that when people give you scary data about how much less potent they are against the variants, um, even South African or or or Brazilian, and say they're six-fold down or ten-fold down, sure that's scary, but most people's vaccine responses are so huge, um, and so protective that for many of us, you could probably drop a hundredfold and still be in the sort of safety zone. Yeah? So, um, so so don't kind of like, you know, throw out the baby with the bath water because, you know, it's never going to work because we've got variants out there. For most of us, most of the time, you know, we're we're still in the lead against the virus. Um, so I think that. On the other hand, um, one of the things that bother bother me, one thing that bothers me is that in in lots in many parts of the world, including, you know, European mainland, not too far away, we've got quite a lot of vaccine hesitancy, quite slow vaccine roll out and quite a lot of percolation of, um, some of this quite scary mutant strains. Um, so I worry that we need more vaccination faster, and I worry that I see some politicians trying to sort of nag us to book our holidays and go there, which I think at the moment would be a really daft thing to do. Um, and really asking for trouble. Um, and so all that leaves is, um, you know, what does the future hold? I think the future holds a few things. Sure, obviously there's work in progress to tweak and modernize, you know, second generation vaccines that can deal with the variants. And that's, you know, so doable and so easy and so going to work. And I know that some people got kind of conflated this with seasonal influenza vaccines and the idea that we might be revaccinating people every year in perpetuity. Um, I I I probably don't see it like that because influenza is a much, much, much more variable family of viruses with far more ways of changing than this one has. And I think that the fact that we're seeing convergence of different mutations popping up sort of similarly around the world shows me that those are the kind of those are the tricks that this virus has has up its sleeve to evade immunity. And there aren't an infinite number of them to come. Famous last words, I may be proved wrong. I don't think we'll be having this conversation in 20 years time.
Dr Rupy: Yeah. Yeah. You you mentioned a a couple of words that I wanted to to pick up on, neutralizing antibodies in particular. So that was something that was demonstrated in the vaccine trials. Can you distinguish between neutralizing antibodies and antibodies that I think are being conflated in the press, um, especially when people believe themselves to have the the right antibodies after having the COVID infection and then that might lead into people thinking that they don't need the vaccine.
Professor Danny Altman: When I talk about the B cells making the antibodies and people will have heard a lot about, um, antibody screening and public health England antibody testing and do the antibodies wane with time and how many people in the population have antibodies, that's a very simple measure of antibodies, which is all the antibodies in a person's blood at any given time where if you took a plastic plate and, um, stuck some COVID spike antigen to that plate would bind to that plate. And that's a sort of, you know, quite useful, um, really rough and ready measure of does this person have antibodies at the moment in their blood, okay? And it's a kind of very, very distant cousin of the much fancier measure that I'm talking about, which is the small subset of all of those antibodies that really do the business. So so when I say really do the business, it's a subset of them that are so targeted to the business end of the virus, what's called the, um, the RBD, the receptor binding domain. And it's that RBD that binds to ACE2 on your cells and gets into your cells and infects you. So if you're a person that's got loads of antibodies on board that are going to hang on to that RBD and stop it getting into your cells, you can't get infected. And so, so the assays to test for that are really quite fancy and quite demanding and not that many people in the world do them well. We've been very lucky to collaborate with people who do them absolutely brilliantly. And if you measure those, that's what I was talking about. You get very excited, or I get very excited because there are many people out there who've had the vaccine, who've got enormous levels of these neutralizing antibodies, and you could never ever imagine them being susceptible to infection. But the levels that we're seeing in vaccinated people are, you know, 10, 100, 1,000 times greater than the levels we're seeing in people who just got infected and never got a vaccine. So if there's anybody out there who still believes in the kind of old version of the herd immunity argument, like I had COVID so I don't need the vaccine, no, don't don't go there because it's not it's not the same level of immunity at all.
Dr Rupy: Yeah, absolutely. I'm really glad that we clarified that because, you know, if one of the mechanisms behind long COVID is in fact a lingering infection, then that's another reason why a vaccine which elicits such a significant response in neutralizing antibodies would be useful against, uh, reducing their risk.
Professor Danny Altman: Yeah, and I think I think there'll be a lot of work published on that in the coming weeks and months, including especially from the long COVID groups that I think will be quite persuasive.
Dr Rupy: Yeah, absolutely. Danny, this has been fascinating. Thank you so much for your time. I really do appreciate it and I hope it's been a great pleasure.
