Webinar: Weekly COVID-19 Pandemic Briefing – The Role of Therapeutics

Emma Ross

Good morning, and thank you for joining us for this week’s COVID-19 briefing with Chatham House Distinguished Fellow, David Heymann. Our guest today is Sir Jeremy Farrar, Director of the Wellcome Trust. Before joining Wellcome in 2013, he was Director of Oxford University Clinical Research Unit in Vietnam for 18 years, and his research interests were infectious diseases and global health, with a focus on emerging infections, so extremely relevant to today. He was knighted in the Queen’s 2019 New Year Honours List for services to global health. The Wellcome Trust, as many of you know, is one of the world’s largest providers of non-governmental funding for scientific research, and, in the COVID-19 space, it’s a key supporter of research and development, mass production and access as well to vaccines, tests and treatments. Today, we’re going to focus on the discussion on what’s going on with COVID-19 treatments, which are expected to come along sooner than a vaccine. Before we launch in, I’ll just cover the housekeeping stuff. As always, this briefing is on the record, and questions can be submitted using the ‘Q&A’ function on Zoom. Upvoted questions are more likely to be selected, so if you have a question that’s similar to one that’s already on there, just upvote it, that would be great. So, a very big welcome to you, Jeremy, and thank you for joining us today.

Sir Jeremy Farrar OBE

Thank you very much. Thank you very much.

Emma Ross

I thought we could start with you giving us an overview of what therapeutics treatments, can do for us, what’s the hope, versus a preventive vaccine, and what they call non-pharmaceutical interventions, and, given the challenge that viable vaccines are – and the prospect that we may not even get one, are treatments our best hope for a sustainable way out of this, easier to achieve, so, kind of, lay the landscape on what is the role of therapeutics in fighting this pandemic?

Sir Jeremy Farrar OBE

Emma, thanks very much, and thanks to Chatham House, it’s a great pleasure to be able to join you, and it’s, as always, a real pleasure to link up with David Heymann, so, yeah, thank you very much for the invitation. I know you’ve run a series of these and they’ve been superbly run, but I think it is just worth pausing and just reminding ourselves where we are, that we’re six months in, essentially, to what is, effectively, a brand-new human pathogen. A brand-new human pathogen that jumped across from the animal kingdom, came into humans, we humans had no immunity, it came into a situation in a big, big city, urbanisation is a key driver here, and, of course, cities are now so interconnected. And, at the start of this, in December or so of last year, we had no diagnostics, we had no therapeutics, and we had no vaccines. And within six months, I would say the global community has come together in a truly quite remarkable way and has speeded up the normal cycles of research and development, indeed manufacturing and access, that would take years, if not decades.

To focus on therapeutics now, therapeutics are not a magic bullet to answer everything. It’s really important, in these discussions, I think, we start with public health, we start with prevention, and we start with strong health systems. If you don’t have strong health systems and you don’t have strong public health, then having the therapeutics, diagnostics and vaccines is only of added – marginal added value. You have to have all of those, and we cannot see any one of these as the answer to everything.

On the therapeutics side, there has been massive advances, but to bear in mind that we are dealing with that new pathogen on which we’re having to learn all of the time, and – but already, within six months, due to the Recovery trial in the United Kingdom, we have answers to at least three questions, and with the NIH funded trial in the United States to another question. That is that we have a drug, remdesivir, which shortens hospital stay, that’s a very important finding from the NIH in the US. We know that dexamethasone, a steroid which is very cheap and widely available, can save lives, 30% reduction in mortality in those ventilated, and we know that chloroquine and hydroxychloroquine do not work as treatments. Those are very, very important findings, both positive and those that don’t work, so that we can exclude them from use. So, huge advances, a very, very long way to go, and we must keep in mind that therapeutics are part of an approach to this, rather than the answer to everything.

Emma Ross

Okay. David, have you got anything to add on the role of therapeutics and how much hope we should hang on them to get out of this?

Professor David Heymann CBE

Yeah, well, just to follow on what Jeremy said, we need to be looking at everything. We have diagnostic tests, there’s a whole series of needs in those, and there’s also a need in therapeutics. And one of the areas that’s being studied in Germany, we’ll be able to speak more about that, is looking whether convalescent plasma, that is antibodies created by people who have had the infection and then is collected and concentrated, whether that, or whether some of the monoclonal antibodies that are being developed in commercial laboratories or in research and development, might be effective either in treating early on in infection, to prevent serious illness, or even be used prophylactically to prevent infection, as was done for hepatitis A and many other diseases in the past. So, I think Jeremy’s very up-to-date on this, so, Jeremy, I wonder if you could say a word about that?

Sir Jeremy Farrar OBE

Yeah, it’s a great point, David, and, actually, I mean, remarkably so, I think I’m right in saying, David, you know this history better than I do, that actually convalescent plasma was used in 1918 in the pandemic of influenza, and David was very involved in starting to trying to get convalescent plasma used in Ebola. And I think it is a very, very important – there’s a trial here in the UK that’s going to be looking at convalescent plasma. One of the important things for the convalescent plasma treatment is to make sure we know what we’re infusing, so we take blood from somebody that’s recovered, we concentrate the antibodies, as David said, and then we infuse that back into somebody that is infected. And it’s just critical that we know how many neutralising antibodies, which we believe are what’s going to matter here, are in that plasma that we put back in. And, of course, that then leads on to the development of specific antibodies, which can be made in the laboratory, and called monoclonal antibodies, that can both used as prevention and as treatment, and those are, I would argue, some of the most exciting developments at the moment.

Emma Ross

Ah, okay, so, is that where the most promise is, or what would be the biggest gamechanger?

Sir Jeremy Farrar OBE

Well, I think the – firstly, a point going back to the point I made earlier, and both David and I, I’m sure, would agree, we’re pushing very hard also on the vaccine side, but, again, our careers have overlapped. I grew up as a Junior Doctor here in London at the start of the HIV epidemic, and we have no HIV vaccine, and we have no vaccine for tuberculosis, effective vaccines, and we have no vaccines for malaria. So, although I am a great believer in vaccines and doing all we can to support the vaccine development, we have to also have more approaches to this, where therapeutics, I think, come in. And therapeutics should not just be seen as treating patients who are very sick, therapeutics can also play a critical role in prevention. In fact, if there is going to be an effect of chloroquine, and I’m not being overly optimistic, but if there were to be an effect of chloroquine, I think it is much more likely to be in prevention, given to healthcare workers, for instance, to prevent them getting sick, rather than as treatment.

So, I think we need to see treatment as starting with prevention, and actually that would be the huge gamechanger in the absence of a vaccine, to be able to protect healthcare workers, to be able to protect people from getting infected, household family members, etc., that would be a gamechanger. So, think of therapeutics also in prevention, also in primary care. Therapeutics should not be just used in patients that are very sick and on a ventilator. We can – a gamechanger would be access to a primary care treatment that could be available to everybody, of all ages, young children all the way through to very senior people. That would be a gamechanger, and that might also stop transmission, which would be very important and then we’d come through and think in the more severe hospitalised group, but, globally, if we could find prevention or early treatment in primary care, that would be game changing.

Emma Ross

So, when you see prevention for health workers, are you saying you’re not envisioning that the whole population take a pill or take a treatment as a preventive instead of a vaccine?

Sir Jeremy Farrar OBE

No, I’m not, at the moment, although I don’t see why we shouldn’t include that as a possibility. In fact, many, many years ago, I was involved in looking at chloroquine actually for a population-based treatment for dengue, for instance. Actually, I don’t think it worked, but, nevertheless, we had to try. Chloroquine has an enormously long half-life and potentially could be used, but that’s a little bit left field and didn’t pan out. So – but no, I think it would be – healthcare workers have suffered disproportionately in this epidemic, as have senior people, as we know, tragically, as well, people from BAME backgrounds, and I think if we could target preventative, household members, healthcare settings, prisons, other environments where transmission is clearly very high, then we could potentially reduce transmission with an early and safe treatment that prevented infection taking hold.

Emma Ross

Okay. I wanted to ask you about the whole system, the whole effort, to find therapeutics, how well organised it is, and why – the Recovery trial seems to be held up as an example of a well-run situation, as an example. There has been some research recently about the system of finding therapeutics in the US, it’s been characterised as a bit chaotic, actually marked by disorder and disorganisation, with huge financial resources wasted, and that, with this intense pressure to produce these at speed, that Researchers may actually have slowed down the rate of progress. What’s your feeling on a global level, the whole system for finding decent therapeutics, how are we doing on that and how well organised is it?

Sir Jeremy Farrar OBE

Yeah, I think that’s harsh, but there’s certainly truth in what you just said, Emma, and, actually, again, if we look back over the last 20 years, when these epidemics have become much more frequent and much more complex, we have not, I think, learnt the right lessons from the last 20 years. When you come into these epidemics, it’s always frightening, particularly those healthcare workers on the frontline, it’s very frightening being involved. It is chaotic, and it’s disorganised, and that’s a sad thing to say, but it does remain true, and I think particularly on the clinical side, perhaps a little bit more than on the public health side. We could debate that. There were approaches, over the last ten years or so, to try and bring some order to that.

The WHO played a key role in setting up the R&D Blueprint to try and organise research around these epidemic diseases. David chairs the STAG-IH at the WHO. ISARIC was set up to be a clinical programme that would be able to study clinical research, in the context of epidemics, and others. But the trouble is that we didn’t – as so much with these epidemic diseases, we didn’t all get behind those and solidify them and then the epidemic came. And we need to learn that lesson and make sure that, in future, the positives that came up, ISARIC, the Recovery trial, the WHO Blueprint, STAG-IH David chairs, and the Solidarity trial that WHO have been running very successfully, these are the things we have to have in place before an epidemic so that, when an epidemic hits, you’re not trying to cobble together partnerships, relationships, signed contracts, get grants, identify patients, recruit them, decide which drugs to use.

You’ve got to think about that in advance, and you’ve got to have those things in place, those partnerships agreed and organised, otherwise it is very disorganised. And I’m afraid to say, I do agree with some of your comments, I mean, apparently – I think there are 1,200 clinical trials currently in place around the world, of which 16% are looking at chloroquine or hydroxychloroquine, and that doesn’t make any organised sense, you’re absolutely right. And many of the trials– and I think here the clinical community does need to take a harsh look at ourselves. Many of the trials are too small. I think 40% are less – will enrol less than 100 patients. It’s very unlikely, in less than 100 patients, you’re going to provide definitive evidence of the efficacy and safety of a treatment. You have to do things at scale, as Recovery and Solidarity have done, and small trials will often be unhelpful, and will often be politicised, as we’ve seen in this epidemic, where Politicians, sadly, made statements about certain drugs, which proved not to be true, and, I think, delayed and slowed down our progress in developing treatments.

Emma Ross

Yeah, David, I wanted to ask you, how important do you think it is to co-ordinate? Is chaos and, kind of, ad hoc just the way it is and it doesn’t matter? Do we need more co-ordination of this, and how does it compare – it appears a lot of people say that the effort to find a vaccine is far more co-ordinated and organised than it is in the drug space?

Professor David Heymann CBE

Yeah, so, I think, you know, you have to be careful with co-ordination because many times it stifles innovation, and that’s what is absolutely necessary, in all the research that’s going on at present, is innovation. And so, you know, I think, as WHO looks at this, what they’ve been doing is bringing together all the Researchers in a certain field, in therapeutics and in vaccines, and trying to help them inform others of what’s going on, and, as Jeremy said, unfortunately, many of the studies have been poorly designed, have not been designed to give a result that can be meaningfully interpreted and, as a result, Politicians have picked up some of this and just pushed it ahead as being truth. And so, it’s very important that we don’t collaborate to – in – and, in the end, stop innovation. So, maybe a better word would be informed co-ordination, making sure that everybody is collaborating and informed, but not necessarily being told, “You do this, and you do that,” because that’s where the innovation is destroyed.

So, WHO, I believe, is doing – and Jeremy will correct me if he thinks that’s not so, but I think they are doing well. I’ve participated, as has Jeremy, in meetings of up to 300 people on the internet, where people are talking about what they’re doing, what – they’re showing their results, and they’re trying to move ahead in not a co-ordinated way but in a collaborative way, and I think I misspoke, it’s collaborative which is important, not co-ordinated. Jeremy.

Sir Jeremy Farrar OBE

Yeah, I agree with that, and I agree with you, David, on WHO, as well. I mean, the Solidarity trial, I think, has now recruited five or 6,000 patients across multiple countries looking at treatments, and it will provide, alongside Recovery, with definitive evidence that can be used, and these are drugs that are available and can be used globally. The trouble with co-ordination is two things. One, David says, is it – the danger is it stops innovation, I absolutely agree with that, and the second is everybody wants co-ordination, but nobody wants to be co-ordinated, and, I mean, that’s just the nature of this field, I’m afraid. I think you need a balance. I think you need the innovation that comes through and asks left field questions that nobody else had thought about and gets through and provides evidence, and then – but you do need those organised, largescale studies, such as Solidarity at WHO and Recovery in the UK, which then can provide the definitive evidence of which those early innovative ideas that David talks about can then prove to be really effective or not. You need both, and we need to get better at having both. But David’s absolutely right on the collaboration, I mean, the 300 calls that we’ve been part of I think have shown the scientific community, from China to America to Africa to Europe to Australasia, South – Central and South America, has been very willing to collaborate, and that is academic and industry.

Professor David Heymann CBE

Emma, I might also say that Jeremy and the Wellcome Trust were really also instrumental in making sure that journal – medical journals peer-review rapidly the information that comes in in manuscripts and put it out in front of the paywall, in order that the Researchers can get the credit they need as they’re doing the research, but, at the same time, if the public can share with this globally, and I have to say the Wellcome Trust, with Jeremy at the head, has been instrumental in making sure that medical journals understand that they can’t postpone or take a long time in peer review. That it has to be out there rapidly, and that encourages the Researchers to do their research more rapidly and get it out in front of the paywall.

Emma Ross

Okay, now you’ve mentioned that, you’ve opened the door, David, for me to bring up the whole preprint issue and data that has not been peer-reviewed being shared and decisions being made on that. Can either of you bring up – this seems to have been quite a feature in this. I mean, has it – has this come out of nowhere? Did we see this in previous outbreaks of Ebola? It seems to be quite a feature and we congratulate ourselves for getting the data out there, but bit of a double-edged sword, no?

Sir Jeremy Farrar OBE

It is, but I think, on balance, the positives massively outweigh the negatives. You’re right, it’s the first time that David describes that this has happened. Actually, it didn’t happen in this way during Ebola, as – anywhere near to the same extent, although, to give credit, the journals did try, but nowhere near at this scale. Yes, there are some risks to it, and we’ve seen those, if I can mention them, at two journals, The Lancet and The New England, which publish data, which actually may, in the end, prove to have been fraudulent. But I think, overall, getting things pre-printed, getting things into the journals, those and others, and then making sure that the review process happens and any errors are corrected quickly, has meant that far more data is in the public domain than is normally true. And if there is a small risk that one or two things slip through, as it did, and the – both of those journals acknowledged it and moved very quickly to change that, then I think it’s a risk worth taking, because the positives of having that collaborative endeavour and sharing of information, in my view, massively outweigh those risks.

Emma Ross

Before we go onto questions, I wanted to start in with the access issues. Well, maybe even scaling up production for the number of people that might need any treatments that make it through, but the main thing I want to talk about is there is a lot of talk about how we must ensure equitable access for everybody who needs it, but can we talk about what is the most likely scenario? Do we seriously believe that that, you know, is going to be possible, or realistically are we shooting for a massive improvement in equitable distribution? Where do you think is realistic to be expecting, and – you know, or should we be preparing ourselves for not quite a rosy scenario, where everybody gets the treatments they need, the therapeutics they need?

Sir Jeremy Farrar OBE

Well, I think on this one, if you don’t push for a rosy scenario, you’ll end up with a very bad scenario, so it’s not being idealistic to argue that, in this circumstance, which is one of the first in many years, maybe not 100 years, but many years, where the whole world has been affected, high income, middle income, low income countries. I think if we don’t make the case for equitable access, then nobody will make it, and we will have a very inequitable world and, as we come out of this crisis, that is not a world that we want to be part of. So I think it is crucial we make this point, again, to pay tribute to many, but particularly here the WHO, in bringing together something called the ACT-Accelerator, which has therapeutics, vaccines, diagnostics and public health systems under a single umbrella, all with their own leads, but which combine together to make sure that we’re not just doing the research, the development, but we’re also considering manufacturing, we’re considering distributed manufacturing, we’re considering access and IP issues upfront rather than later, and we’re making sure that those pillars, within that publicly funded and privately funded endeavour, are made available as the default to the world in ways – in places that are needed, rather than the ability to pay, and that is public – global public goods. It’s also enlightened self-interest, because this is something, which will affect all of us, until every country manages to steer a way through it. So, there’s no point being nationalistic. There’s no point saying, “I’ve got my vaccine in America and nobody else will have it,” ‘cause that won’t work, and it won’t actually protect Americans, so this is – vaccine nationalism, therapeutic nationalism, has no place in enlightened self-interest, and they have to be seen as global public goods.

Emma Ross

David, can you…

Professor David Heymann CBE

Yeah, let me add…

Emma Ross

…talk about what’s actually happening out there? I mean, yes, that sounds totally sensible, but we do have, okay, not only America, but President Trump saying – you know, boasting that he’s bought up the entire global supply of remdesivir. What is actually going on and the prospects for this coming off in the way that we would envision?

Professor David Heymann CBE

You know, Emma, we’ve had glimpses of what’s possible, and that’s been in the last 20 years, really. We see the Global Fund, for example, which is making access to antiretrovirals, to antimalarials, and to antituberculosis drugs, available to countries in need. I think that what we are going to see, and I think Jeremy will likely agree, is that the production capacity will be the bottleneck. To get enough of this product produced will be a bottleneck. Once it’s produced, the innovations will occur, and there will be ways of getting these drugs, or these therapeutics, to the people who really need them. And I think we can count on that, we’ve seen that in vaccines, we’ve seen 100% access to polio vaccine and to smallpox vaccine, and people who needed it, by global mechanisms. We’ve seen the same with the Pandemic Influenza Preparedness Framework. Companies have been willing to set aside 10% of their production capacity for WHO to distribute to countries that need it. So, we have many models in place. What we need to be sure, though, is that that production capacity is not limited, and is the limiting step in letting the innovators and the good people in the world move ahead with the right mechanisms. And I have to say, if you went back in the 1990s and asked a development agency to provide funding for a drug or a therapeutic, they would say, “We only invest in vaccines because that’s cost beneficial.” Today, the Global Fund is sustaining the life of people around the world with the drugs that they’re providing, so I think we can be optimistic.

Sir Jeremy Farrar OBE

I agree with that, and just to pay tribute, Global Fund guard the – what they’re doing is they’re providing a pooled mechanism to pull through innovation that happens in the R&D sphere, and there wouldn’t be an academic or a company now that would argue against that utility. And we’re going to have to have that as mechanisms through both of those agencies, for both vaccines and therapeutics, for COVID. We also need, though, and this is controversial, but we need to see this, because it is a whole world problem, that the high-income countries cannot see this as only part of their overseas development assistance money. This requires money at a scale that is different to ODA money, and that is going to require money from domestic resources, from high-income countries, to make these available in ways that we haven’t traditionally done. Whereas Gavi and Global Fund are funded through ODA money, we need to broaden that financial commitment because – to those vaccines and therapeutics and diagnostics.

Emma Ross

Okay, well, that gives a nice segue into my last question before I take audience questions, and that’s what about beyond COVID? Jeremy, what are your hopes, as all the efforts that are being done for this pandemic, what that might entrench for the future in the way that therapeutics are made, produced, delivered, or the way we look at it?

Sir Jeremy Farrar OBE

Well, we have to – this is an absolutely unprecedented event, certainly in any of our lives, and if we don’t learn lessons from this and put in place stronger public health systems, we realise the world is very small now, and great challenges of the 21^st Century, epidemics, drug resistance, climate change, has to be addressed at a global level, absolute critical need for a very strong WHO. And then, specifically on the therapeutics, my hope is actually this event catalyses and galvanises a whole group of young people particularly that come into the whole area of, yes, epidemic diseases, but also, of acute viral infections, because we don’t have enough treatments for viral infections, whether it be dengue, chikungunya, yellow fever, influenza even, and certainly for COVID. So, my hope is that this catalyses a whole new generation that come in, in the R&D sphere to acute viral infections, and we learn lessons from this, as we did with HIV, and we transform the whole field of therapeutics for these very important conditions. And then we democratise that, so whether those are monoclonals, which are currently expensive to make, but we need to make monoclonal antibodies available, if they be approved to be safe and effective, in an affordable and accessible way globally. And I think this is the, if you like, cathartic moment, when the world has to come together to make those sorts of commitments.

Emma Ross

David, anything to add on…

Professor David Heymann CBE

Yeah.

Emma Ross

…catalysing for the future?

Professor David Heymann CBE

No, I absolutely agree with what Jeremy says. You know, what we have to do is figure out how intellectual property, which is what stimulates research and development now, can either be applied in a different way or there be some type of a substitute for that, in order that we don’t kill the innovation which is going on, and we need to broaden that innovation from just the pharmaceutical companies to other areas of work, as well. So, hopefully, these intellectual property issues, which have been discussed and discussed and discussed in the past, will now be discussed in a new light and be able to help us move ahead in continuing the innovation necessary, while at the same time, respecting the current situation, unless we can replace it, unless we can replace intellectual property with something else, because that’s what’s driven the products we have today. It will continue to drive that, but it may be that we can make a different way of it driving it, as Jeremy said, which will permit everyone to treat some of these things as global goods and get them out to the people who really need them.

Emma Ross

Well, that’s a good last question for that, ‘cause next week, as you know, David, we’ll be talking with – talking about the pharmaceutical industry and perspective, and I’m sure that that will be a big topic of our conversation next week. But I’m going to move onto the audience questions now, and here is one from John Watson, “New pathogen, no immunity in the population, is that right or might there be some innate or acquired-previously immunity that could give clues to mechanisms for protection?”

Sir Jeremy Farrar OBE

Yeah, it’s a great question, John, and you’re right, I should’ve – it was too blanket a statement. You’re right, there may be, it’s a maybe, evidence of particular T cell immunity, maybe to other coronaviruses that we are exposed to, which may give you some protection. We’re at the very early days of understanding that, but there may be some people that are either protected through their immune system, or, of course, potentially genetically protected against these sorts of infections. There is so much to learn still, only six months into a novel pandemic. It is very important to understand that for future vaccine development. And just one caveat on top of that, and it’s come up in some studies, just a concern that whether pre-existing immunity may make disease worse, so-called dependent enhancement – immune-dependent enhancement, and we just need to be cautious of that, as well.

Emma Ross

Thank you. Going back to basics a bit, this is from Catherine Wylie from Press Association. For any of us novices listening, could we please have an explanation of how a preventive differs from a vaccine? To the untrained eye, they’d seem to be the same, or as good as each other.

Sir Jeremy Farrar OBE

Yeah, it’s a good – and, actually, if I look to the future, I suspect that the words ‘therapeutics’ and ‘vaccines’ will blur a little bit. But a preventative treatment is something like if I were to go to a malaria-endemic region, I might take a drug that would prevent me getting malaria. There isn’t a vaccine for malaria, but there is a drug, which, if I were to be bitten by a mosquito with malaria, I could take a drug every day or every week that would prevent me getting it. So, it’s most – usually short-term, it’s preventing you getting infected, and it’s not the same as a vaccine, which gives you, you hope, long-term protection.

Emma Ross

Okay. This is from Sarah Newly, an upvoted question. “How do the recent findings that antibodies are not necessarily long-lasting after an infection affect convalescent plasma and monoclonal antibodies?

Sir Jeremy Farrar OBE

So, another very good question. Again, we’re learning. Of course, we’re only six months in, so the longest patient that we have antibody data would only be six months after their infection now, but it does seem as if antibodies measured in the blood do start to wane after three to six months. You’re absolutely right. What that means for immunity, though, is a very different question. The body’s immune system is remarkable. If you look to the patient that survived the 1918 pandemic of influenza, you could still find cells in their body a 100 years later, which reacted against that virus. Remarkable. You put down those memory cells that allow you to make a response later. So, although the antibodies may wane, we don’t know if that means that you don’t have longer lasting immunity. That is something we have to understand and has real implications for future vaccine development.

On the monoclonals, as David was talking about, those, again, are usually for shorter-term, maybe two or three months’, protection, in a preventative way, as David said, in hepatitis in the past, and in a treatment way to neutralise the virus when somebody is infected. So, you could use monoclonals both for prevention and for treatment, but only short-term, rather than as long-lasting immunity.

Professor David Heymann CBE

Emma, I might just jump in here and say that, as Jeremy said, the antibodies can play a role, and in rabies today, for example, when someone is bitten by a dog, which is a crossing of a virus from an animal to a human, there are many different ways that those people are treated. Number one, they’re given antibody in order to feign – to decrease the virus, if possible, and at the same time, they’re given a vaccine to give them long-lasting immunity. So, antibody will give a short-term immunity protection if they’re concentrated in – from very strong and sturdy antibody, but they won’t give a long-term protection, and that’s why, in rabies, the short-term is necessary with the antibody, the long-term with the vaccine. It’s a strategy, which has been developed over the years, and which is quite effective.

Emma Ross

Okay, thank you. I’m going to go to Amanda Bond at the Telegraph now. Prevention has been mentioned. What has been absent in the majority of discussions around treating and recovery of COVID-19 are the remedies available through herbal medicines and homeopathic medicine, as well as measures to build a healthy immune system, such as spending more time in nature, creating greener cities, etc. What is being done to look at these measures by public health authorities?

Sir Jeremy Farrar OBE

Well, I take a view on this. I mean, some area – some drugs do come from herbal medicines. Digoxin, for the treatment of some heart conditions, comes from herbal medicines, as, indeed, does the most powerful drug ever invented to treat malaria, artesunate came from a plant, and Chinese traditional medicine. And so, looking at those herbal traditional medicines is important, but, in my view, homeopathic medicine doesn’t – does not have a place in modern medicine, that’s a personal view, and anything that comes from any endeavour scientifically, whether it be herbal medicines or drugs that come from herbs, must be taken through the same processes of assessment that would be a drug coming from anywhere else. That means to prove it is safe, and that means prove it is actually effective.

On the question – the broader question of being healthy and what that does for immune system, that I entirely agree with, and it’s clear that whatever infection you’re talking about, it is important that people are well. Clearly people who have been obese have suffered more through this, people who have other conditions have suffered more. So, a healthy lifestyle and everything that goes with that is clearly very important in our ability to fight off infections.

Emma Ross

David, anything to add?

Professor David Heymann CBE

Yeah, I would – I agree on the homeopathy. Certainly, homeopathy has no role in modern medicine, as far as I can see, except in a couple instances where it’s really a modification of homeopathy, where you give a living vaccine that’s been attenuated, that does cause the body to act as if it is being infected, and therefore it protects against future infections. That’s the only variant of homeopathy that I see that might be useful, and it’s really not traditional homeopathy. So, I think, you know, it’s very important that we look at these. And the other thing is that the National Institutes of Health in the US has a screening programme that they put drugs into to see if they are active – these are traditional drugs, to see if they are active in the laboratory against certain pathogens. And I’m sure, I would imagine, that that system, maybe Jeremy knows, has been revved up now to be looking at traditional medicines, and all repurposed medicines for – in fact, that might be useful in the laboratory in either neutralising this virus or decreasing its reproductive capacities. So, I don’t know, Jeremy, do you know if those screening programmes are going on at present?

Sir Jeremy Farrar OBE

Yeah, they are, David, as you – just as you describe, and, actually, all of that data is publicly available for people to share that information, as these libraries of different compounds are screened against this virus. Yeah.

Professor David Heymann CBE

The difficulty comes in places where they have such a strong tradition of traditional medicine that they don’t want to do the clinical trials, and that’s happening in certain countries. Especially it’s happened in China, where they’ve tried to use these drugs, without having the clinical data they need to make sure that they are effective, and they’re coming around now to doing the same thing, because WHO recommends that all drugs, as Jeremy said, go through the same process of testing to make sure that they’re compared to a group that isn’t treated, and to make sure that they are effective. So, where Chinese have used this traditional medicine in the past, they’re now beginning also to develop ways that they can test this and get it licensed clinically and show that it is really effective instead of just using hearsay.

Emma Ross

Okay. This is the most upvoted question at the moment. It’s rather technical, so hopefully, the rest of the audience can follow this. It’s from Malcolm Lowden. “The observation from myself and clinical colleagues, and supported by ICNAR data, is that severity of COVID-19 is decreasing. Increasingly reporting is of cases, however, we hear no clinical definition, and the strong inference is that a positive PCR swab is considered a case regardless of context. This, of course, has major implications for everything from IFR through therapeutics to the public health response. In this context, I note the latest IFR data from Switzerland in The Lancet, based on seroprevalence, which supports an extremely low infection fatality rate.” Any comments on that? Who wants to go first? I think either of you…

Professor David Heymann CBE

Go ahead, Jeremy.

Emma Ross

…could address that, but David go first, then?

Professor David Heymann CBE

Yeah, I was going to say Jeremy can go first. I’ll just say a few things and turn it over to Jeremy. In fact, that’s right, what’s reported as cases is not necessarily cases, it’s positive tests. And that’s where people around the world are falling into difficulties because one country may only be reporting hospital admissions as cases, whereas other countries are doing surveys in the community and doing testing on contacts and reporting that. So, it’s really apples and oranges in the same basket, and it’s very wrong to be comparing countries, based on what they’re reporting as cases, because what they’re reporting is infections, and we don’t understand really the criteria that they’re using to report.

Severity decreasing. Severity could be decreasing for many reasons if it is decreasing. Number one, we know that early on, China was using a case definition, which was serious illness, and therefore, people who died were those who died among those who had serious illness, and the rate was very high, the ratio was very high. It’s decreased considerably now in China to even below one, in some areas, 1% in some areas. So, we know that case definitions are important in putting that denominator on the case mortal – or the mortality ratio.

We also know that, as people gain experience in treating patients, and remember, Jeremy said this is a new disease where no-one has any experience with it, as they gain experience, they understand what to do better and how to do it better. For example, people now are trying to keep people off ventilators, understanding that, if a person goes on a ventilator, there’s a 50% chance that they won’t come off alive. So, people are trying to avoid that with other means, which are innovative means in some instances, and which are having an impact on mortality. So, that’s what I had to say, but, Jeremy, I’d like to turn it over to you because you’ll have some more important views, I’m sure.

Sir Jeremy Farrar OBE

Not really, David, I think that does summarise it. We – in truth, we won’t know the true infection fatality rate for some time, actually, when we understand how much has transmitted in the community, as you rightly say, and you always have this problem with a very common infectious disease. If somebody has a positive PCR in this case, or in malaria, they have a parasite in their blood, are they sick or do they die of that thing, or is it in addition? And it is sometimes difficult to work that out. I’ve always felt, in the end, the infection fatality rate would be in the region of 0.5 to one, with variation globally, depending on access to healthcare and other issues, and demographics, but that’s always where I’ve guessed it would end up.

On the severity decreasing, my view of this is the true severity is not changing. I do think we’ve come a lot better at treating it, as David says. We treated, initially, these patients as if they had an adult respiratory distress syndrome, ARDS, heavy ventilation, etc., and it’s clear that now that was perhaps not the ideal treatment, and that there are better ways of treating. The other thing I’d say is we’re learning all the time, and although the severity and hospitals may look different, we’re also learning that people who recover are suffering from more long-term consequences of this, whether through their – through long-term heart disease, mental health problems, kidney disease and others, and I think we’re only just starting to learn what the long-term consequences of people who’ve been infected with this virus are going to be.

Emma Ross

Okay, thank you. I think we have one more question – time for one more question, and this is from Steven Wright. It’s an upvoted question. “Jeremy, you noted the failed vaccine development in other major infectious diseases, malaria, HIV, TB, over many years, decades, of trying. Are there technical reasons why a coronavirus vaccine development might be more feasible than for these other diseases?

Sir Jeremy Farrar OBE

Well, so often, when you’re making a vaccine, if there is natural immunity to infection, and that is long-lasting, you have a better chance. There is – you know, after any of us have measles, we have, essentially, lifelong protection after infection, and we’re able to replicate that with a vaccine. That is not true, in any way, in the same of HIV and, indeed, malaria, and probably also TB, which is making vaccine development in those three diseases so difficult. So, a lot will depend on whether there is actual – an actual immunity to this infection or not, and can we replicate that with a vaccine? I would be optimistic. Whilst we may not have the perfect vaccine, in the first generation of vaccines, may not protect everybody, it may not protect everybody forever, I think we will gain protection of – certainly for a period of time, that would allow the world to come out of this initial first wave and, in subsequent generation of vaccines, we will get better at them. But the other thing I’d say is that the world’s efforts are currently going into vaccine development for COVID-19, not enough, and the world needs to appreciate we’re going to lose $12 trillion, and we’re not putting enough money into the development of diagnostics, therapeutics and vaccines, and we need to put more in. But, nevertheless, the – there is a better chance for this, I think, than some of those other, more complicated diseases, where we have struggled in the past.

Emma Ross

Thank you. Okay. Well, to round this up, just to segue into next week, when we will have Thomas Cueni, the Director-General of the International Federation of Pharmaceutical Manufacturers & Associations, to talk about the pharma industry perspective, ‘cause obviously, they’re big players in this whole space. What would be your main call to the industry, your main concerns and your main call to them, in playing their part in this fight? As your parting shot.

Sir Jeremy Farrar OBE

Well, so far, I – to be – I think industry has really stepped up. They’re an integral part of the ACT-Accelerator, they’re very engaged in the vaccine development and the therapeutics side, pay tribute to Unitaid here, who have been such a great partner in the therapeutics accelerator, within the WHO-led ACT-Accelerator. Sorry for too many acronyms there, but Unitaid have been a great role model in all of this, and industry has stepped up. But I think this will redefine also, the relationship between industry, private funding and public funding, and, yes, philanthropic funding, and we will need to find a different paradigm effectively for these diseases, which are of such global significance. We’ve effectively outsourced so much of R&D to the private sector, and that has been mostly positive, but when we come to these diseases, which are orphan diseases, or are difficult to make, or may not happen, then I think we need – going to have to think of a slightly different public private partnership model, whether it’s public money put in at scale and we use the best of only industry can bring, in terms of the knowhow of developing new products. But I think we’re going to have to rethink that and organisations like CEPI, on the vaccines side, Unitaid, and the therapeutic [inaudible – 46:18] on the therapeutic side, are thinking about how best to do that for the future.

Emma Ross

Thank you, Jeremy. So, I think we ought to wrap up, ‘cause I know, Jeremy, you’ve got to go onto a call soon and you need a bit of a break. So, thank you both for a really interesting discussion. Very – I think we got to quite a bit of depth there, and please join us next week for more discussion on the pharmaceutical industry perspectives on this. And we have just two more of these sessions left before David and I take a break, and, after we have Thomas Cueni next week. We’ll be finishing up with the Editor of The Lancet medical journal, Richard Horton, talking about how the science unfolds and the relationship between Scientists and Politicians in this response, so that will be the end, towards the summer. So, thank you so much all for joining us, and have a great rest of the day, and thank you to Jeremy for joining us, and for David, as ever. Thank you.

Sir Jeremy Farrar OBE

Emma, David, thank you.

Professor David Heymann CBE

Thank you, Jeremy.