Controlling Covid-19: lockdown, or let rip?

Do we allow the Covid-19 virus to spread, or try to suppress it with more interventions...
27 October 2020

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This week, news of the people catching coronavirus on purpose; those waiting-out the pandemic in an old nuclear bunker, and the good news that lullabies send babies to sleep regardless of what language they’re in! Plus, “lockdown, or let rip?” what’s the best way to control the coronavirus pandemic? Opinions are divided, and we're joined by four leading experts to debate the best solution...

In this episode

Syringe and needle for administering injections

00:59 - Human Challenge Trials for Covid19

Purposefully infecting healthy people with coronavirus to better understand covid

Human Challenge Trials for Covid19
Chris Chiu, Imperial College London

At a time when most of us are doing our best to avoid catching coronavirus, it seems surprising that there will soon be some individuals in the UK getting infected on purpose. But that's the goal of a new study announced this week by UK scientists who, supported by a £34 million Pound investment from the British government, are setting up what are called "challenge studies". Volunteers, isolated in a laboratory, will be exposed to the SARS-Cov-2 virus that causes Covid-19 so researchers can study how the body responds to the infection. The initiative will help to speed along the development of safe and effective vaccines. Chris Smith spoke to Chris Chiu, who is leading the project...

Chris C - This is likely to be the first time that anyone has developed a human challenge model for SARS-CoV-2. Human challenge models are a special kind of clinical study where we deliberately infect volunteers with a virus to look at how they respond to the infection.

Chris S - Who are you going to recruit?

Chris C - Our immediate top priority is safety. It's really important to us that the participants in this study are at as low a risk as possible of developing more severe symptoms. So that means that we'll be focusing on people who are young, aged 18 to 30; and who are essentially completely healthy, so people who have no other medical conditions such as diabetes, high blood pressure, anything wrong with their lungs or their heart.

Chris S - And when you do these sorts of studies, how are they done? How do you actually get the people, where do you put them, and how do you infect them?

Chris C - We recruit from the general population, and we go through a very complex process of working out whether they are completely healthy. Then we will bring them in to, in this case, the Royal Free Hospital in North London. They have a unit there specially built to have the highest quality of air handling, which means that infected people who are staying with us will not be at risk of transmitting the virus to people outside. When these volunteers come in, we will take some virus and we'll drop tiny drops in their noses. At that point they may or may not become infected, but we will keep them with us in the units for at least two weeks to monitor them as they develop the infection, and then as they get better.

Chris S - And how are you going to study them? What sorts of samples will you be collecting, and what are you hoping to learn by doing this?

Chris C - So one of the major strengths of these types of studies, human challenge studies, is that we can measure immunity and inflammation in these volunteers before they get the infection, during the course of their infection, and as they get better, to better understand how their immune system is responding to the infection. And what's really unique about these studies is that you can look at their immune responses even before infection has got going. In any kind of normal study, you would only be able to detect if people were infected by their onset of symptoms, and so at that point you're already five days or more into the infection; whereas here, we know exactly when they received the virus, and so we can start looking to see the development of immune responses straightaway, and potentially the immune responses which may help them from more severe infection.

Chris S - How do you know how much virus to expose an individual to, to guarantee that they're standing a good chance of catching it? And presumably there are some people who it'll take more virus to infect than others; so how do you make sure that's safe but also informative? Because people have made a case for -  perhaps the amount of virus we're exposed to at the onset of infection makes a difference to our clinical outcome.

Chris C - Yes, you're absolutely right. And I think part of that is based on our experience. But obviously this is a brand new virus, and we don't know exactly how much virus is going to be needed, so what we're planning on doing is starting with an extremely low dose. If those first few people don't develop any infection, then we will increase to the next level. And we will gradually do that until we reach an optimal dose.

Chris S - Given that the people who tend to have a problem with this infection are not young people, is there not quite a significant limitation to this study? Because you're studying people in whom you expect - and for very good reason - they will just recover. May we not therefore be completely missing the thing we really need to capture, which is what happens when people don't end up with that trivial infection?

Chris C - That's a completely valid point, but I think there are some really unique strengths to human challenge; you can really study the immune response in uniquely detailed ways. And we need to understand those to make better vaccines, make better treatments. The other application is in vaccine development and drug development, because you can do a study with perhaps only a hundred people and you will get a very early indication whether or not your vaccine does anything at all. And if it does nothing at all, then you might decide to deprioritize it; and if it does really well, then you can really put a lot of extra effort into it, and you can compare different vaccines in a short amount of time to be able to triage those.

Chris S -  When does it kick off?

Chris C - We'll be starting recruitment quite soon - within the next few weeks, we hope - and then if all goes well, then we should be inoculating the first volunteers at the beginning of January 2021.

A bag for intravenous therapy.

06:52 - Remdesivir: Goldilocks Drug

New results suggest Remdesivir is ineffective against Covid-19, but is there more to the story?

Remdesivir: Goldilocks Drug
Roger Shapiro, Harvard

Recently, the World Health Organisation announced the results of a clinical trial called SOLIDARITY that had investigated the effectiveness of the drug remdesivir for treating Covid-19. The trial results suggest that this anti-viral drug has little or no impact on a patient’s chances of surviving the illness. Following that announcement, a row has blown up with the drug's developers, Gilead Sciences, who cite the use of remdesivir in the apparently successful treatment of Donald Trump, and some other smaller trials, which also appear to show that remdesivir does make a difference. Independent statistician Richard Peto, though, hired by the WHO to scrutinise their results, has dismissed Gilead’s criticism saying the results are reliable. So where does this leave us? One possibility is that we might be treating the wrong groups of people. Used in the right set of patients, at the right time, says Harvard's Roger Shapiro to Chris Smith, it might be quite effective…

Roger - I think of Remdesivir as a Goldilocks drug. And what I mean by that is people who are too early in the disease, or don't have a very severe disease, we won't see an effect with remdesivir because almost everybody will get better in that group. Too late in the illness, and among those with very severe disease who are requiring mechanical ventilation, in those people we're not seeing an effect with remdesivir either because they're at a point of illness where a drug that targets the virus is not really helping them. And what they really need is steroids to lower their immune response to the virus. But that middle group, those who are on oxygen and early in the disease, they're the ones who are in that just right sweet spot where remdesivir can benefit them.

Chris - Do you think that's why Donald Trump did well, because he was got at, very early on in illness?

Roger - I think Donald Trump was the ideal person to get this drug because he was very early in his illness and he did appear to have a drop in his oxygenation, suggesting that he was heading down towards a more severe illness. I don't know that this is why Donald Trump got better quickly because he also received several other agents, including an experimental antibody, that may have benefited him. But I do think that he was right in that Goldilocks zone of who might benefit from Remdesivir.

Chris - Do we know then who the right people are? The right Goldilocks individuals? Have we got some insights into what the right time is to intervene, and in whom, now with this?

Roger - I think we really are learning that now. I think that it's very clear late in the disease, mechanically ventilated patients, that ship has sailed and they are not benefiting from this drug. It's very clear that those who are hospitalised and receiving oxygen, but not yet on mechanical ventilation, those are the people that are definitely benefiting. And in that group, those who are the closest to their symptom onset, they seem to benefit the most. And in the best trial of this, there was a three-fold reduction in mortality in that subset.

Chris - Putting all that together then, when a person catches coronavirus and we intervene with Remdesivir at the right time in the right person, what do you think is going on that means that they don't then turn into a person who's severely unwell?

Roger - It gets a little complicated because the people who do poorly with COVID-19 are those whose immune systems can not lock onto and control the virus. And so at seven to 10 days into the illness, there's a subset of people who will, basically their immune system is still calling for help and saying, "we are not handling this. We are not fixing this, send more cells and more reinforcements". And when those reinforcements are, for whatever reason, unable to lock onto the virus, those are the ones who really get into trouble with this disease. And at that point in the illness, it's too late for the antiviral to work. Because at that point, the immune system has gone into overdrive and it's really causing the harm that we see in many of our hospitalised intubated patients.

Chris - So by intervening early, in the right person, you basically stop the production of virus before it breaches some kind of critical threshold and drives the immune system into this sort of tail spin from which it's very hard for it to pull out. And, and it's actually the immune response that goes on to, in a person who's going to become severely unwell, kill the patient.

Roger - Yes, that's right. And I think the reason that we see the benefit of the remdesivir in the hospitalised patients who are receiving low oxygen is that those are the patients who might be heading in that direction. And if we go too far back into the community and we give remdesivir to everybody, well, we're going to be giving a lot of unneeded Remdesivir because most people's immune systems are able to lock on and control the virus. By targeting those admitted to the hospital often because their oxygen levels are below 94%, they're on the path towards that overstimulated immune response that causes people so much harm. And if we're at that junction and remdesivir can help a certain subset of them kind of handle the virus, damp down that stimulation early enough in the process, then I think that is the reason why in that subset, we see a mortality benefit from using this drug.

black and white image of someone hugging their knees to their chest

Covid-19 Social Study update
Daisy Fancourt, UCL

Back in April, UCL’s Daisy Fancourt joined us to talk about her “COVID-19 Social Study” she was running, checking in weekly on more than 70,000 people across the UK. Six months have passed and Daisy’s back to update us on how people are feeling now, especially as we head into winter and what some are calling the second wave

Daisy - Well since we last spoke in April, we've seen that many people's mental health has actually improved quite a bit. We found that anxiety and depression decreased as lockdown went on, and especially as locked down was eased over the summer. But actually as we're now heading into a period where cases are rising again, we have seen that for many people, they are starting to experience higher levels of anxiety and depression again. And at the same time, there's a small percentage of people who haven't actually benefited from that recovery period; their mental health has stayed bad or even got worse since April.

Eva - That's hard to hear... what about those with mental health conditions like severe depression, or bipolar disorder, schizophrenia, or eating disorders?

Daisy - We found that people with higher levels of mental health problems prior to the pandemic unfortunately tended to have a worse experience, so typically they've had higher levels of anxiety and depression; but we've seen on average the same kinds of patterns, the same pattern of decreasing symptoms over the summer, as we've seen amongst the general population. But actually we've had a lot of reports now coming through from people with quite specific mental health conditions, suggesting that they're actually having a more unique experience. And for some people that seems to have got worse, whereas for others, they've actually found that perhaps their prior experience of managing a mental health condition has sort of strengthened their ability to cope in a stressful situation. We're doing more research at the moment to try and unpack why some people with mental health conditions have found things better and some have found things worse.

Eva - I see. So in part, having already learnt coping mechanisms for what you do when you're in a dip, you might now be able to apply them.

Daisy - Exactly. But then at the same time for other people, they found that they already were experiencing high levels of stress day-to-day, and therefore the experience with COVID-19 has felt like it's too much on top to cope with. So for them it's actually made things worse.

Eva - What about the fact that mass unemployment, other financial uncertainties are forecast? How might that change things?

Daisy - I think this is something we should be quite seriously worried about, because what we've found from our research is that people's worries about these kinds of adversities - whether it's unemployment, or financial issues, or difficulties in coping with worries about the virus - that these worries are actually just as bad for mental health as actually experiencing these things. And particularly we've actually found that people who have got fewer financial resources are particularly finding this relationship between worrying about potential adversities and poor mental health. So this has a big kind of policy implication because it suggests that it's not just about bringing in job support schemes or fairly schemes to save people at the last minute. It's actually about trying to reassure people weeks or months in advance to stop these adversities building up psychologically and the stress of these making people's mental health even worse.

Eva - And do you ask people in your study, do you ask them what specifically is worrying them? Or is it more "generally, how is your mood"?

Daisy - We do both. So we look at different aspects of mood and mental health, but we also look at particular factors that could be worrying people. And it seems that some of the most common worries have been about employment and finances and also actually about COVID itself. And we found that at the start of lockdown, about two thirds of adults are worried about either catching COVID or becoming seriously ill from it. And we found that that decreased over lockdown and over the summer, but it's been creeping up again over the last few weeks. So I think the population as a whole seems to be getting a bit more anxious as we head into winter.

Barbed wire

17:28 - Bunker: meet the apocalypse preppers

A new book tours fallout shelters, wilderness communities, and others escaping the collapse of society...

Bunker: meet the apocalypse preppers
Bradley Garrett

The pandemic is changing society drastically. And rather than engaging with it, some people are choosing to hide and wait out that change - whether in the woods, in their homes, or in underground bunkers. What is life like in these places - and the minds of these people - who are cutting themselves off from the world? Bradley Garrett is an ethnographer trying to answer that question. His new book, Bunker, recounts his experiences living with these groups - he told Phil Sansom more about them...

Bradley - It's a wide range of people. Evangelicals who thought that in order to be raptured, they were going to have to make it through the period of tribulation. And so they were stockpiling for that period of time. I spent time with people from the Church of Latter-day Saints, Mormons, who were actually not interested in escaping the disaster, but going into it. But I also met people who were anarchists and had dropped out of society and were living in off-grid communities and we're very focused on sustainable technologies. And then there were some people that kind of had a bit of a harder edge, ex-military types who were, um, very interested in being able to build defensible architecture, to protect themselves and their families.

Phil - How extreme does this kind of prep get?

Bradley - I went to one in Kansas, built by an ex-government contractor. Now this is a guy who built bunkers for the government. So he was, he was working on those projects and he decided that he needed his own bunker. So he bought an Atlas F nuclear missile silo from the federal government for $300,000, and spent about 10 million turning it into a subterranean condominium complex. I saw photos of it before I arrived there, but it really didn't prepare me for the scale of the place and the level of ambition, I guess. But he, I mean, he had a shooting range, a rock climbing wall, a swimming pool, an education centre, a library, and of course, space for seventy-five people. And after spending 10 million building this -I called it a geo scraper. It's like an inverted skyscraper - he sold every single one of those condos inside there and made about 20 million in profit. And he's now using that to build a second silo. And I, you know, I don't see any end to this. There's a thriving market of people who have millions of dollars of disposable income and are perfectly willing to spend one and a half to 3 million to buy into, you know, the ultimate security, something that was only available to governments a few decades ago.

Phil - Is it like a prison down there?

Bradley - It's not like a prison at all!

Phil - Just because it's underground. And it sounds like it's windowless. It's the only thing I can imagine.

Bradley - There are windows. I'm putting windows scare quotes here because they're vertically installed LED screens. And what he's done is he pipes in a 4k feed from outside of the bunker, so that if you're standing in a living room in one of the condos, you have a very real sense that you're looking outside. He's also installed lighting that emulates the circadian rhythms. So you feel a sense of the sun coming up and down, which is really important if you're going to maintain psychological equilibrium. Some of these are strategies that were learned during the cold war. For instance, there's a particular colour of green paint that is somehow soothing to the human mind. It's the same colour paint that you see in hospitals very often, that color paint was also used on the walls to keep people in a calm state. And he was very explicit - Larry Hall, the guy who built the condo - was very explicit in telling me that for him, the technical barriers to building the condo were not actually very challenging. The challenge was maintaining social order and making sure that people's psychological needs were satisfied. And, you know, having gone through this pandemic and, and all of us having to suffer self-isolation, I think we can all understand how important it is that you keep yourself healthy and distracted. And that's precisely what he had built that bunker to do.

Phil - Has anyone - who hadn't already before the coronavirus started - hunkered down in a bunker somewhere?

Bradley - I mean, it's difficult to get a sense of it, but I ran into one statistic that there were 3.7 million Americans in 2011, that self identified as preppers. And I had someone get in touch recently from Cornell university. And his new estimate now is that 11 million people are seriously prepping in the United States. I don't have numbers outside of the country, but you know, that's significant. This is a reflection of condemnation almost on society, right? That people no longer have faith in government and corporations to take care of them.

Two twin babies sleeping.

22:49 - Infants are soothed by unfamiliar and foreign lullabies

A lullaby in any other language would send me off to sleep...

Infants are soothed by unfamiliar and foreign lullabies
Constance Bainbridge and Mila Bertolo, Harvard

As exhausted parents know, at 3am it feels like there’s nothing more important than soothing a crying baby, and a lullaby can sometimes do the trick. Incredibly, it turns out that your baby doesn’t have to understand the language, or even be familiar with the music style, to nevertheless find lullabies relaxing, as Eva Higginbotham heard from Mila Bertolo and Constance Bainbridge...

Constance - So we wanted to see if listening to these lullabies would relax infants compared to songs that were not lullabies. And that was indeed what we found.

Eva - What age were the babies that you were looking at?

Constance - We looked at babies from the ages of 2 months up through 14 months. And we did actually make sure that we had an even distribution in each age category so that we could examine for age effects, which we did not find, which is super interesting because this suggests that the response to these lullabies is not something that the infants learn during that first year of life, but there might actually be some inclination to relax to these from a very early age. We had animated characters sing these songs to the infants that came into lab. All of these songs actually come from the Natural History of Song discography which is from previous research in our lab. And these songs include small scale societies, they're really scattered across the world. And the songs include these lullabies as well as dance songs, love songs and healing songs.

Eva - Mila, you also worked on this project. How did you actually collect the data from the babies to see if they were being soothed by the lullaby?

Mila - When the babies came into the lab, before we sat them in their seat where they watched this little animation and heard these songs, we fit them with a little monitor that's similar to a Fitbit that recorded their heart rate and electrodermal activity, which is this measure of sweat gland activity, which is basically how excited you are. And in real time, while they were listening to the songs, we could track how their heart rate and electrodermal activity was changing in response to those songs.

Eva - How long were the songs? Because I would imagine that it would take a few minutes for music to produce a, you know, a calming or an exciting reaction. Is that what you found or were they just short clips of songs?

Mila - The clips of songs that we used were only 14 seconds each and they alternated pretty rapidly. So obviously in the real world, infants' experience of music is much richer. They listen to music for minutes on end, in their parents' laps and things, but in order to really isolate any possible effect that purely musical features might have, we chose to snip down the songs to about 14 seconds each and to alternate them, just to see if the infants were immediately reactive to the musical features.

Eva - And what did you find?

Mila - There was a main effect that if you compare their heart rates between the lullabies and the non lullabies, we found that the heart rates dropped in response to the lullabies and something similar also in their electrodermal activity where it was lower during the lullabies relative to the non lullabies.

Eva - And you've actually sent me some samples to listen to. And this is your favourite lullaby, right?

Lullaby

Eva - Oh, it is very relaxing isn't it? And then the babies would have listened to that, and also to this other song, it's a love song I think

Love song

Eva - Yeah, certainly sounds passionate! Were you surprised by the results and what might this tell us about how humans actually relate to music?

Mila - I think this result really is quite surprising. On the face of it it might seem pretty obvious that of course lullabies are soothing, but it's actually not at all intuitive that what we as kind of Western listeners deemed to be relaxing, musical patterns are the same musical patterns that people in other societies would find relaxing.

Constance - It is potentially surprising that even across many different cultures, producing vastly different music in other dimensions, that these lullabies still have something about them that makes them recognisable. And I think one of the coolest things about this is this may very well suggest that there is actually an evolutionary function to lullabies. So sometimes there can be debate over, is music just this sort of, in the words of Steven Pinker, "auditory cheesecake"? Is it just something fun that we kind of came up with as a culture? Or is there actually a purpose to music? And maybe lullabies are one of the first links for us to kind of get to that question.

image of phrase lockdown in Scrabble tiles

28:52 - Let rip or lockdown: controlling coronavirus

What approach should we take to get through the pandemic?

Let rip or lockdown: controlling coronavirus
Deepti Gurdasani, Queen Mary University of London; Angus Dalgleish, St George's Hospital University of London; Richard Parker, University of Connecticut; Philip Clarke, University of Oxford

This week we’re discussing how we get out of the Covid crisis: let the virus go and nature take its course, or continue to attempt to suppress the spread but at great cost to livelihoods, education, well being, freedom and the economy...

Chris - Worldwide, we estimate there have been close to about a billion coronavirus cases, and at least 1 million people that we know of have lost their lives. Some countries, Australia being one of them, have controlled the virus very well. Across Europe though, outbreaks are surging again, and many countries are re-introducing significant restrictions, such as curfews in France and Spain, tiers in England, firebreaks in Wales, and some are even calling for another total UK lockdown as we attempt to control the spread of the virus. That's something though the government has so far resisted doing.

Boris Johnson - There are those who say we need now to lock the whole place down, from John O'Groats to Land's End, turn the lights out, shut up shop, close schools and universities, and go back to the same kind of lockdown we had in March and April and May. And I have to say, I don't believe that is the right course now. Not when the psychological cost of lockdown is well known to us, the economic cost and not when it's being suggested that we might have to perform the same sort of brutal lockdowns again and again, in the months ahead. And not when there is such an obvious variation, unlike last time, between different parts of the country. So that's why we're going for a balanced approach, a middle course between the scylla of another national lockdown and the charybdis of an uncontrolled virus.

Chris - But is it the right balanced approach? That's what we're going to find out. That was the UK prime minister, Boris Johnson there. Now many are still very unhappy about the actions that are being taken, arguing that they infringe on our civil liberties, they're economically ruinous, they'll prove more costly in the long term on many levels than allowing the virus to spread more naturally. The pill, they're saying, is worse than the ill. Now, early in October, one group authored the Great Barrington Declaration advocating an alternative approach that was based on what they called focused protection of those most at risk and thereby minimising the broader societal harms of the Covid-19 pandemic lockdowns. The World Health Organisation on the other hand, despite advising against lockdowns have described that strategy as dangerous, unethical and lacking in a sound scientific basis. Writing in the Lancet medical journal, another group of researchers have set out what they're calling the John Snow memorandum, arguing why taking our foot off the brake and allowing the virus to spread is the wrong approach. This is what Boris Johnson had to say about the issue in a recent Downing Street press briefing.

Boris Johnson - I know that there are some people who say this economic objective is so important that we should stop all measures to control the virus and stop restrictions of any kind on our social lives and on the way we run our businesses. We can't do that because, alas, the maths is inescapable. We would face many thousands more deaths and no, to answer one commonly posed question, we would not be able to insulate the elderly and the vulnerable, not in a society with so many multi-generational households. No country has been able to do that. And an uncontrolled expansion in the number of Covid patients would mean that the NHS would have even less capacity to treat heart patients and cancer patients and to deal with all our other medical needs. So that's why we reject that extreme laissez-faire approach.

Chris - What is then the best way to walk this tightrope between the cost of civil liberties, the economy, education, and the future prosperity of the country, balanced against the risk of loss of life? Well, that's what we're going to try to discuss over the next 25 minutes or so. And with me to do that are Deepti Gurdasani, she's an epidemiologist from Queen Mary University of London, also Angus Dalgleish a cancer doctor at St George's Hospital University of London, Phillip Clarke who is a health economist at the University of Oxford, and Richard Parker who is from the University of Connecticut School of Law. So hello to all of you.

Deepti, if we may begin with you, can you just sort of summarise for us where we are numbers wise at the moment, where are we across the world? And in the UK specifically?

Deepti - Worldwide, we've had over a million reported deaths from Covid and this is very much likely to be an underestimate. Within the UK we've had over 58,000 confirmed deaths as a result of Covid-19 and at the moment we're seeing exponential, so that's very rapid, rises in cases. We are currently at about more than 20,000 confirmed cases a day, which again is likely to be an underestimate because we've reached testing capacity and we are seeing around 200 daily deaths, with them approximately doubling every two weeks.

Chris - And how does that compare with the other thing that we see a lot at this time of year and that's the flu? So in a bad flu year, how many deaths would we normally get from the flu in a country like Britain?

Deepti - Nowhere near what we're seeing with coronavirus. I mean, usually I think it's under 20,000 deaths that we expect and definitely flu does not rise at the rate that coronavirus does because a lot of the population is immune. We have a vaccine against flu. And also we know that flu doesn't spread as rapidly as coronavirus. Flu also has a much lower risk of people dying when infected, compared with coronavirus. The rate of dying with coronavirus is several fold higher.

Chris - The thing is though that if we look at the death toll in the UK every year, about 600,000 people die in the UK every year, don't they? And the fraction that is coronavirus deaths at the moment is single numbers of percent, maybe 4%, I think is one number that's been listed for September. So it's actually a very small proportion of the overall death toll in this country.

Deepti - Yes. And that's because of all the measures that have been taken to control it, it's actually well accepted in the scientific community that if it was allowed to spread in a susceptible population, it would lead to hundreds of thousands of deaths, more in the range of about 300 to 400,000, if it were allowed to spread. Because unlike many other causes of deaths, they don't actually expand exponentially. So for example, people talk about deaths due to road traffic accidents, but road traffic accidents don't multiply over time. With coronavirus, if a person is infected in another five days you'd have three people infected in another five days you'd have nine, and then 27 and so on. So the potential for causing death and infection is huge.

Chris - But it's not an equal opportunities virus in terms of age, is it? Because it's not a valid comparison to say, well, road traffic accidents, because actually the people that have the most to lose from this virus are the people who are the oldest in society.

Deepti - Yes, definitely the fatality rates are higher in older people, but we know that young and healthy people can get long-term effects. Things like type one diabetes, which can lead to permanent or long-term effects. We don't know yet. So it's not just that old people are vulnerable. We know that people who are, let's say obese or people who have diabetes, hypertension - so this is about 20 to 30% of the population in many countries - are vulnerable to what we call severe Covid-19 disease. So it's not true that this is a disease that mostly just occurs in older people and doesn't affect young and healthy people because it certainly does.

Chris - Thank you Deepti for that overview. Let's bring in Richard Parker at this stage, Richard, I appreciate that you are a law person rather than an epidemiologist, but what's the situation across the States at the moment?

Richard - Well, greetings from America where we have 8.6 million positive cases diagnosed to date, 224,000 deaths, we have 4% of the world's population and 20% of the deaths. We have new cases rising at a rate of about 80,000 per day, which is more per day, even on a population adjusted basis than New Zealand experienced in its entire pandemic trajectory for the year to date. So we have not handled the pandemic well, and we're having very much the same kinds of discussions here in the United States that I hear you're having in the UK.

Chris - When you say you've not handled it well, you can only really say that if you have a comparison. So what are you comparing it to when you make that judgment?

Richard - Well, that's been my area of research. I compare the US response to the response of the benchmark practices and results set by successful countries like New Zealand, Australia, Korea, Taiwan, China, Japan, Vietnam. These countries have handled this much better, just following the pandemic playbook. And what you find is that if you just look on a population adjusted basis at the number of deaths per capita in these countries, our death rate is many times higher than theirs. And you can actually calculate how many Americans would still be alive if we'd handle things as well as New Zealand. And that number is over 200,000 who would still be alive who are now dead. If we'd handle things just as well as Canada, over 130,000 Americans who are now dead would still be alive. So there was a tremendous price to be paid. And all the evidence shows that the response that countries take to the virus determines how many people die. It's just a matter of following the playbook. And I would also note in closing that these countries that have actually eliminated or conquered the virus are now able to reopen. Life is going on more or less normally across most of New Zealand, with precautions, but at a much higher level of economic activity. The same is true in China. The same is true in Japan and Korea. So it's not a matter of, you know, opening the economy versus defeating the virus. If you defeat the virus, you can open your economy quickly.

Chris - But you mentioned countries that actually have had a good track record. Vietnam is one of those countries that has a very good track record. We also spoke to one of your fellow countrymen, Todd Pollack. Now he's an infectious diseases doctor from Harvard, but he's based in Vietnam. So what did he think, we asked him, made Vietnam so successful in controlling their outbreak?

Todd - Not one intervention alone is enough to contain Covid-19. The key to Vietnam's success is that they did many things that are proven to be wise policies. And they did them earlier than most other countries. Some of the key interventions were a very effective and comprehensive contact tracing program. Having rapid responses to contain clusters of outbreaks, such as locking down entire villages or neighbourhoods. Increasingly strict border control policy with very early mandatory quarantine for all arrivals, early recommendations and requirements for mask wearing, and a communication strategy that unified and mobilised the population to do its part to control the virus.

Chris - Is that basically, Richard, what is wrong with the response in countries like the UK? Countries like the US?

Richard - I haven't studied the UK, but I can say that that is a perfect summary of what went wrong in the US. And if you compare the way we handled the virus on all those points, contact tracing, testing, isolation, travel restrictions, dramatic contrast at all those points between what the US did and what New Zealand did and Australia did and Korea did. And I think that accounts for the difference in results.

Chris - Thank you, Richard. I want to bring in Angus at this stage, Angus Dalgleish is a cancer doctor at St George's. One of the big worries here is that while we prioritise the health provision to try to cope with coronavirus, we are potentially storing up this enormous clinical iceberg of people out in the community who might not be seeking treatment. They might have treatment deferred. They might have missed treatment. They might not be having screening that would pick up treatment. They might not be having vaccines that prevent ultimately cancers. For instance, the human papilloma virus vaccination programme has been interrupted for some girls in some schools. Is this really your concern, that basically we're robbing Peter to pay Paul clinically here?

Angus - This is a major concern, I believe, and it has been grossly overlooked -  that the number of patients who have missed screenings are in the millions. The number of patients who have had their diagnosis of cancer deferred... And I know personal cases, and I've seen those who've been deferred, they've been deferred to have their procedure, their biopsy, by two or three months during this pandemic; and then when they get it they're now stage 4 cancer, and they're going to last months, whereas they were curable. And there are thousands of cases like this. And it's not just cancer; the same goes for heart attacks, strokes, all these things, and that's before we get onto the mental health problems. The knock on effect of this is enormous. And for those who like to speak in figures, we've only just gone over 40-odd thousand people who have died of this virus. In the first two months of the pandemic, in April and May, the death rate was of course a lot higher - we had a crisis, and the lockdown was the right thing to do - but after that was controlled, the death rate actually went down. And so basically this showed that the pandemic basically brought forward deaths that were going to happen anyway. And I think when you look at it, this is very clearly what's happened. It's a very interesting virus. It has replaced, actually, the flu; let us not forget the flu killed 28,000 people in 2015, and if you actually look at that 42,000 figure, quite a few thousand of those are probably not people who died of COVID, but had had a diagnosis of COVID. So I think we have to be very, very careful. Whereas we're not hypothesising about the tens of thousands of people who are going to die early of cancer, and many of these people are in their thirties, forties, fifties; they're economically productive. Whereas most people who are dying of COVID -  the majority are in their eighties and nineties, and no longer productive.

Chris - There was a letter written to the Daily Telegraph yesterday -  "Letters to the editor. Sir, it's impossible to prevent death. The best anyone can expect is that we can postpone it for as long as possible while we have a reasonable quality of life. The government has decided that it can postpone some deaths by imposing draconian restrictions on people, to the detriment of their quality of life, while bringing forward a significantly greater number of deaths than those they're trying to postpone." Is that sort of what you're arguing, that basically we are actually going to store up a pill that is worse than the ill, as some people are saying, with this sort of measure?

Angus - Yes, I saw that letter and I totally agreed with it. And if you go through the letters to the Telegraph for the last two to three weeks, there is an incredible outpouring of people who are in their eighties and nineties, at risk, who are basically saying that they would far rather take the risk and have a normal life... they know they haven't got that long, but the last thing they want to do is spend their last few years in lockdown, unable to see their family, unable to have a normal social life. And this is what brings in this terrible mental angst, because even my own colleagues have committed suicide, let alone people outside. I subsequently found that my friend's GP's committed suicide. And you've seen the number of people locked in halls of residence who've been found dead. The knock on effect is so enormous. You cannot justify another lockdown.

Chris - Philip, you're a health economist. I suppose one of the big problems that the government have to balance here is that on the one hand, an epidemiologist like Deepti comes and answers a question, which they're asked, "how do we minimise the deaths from COVID? What are the risks? What's the potential death toll?" And then you have an oncologist like Angus, who's saying, "well hang on a minute, we're actually already seeing very profound numbers of deaths in society for other reasons." How do they make those sorts of judgements and turn this into a policy that is not just justified, but also meets the ethics and meets the economics?

Philip - Yes Chris, I mean economists have been working on what's known as a QALY, which is a 'quality adjusted life year'. It takes into account, say, how it might extend someone's life, but also how it may impact on someone's quality of life. And this has been routinely used in the United Kingdom for many years and in the evaluation of many different types of interventions. In the case of the lockdown, there has been some efforts, but some of the broader questions - which I think here, where we're trying to balance off the impacts of the lockdown on reducing the risk of the COVID-19 virus, versus the impact on other treatments - this hasn't been done. And perhaps it really needs to be done to make evidence-based decisions to balance off the benefits to reducing this infectious disease, versus the cost of many other diseases, and also people's mental health.

Chris - I'd like to play you a clip from Quentin Grufton, who is an economics professor at ANU, the Australian National University - one of your countrymen! And we asked him why, in his view, the lockdowns that have occurred in Australia have been so successful compared with, say, the UK?

Quentin - Some people say that you need to open up, get away from lockdowns, to save the economy; it's absolutely not the case. It's certainly not the case in Australia and many of the economies that I've looked at. When you get to low numbers, the payoff is that you don't have a lockdown! You go to New Zealand right now, it's like pre COVID. You go to Western Australia, it's like pre COVID. That's a huge payoff for the economy. And then you can manage the infections that maybe come out of quarantine, for example; you can manage them effectively through testing and contact tracing. But that's a payoff. I can tell you, Australia and New Zealand are going to do a lot better than the United Kingdom, and why? Because they went early, they went hard, and they've actually been able to get this virus and this infection under control. Those countries that have failed to do so are going to suffer not only in 2020, they're going to suffer in 2021. So a failure to act, a failure to act soon enough, is going to generate bad outcomes in public health, but also in terms of the economy.

Chris - That's the other way of looking at it, of course, isn't it -  that we spend a bit of money up front, and actually there is a long term benefit. There is going to be a health cost, we are going to rob Peter to pay Paul in the way that Angus was saying, but actually the pain will be less than if we carry with this cycle of boom and bust. Philip, what do you think?

Philip - That's certainly been an argument that many have put. I think it involves policies that are obviously quite draconian, and these occurred in New Zealand and Australia, but also these are island nations; and then you've basically got to close your borders. And so for example, a country like Australia is only accepting a few hundred passengers from outside, and only Australians are effectively going back to the country. In Europe I think that would be extremely difficult, to close the borders. It's an interesting question for the UK, but that would have to be a part of a decision. Part of this involves a bet on whether there will be an effective vaccine and when that would occur, which would of course potentially mitigate the current second wave, as it were. So it's a very difficult and uncertain policy environment. You can see why there are many different views about the ultimate sort of costs and the benefits of lockdowns in these circumstances.

Chris - Speaking about the whole concept of a lockdown though, the policy is that we have a lockdown, it buys you important time. It buys you breathing space to implement some kind of strategy that you have to have in place things ready to go, having come out of that eye of the storm that you create. Richard, so have we missed the boat for instance, in the US and also in the UK, have we fiddled while Rome and in fact, London and New York, have burned?

Richard - Well, I think that's a very good way of describing it actually. Lockdowns are part of a larger strategy that include contact tracing, testing, isolating people who get the virus, healing them and keeping them from transmitting the disease, and ultimately breaking the chain of transmission. If you do a lockdown really, really effectively and correctly as the successful countries have done, you can break the chain of transmission and you can do it quickly. And that is the compact that Jacinda Ardern made with her fellow Kiwis in March. She said, if we do this hard and we do it now, we can lick this virus in a month. And that's exactly what they did, it took a little bit more than a month. They were able to not only block the chain of transmission, but they were able to get in place procedures for contact tracing and testing that can contain any future outbreaks. So that is a social compact that a lockdown entails. Go hard, do it effectively, and it will be short -  but they did it really effectively and really hard. They had a population equivalent of 23,000 US prosecutions for violations of their lockdown. And so the other lesson from all of this is that you can't fake a lockdown. You have to actually do it. And if we'd actually done it harder in the United States and harder in Great Britain, when we were actually doing it, I think we would be done with the virus by now. There would still be obviously pockets and outbreaks that we would have to monitor against, but we would have a much, much lower base of cases and the economy would be reopening again here as it is in New Zealand.

Chris - Angus, if I could come to you, because you made the point that obviously this is storing up a lot of trouble, and it's going to cost a lot of lives in other respects. What would you do differently then?

Angus - I wasn't against the lockdown at the start. I mean, the lockdown was the right thing to do, and it didn't work here in the UK. It worked in New Zealand, but I mean, New Zealand is so completely different from anything else we have in Europe that they had that chance. But this virus is not going to go away worldwide. You're basically going to have to shut down all trade, everything, if you're going to completely lock it down like New Zealand and let nobody in or out. We will lock down until we die, and we will destroy the economy. If you're really going to try to get rid of this now, it's just not possible. I also think the epidemiologists have got it really quite remarkably wrong in many of their predictions and everything about it. And it's made worse because of the testing. The lockdown might've been a lot more effective if we had track and trace. And we just know the fiasco that that is, we still can't get that right. But as regards to the incidence of it, they worked from the wrong figures - they say it didn't come into the country, that it started on the 29th of January. I mean, I've got friends who clearly had it in mid-early December. And I knew they had it because we've had them tested and they're antibody positive.

Chris - What is the point you're therefore making? That in fact far more people have had it than we think and therefore it's less dangerous than we think?

Angus - Absolutely. You've got it in one. I know an enormous number of people who've clearly had it and they haven't died. And in many ways this is probably going to be the biggest problem, you know, the long term effects in young fit people. I think that's a far bigger problem than deaths which seem to be confined to people who are most likely going to die at any rate.

Chris - Returning to the point I put to you then, which is what would you like to see as the optimal way to manage this now?

Angus - The optimal way to manage this now is very much a mixture of the Swedish model and Barrington declaration, et cetera. That is those people who are known to be at higher risk have got to be very careful and shield themselves. And they've got to take a major role into it. But otherwise people have to get on with their lives and just beware, you've got to change the modus operandi. Remember Sweden was not a lockdown, but it did everything else. And the high death rate is quoted as this doesn't work. Sweden's high death rate was because they did the same stupid thing as the NHS and sent all the old people into care homes without testing them. So the high death rate in Sweden is all old people. Let us look at the death rate in Sweden in one year's time, because I think by doing what they're doing, they're not going to get the wave after wave that we are going to induce from having lockdown after lockdown

Chris - Deepti - this seems like a good one for you then. One of the points that Angus raises is the fact that there might be reason to doubt the severity of the infection and certainly the mortality rate. And in fact that's interesting because there was a WHO bulletin recently, wasn't there, a co-authored from Stanford, where they looked at the infection fatality rate. In other words, the people we know have had it, the people we know have had it and died of it. And those numbers, looking across tens of countries, seem to suggest that the mortality rate is about 0.2% over the age of 70. And in fact, if you look under the age of 70, it's 0.5%, which is less than the flu.

Deepti - Those studies that you're referring to have been widely discredited in the scientific community and are based on very, very selective evidence from certain studies. I mean, I guess just to give an example, if you consider that 58,000 people within the UK have died of COVID-19, which is what the Office of National Statistics say. And the IFR is, as you say, 0.05%, you would need, I think 120 million people to have been infected, which we know hasn't happened because the population of the UK is only around 66 million.

Chris - Philip Clarke, how are we going to pay for all of this in the long run? It just seems at the moment that Theresa May's magic money tree that we were told didn't exist, at the moment does exist. It's been reincarnated in the form of Rishi Sunak, the Chancellor of the Exchequer. This can't go on forever, though. There has to be ultimately a price to pay.

Philip - Yes, Chris. I mean, it really is initially by debt and I think governments have decided they are going to spend up and they have learnt lessons of the past that you've got to try to protect vulnerable people, such as people furloughed. But then I think there is going to have to be a conversation. And also then think about as our economy recovers, who will pay. And one of the interesting problems here is that, of course, this has mainly been about protecting older people, but it's of course younger people who have been most affected economically. So I think one's got to think about ways where you can actually have some of the payment back from that debt rather than falling on income and income of the younger people in society, have it actually be falling on older people. One's going to have to think about novel ways to collect taxes to pay for that debt in future, but also to put in place protections to stop the next pandemic. And that's another conversation we need to have

Chris - People thought or suggested that the NHS was underfunded before all this. Now the country has borrowed basically the amount of money it makes in a year and 50% of that again, we're estimating the cost by the time we get to about this time next year, it's going to be well north of half a trillion pounds. If the NHS was hard up to start with before all of this, and we've just borrowed that amount of money, it's not going to be a wash with money in a year's time is it?

Philip - I mean, I think there will be some, I suppose, difficult decisions for governments. I think they won't necessarily go back to the sort of austerity that people I think have viewed as having very big consequences for the health system and other parts of social care. But I do think it does give you an opportunity to also think about whether you can perhaps make the healthcare system more efficient. And of course, an obvious way is to be able to access GPs or healthcare professionals virtually to increase productivity. But yes, I think at the moment governments are borrowing and they are really leaving it to the next government and future governments to make decisions about how to pay for this in the long run.

Chris - Of course, one country that we keep returning to, people keep citing the Swedish model for how you can play out without potentially having to go down the route of a lockdown. We also heard from Jonas Ludvigsson, who's a clinical epidemiologist, he's also a paediatrician at the Karolinska Institute in Sweden. This is what he says.

Jonas - The Swedish strategy over the last eight months has been -  protect the vulnerable and risk groups. It's also been to keep society functioning, to slow the pandemic rather than to completely stop the spread of the virus. It's been to try to take other aspects of health into consideration so that despite the fact that we're in the midst of a storm of a pandemic, there are other aspects of health such as psychiatric health, cardiovascular health, cancer, et cetera, which we need to take into account...

Chris - Deepi, coming back to you, you must have been asked this an enormous number of times or had to consider this, what Sweden have done, which is to have less restrictions than we have had here in the UK. How does it compare? Is it a valid comparison or are we comparing apples with oranges and we really shouldn't do it?

Deepti - I think the scientific consensus on the Swedish strategy, including from the people who led it initially, is that it definitely wasn't the best strategy. And it's very clear that if you look at the death rates in Sweden, they're much higher than those of their Nordic counterparts - actually about 10 fold higher. So it's about 600 per million versus about 60 per million in many other Nordic countries. I think the worst part of it is that despite a more lax approach and trying to avoid lockdowns, they did not fare any better economically. In fact, there's very strong evidence now that how well a society does economically correlates very well with COVID-19 control. So Sweden has actually done as badly as Denmark, Norway and Finland, despite following a different strategy, but with about a 10 fold higher mortality rate.

Chris - And you don't think that the rest of Europe will catch up on the mortality stakes, because there is this concept of harvesting, bringing forward the inevitable, where someone's got to die of something let's face it, they could die of flu, they could die of Covid. Covid happened to claim them this time, they're not there for the flu to claim. Could it be therefore other countries will catch up and the numbers will equalise or do you think the countries like Sweden and the UK will always be outliers?

Deepti -  Well, I mean, the idea of catch-up has been promulgated for a very, very long time. And in seven months we haven't seen this happen. In fact, what we've seen is that the differences between countries that performed well and the ones that performed worse have become more and more stark over time. And that's what's likely to happen. In fact, we're hearing very much about the potential of successful vaccines being available quite soon. And it makes complete sense to try and control this pandemic as well as possible rather than letting it rip.

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