Are we already immune to coronavirus? Professor Sunetra Gupta, a theoretical epidemiologist at Oxford University, discusses her recent study on the herd immunity threshold, as well as her views on the social costs of lockdown, the inaccuracy of epidemiological models, and the curtailment of academic debate
A study produced by a team at Oxford University indicated that some parts of the United Kingdom may already have reached herd immunity from coronavirus. A significant fraction of the population, according to the study published last week, may have “innate resistance or cross-protection from exposure to seasonal coronaviruses”, making the proportion vulnerable to coronavirus infection much smaller than previously thought.
The Oxford team is led by Sunetra Gupta, a professor of theoretical epidemiology. In recent months, she has argued that the cost of lockdown will be too high for the poorest in society and questioned the language and quality of debate on the pandemic’s impact.
Reaction interviewed Professor Gupta about these matters and more, with questions from Maggie Pagano, Alastair Benn and Mutaz Ahmed.
Alastair: In the debate over T-cell immunity or cross-reactivity with coronaviruses, the common-sense view is that exposure to things that are similar does give you some protection, and it seems to be borne out in recent studies.
Yes, exactly. The principle of protection from exposure to related viruses, and indeed any kind of pathogen, is one that we’ve known for a very long time. The very first vaccine we had, which is smallpox, was based on the idea that cowpox protects against smallpox. This idea was already there well in advance of us knowing that smallpox was a virus – and indeed in advance of germ theory having been properly established. So we knew about this cross protection even before we knew that diseases were caused by germs. It’s a very old idea.
In my own studies, beginning with malaria and then later thinking about flu, the role of cross-immunity in protecting against disease seemed to be something that very much needed to be factored into our thinking. Most of the people who die from malaria are children, and they die upon their first exposure, because they have no immunity at that stage. That was one of the first things that struck me when I was working on malaria.
And then later when I was working on flu, it seemed to me a very good way of explaining why the 1918 flu had killed so many people, but why that didn’t seem to be repeating itself, was that it was likely that people hadn’t been exposed to flu. Many people would have not had the flu at all. So then that built up this population of naive immunity in people under the age of thirty who were very badly affected when the pandemic came through.
Having those ideas in mind, when the Covid-19 virus started to spread, I was pretty certain it wouldn’t have a huge, devastating impact in terms of mortality, because we had all these other coronaviruses circulating.
What I didn’t anticipate was that some of our responses to previous exposure to seasonal coronaviruses might actually protect us from infection. It’s one thing to get infected and not ill, but what the new studies are showing is that people are actually fighting off infection. So at an even more basic level, the pre-existing antibodies or T-cell responses against coronaviruses seem to protect against infection, not just the outcome of infection.
Mutaz: When the serological studies were conducted a couple of months ago, antibody rates were very low in the UK. Is that because people weren’t vulnerable to infection, or because once they were infected they had some level of innate immunity?
What we know is that the seropositivity rates in many parts of the world are much lower than we’d expect them to be if we assume that the epidemic has passed through and that people are resistant. If you take a very simple scenario where everyone is susceptible, you’d expect 60-70% of them to have some marker of exposure. And that is not what’s been observed.
I mean, there are areas where it is very high. There’s a paper published recently of a seroprevalence study done in the slums of Buenos Aires, which reports a 50% seroprevalence. And there have been studies from Lodi, Italy, where it is I think 60%.
So there are studies on the high side, but I think one can’t really trust studies on either side completely. One has to take all these measures with a certain degree of caution. What we have here are a range of measures. In cities, it’s typically much higher than in rural areas or areas that are non-urban.
One of the things that’s been done in reporting the seroprevalence, which is not correct, is that they’ve been homogenised. When people say only 5-6% of the UK population has been exposed, that’s not correct. I think very few people would agree that exposure rates in London are less than 20%.
The picture that we’re getting is heterogeneous. But even in hotspots, apart from a few reports, they’re still quite low. So why is that?
One reason might be that lockdown stopped the spread of infection, so it was halted at a stage when, say, 20% of people were immune and the rest of the people were still susceptible to infection. Well, under those circumstances, the easing of lockdown should result in fairly rapid growth of cases. And that’s not something we’re seeing.
So we’ve got those two bits of information. The third bit, the missing piece of the puzzle, is this idea that some people are fully resistant to infection, because they just have really good defences. That could just be part of our innate immunological makeup. It’s also becoming clear that some of the people that have beaten it off have had responses to other coronaviruses which could have played a role.
The other bit of the puzzle is that some people do get infected and they make antibody responses, but those responses die very quickly. So if you’re trying to measure exposure, you won’t get the full picture. Some of the measures of seroprevalence might be underestimates.
We’ve got four pieces of the puzzle, then. If we put them all together, which is what the paper that we published on Friday does, it gives you a theoretical framework that you can use to look at how these bits connect up together.
You can see two things. You can see why the seroprevalence level might be low, and you can also infer that the level of herd immunity needed to stop the thing from exploding again is actually much lower than the figures that are currently being thrown around quite incautiously might suggest.
Alastair: In a sense, there’s a control group, Sweden, which is a heterogeneous population with a couple of decent sized cities and a lot of towns, and it’s precisely as you illustrate. Something happens to the epidemic and it dwindles.
The fifth piece of this jigsaw could be that there is some seasonality. I suspect that in the winter it will probably come back, but hopefully only to the regions where it was kept from going by lockdown, and where the seroprevalence levels are genuinely extremely low.
We can be cautiously hopeful that in areas where the seroprevalence levels have achieved a certain value that’s compatible with there being a proportion who are resistant, that it might not come back with such vehemence.
Mutaz: Your paper said that in this framework, if you combine all factors, the exposure requirement could be as low as 25% for a certain area to reach the herd immunity threshold.
So, there’s the herd immunity threshold, which is the point at which enough people are immune to a pathogen that the rate of growth will start to decline. But there will still be more cases. Typically in an epidemic, we overshoot that threshold. So if you see an area that has a seroprevalence with 60%, that doesn’t mean that herd immunity can’t be much lower than that. What that threshold does define for us is how many people in the community you need to be immune for that thing not to take off.
Alastair: It’s interesting that you mentioned folklore. In the West we have this idea that we want to eliminate disease – that there’s a heroic figure who intervenes and then resets the social order. In some parts of Asia there is a very different approach, it’s more about accommodating yourself to the natural world, and cultivating a more holistic view of how you live with disaster. Things like lockdown have their own folklore.
Yes, that seems to be much of the language of it. It’s semi-religious, actually.
As you say, I’m astonished at two things. One is the bellicose language used with respect to the virus, which does point to this desire to annihilate, which seems to me strange. Maybe it has something to do with coming from an eastern tradition, but I’d like to think it’s strange because we live with infectious diseases. We do accommodate infectious diseases into our social contract, really. We know that this is a threat we have to deal with.
The other interesting issue that I’ve suddenly realised with this particular threat, is that people are treating it like an external disaster, like a hurricane or a tsunami, as if you can batten down the hatches and it will be gone eventually. That is simply not correct. The epidemic is an ecological relationship that we have to manage between ourselves and the virus. But instead, people are looking at it as a completely external thing.
What’s disappointed me about the way this has been approached is it has been approached along a single axis, which, if you like, is a scientific one. Even within that context, you could argue that it’s too one-dimensional, so we’re not thinking about what’s happening with other infectious diseases or how many people are going to die of cancer.
That’s the axis of disease, but then there’s the socioeconomic axis, which has been ignored. But there’s a third, aesthetic access, which is about how we want to live our lives. We are closing ourselves off not just to the disease, but to other aspects of being human.
Alastair: We talk about international travel as a disease vector, and talk about how we’ll never get back to that normal. It’s the sledgehammer idea that you can eliminate it by stopping mixing. It’s a kind of false trade-off.
I think the trade-off is very extreme. Obviously the most extreme manifestation of that trade-off is the 23 million people who will be pushed below the poverty line as a result of this sledgehammer approach. The costs to the arts is I think also incredibly profound – the theatres and all other forms of performing art. But also the inherent art of living, which I think is being compromised.
Acts of kindness are being eschewed. Someone was telling me yesterday that their mother said to them “please don’t come home, you’re going to kill us”.
Maggie: The lockdown has been so successful that people are terrified. What do you think policymakers and politicians, and others such as yourself, can do to help us return to normal?
What politicians can do is maybe alter their language to reflect that we do live with risk, we have to make quite difficult decisions about trade-offs that exist between ways of life, between livelihoods, and sacrifices that have to be made at a societal level. They would do well to urge people to think at a communitarian level.
I think the lockdown is really individualistic in its general construction. Things that we normally disperse within the community, such as individual risk, and individual blame. Now I see young people being terrified, even though they realise the risk to themselves is low, that they might infect a friend who will then give it to their grandparents. This chain of guilt is somehow located to the individual rather than being distributed and shared.
We have to share the guilt. We have to share the responsibility. And we have to take on board certain risks ourselves in order to fulfil our obligations and to uphold the social contract. So I’d like the politicians to remind people of that, because that’s what they’ve been elected to do – to see the social contract is being properly transacted.
Alastair: There’s an essential sense of contamination that pervades everything. You see repeatedly people reacting with total vitriol to pictures of young people going to the park or the beach. How do you transform a collective sense of contamination and sin into something productive?
It’s very difficult. I think there’s nothing to do except remind people that that is not only puritanical, but misguided. Because actually, the only way we can reduce the risk to the vulnerable people in the population is, for those of us who are able to acquire herd immunity, to do that.
Even if there is a little bit of a risk. I’m 55 years old, there’s some slight risk out there. But I would be willing to take that, just as I do with the flu. There’s a risk I might die of flu, but I’m willing to take that risk, because I know that if I don’t then flu will appear as it did before, it will enter the population of immunologically naive individuals, and then there will be a high risk of infection which will have a disproportionate effect on the vulnerable sector of the population.
Maybe the way to counter it now is to say, actually, not only is it a good thing for young people to go out there and become immune, but that is almost their duty. It’s a way of living with this virus. It’s how we live with other viruses. Flu is clearly a very dangerous virus, but the reason we don’t see more deaths from flu every year is because, through herd immunity, the levels of infection are kept to as low a level as we can get.
I think there is a way of living in a community where we do take some risk. We do the same with motorcars and whatnot. We say, ok there’s a risk, we’ll take it, because if we didn’t take that risk we’d be living our lives in a way we don’t want to.
Maggie: The expression “herd immunity” has entered the same realms as austerity and Brexit. It has become a sort of danger word because of that whole debate at the very beginning. The minute you say herd immunity, the popular newspapers say you want to kill all the old.
It’s just a technical term. It’s just a technical term for the proportion of the population that needs to be immune in order to prevent the disease from spreading, which is the central concept in vaccinations. It’s a fundamental epidemiological concept, which clearly has been subverted. I guess the fact it includes the word herd has made it easier.
The truth is that herd immunity is a way of preventing vulnerable people from dying. It is achieved at the expense of some people dying, and we can stop that by preventing the vulnerable class in the process. In an ideal situation, you would protect the vulnerable as best you can, let people go about their business, allow herd immunity to build up, make sure the economy doesn’t crash, make sure the arts are preserved, and make sure qualities of kindness and tolerance remain in place.
We live, it seems, in this state of terror. Yes, international travel facilitates the entrance of contagion, but what it also does is it brings immunity.
Why don’t we get flu pandemics anymore? Because before 1918 there was not sufficient international travel or densities of individuals to keep flu on as the sort of seasonal thing it is now. Pockets of non-immune people would build up, and then they would be ravaged.
That was the pattern until the end of the First World War. Since then, many of these diseases have become endemic. As a result of which we are much more exposed to diseases in general and related pathogens, so if something new comes along we are much better off than we would be if we hadn’t had some sort of exposure to it.
If coronavirus had arrived in a setting where we had no coronavirus exposure before, we might be much worse off. It also seems that in addition to protection against severe disease as a result of exposure to related coronaviruses, some fraction of us seem to be resistant to infection.
That’s just fantastic news, actually. Hopefully that will be consolidated at a scientific, laboratory level. We ourselves are looking at how antibodies to seasonal coronaviruses can impact on protection against infection and disease.
Maybe we will be able to build up a picture that will reassure the public that actually we are much better off having been exposed to related coronaviruses. We are in a better place to fight off this infection than we actually thought.
Mutaz: Do you think we are overestimating the size of a potential second wave, or if there’s going to be one at all in London, given how much exposure there’s already been?
There is no reason to be so confident, as many modellers are, that the proportion proposed is extremely small. What you see regularly in articles and opinion pieces is this idea that herd immunity has to be over 70% at least and only 5% of the population has been exposed. That is still a possibility, but actually it’s a possibility within a very small part of the whole parameter space that we should be considering.
There is also the possibility, as we suggested in March, that a large swathe of the population has been exposed. Some have become immune, and therefore exhibit antibodies, or don’t because those antibodies have decayed. And some were resistant to start with. Under those circumstances, no, we shouldn’t see a huge surge in infections in those regions like London and New York where we’ve had a major incidence of infection and death.
Maggie: Would you like to see a national antibody testing regime?
Oh yes, even though it’s flawed. The tests themselves are not perfect, and we now know that some people just don’t make the antibodies even though they’ve been infected, or if they make the antibodies they’re at such low levels that they’re below the cut-offs of the tests. Knowing all of that, I think we should still go out and produce a very fine map of what the exposure levels are. That will help us allocate resources in the winter, when it’s very likely to come back. So yes, that should happen and I don’t know why it hasn’t.
Alastair: How can journalists do better when reporting crude statistics that often come out? The framing of it is so crucial, and what you see so many times is people misreport and exaggerate stats.
Yes, I think the reporting has done us no favours and continues to remain that way. One of the things that I find very difficult is the focus on national statistics. Among the various manifestations of individualism, nationalism has certainly become greatly underscored. It’s really become a guiding sentiment in this miserable mess.
We should have dealt from the outset with this pandemic as an international problem. Instead it was “let’s lockdown my country, let me protect my citizens”, which is incredibly individualistic.
These absurd comparisons between large countries and small countries. It’s not a song contest, it’s just absolutely ridiculous. It’s also very harmful. When you think of the US as a whole, you’re missing the fact that the epidemic appears to be over in the north east and growing in the south west. Why would you put them together? There’s no reason to lump a rise in cases in Arizona with everything else.
And then finally the whole business of reporting cases, which is deeply problematic because it depends on how many people have been tested in the first place and where they’re being tested. I’m not saying journalists shouldn’t report case numbers, it should just be heavily caveated. Deaths are deaths, but cases can be anything.
Obviously there’ll be some confusion, because this is a new virus and some of it is technical. But these are simple things. You could ask this question of a 10 year old. Do you think it’s right to compare the number of deaths in Brazil with those in Italy, and the ten year old would say “I don’t think so”.
Alastair: What can states do better? There aren’t many examples of countries doing a national quarantine in the past. You can think of cities or ships…
There’s that village of Eyam which locked down during the plague to stop the plague from exiting. Now that’s a decent reason to lockdown. To lockdown to keep something out is highly individualistic. To lockdown to keep something under control is, in the long term, quite misguided.
Maggie: Would you have kept the lockdown purely to care homes?
Certainly. Shielding the vulnerable is what we also got wrong. I think nations should follow both in the practical recommendations and the rhetoric of Sweden. They made the decision, and it was presented without the hubris of “this is the right thing to do”. They could have protected the care homes better perhaps, and we can’t get all of these things right, but we should try our best to shield the vulnerable.
A certain degree of humility and logical dialogue about this might have prevented the whole nation from being paralysed by fear. People are terrified. Even with the measures easing, you can see that that terror has not dissipated.
Alastair: So you think that the New Zealand approach, eradicating the virus, is both functionally silly and also immoral?
Well, I don’t know whether I’d go so far as to say it’s immoral. It seems to be very short-sighted, how can it possibly keep the virus out?
I think the smugness, the self-congratulation with which it’s presented is misplaced. The self-righteous attitude is completely ridiculous. If it turns out that the rest of the world, through herd immunity or vaccination, manages to reduce the risk of infection, then what New Zealand will have done would be tantamount to not vaccinating your own child. Just waiting for everyone else to vaccinate their children and then go “ok it’s all safe now”.
Mutaz: At the start of the crisis, some epidemiologists seemed more concerned about predicting deaths than working out immunity. Do you think some public-facing scientists contributed to the sense of terror and fear in an unreasonable way?
You could argue that was the worst case scenario, and they felt that that was what they needed to present to the government. After that, there was no further consideration. The debate was interrupted. Any attempt that I made to keep that debate alive and to try and get the right data on board to make decisions, was essentially ignored.
And if anything, we came up for a lot of censure, and we were told we were doing something dangerous, which is really rather heartbreaking because right from the beginning we’ve all been very concerned about the effects of lockdown on underprivileged people, both in this country and globally. So it hurts when we’re told we’re doing something dangerous.
Alastair: How is epidemiology developed in different parts of the world. Is there a British approach, is there a diversity within epidemiology?
There are some schools of thought, it’s true. What has come to prominence during this pandemic is the field of theoretical epidemiology, where you use mathematical and computer models to predict what’s going to happen.
The school of thought I belong to likes to use simple mathematical models, and use these to make fundamental qualitative inferences. For example, one of the things I do is work on flu vaccines, which come out of very simple mathematical models. These simple models are where the main power lies.
But at the other extreme, people use very large, complex computer models. They fit these computer models to data, and then use them to predict what’s going to happen next. That’s a school of epidemiology with which I’m less comfortable.
Maggie: Is that Professor Ferguson’s school?
The model that was used to predict what would happen was certainly of that ilk.
There are schools of thought in epidemiology. But like schools of thought in English literature, we tend to respect each other normally, rather than going on Twitter in issuing rather defamatory statements as some of my colleagues have been doing.
Maggie: Do you feel that Chris Whitty and Patrick Vallance could have done more to try and make it a more open, scientific, natural event. Or were they imprisoned by the politicians?
Well they seemed to be imprisoned within the system. You know, that stage where they had to appear and present their viewpoints. The stage was set so that they really didn’t have much room.
Mutaz: Do you think the social construct is repairable, can society bounce back from this terror, and can science bounce back?
I hope society can bounce back. We have shown great resilience, certainly in other times. It’ll be interesting to see how this all gets represented in the literature. There’s very little in literature in terms of the 1918 flu pandemic.
I just wonder what we will do with this. In the best case scenario, it will be something that we will look back upon and say we never want to go back there again. Maybe it will make us more thoughtful in our future dealings, and maybe it will alter the way we think about risk. So there could be good things that come out of this rather terrible experience.
In terms of keeping the debate alive, it’ll be interesting to see. At some level, universities should be charged with that responsibility, but it’s hard to be confident they will provide the forum for these debates to take place.
At the moment, I personally feel that the calumny that’s been heaped on us that dare to disagree with what is believed to be a communitarian imperative, but to my mind is utterly individualistic, is really quite scary.
It’s been very tough.