Can we eliminate COVID-19, what's the endgame and a reality check on a vaccine

Norman Swan: Hello, and welcome to this week's Health Report, I'm Norman Swan. Today, developer of the human papilloma virus vaccine, Professor Ian Frazer, on the prospects for a coronavirus vaccine.

And, the growing debate about how we get out of this; what's the offramp and what's at the end of that sliproad? Is it life as we knew it BC, Before Coronavirus? And is elimination of the virus from Australia not just feasible but in fact the only sensible option? The clamour from Australian business is growing, the back room lobbying intensifying. The numbers of new cases are small, people are saying, so let's take the foot off the brake now and get the economy back on its feet and people back to work. Last week the federal government under pressure released the modelling on which they have relied for their early decision-making and implied that their future decisions on controls would also be guided by modelling. So, what are we facing and does modelling help?

Well, the first thing to state and most governments are stating it clearly, the economy won't be fixed until you've fixed the pandemic, and Australia has a better chance than most because our borders are closed and will be for a long time to come and we have, as a community, socially distanced, with wider criteria for testing and more effective contact tracing, isolation and quarantine.

But under the surface we have local spread in the community that's either steady or, as it is in Tasmania, spiking. And remember, 50% of the spread of COVID-19 virus comes from asymptomatic people, and without social distancing and other controls, each person passes it on to nearly three other people. So if we are seeing, say, 50 new cases a day and we lift the lid on social distancing (that's the most effective containment measure we have), then 50 can become a very large number of new cases each day all too quickly. Remember, there was a time some time in December when Wuhan had only one person with what would come to be known as COVID-19. Only one person. And we are now at well over 1.8 million cases with more than 100,000 deaths globally in just four and a half horrific months.

In Australia we have the luxury of a debate about what comes next; do we keep up the rhetoric of flattening the curve, which means squishing the epidemic out for months, or do we do what the New Zealanders have aimed for, which is elimination of spread altogether or as close as you can get to that?

Michael Baker is Professor of Public Health at the University of Otago in Wellington, and sits on New Zealand's national technical committee advising on their response.

Michael Baker: Like most countries, we were pursuing the standard pandemic model and response to COVID-19, and of course that is written for influenza. And it did start to dawn on quite a few of us that maybe we should look or learn more from the experience in China and what the Chinese had done to halt the pandemic really in full flight. And other Asian countries were pursuing a similar approach, particularly South Korea and Hong Kong and Taiwan. So we really advocated very strongly in New Zealand that we should look at containing this infection. And also I think probably like Australia we had a little bit more breathing space. New Zealand then really had that choice. I mean, we were heading down a mitigation path, trying to flatten the curve, but then we suggested to the government (and I'm on the technical advisory group for the response) that an elimination strategy could work. And there was obviously quite a bit of internal discussion, but eventually we switched tacks.

Norman Swan: So you switched tacks from potentially flattening the curve and making sure you didn't get a horrible peak with lots of people dying, to saying, well, maybe we could bottom this one out?

Michael Baker: Well actually we could actually eliminate the virus entirely from New Zealand. And there was a lot of doubt from many of my colleagues that that was going to be possible, but we were tracking down the standard influenza model which I think the pandemic plan is written for, but we felt actually this was more like a SARS virus and that basically containment with the goal of elimination was actually viable.

Norman Swan: So just as in 2002, 2003 SARS disappeared, this is what you think you could do with closed borders with SARS-CoV-2.

Michael Baker: That's right. Even though obviously it's very infectious, which made it difficult, because it had the longer incubation period, which is more typical of a SARS virus or other coronaviruses, more like five or six days compared with influenza which is one to three days, it meant that those containment measures of stamping it out, so that's case identification, isolation, contact tracing, quarantine, they can work if they are done very rigorously. But the difficulty is when you're in this intense response mode, it's very hard to change your direction. And our politicians weren't initially convinced, but they came round. But the difficulty was that we just didn't have the infrastructure really to manage a containment process very well because the public health system in New Zealand has been wound down, as it has I think in a number of countries. So it was completely in reactive mode, we didn't have large numbers of staff to do the contact tracing, and our borders were still a bit porous, we were relying on a fairly soft form of self-isolation, home quarantine. So a lot of things had to happen very quickly, and it became fairly obvious that we needed a complete rapid shutdown of the country, just to give us time to get these systems operating and also to extinguish some of the chains of virus transmission.

Norman Swan: So Jacinda Ardern announced a strict lockdown. When was that again?

Michael Baker: Well, it was basically announced on 23 March and it came into effect on 26 March. So we are now a bit over two weeks into it.

Norman Swan: And you're using this time to ramp up your testing infrastructure and your contact tracing infrastructure.

Michael Baker: That's right, and of course we went into a full supervised border quarantine system about a week ago.

Norman Swan: So what are you driving for? You're driving for zero spread in New Zealand?

Michael Baker: That's right, and since the lockdown started two weeks ago we've seen the numbers track down. I mean, it is a very effective way of dampening down transmission.

Norman Swan: Do you have modelling or anything that tells you when you might hit the deck here? What's the prediction about when New Zealand might actually get to zero transmission?

Michael Baker: Well, there is one model and it's still being reviewed very actively, and it says that after four weeks of lockdown we might just be there.

Norman Swan: So, give or take, and of April, beginning of May.

Michael Baker: That's right.

Norman Swan: And how many new cases a day were you having before the Prime Minister announced the lockdown and the border controls?

Michael Baker: We were having about 90 cases a day, and yesterday we had 18 cases, so it's been tracking down now for about a week.

Norman Swan: So, in other words, we can't use the excuse in Australia that you're smaller than us because we've got about 100 cases a day and the community transmission is about 50 or so, so it's very similar numbers when you started.

Michael Baker: Yes.

Norman Swan: So what does the offramp look like? Let's say you get down to zero spread at the beginning of May, what happens next, which is the question that everybody is asking around the world, particularly in Australia but I'm sure you are in New Zealand.

Michael Baker: Yes, I agree, that's a huge issue, and it's not going from lockdown…there is no question that we are going to remove everything, it would be gradually ramping things down. There's a whole lot of things that obviously have to be working very well, we have to be very confident in the border quarantine, the ability to rapidly identify cases and stamp them out. And also thinking about all of the backstop surveillance systems that have to be operating, so lots of testing and starting to test in other settings. We are thinking about other things like testing sewage, for instance, for traces of the virus. That's far more speculative.

The other thing is all these other surveillance systems that are giving us an idea of how the population behaviour has changed. So we are using Telecom data and Google mobility data, and all of that is pointing in the right direction.

Norman Swan: But what gets allowed first? Have you modelled that, have you thought about it?

Michael Baker: The opportunities to de-escalate the levels is particularly more people going back to work and schools are likely to open actually at the end of this month on a limited basis.

Norman Swan: And then you just watch and see what happens.

Michael Baker: Yes, watching very carefully. And there's huge public support in New Zealand, and I think the thing that happened here was the government took a very decisive approach and basically everything in New Zealand was shut down unless it was an essential industry, and the public was informed they could only travel for very limited reasons, for very short distances, just to the nearest place they could get food and for medical care. The government did take on the message that you're doing things almost in a reverse way from what you normally do in a pandemic response. With an elimination approach, you have to almost reverse the normal pandemic response, because with influenza, and it is really built into the planning, you gradually ramp up the response as the pandemic gets more intense, and you hold and reserve the more difficult or disruptive measures like shutting schools and so on to a later stage, maybe to take the edge off the peak. Whereas with an elimination approach you do things almost in reverse. As soon as you get any evidence of local transmission, you throw everything at it to suppress the transmission while you've got all your other systems…while you are getting them all working properly, and that is really what New Zealand has done.

Norman Swan: Michael Baker is Professor of Public Health at the University of Otago in Wellington.

You're listening to RN's Health Report with me, Norman Swan.

So let's get down to this debate about whether we should target elimination of spread in Australia. The modelling released by the government last week doesn't help much, apart from reminding us how bad COVID-19 could be. Professor Jodie McVernon led the modelling exercise for the government at the Doherty Institute in Melbourne.

Jodie McVernon: What we were trying to achieve with this modelling was to give our government some perspective on what this epidemic might look like without control, and then to think about how we could use the various public health measures available to us in the absence of definitive treatments or vaccines to reduce its impact. And the models that we had developed in the preparedness phase were expressly focused on the impact on the healthcare system, and being able to ensure that we would have sufficient capacity in the healthcare system to manage cases, particularly severe cases, was a real priority.

All of us as modellers were putting scenarios to our governments, those of us who were working with policy, that were jaw-dropping. It was very hard to countenance this threat. I think all of us saw the lockdown in Wuhan and thought, well, obviously we could never do that here, and then in a very short space of time we realised this was part of the toolkit. You know, we'd had a discussion about what social distancing would look like in Australia, and most pandemic plans talked about things like school closure or less intrusive measures but talked about how economically costly those measures were, and suddenly we were in a ballpark that was completely different. The problem was clearly one nobody wanted to have, but the solutions really became universally clear that this needed a really combined suite of interventions.

Norman Swan: Was there a lightbulb moment for you where you were really shocked?

Jodie McVernon: Most of us in the modelling community were really, really worried early on and I think one of the things that worried us was the public complacency in many situations, and we've seen that spill out in policy in other parts of the world. I think when something is so bad and so hard to believe, it's easier to wish it away. But seeing then the further epidemics rolling out in other parts of the world made it absolutely clear that this was not a bad dream.

Norman Swan: Professor Jodie McVernon of the Doherty Institute.

It's important to appreciate that our pandemic planning, like New Zealand's, had been based on influenza, which helps to explain the slow ramp-up of control measures rather than going hard early. For a while the government appeared to be stuck in the flu mode of thinking, but the COVID-19 virus isn't the flu, it's a SARS-like virus and needs tough, prolonged action with the tantalising prospect, perhaps, like SARS, of elimination of spread within our borders, assuming our borders stay closed for many months.

The difference though with SARS-CoV-2 is that it spreads from asymptomatic people who can be hard to find. Associate Professor Kamalini Lokuge is in the Research School of Public Health at the Australian National University. There is probably no Australian public health researcher with the range and depth of on-the-ground experience of controlling outbreaks and the health consequences of humanitarian crises. For example, she was heavily involved with Ebola control in Africa. Kamalini Lokuge is a strong proponent, when there is no vaccine, no treatment and a non-immune population, of aiming for elimination of spread, having seen it work on the ground, and also argues that modelling won't help you much in getting there. What's required is traditional epidemic control.

Kamalini Lokuge: What we need to look at, Norman, for achieving elimination and staying there, is particularly how do we make sure we are finding out about community transmission of COVID-19. So the way we do that is to expand our testing capacity to do very effective, thorough contact tracing, so following up of those who may have been in contact, and quarantining and effectively managing those contacts. Modelling is a part of that process of knowing how many we might need to look at, where we need to look, but really the key to controlling the disease is the public health response, and by the public health response I also mean the public's response. And the Australian community has, through taking on these very strong measures, bought us, the public health expert community, time for us to put in place those measures. And we need to recognise the value of that gift they've given us and really work hard to make sure that we have the systems in place that allow us to know we've eliminated disease and then make sure we know, once we start lifting containment measures, that we are still on top of it.

Norman Swan: Associate Professor Kamalini Lokuge.

Having said that modelling has limited value in working towards elimination, a group at the University of Sydney has indeed modelled how we get to elimination of spread in Australia, and social distancing is the core strategy. Professor Mikhail Prokopenko is director of the Centre for Complex Systems at Sydney University.

Mikhail Prokopenko: We tried to focus on modelling covid at the scale of all of Australia but using an individual-based approach. So essentially we have in a digital form 24 million agents, each of which represents anonymously a single individual and distributions of households, household compositions, places of work and schools, to a large level of detail. Then once the pandemic starts, we try to model every single day by estimating interactions within different social contexts, households, neighbours, communities, working groups, schools, different grades and so on. Then we can estimate the dynamics and jumps of the new daily cases and correlate it with the actual plan lines.

Norman Swan: And what do you find when you plug in for, say, social distancing and effectiveness of current policies?

Mikhail Prokopenko: So this model allows us to specifically evaluate different degrees of compliance with social distancing and different degrees of compliance with case isolation. We've focused on comparing compliance with social distancing between, say, 70%, 80%, 90% of the population following these rules, and one interesting result was that there is a sharp divide, a transition between 70% compliance and 80%. So if we as a population follow the 80% or, better, 90% compliance, we could hope to get the numbers of cases down by July to pretty much near zero trajectory. However, if we relax it and stay on a 70% trajectory, the numbers don't even go down, they keep rising, even after some inflection point. What it means is that we can't really relax what we have been doing so far in the near future, so the models show us that we are pretty much at the peak, not only at the incidence peak, the new cases, but we are pretty much as we speak sitting on the prevalence peak, so the active cases are probably reducing. So if we are continuing on this path, we are quite likely to get to a really controlled situation by July. If we relax it, the curve will start shooting up.

Norman Swan: One of the arguments is that you could mitigate that by a very wide testing regime, more effective isolation and quarantining and contact tracing.

Mikhail Prokopenko: I understand that it is a necessary part but it would not be sufficient if we only stay with case isolation and home quarantine and tracing immediate contacts, and the reason is that there are those asymptomatic cases which do have probability of passing this infection in a stealthy, silent way. If we just reduce our intervention to pure mitigation, like what you just said, that would not be sufficient. We have to realise, if I use this analogy of playing a football game, we started this game against an opponent which overplayed us and we were conceding goals left and right, and now we are getting to half-time and we are almost equalised, but should we start the second half and again relax, we will be, at best, just maintaining control, we will end up in extra time and who wants to be in extra time. So what I'm saying is we have to be vigilant, we have to go on the offensive, and that means we have to be aggressively stopping these social interactions and maintaining social distancing. Then, by the end of maybe June, by early July we should be in a winning position.

Norman Swan: What does winning look like when the virus is still around?

Mikhail Prokopenko: That is also a very good question because we are in a preferential position here, being isolated naturally geographically from land traffic, and if we maintain this international travel restrictions on air, we should be able to get back our economy to some decent level, maybe not 100% level but to some decent level and maintain that for as long as needed to get an efficient vaccine available. Our model showed that even a three-day delay in introducing the tough social distancing measures means that three weeks need to be added at the end of this suppression period. So essentially have a week for a day, approximately.

Norman Swan: Just to clarify that, what you're saying is for every three days delay in getting to lockdown, you get three weeks extension to the epidemic at the other end?

Mikhail Prokopenko: That's right, basically it's an approximate equation here which came out of the model…for one extra day of a delay you get one extra week at the end of the epidemic that we need to be in this social distancing, almost in lockdown.

Norman Swan: Just pursuing that for a moment, our community transmission levels are at low levels, doesn't that make us like New Zealand, that we are actually at low numbers and we've got the chance to turn it down quickly, or is that just wishful thinking on my part?

Mikhail Prokopenko: It's a good situation to be in, but you could still multiply those numbers to a sufficient level. You know, in modelling there is this old saying that all models are wrong but some are more useful than others. For example, in the model I was describing, the one which we've done at the University of Sydney, there is a clear divide between 70% compliance and 80% compliance. It's a transition. So when you have those sharp divisions, it means you've found a gem which clearly could be used in decision-making, and that is something which could be immediately actioned by the society. One message here is that it's not just reliant on the government, it's our own social behaviour that has to change, and change to some extent which will get us out of it.

Norman Swan: Professor Mikhail Prokopenko is director of the Centre for Complex Systems at the University of Sydney.

So, everyone is hanging out for a vaccine, and lots of research groups around the world are having a go. The Australian with the most success in vaccine development is Professor Ian Frazer. The virus was the human papilloma virus which causes cervical cancer, and the immunisation took years of work. Ian is still active in vaccine development. Ian, welcome back to the Health Report.

Ian Frazer: Norman, it's good to speak with you.

Norman Swan: What's the challenge here?

Ian Frazer: The challenge is the coronavirus, let's face it, we have a lot of people who are working to develop vaccines against this particular coronavirus, but we haven't had much success with coronavirus vaccines in the past, and that's partly because it seems to be a difficult virus to get a successful and safe vaccine against, and partly because the virus infects a bit of us which our immune system doesn't really do very well at protecting.

Norman Swan: Meaning the upper respiratory tract, the nose and throat.

Ian Frazer: Indeed. I mean, it's a separate immune system, if you like, of its own, which isn't easily accessible by vaccine technology.

Norman Swan: So just explain why not. Because there is a blood supply, we've got white blood cells, why is there this problem with the upper respiratory tract? And it's true of influenza as well, we've got a pretty lousy vaccine for influenza, it's the best we've got but…

Ian Frazer: We want to get a vaccine that stops the cells getting infected, and that really means that you've got to have something that can neutralise the virus outside of the body because effectively our upper airway is outside of the body.

Norman Swan: This is mind-bending but really it feels as if it's inside but in fact it's an external surface, even though it might be surrounded by your nose and throat.

Ian Frazer: Yes, it's a bit like your skin, you know, it's trying to get a vaccine to kill a virus on the surface of your skin. We do have of course the ability to put some antibody in there and we have a local immune system in our lungs which makes the right sort of antibody, but that doesn't connect quite as well as it should do with the systemic immune system that would respond to a vaccine. And one of the problems with corona vaccines in the past has been that when that immune response does cross across to where the virus infected cells are it actually increases the pathology rather than reducing it, so that immunisation with SARS corona vaccine caused, in animals, inflammation in the lungs which wouldn't otherwise have been there if the vaccine hadn't been given.

Norman Swan: Because you're trying to get the virus once it's in. This virus mutates, in fact they've been able to track the virus through the world and where it came from by its mutations. It is the mutation rate changing its coat enough to confuse a vaccine?

Ian Frazer: I don't think so. The total number of mutations to date has been quite small, it seems to be very small point mutations in the genetic information, and from what we've seen so far over the course of basically now four or five months of keeping track of this virus, nothing has changed enough that it would prevent the immune system having a go. We still have to identify what the best target in the virus is. It seems likely that it would be some part of the spike protein, which is the bit that allows the virus to stick to cells. But there hasn't been enough change there yet to prevent a vaccine that worked against the first version of this virus, now coping with the minor changes that have occurred.

Norman Swan: What's the story with antibodies to this coronavirus with SARS-CoV-2? Every day goes by and you seem to get a different story. Some people get a strong antibody response, some people get a weak antibody response, there's a story of do people get reinfected, how long does immunity last. And that's critical to whether or not a vaccine is going to work, is it not?

Ian Frazer: Indeed, and for data on that we really have to go back to when people were doing research on the coronaviruses that cause the common cold, and at that time there was quite a lot of work done on how long antibody responses lasted after infection. And yes, you get antibody after an actual infection, and yes, it lasts for a while, but it's not lifelong by any stretch of the imagination, sort of months rather than years, and of course we don't know what would happen with a vaccine in terms of longevity of immune response. We've got to first of all find a vaccine that will work and then we can see how long it's going to work for. But I think it would be fair to say that the natural immunity that you get after infection from this coronavirus is probably going to turn out like the coronaviruses we've seen in the past. Yes, there will be some natural protection over a period of months, maybe even years, but it won't be lifelong. On the other hand, the good news is that if you get reinfected with the virus a second time some months down the track, probably there will be enough immunity there to stop you becoming seriously ill.

Norman Swan: There's about 70 different technologies being deployed from using the virus like you would in influenza or you'd kill it and try and put it in, there's putting it in little parcels of messenger RNA to tell the cell to produce antibodies, really clever stuff. And in the University of Queensland they are clamping the molecule and trying to get an antibody response to that, and they are trying to get very specific…what I understand is there is a 90% attrition rate in vaccine development, so 90% of these are likely to fail. I mean, where's the smart money on the vaccine development at the moment?

Ian Frazer: Well, the smart money has to be on something which will produce a strong antibody response, and the best way we know to do that is protein plus adjuvant and that would probably…

Norman Swan: So to translate that, that means a significant part of the virus attached to a chemical which induces an immune response.

Ian Frazer: That's exactly right, and that has been successful in animal models for coronaviruses in the past and that is of course where the money is being put I suspect in large measure at the moment. I mean, another sort of vaccine would be just antibody transferred from somebody who had been infected already and had got rid of the infection. It's not strictly a vaccine but it would be an immunological means of preventing infection. That would probably be something that would be more quickly developed than an actual vaccine.

Norman Swan: Some people argue that that's a dirty vaccine that you've just described, and that's why you got the problem with SARS in 2003 when they reinfected the monkeys and they got this strong and nasty immune response, and that's why they're going for targeted very specific antibody responses.

Ian Frazer: Well, that's probably correct. We don't know exactly which bit of the virus would best protect us if we got an immune response against it, but even with the SARS vaccines there was pulmonary immunopathology, in other words the lungs got inflamed after vaccination with some of the virus-like particle-based vaccines that were also tried for this SARS infection. So it's not just dirty antibody, if we pick the wrong antigen for a vaccine where we are making a defined vaccine, a controlled vaccine, if we pick the wrong antigen we may get the same problem.

Norman Swan: Ian Frazer, you're not painting an optimistic picture of a vaccine in 12 to 18 months.

Ian Frazer: Well, the good news is, as you've pointed out, that there are at least 80 known vaccine experiments going on at the moment, including five that are in human trials, so that we've got the best possible chance of getting something. I guess the slightly less good news is that the reason we are doing all these different methods is because there isn't an obvious winner. And I think it would be fair to say that because of the safety issue, and the safety issue is a real one, even if we get something which looked quite encouraging in animals, the safety trials in humans will have to be fairly extensive before we would think about vaccinating a group of people who have not yet been exposed to the virus and therefore might hope to get protection but certainly wouldn't be keen to accept a possibility of really serious side effects if they actually caught the virus.

Norman Swan: Ian Frazer, thanks for joining us.

Ian Frazer: Thank you Norman.

Norman Swan: Professor Ian Frazer is at the University of Queensland.

This has been the Health Report, I'm Norman Swan. Don't forget Coronacast, which you can get wherever you get your podcasts.