COVID-19: 2 months on, what do we know now?

Professor Allen Cheng is Director of Infection Prevention and Healthcare Epidemiology at Alfred Health and Professor of Epidemiology and Preventive Health at Monash University. Professor Deb Williamson is Director of Clinical Microbiology at Royal Melbourne Hospital, and Deputy Director of the Microbiological Diagnostic Unit Public Health Laboratory at the Doherty Institute. This conversation is available as a podcast here. Edited highlights are below.

InSight+: Allen, the last time we did a podcast on [coronavirus disease 2019 (COVID-19)] was back in March [2020]. How do you read the situation now, compared with how it was back in March?

AC: We’ve had a big surge of cases [since March], mainly related to people coming back from overseas and then it’s largely settled down [to a level] a lot less than it was at the height of the epidemic. We’ve really moved into a second phase of what to do now. In the last couple of days, there have been the announcements about relaxation to some of the restrictions, but it’s going to be a really important time to keep an eye on things and make sure that we don’t get any new outbreaks occurring.

InSight+: Deb, what’s been your unit’s role and what have you been up to in the last couple of months? What’s been your big focus?

DW: The laboratory has been providing testing for Melbourne Health. There’s this real paradox at the moment whereby physical distancing measures are being relaxed and there are very few cases in Australia and we’re in this fantastic position globally, where we’ve really done a marvelous job, but the laboratory is almost busier than ever.

The rest of the country is breathing a little, almost a sigh of relief I should say. And in order to support that, in order to support them with physical distancing, relaxation, the laboratory has to provide a very high intensity testing service. We’ll continue to do that for the foreseeable future. We’ve really been through the mill I think, not just my laboratory, but laboratories across the country. It has been absolutely disruptive. Many of us have never seen anything like this.

AC: So just for context, how many respiratory PCRs (polymerase chain reactions) would you normally do a day, and how many COVID-19 PCRs are you doing now?

DW: In the height of winter, [we would do] maybe between 50 and 100 tests for influenza on a very busy day – that’s just my laboratory. But over last weekend, for example, we did upwards of 500 tests a day for coronavirus and that has stretched the laboratory work for us to the [maximum]. Overlaid onto that, are challenges including external pressures, like shortages of testing reagents, quite a complex regulatory framework, complexities in interpreting positive and negative results in certain settings and a pressure to get results out quickly to certain populations.

So, the challenges in the laboratory setting have been at some points overwhelming, but you know, the workforce has more than risen to the challenge.

InSight+: Do you feel that there’s a second wave coming?

AC: It’s something we always need to watch out for, particularly as restrictions are relaxed. I’m hopeful that the relaxations on restrictions are relatively small steps, but I think it would be fair to say that there are indications that a lot of people are getting pretty sick of them. It’s possible that compliance with restrictions mightn’t be quite so strong going forward, but we really need people to try and do their best to stay with it, because we certainly know what happens, where there aren’t restrictions, that things can get out of hand very quickly.

InSight+: Compared with what we knew about the virus in March, what are some of the things that have changed about what we know? Have there been any surprises since then?

AC: One is that asymptomatic or I’d say, is that pre-symptomatic infection and possibly transmission seems to be a bit more common than we had thought. In SARS (severe acute respiratory syndrome) in 2003, that almost always didn’t occur. We think that it probably does occur [with COVID-19]. We’re not entirely sure to what extent and for how long people are infectious. It probably is 24–48 hours. That’s a really important thing. It does seem to be more transmissible than SARS in that regard. So, the degree of how we can control it is probably a bit more difficult because of that.

InSight+: What’s the R₀ at the moment? Do we know?

AC: It varies with the context. In general it is thought to be between 2 and 3 still, but at the moment, because of all the control measures, that’s probably well under 1. Having a small number of cases makes it quite hard to work out what it actually might be at the moment.

InSight+: What can we learn from what’s happening, for example, in the US where it all seems to be fairly chaotic and uncontrolled. Does that situation act as a bit of a Petri dish for the rest of the world?

AC: All the big outbreaks in the US are really in three major settings, whether that’s aged care settings, detention facilities, and then, curiously meatworks, where people work quite close together and they often get transported together. Obviously, the context is different in Australia. We don’t have meatworks on the same scale that they do in the US, but it’s probably no coincidence we’ve had an outbreak in the meatworks in Victoria as well.

It really does seem to find the weak spots in lots of different countries. Where people might have missed the message or not understood, or have a disincentive to be tested because they’re casual workers and can’t take time off to get a test. Or maybe they are marginalised for some other reason, or don’t have good access to health care. So, for example, the foreign worker dormitories in Singapore are probably a very good example of those sorts of factors coming together.

When we’re thinking about Australia, they’re the sort of factors that we really need to think about. Where are our vulnerable populations? Where are our weak spots? Obviously, remote Indigenous communities is one of those.

InSight+: Deb, is this thing mutating?

DW: That is an excellent question. There has been a recent study published around some fixed mutations, but all bugs will mutate to a certain extent. One of the difficulties that we have at the moment is standardisation in how we sequence and how we analyse the genome of the virus. And that makes assessing mutations quite challenging.

One of the key things that we really need as a global laboratory community is some consensus on best practice for sequencing the virus and for assessing mutations and reporting on them as well.

One of the things that is a real hallmark of this outbreak is open sharing of scientific data and that was a very early feature. The Chinese investigators released the genome of the virus quite quickly, and what that enabled rapidly was a development of diagnostic assays, which were subsequently rolled out across the globe.

So there has been a lot of work done by regulatory agencies to try and develop frameworks for validating and monitoring the performance of the diagnostic assays. But one could argue that the same principle should be applied to some of the genomic assessments of the virus as well.

The flip side to the open sharing or early sharing of scientific data is that it can sometimes be difficult, particularly for the media, to distinguish between high quality, robust, scientific data and things that may not make it through to high quality, peer reviewed publications.

InSight+: Recently, we’ve heard about cases in children, in the US in particular, presenting with Kawasaki-like illness. The Chief Medical Officer Brendan Murphy has called for more research into this. What do we know about that, Allen?

AC: It’s not entirely clear whether this is Kawasaki disease. There are a number of features that are similar and some of them are actually different. [Something that is] similar is that kids can get a rash. One patient has been described as having some coronary artery involvement, which is characteristic of Kawasaki disease, but equally, it looks a little bit like a quite unusual and severe form of Kawasaki called Kawasaki shock syndrome, which is found in about 5% of the [cases of] Kawasaki disease, so it’s a pretty uncommon disease.

Obviously, it’s not been described in relation to coronaviruses before, but we don’t know what the cause of Kawasaki disease is. The age of patients is different. The average age [of these recent cases] is, I think, over 10 years, and that’s an unusual age for Kawasaki disease.

And then, the last thing is that Kawasaki disease is traditionally described in East Asian populations, particularly Chinese and Japanese, and in the cases that have been described, there are other ethnic minority groups like [African American] and [African Caribbean] children involved. So it’s probably early days to work out if that’s actually a thing.

InSight+: The other thing we need to talk about is vaccines. Is there any news on that front?

AC: There’s a bit going on. There are more than 110 vaccine candidates that have popped up around the world. And obviously, there’s a lot of work going into getting those through. There are still a lot of steps to go. Only a couple are into phase 2 trials to see if they can make antibodies that might be protective.

It’s still early days. We don’t have a good read on how protective they might be and how we would use them and how safe they are, but at least there are things happening in that area.

InSight+: Do you get a sense of the timeline? Are we still looking at 12 months or so?

AC: If you think of all the steps that we need to do – they need to have shown that there are antibodies, that the antibodies are protective. They need to do some sort of field trial to make sure that it doesn’t make it worse and that it’s safe to give and so on. After that, it’s got to be approved by regulators and the program has to be delivered and they have to be manufacturing at scale.

Even 12 months would still be an ambitious timeline.

InSight+: Deb, I know there are diagnostic tests and antibody tests. Are we doing enough of them in Australia?

DW: The testing for SARS-CoV-2 (SARS coronavirus 2), can broadly come under the umbrella of diagnostic testing and it can be nucleic acid testing. That’s the PCR testing that’s related to the swabs that people have up their nose and that’s the gold standard for the acute diagnosis of COVID-19.

Some of the emerging work around antibody testing is the place of serological testing. It’s still finding its feet and there are a lot of complexities around that. Serological tests rely on the detection of specific antiviral antibodies and one of the complexities at the moment is that we don’t really know if the amount or the type of antibody that’s produced is actually protective.

Another challenge has been determining the right antigens to use in the test to maximise the sensitivity of the test, but also minimise cross-reactivity to other coronaviruses. What that means is that the development of high quality serological tests has been much slower than molecular-based diagnostics.

InSight+: Would you rather [have] it that way than the way the US went – privatised the lot and said, “Go for your lives?”

DW: We’re very fortunate here in Australia. We’ve got these regulatory agencies and frameworks in which we operate. Yes, there has been some fast-tracking of diagnostic tests, necessarily so, into the Australian market, but we’ve got enough checks and balances in the system whereby we can monitor the performance of those tests and recall them or modify them as needed.

And we’re building a strong public health infrastructure here around development and testing and deployment.

InSight+: Australia’s response to COVID-19 seems to have been pretty agile. Is that a fair description?

AC: We can look to countries that haven’t responded so well, and we’re certainly very happy that the Australian governments have listened to medical advice. As you know, there are a lot of very experienced people that are in charge of the jurisdictional public health units around the country and have dealt with infectious diseases for a long time. There’s a whole system behind that. They’re getting good expert advice. And that advice has been taken. But again, we don’t know what we don’t know and we all need to be very watchful.

InSight+: Deb, has this pandemic brought about some changes in the way you operate that will stay in place even after this is over? In other words, has there been a silver lining to some of this?

DW: It’s hard to gauge at this point, but it’s really fostering a sense of teamwork in the [laboratory]. I have to say I’m enormously proud of the work that my [laboratory] has done in this regard, but also the [laboratories] across the country. The response has been overwhelming. In terms of being able to scale up testing quickly and put measures in place to do that, to respond to the next pandemic – and there will be one – that sense of preparedness has been very useful in the laboratory.

InSight+: Have either of you got any doubts or worries about the next, say 3 or 4 months?

DW: Managing the sustainability and resilience of the workforce, particularly in relation to testing. We’ve got a pretty fatigued workforce at the moment and I think that is something that we need to be cognisant of.

AC: I don’t think there’s ever been a public health intervention that is a test. Using testing on a population wide scale – where anyone who has symptoms or even doesn’t have symptoms, can get a test – isn’t something we’ve ever tried before. That is a whole level of magnitude more than we’ve done ever for anything else.

It’s very much stretching every part of the supply chain, the workforce and how many swabs you have, the reagents we use to run the test and just having the machines … All of these things haven’t been used in this sort of [way] before.

When this is over, there will probably need to be some thought as to what the best models for doing this are, if this ever happens again. Maybe there are better ways of doing it than to stretch all of the [laboratories] up to the limit.