COVID-19: Nearly one year on, what do we know?

Andreas Suhrbier:
Hey.

Clare Blake:
Over the recent years, we’ve had, SARS and MERS have appeared, but nothing really compared to COVID-19, Andreas. Was this a surprise?

Andreas Suhrbier:
Yes. Clearly, nobody can predict such things. So many people, including myself, are very surprised. Perhaps a better question is that, should we be surprised? We’ve had outbreaks of Ebola, Chikungunya, Nipah, West Nile, Zika, SARS1. These things seem to be a fairly regular occurrence on the planet. There’s more humans on the planet. We travel a lot further. We destroy the ecosystem. We have climate change. It’s perhaps not surprising that these sort of things are likely to appear.

Clare Blake:
So the surprise is that it didn’t happen before this?

Andreas Suhrbier:
Well, I think it has happened to a small extent for all those virus epidemics that I mentioned before, perhaps not as severe as COVID-19 is, but certainly these kinds of epidemics are certainly appearing on a regular basis.

Clare Blake:
When I say COVID-19, that’s not the name of the virus?

Andreas Suhrbier:
No, it’s slightly confusing. The virus is called severe acute respiratory syndrome coronavirus 2. That’s the name of the virus, SARS-CoV-2. The disease is called coronavirus disease 2019. In other words, COVID-19. So yes, slightly weird nomenclature and it’s taken us a little while to work out what all that means.

Clare Blake:
Can we say for sure now exactly where it came from?

Andreas Suhrbier:
We can never really be sure about these things. I think most of the folks now believe that this virus came from a wet market where wild animals, wild-caught animals, are caged and stressed and treated really very badly and probably end up with lots of virus infections emerging, because they’re in very bad conditions. And in these markets, all kinds of wild animals are sold. And we probably now think bats are a likely origin for this virus. Perhaps also pangolins where there’s a reasonably large illegal trade in these animals. But the two closest viruses to the one that [is] infecting humans are found in bats and pangolins.

Clare Blake:
Are any of those viruses the same as this, in that some people have no symptoms and yet some people get horrific symptoms?

Andreas Suhrbier:
The notion that a virus will always give you the same disease outcome is not true for most viruses. I mean, let’s take Ross River. About half of the people that get infected with Ross River have no idea they’re infected. Whereas other people get quite sick. Although, of course nobody dies of Ross River. So this large range of symptoms, all the way from no symptoms, all the way to dying is not entirely unusual and it depends on a number of factors. For coronavirus, we think the dose of virus that you end up with is a really critical factor here. If you get a large dose of virus, then you’re going to get sicker than if you get a small dose of virus, that basically your immune system is overwhelmed by the vast amount of virus, so it’s very difficult for you to avoid being severely sick or dying. And of course that’s why face masks are so useful. They may not prevent you from being infected, but they will reduce the dose and therefore, hopefully, reduce your chance of getting a severe disease. And other factors also come into play, like co-morbidities, other things that you might be suffering from like hypertension or some form of immune-suppression or heart disease and perhaps obesity. And these make a big difference to how likely it is that your immune system can fight off this virus without you becoming too critically ill.

Clare Blake:
What happens in the body when somebody is infected?

Andreas Suhrbier:
We think that the virus comes in through the nose, the mouth, starts replicating up there in the upper respiratory tract and then travels down into the lungs right down at the bottom of the lungs and causes a huge so-called cytokine storm, which on one level that’s trying to stop you from dying and on the other side, it causes a massive inflammatory response. And then you get something called acute respiratory distress syndrome or ARDS, which is what most people ultimately die of.

Clare Blake:
You talked about the dose being relative to the symptoms before. What about the people who get infected and then they’re okay for a week or so, and then deteriorate rapidly?

Andreas Suhrbier:
That’s a slightly strange story. And I’m not really sure I have a good answer for that because I don’t really believe that’s the experience that the clinicians are describing, in general terms. You are infected. After about two to five days, you are infectious. In other words, you can then after that period of time, as little as two days, you can then pass on the virus to the next person. Around about day 10 post-infection, a serious illness usually starts around about then. And death is then about day 15, day 30 post-infection. So that’s the kind of timeframe that clinicians have been describing.

Clare Blake:
Some people are left with long-term effects. And is that common or uncommon for a respiratory response, respiratory disease?

Andreas Suhrbier:
Yeah, that’s a big question. So let’s just break that down a little bit. I mean, there’s one thing that’s for sure is that people who have nominally recovered from COVID-19 spend a long time before they’re really well. In the US, these guys are being called the long-haulers. It’s not terribly uncommon for a severe viral illness to cause long-term effects. I mean, it takes a long time for you to really feel 100 per cent again. Exactly what is going on there is not entirely clear. I mean, people talk about post-viral syndrome and other issues, but there may actually be some really serious sequelae. There may be some actual damage, some actual lung damage that doesn’t recover, some other damage in the body that doesn’t recover well. So I think we’re not quite clear at this stage to what extent those long-term sequelae are permanent or how long they will actually last.

Clare Blake:
What’s a sequelae, Andreas?

Andreas Suhrbier:
A sequelae is a consequence of the disease. So a good example for instance, is a sequelae of Ross River virus, which we know well in Queensland is that you get very depressed. You can’t work, your joints hurt, and some people just end up being really quite depressed for quite some period of time. So depression is therefore a sequelae of Ross River. You don’t have the disease anymore, but you’ve developed a sort of depressive illness afterwards.

Clare Blake:
Oh, as if you didn’t have enough with Ross River fever. That seems very…

Andreas Suhrbier:
Exactly, I mean, but that’s not uncommon. People with severe injuries, they end up with quite… get to be quite sick afterwards and mentally ill. So that’s not a difficult concept to understand. But for coronavirus, we don’t really know all of it at this stage, but there’s probably going to be more and more research into this. And I think that’s an area where a lot of people would like to get some answers. What are the long-term sequelae of coronavirus and what do we need to do for those patients in particular?

Clare Blake:
That’s going to be one of the new words that we’ve learned. We’ve learned PPE, PC3 and sequelae will be, I guess, a little further down the track. There are suggestions that the rates of Parkinson’s disease may go up in the coming years, which also happened after the Spanish flu outbreak. How do these viruses cause Parkinson’s?

Andreas Suhrbier:
Right, this is a very recent study and I’m not really a neurologist, so I can’t really make good comments on exactly whether that study is now well accepted internationally. This is one of the sequelae, of course, is potentially Parkinson’s disease and that’s something we need to map out to see whether that’s true in reality. After the Spanish flu, there was also a report that Parkinson’s disease went up, but there’s probably going to be all kinds of other sequelae that are going to go up as well after this. There is some notion in the literature that there will be other problems, brain problems, brain infection has been thought possible. And some people even think that the acute respiratory disease syndrome actually has some neuropathic origin in part. In other words, that there are other neurological complications that are part of the long-term spectrum of sequelae. Again, a lot of work needs to be done to really map all that stuff out and really clarify what’s cause and effect.

Clare Blake:
I hope the people who think wearing a mask is an invasion of their personal liberties are listening to this Andreas.

Andreas Suhrbier:
Well, I mean the really telling data is that the people that tend to die quickly are doctors and they’re exposed, and nurses who are exposed to high doses of the virus, and that’s what causes, in many cases, the reason why they have a lethal outcome. So wearing a mask could save your life.

Clare Blake:
There’s been some debate also around whether or not the virus can be spread via aerosol transmission. Is the jury out on that?

Andreas Suhrbier:
Right, this is a very large debate. And this is a new field for me, as it is for many people and we’re not entirely clear how important aerosols are in this epidemic. In other words, if you got rid of aerosol transmission completely, would we still have the same epidemic? Not clear. Is it possible to infect somebody with aerosols? Extremely likely to be true. There are things called aerosol-generating procedures in hospitals, which are considered to be high-risk procedures, and intubation and ventilators and stuff are likely to be producing aerosols, which are likely to be a risk. Then there’s a recent phrase that’s come up called aerosol-generating behaviors. I suppose the archetypal concept there is people singing in a choir infecting each other because singing produces aerosols. So we’re not quite there yet. The jury is still out on exactly how important aerosol transmission actually is in the grand scheme of things. It most probably can occur and in certain settings, it’s probably a much higher risk than others.

Clare Blake:
We should clarify aerosols too. So that’s when you breathe out?

Andreas Suhrbier:
Oh god, defining aerosols is a real problem. Masks really prevent droplet transmission. Staying 1.5 metres away from somebody also helps you not get a droplet because droplets are bigger water particles that fall to the ground and masks will also prevent them getting into your mouth and nose. Aerosols are generally felt to be things that are suspended in the air, but they can be a vast range of different sizes. So it’s quite difficult to know how to define them. But essentially what we mean by that is airborne transmission. They float around. They’re small enough and light enough that they can be blown around in the wind sort of thing, rather than falling to the ground.

Clare Blake:
When we talk about the new language that we’re learning – aerosols is another one of them – we’ve got PPE and also PC3 lab. When people talk to us about us having the virus or people working with the virus, why do you need a PC3 lab? And what is it?

Andreas Suhrbier:
The international definition of PC3 is actually a bit easier to understand – it’s called Biosafety Level 3. People working inside a PC3 facility undertake a huge amount of training, and protocols, and procedures, engineering, and behavior to make absolutely as sure as we humanly can be sure that they are not going to be infected by the virus they’re working on. Now, when you’re working inside one of these laboratories, you’re growing very large amounts of virus in vitro – much larger amounts of virus than you would encounter out there in the real world – because we are trying to do experiments on these viruses so we need a lot of them. Of course, that increases the risk and therefore we have these really quite extensive procedures. I mean, our facility here is state-of-the-art. We’ve spent $20 million building it initially and we spend millions a year refurbishing it and making it better, and ensuring that the risk to the people working in there, and of course people outside, is kept to an absolute minimum.

Clare Blake:
What are you focusing on?

Andreas Suhrbier:
With this PC3 [laboratory], we decided back [in] early 2020 when it became clear this was going to be a pretty serious problem, we decided to refurbish the PC3 facility that we have. We work in there with other diseases like chikungunya, and HIV, and malaria, and dengue. So we decided to take one of those suites that we have in there and completely refurbish it for SARS-CoV-2 work. That’s taken us a few months because there’s an awful lot of paperwork and equipment and other regulatory issues you have to go through and that’s been a huge undertaking for us. And we’ve been very grateful for support from people who’ve donated money to QIMR, like Clive Berghofer and Lyn Brazil, who’ve made that possible because this is not a cheap endeavor by any stretch of the imagination. In one day I spent $50 000 just buying essential new equipment that we needed to be able to do this kind of research in a very safe environment.

Clare Blake:
We’ve got different arms of research going on here. What’s yours?

Andreas Suhrbier:
My research at the moment, we’re actually in the process of signing a whole series of deals with a range of biotech companies, pharmaceutical industry, and little groups around Australia and internationally who have come up with their own interesting ideas for intervening with this disease. They’re vaccine manufacturers, diagnostic people, people who are trying to get rid of contamination of aerosols and people interested in producing better disinfectants…[we’re] trying very hard to allow this facility to get research up and rolling in Australia so that we have a hub where these companies can come and test out their ideas. We’ve also got a series of academic collaborators who also have some really interesting ideas that we’re testing out to see whether or not we can show that what they’re trying to do is actually working, and so they can go off and raise more money and then come back and perhaps get to the next stage of development.

Clare Blake:
This is quite unique. All the scientists all over the world are collaborating at the moment and it’s an urgent need. Are you feeling the weight of all that pressure?

Andreas Suhrbier:
I would have to say that we’ve got now, what a million dead people from this disease? I think in my professional career, I’ve never been as stressed as I have over these last few months trying to get this up and rolling. There are obviously constant problems with assuring our funding. For me, it’s been a very steep learning curve.

Clare Blake:
What’s your feeling about a successful vaccine?

Andreas Suhrbier:
Yeah, look this has been a big debate. What does a perfect vaccine look like? And what does the reality look like? I think we can perhaps ask what does successful vaccine actually mean? One might be reasonably comfortable in saying that a vaccine will protect you from dying. A vaccine might even protect you from being seriously ill. That’s perhaps likely from what we see. But then the next question is, would a vaccine protect you from being infected and passing on the infection to somebody else? And that’s where we are not really quite that clear. I mean, this virus can enter your respiratory tract and two days later you have enough virus to pass it onto somebody else. Is that enough time for a vaccine to really kick in and get rid of that virus before it spreads to the next person? Lots of people think that that may not be feasible. So in other words, the vaccine will perhaps not be able to prevent you from being infected and from spreading the virus, and we’ll just have to wait and see.

Clare Blake:
How long does it take the immune system to respond?

Andreas Suhrbier: 
Well, that’s a difficult question because it depends exactly on the disease and the virus and the load and so it’s not exactly an easy answer… And it also depends where the virus is replicating. So for coronavirus it’s replicating in the nose and upper respiratory tract where it’s actually quite hard for the immune system to get at it. So the immune system will be pretty active in stopping your lungs from getting filled up with virus, that’s probably likely. But is it going to stop that upper respiratory tract infection? And that’s really quite a difficult place for an immune system to get to, [to] get working. And we don’t really know that answer yet. There’s hope there but I think several people have cast doubt on the notion that we can make a vaccine these days that would actually protect you from infection in the upper respiratory tract and nasal turbinate areas.

Clare Blake:
Your nose and mouth aren’t right in the middle of your bloodstream…

Andreas Suhrbier:
Well, they’re outside your body. Pretty hard to attack things that are outside your body. I mean, they’re right on the surface, on the mucosal surface. So maybe it can do something there, but in the past it’s been very hard to produce good immune responses at mucosal surfaces and we know that from past experience, with the whole range of different vaccines. So are we likely to achieve that with a current batch of vaccines? Don’t know. I mean, there’s going to be improvements. I mean the first vaccine off the rank probably won’t be the best one. So over the years, these vaccines are likely to be improved and maybe eventually we’ll get there.

Clare Blake:
So clever to evolve, to enter a space where the immune system isn’t at its peak. Do you find the more you study the viruses that you get an incredible respect? This is a thing that can’t even survive outside the human body yet it just can wreak havoc.

Andreas Suhrbier:
Yeah. Well, that’s why I’m a scientist. I’m always amazed and astounded by how nature operates and works and it’s my job to try and shine a little bit of light onto that when I can. But yeah, look the way in which these things operate, it’s astounding really how little we know as a human race in terms of how these things work and how long it takes us to actually work out what is going on. It’s not a… These are hard sums. They really are hard sums. They’re not easy to quickly understand. And it takes an awful lot of effort by an awful lot of people to get some kind of clarity of thought. And indeed, during that process, we get continuously surprised about what the natural world can and can’t do.

Clare Blake:
Very clever, but could that have been made in the laboratory? Is there any truth to that?

Andreas Suhrbier: 
Right. This has been presented to lots of different agencies around the world and the sequences of this virus [are] publicly available. All the scientists in the world can look at it, and look, essentially, there’s no evidence in there that somebody has been tinkering around with the virus to make it into what we have today. We have bat viruses, pangolin viruses that look very similar to this. And the whole series of changes from them to the current one looks just like natural evolution that we know and understand to some extent. So, the evidence that this was artificially constructed just isn’t there. And we’ve had millions of eyes on these sequences and nobody’s come up with any cogent evidence really that these were man-made or constructed in some laboratory under nefarious purposes. So it’s just extremely unlikely and really a bit of magical thinking in some sense that we’re actually good enough as scientists to be able to do this stuff. It takes us so long to work out one of amino acid chain in a virus actually does or means or what the implications for that in the human disease population actually are… In my field chikungunya, one mutation, there’s over 300 publications on one mutation and we still don’t really know what it does. So this notion that there’s some really brainy people somewhere that know exactly how to do this and create the perfect monster virus, it’s just magical thinking.

Clare Blake:
Thank goodness we can put that conspiracy theory to bed, Andreas. That is fantastic. If you’d like some more information about Professor Andreas Suhrbier’s work and any of our research go to qimrberghofer.edu.au. Thanks so much Andreas. That was great.

Andreas Suhrbier:
Thank you.