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24 Apr, 2020 06:21

Labs suffer virus breakouts – pathologist

Viruses, one of the most ancient inhabitants of our planet, have once again proven that we must take them seriously. What is the nature of viruses, and why are they there to mess with us? We asked John Nicholls, clinical professor of pathology at the University of Hong Kong, who’s been studying coronaviruses for 25 years.

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Sophie Shevardnadze: John Nicholls, Clinical Professor in Pathology at the University of Hong Kong, it's really great to have you with us. So much to talk about. Now, Hong Kong was one of the epicentres of SARS epidemic back in 2003, and you were right in the middle of it being one of the key members of the team which actually isolated the virus. Why do you think the world hasn't learned the lessons of it, and we are where we are right now?

John Nicholls: Well, we did learn the lessons in 2003 and we learned them the hard way because wein terms of... We weren't prepared like, I think, none of the world was prepared in 2003 for dealing with such a severe disease. And so the society had to learn about things like social distancing, about the use of the face masks and also for the preparation within hospitals having special wards which could cope with these emerging diseases which were transmissible and which had high mortality. So we learnt the lessons the hard way. So that's why when the outbreak occurred in January this year, we were well prepared. And so it was like, “OK, this one is like SARS again”. So it was Hong Kong, it was “let’s open up the wards, let’s stop the elective admissions, and then we'll just put on the mask again”. And then that seemed to work.

SS: OK. So you're saying that Hong Kong actually drew lessons from SARS and is doing OK. But I'm thinking about the entire world because we did have SARS, and it's kind of a rehearsal for whatever it is that we're having right now...

JN: You see, both Hong Kong and Singapore, because we were both hit hard by SARS in 2003, we were well prepared. And so even though we put in there the mechanisms and we did let other parts of the world know, I think that the problem was still this lack of... People thought it wouldn't happen in their own country. So they looked at Hong Kong and China and in Singapore and even though they saw what was going on, unfortunately, I don't think they were properly prepared for dealing with the virus coming into their own countries. And that's why I think some parts of Europe and in America... that's why they had the more severe disease.

SS: But also, I can't help but notice that actually the quarantine measures themselves in Hong Kong are less strict than [in] Europe, for instance, restaurants are open, right?If I get it correctly. Yet the number of cases and deaths from coronavirus is low compared to the rest of the world...

JN: That's right. You see, we closed the borders very quickly. And also we also instituted quite rapidly . the testing. So because we were able to develop the tests very rapidly, even towards the end of December, we had the tests available. And so there's rapid testing. We are able to have the isolation. And so we are able to keep the numbers well down. So most of the outbreaks which happen in other parts of the world, it's been into where there's been a large concentration of people like on the cruise ships, especially the cruise ships, and also where there's been large meetings or public gatherings. So if we hadn't had those areas, I don't think we'd be in such a bad situation as we are now.

SS: Do you think it would have been worse in Hong Kong if it hadn't lived through SARS? I mean, how much do you think it actually helped the situation today?

JN: Well, I think SARS was also very useful in terms like the treatment methods. You see in SARS, when we found that the patients had such severe lung disease, we were using things like steroids and other things which caused quite a few problems. But in this new outbreak, people learn from that. They learned what therapies were working and what therapies were not working. And so that was actually quite useful. I think we were also a bit lucky because also remember, Hong Kong and Singapore are very compact. And so you only have one central authority which is able to give dogma and give a policy. And so you don't have large states or regions which can actually institute their own policy.

SS: You know, I've read that people of Hong Kong are so used to washing hands or wearing masks and generally being germophobic after SARS. Is that how the whole world is going to be after this pandemic, do you think?

JN: You have a very interesting point because in Hong Kong after SARS, we were, you know, if anybody had a flu or infection, then they'd put on a mask and it wasn't considered any sort of social stigma. It's just, you know, a way of saying, "I've got an illness, a respiratory illness, and I don't want to infect other people". So there's no social stigma about people wearing masks in public. Also, my understanding is that in some of the Western countries there's still a reluctance to put on masks. But in Hong Kong, I don't say they're very obedient but I think they know that by putting on mask, there would be some sense of helping the community and not transmitting. Also, the important aspect about after SARS is that in all of the public facilities there would be hand sanitizers, people would be cleaning lift wells as [well as] elevator buttons. And so, that sort of thing automatically went into effect. Whilst I think other countries have been quite slow to adopt those techniques and realising is that these viruses spread through direct contact and so making sure you have a clean environment. So these are just lessons learned in 2003. And so it was not that much effort to try and put them into effect in the end of January and February.

SS: So is there any vaccine research made on the virus back then, that is of use to science now and scientists?

JN: OK. So it's interesting to think it's only been about three or four months, and we've now learned quite a bit about this virus. When it first started, we weren't all that clear initially about the mode of transmission or how lethal it was. But there's been quite a lot of research and so even now - three, four months down the road, we actually, you know, in our laboratory... You know, we've had the virus been growing there since Chinese New Year, which is the end of January. And so we've been trying to work out what type of cells in the respiratory tract it can infect, what damage it does to cells and also modes of transmission. So, you know, I think within, you know, two or three months, we've actually done both in Hong Kong and also around the world, there've been lots and lots of publications on this virus. But the problem is that the spread of the virus has been faster than the amount of information. I think many people underestimated just how fast this virus would spread from around the world.

SS: We're just getting the latest news: there is another outbreak in China's city of Harbin, a patient has contracted the virus to 78 people. The city has been put on lockdown. Can the second wave be in the way before we're even done with the first wave, I'm thinking right now, reading this news?

JN: So basically Hong Kong went through, you know, - similar to other places - the three waves: the initial one, which were the people coming across the border from China, then the second one was when we had the local transmissions and the third wave was when the government decided to close the borders and they gave about four days notice. And so lots of people came back from… mainly from Europe, especially because they closed down the schools. And so many school kids came back and university students. And those are the ones responsible for that third wave. And so by having the quarantining and the testing at the airport, we've been able to sort of nip that one in the bud. So now when people arrive at the airport, they'll have a test and they'll remain at either at an airport location or in one of the hotels until they're found to be free. And if they're free, they go home for two weeks of home quarantine, if they turn out positive, then they go straight to hospital -  do not pass go, do not collect $200 - where they will be monitored and if necessary, receive treatment. So, by that way, we are basically able to monitor and manage all the new cases very, very rapidly.

SS: We know that the genome of the new coronavirus is very much like SARS virus. Is there any evidence to suggest that those who survived SARS are immune to this COVID-19?

JN: OK. This whole question of immunity is a very challenging one. And what you say, it is right, it is because they are both coronaviruses and they do have a similar genetic makeup in many of their genes. Unfortunately, at this stage, it doesn't look like there'll be much cross-protection with SARS or with some of the other seasonal coronaviruses, because you're probably very much aware that every year there are seasonal coronaviruses which tend to cause very mild disease. And so one of the hopes is that those actually provide some cross-protection. At this stage, I think probably not. But this whole issue of the immunity is one which is evolving, one could say, almost day by day because initially people were thinking once you get it... What we found with SARS is that once you got infected, then you'd get a nice, what we'd call an immune response. And so that could philosophically protect you against re-infection. But what we're finding with this new coronavirus is that it's a very complicated situation and many patients who get mild disease, who don't develop any antibodies. And then even some people we've been screening, they say they can't find the antibodies. So this raises the problem is that, you know, will infection lead to this what's called the herd immunity? The other problem is it that we've got problems with the tests? Because many of the tests, there are about 40, 50 companies which are producing tests to develop antibodies and just last week, the National Academy of Sciences in the US came out with a policy, which they said, unfortunately, many of these tests are not all that great, you know, there are false positives, they cross-react. So I think one of the problems is we have problems both with the diagnosis of the past infection and also some patients apparently don't appear to seroconvert. So the whole concept of immunity is a very challenging one and it's a very confusing one.

SS: Most of the epidemiologists that I've spoken to about COVID-19, and we've done a series of interviews about that, they're saying that we should expect the second wave, but the second wave is going to be less scary and milder. But are we really sure of that? Because I'm thinking Spanish flu, which came like in three waves and the second wave was the most destructive one with the highest mortality rate...

JN: Well, you see, the second wave which happened in 1919, that second wave seemed to be more severe and also was also more associated with secondary bacterial infection. Certainly what we've seen with this COVID is that you're not getting the secondary bacterial infection whilst you saw that with SARS. And so the whole issue about the immunity and unfortunately we can't really compare this with influenza for a number reasons. You see, with influenza we've all been getting flu either through vaccination or natural infection almost every year. So our bodies have actually got a nice history. They've got, you know, 40, 50 [years], depending how old you are, of history, of exposure to an influenza virus. But with this new coronavirus, it looks like we've got no previous history. So there's actually no existing immunity. So it's going to be a challenge to build up the so-called herd immunity. As herd immunity has been based on - people talk about a 60 percent based on what's called this R0, which is how much the virus can transmit from person to person. The problem with the challenge (as we’re supposed to call it now), is that the new estimation is that because of the spread of this virus is that we may need to achieve about 80 percent of the population having the antibodies before we can get proper herd immunity, so that leads to even more challenges. One of the interesting countries which hasn't done the isolation has been Sweden. They've been very laid back and saying, "well, you know, so let everybody get infected and we'll deal with that". But they also put in place a saying that "well, we still recognise is that… instead of the elderly, we call them the vulnerable, is that keep those sort of more isolated and so... and protected. So try and let society get on as much as possible but making sure that those high-risk groups are very much looked after and that, you know, you have ways of making sure that there's proper infection control procedures and people can't visit them unless they wear a mask. So they're probably doing the right thing on that. I say that probably is that a reflection of the disease burden is more a reflection on the health care system and the ability of the health care system to cope with these infections. And that may be number of intensive care beds, the number of ventilators, the access which the population have to hospitals and aspects like that.

SS: So you're saying if every person who got COVID-19, was able to go to the hospital right away, then the mortality rates would drastically be lower than what we're seeing right now?

JN: Well, see, in Hong Kong, anybody who's found to be positive goes to a hospital, even the asymptomatic. And so, you know, there's a couple of friends of mine, they tested positive and they've been in hospital now. I've just got an e-mail from some friend of mine. She's been in the hospital now for 20 days. She's asymptomatic, but she's in hospital.

SS: How do we know that coronavirus gets eliminated from the body completely? For instance, the HPV settles in the cells for good, it may lay low for a long period of time but can potentially cause serious troubles in the future.

JN: Yeah. So, I mean, this is what we found with SARS is that we say, how long does it exist? And see, the way is that people who have been looking at this is by looking at two things, either fragments of what's called the RNA. And so we found this with SARS is that because we didn't have any good antigens or antibodies, is that in patients with SARS, we're finding fragments of the virus RNA in some of the secretions and in stool samples for about sometimes, you know, two months after. So we said, "oh, you know, this virus is existing for a long time". But more than that, I think the better question should be asked is that how much infectious virus is there? Because that's the thing which actually determines is it still replicating and the potential for it to transmit from person to person. And so one of the studies which have been published in the past month or so, have been just looking at the RNA, they haven't been able to do the infectious virus. The reason is because to actually look for infectious virus you have to culture it in the laboratory and that takes time. You need a special laboratory. And most laboratories are not equipped to do that. So I think you might find the RNA exists for quite a period of time, but not necessarily the infectious virus. So when people talk about things like all these patients become reinfected, you know, it could be that they're just finding a bit more RNA after the first test was negative. So I think we always have to look at some of these reports with just a little bit of scepticism.

SS: Well, there is a view which says that when any virus makes it into a living cell, it actually starts to build into the cell's DNA and thus alters the cell and the whole organism subsequently. So if you look at it that way, does that really mean that viruses in a sense are drivers of evolution?

JN: They have, you know, there’s been people who have looked at certainly both bacteria and parasites have been drivers of evolution in... Because people looked at the great apes and some of the chimpanzees and from hundreds of thousand years ago, things like bacteria or viruses or malaria have sort of driven civilization. Because we've only known about viruses for a hundred years we hadn't been able to really go back and see how much they've changed and how much they were able to change evolution. I think there's this talk about, you know, that viruses may talk to one another, like some bacteria. But the evidence for these coronaviruses is not very strong on that.

SS: So we can't learn the language of the viruses in order to eavesdrop and sort of learn how to destroy them?

JN: Yeah, there have been papers with which look at that. However, viruses are really just a long strand of RNA. You know, they don't really have any intelligence. And they're always changing like the influenza viruses - they change from year to year. And then this coronavirus - it's changing a little bit. You're getting about one or two mutations every month. And is that... I don't say natural selection, it's just a way because these… RNA viruses that they always, their proofreading mechanism isn't totally correct. So it's way, it's just... what’s the optimal way...

SS: Can I precise something? Are viruses to you living or non-living things?

JN: To me they are non-living, they are just fragments of genetic material 'cause viruses cannot replicate unless they have another host. So that's why the research, which was done in our laboratory, says if you leave this coronavirus on the surface at 4 degrees Celsius, it can remain intact for about two weeks. But at 56 degrees Celsius, it'll become inactivated after 30 minutes. So by themselves, viruses will sort of become inactivated naturally.

SS: But when we're saying that viruses need a host and if they don't have a host, then they die, how would you explain that COVID-19 virus actually stays on surfaces for days?

JN: OK. So the battle which occurs is that it is, as you mentioned, that so viruses need the host to replicate. So the challenge is if it kills off the cell what's called a cytopathic effect before it can release enough progeny, then you won't get enough virus being released to infect other cells. And that's why this virus is very efficient at transmission. Because the studies which were done in a laboratory show that you can actually replicate quite a lot without killing off the cell. So by the time it has killed the cell it has produced many hundreds and thousands of copies of itself. So that way it can actually replicate and then spread quite to other parts within the respiratory tract before it starts to cause symptoms. That's why this is far more asymptomatic than other viruses. The influenza viruses, for instance, they start killing the cell within one to two days after infection. With this virus it needs about five to six days. So you're basically getting production of viral copies, but the cell remains intact and not destroyed for about five days.

SS: You know, there's a lot of speculation right now in the Western media that the new virus could have escaped from the Chinese Institute of Virology in Wuhan, which researches bat viruses like the coronavirus. China obviously brushed off any of these claims, but could this be true? I mean, can a virus actually escape a lab and cause a pandemic like this?

JN: Well, this happened in 1977. It's basically thought that the H1N1 which emerged and caused the influenza escaped from a... It was either an accidental infection or release from a laboratory in 1977. And then it circulated around the world until 2009. So there have been instances where there has been release of viruses. But about this release of this from Wuhan, that's sort of speculation is, well, outside my pay scale on that. You know, I think the... I'm sorry, I can't comment on that.

SS: Professor, thanks so much for this wonderful insight. It's been such a pleasure talking to you. We wish you all the best in your research endeavours and hope that we'll get to speak again in better times.

JN: Thank you and have a good afternoon

SS: Stay safe. Thank you.