The Joe Walker Podcast - How An Italian Town Conquered Coronavirus - Andrea Crisanti

Episode Date: March 25, 2020

Andrea Crisanti is a Professor of Microbiology at the University of Padua. He is part of the research team that eradicated coronavirus in Vo, a town in northern Italy.Show notesSelected links •Follow Andrea: Website •Johns Hopkins University's coronavirus dashboard •Data on testing by country •Marc Lipsitch's 18 March STAT articleTopics discussed •The Italian crisis. 8:22 •Why has Lombardy become an epicentre of coronavirus? 9:50 •How does the situation in Veneto compare to that in Lombardy? 11:06 •How did Andrea become involved in the Vo experiment? 11:51 •What is the process for identifying infection people in Veneto? 17:20 •What is the R0 for asymptomatic people? 20:25 •What is the strategy employed at Vo? 24:32 •Is there still time for Australia and the US to implement the strategy used at Vo? 25:21 •Does the Vo strategy need to be implemented in full in order to be successful? 28:05 •Why have some Asian countries been better at controlling the virus than Western countries? 28:47 •Is the Vo strategy scalable? 29:43 •How should we think about the prospects of future waves of the virus? 30:34See omnystudio.com/listener for privacy information.

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Here's your host, Joe Walker. Hello there, ladies and gentlemen, boys and girls, Swagman and Swagettes, welcome back to the show. On the 18th of February, 2020, a 38-year-old man, described as a marathon runner, took himself to the emergency room at a hospital in Codogno, a small town in Lombardy. He had what he thought was a severe flu. After declining to be admitted, he headed home. But then, feeling even worse, he returned to the hospital only a few hours later. On the 20th of February, he was sent to intensive care, where he tested positive for COVID-19. This was Italy's patient one. And February had been a very social month for him.

With heavy symptoms, he'd gone to three dinners and played soccer with his team. If a week is a long time in politics, it is a lifetime in pandemics. Seven days after patient one was confirmed, Italy's infections inched over 400 cases, and Nicola Zingaretti, the leader of the governing Democratic Party, posted a picture of himself on social media, cheersing, an aperitivo in Milan. We must not change our habits, he wrote. Our economy is stronger than fear. Let's go out for an aperitivo, a coffee, or to eat a pizza. Fast forward to today. At the time of recording, a little over one month later, Italy has 69,176 confirmed cases of COVID-19 and 6,820 confirmed deaths. It is an epicenter of the pandemic. In its most productive northern

regions, doctors are facing wartime-like triage decisions, and the New York Times reports that the coffins of COVID-19 victims are accumulating in the very churches that have stopped holding funerals for them. But amidst all the chaos and death, there is one little town that stands out as an island of hope and as a data point about how to control this virus. The town is called Vaux. Vaux is in the hills outside of Padua, or if you're more familiar with Venice, about a two and a half hour train ride west of Venice. Vaux is in the region of Veneto, which is adjacent to Lombardy, and Vaux is famous because it recorded Italy's first COVID-19 death on the 21st of February. By the next day, 3% of Vaux's inhabitants were infected, and Vaux was staring down the barrel of disaster. Most of you are by now aware that South Korea

has demonstrated that this virus can be controlled. So how do you solve a problem like Korea? Well, you learn from Vo. Luke Azaya, the president of the Veneto region, sprung into action, pre-empting the national government with his own lockdown. He focused especially on Vo and assigned a team of researchers from the University of Padua, working in combination with the Red government, with his own lockdown. He focused especially on Vaux and assigned a team of researchers from the University of Padua, working in combination with the Red Cross, to lead the epidemiological effort there. The researchers eradicated coronavirus in Vaux in under 14 days. One of those researchers is an infections expert at Imperial College London. He happened to be on sabbatical at the University of Padua when the pandemic began. His name is Andrea Crisanti, and he's our guest. Andrea is a full professor of microbiology at the University of Padua. He's best known for the development of

genetically manipulated mosquitoes to prevent the spread of malaria, and he has over 100 papers published in leading scientific journals like Science and Nature. This conversation with Andrea covers what we can learn from his research in Vogue. It was recorded at about 9am Sydney time on Wednesday the 25th of March. So without much further ado, please enjoy this conversation with Andrea Crisanti. Professor Andrea Crisanti, welcome to the podcast. It's an honor to speak with you. I thought first we could begin by getting a quick overview of what's happening in Italy at the moment. The last time I did a podcast on the coronavirus was about two and a half weeks ago with Unir Bayam. And at that point, global infections had just passed 100,000 people. This morning on Wednesday,

the 25th of March in Sydney, when I checked the Johns Hopkins University dashboard, global infections have now passed 417,000 people. So the virus is certainly spreading quickly. Firstly, just tell us what's happening at the moment in Italy. Well, I think we are facing probably the worst of the epidemics. I think we have around 600 and around 5,600 new cases every day since a week now, in spite of implementing now a kind of nationwide quarantine. Does the nationwide quarantine appear to be working? Well, in Italy, nothing is under percent so not even a quarantine

unfortunately some some factories are still open some activity are still carried out so is I would say it's not yet an under percent quarantine with the total let's say in a standstill situation it's not not that yet and obviously this probably will have an impact for the effect of the spread of the virus. There are people that question whether this is the strict enough. The virus has been particularly bad in Lombardia, a region in the north of Italy. Why was that the case? What you mean particularly bad because too many deaths you mean? It spread rapidly and there were a lot of deaths. Doctors facing wartime-like triage.

It spread rapidly, I agree with you. For people that have never seen Lombardy, although this is a nice place to see, it's a continuous network or of small cities and factories. It's really one of the business core of Europe. And there are 10 million people living there. And every day these 10 million people commute continuously from one small city to the other. And plus Milan is one of the major financial lamp of Europe so it's not surprising that the virus spread so quickly in Lombardy because the whole

is also very well connected with our plane railways so it's it's a place where you see a continuous movement of people coming out. Right now you're in Veneto, which is another northern region adjacent to Lombardy, sitting to its east. Was Veneto as affected as Lombardy by the virus? Yeah, actually a couple of cities in Veneto were the first to be hit by the coronavirus. Yeah, in Veneto, I'm sure you've heard in this small city of Boa, we had the first case of coronavirus infection with a patient that died in hospital

and was diagnosed just before dying. So that was a 77-year-old man, Adriano Trevisan, who passed away on the 21st of February. Now, we need to talk about Vaux because Vaux has been a data point for the correct approach in battling the virus. And you were one of the people who led the project at Vaux. Firstly, I just want to learn how you came to be in that position, Professor Crisante. So, I understand you were on sabbatical at the University of Padua. Yes. How did you find yourself in charge or part of this project at Vaux? Well, as you correctly said, I was in sabbatical in Padua as professor of microbiology.

And so when this first case was reported, the local authorities of the region of Veneto decided to lock down the place. And at the same time, they ordered everybody to be tested for the presence of the virus in the swamp, which was a kind of unprecedented action. In a way, they have created a unique epidemiological setting. As soon as I heard, I talked to the governor of the region of Veneto, the president of the region of Veneto, and I asked if we could conduct a second survey. Actually, I must say it was quite supportive, so we were able to conduct a second survey conducted the second survey there. Now, let me tell you what we learned from the first survey and what we learned from

the second survey. Of course, this is a kind of general observation because we are just about to publish a paper on this. For more detail, we need to wait one month more. On the first occasion, we found that 89 people out of 3,300 were already infected, which is quite a substantial fraction, which was not recognized on time by the Italian authorities. Then when we started to look at the people who were infected, we immediately found out that a large proportion of them were asymptomatic. What percentage? Yeah, now that we have reviewed and we have interviewed everybody again, about 45%.

So in principle, this 45% didn't have any symptom of the disease. No conjunctivitis, no anosmia, no cough, nothing, no fever. They were totally unaware of being infected. Everybody positive for the virus was put under quarantine and isolation. Then, nine days after, we did a second survey and we found eight people that had new infections. Now, all the new infections were asymptomatic, but the most interesting thing is that by identifying everybody, we were able to drop the rate of people infected from 3% to 0.3%, so it's a 90% drop. Then when we clear these other eight people that were put in quarantine, then no more cases of coronavirus were detected

involved since now four weeks, with the exception of one person who was a relative living in the same flat of an infected individual. Now, the most interesting thing about then this new eight case, that three of them were living in the same house with relatives which were asymptomatic. So there is no doubt that they're symptomatic, transmit the disease. So this small little village gave an incredible wealth of information about the transmission of the virus. And also now we are doing a lot of modeling analysis and understand other properties of the virus. But now, if you now compare a ball, which let's say is a closed environment to what happened with the Diamond Princess, which again is a closed environment with about the same number of people, then they follow the completely different

approach. Go after the case, make diagnosis only with symptoms, and I'm sure we all remember that every day, tens of tens of new cases were reported. If they had followed the approach of Voh, test everybody on the first day, they would have identified all the positive, then test few six days after, they would have clear the case from the beginning. So this, I think the diamond princess of Voh, exactly the two extreme of the approach, follow the case from the beginning. So this, I think the diamond princess of all, are exactly the two extremes of the approach, follow the case or follow the virus. Now, if you follow the virus, you're able to clear the spread of infection. If you follow the case, you'll never come out of it. Tell me a little bit more about what happens if somebody finds that they have symptoms.

Do they call a hotline in Veneto? What do they do? Yeah. Now, well, in Italy, usually if somebody thinks they have symptoms, they call this health hotline. They carry out a kind of a questionnaire. If they believe that the patient is in good health, they tell the patient to stay at home and call back in a few days if things get worse. Now, we are changing approach in Veneto. Veneto is leading a new approach, if somebody called the hotline, we'll go there, we do the test, and we look

for increased complexity of, let's say, network of interactions. First we test the family, then we test the friends, and then we test in Hamburg. This is the approach. Because if we assume that these people have respect for the quarantine, as is the case in Italy, then the infection must have been transmitted within this three-circle of network. This is what we're doing. Of course, in Lombardy, probably it's too late to do that. Probably in Lombardy, the only option now is a total lockdown and standstill situation for four or five weeks. That's the only way to come out from that. Okay, so you're scaling up the strategy of contact tracing from Vaux to all of Veneto.

Yes. Well, it will take a while, of course, because we estimated then for the whole Veneto to do this systematically and also include the category of work at risk and vulnerable people. It will take about 20,000 tests per day. For example, we are now also screening people like cashier supermarket. We are screening pharmacists, we are screening, for example, policemen, firemen or public servants. And then we will also include in our screening approach vulnerable people like those that are housed in elderly homes and their staff, because we want to protect these environments. How are COVID-19 tests done? What does the test look like?

The test is a swab to collect the material, and then the swab is analyzed, is processed to extract the nucleic acid of the virus, which is an RNA filament, which is then amplified on selected region and then there is an algorithm that calculated the probability of them being positive. You told me that about 45% of the infected individuals in Vaux were asymptomatic. That seems broadly consistent with the international evidence. I believe the data from China suggests about 30% of their infected people were asymptomatic and the data from Iceland suggests that about 50% of their infected were asymptomatic. I have an important question for you, Professor. What do you believe the R0 for an asymptomatic person to be?

Do you think the R0 for the asymptomatic is greater than 1? We believe that the are not this significant because we have studied the virus copy number load in asymptomatic and non-symptomatic people and we don't see great differences. And of course the symptomatic people have more opportunity to meet other individuals as they move around and they are socially active, whereas symptomatic people, you would assume that they are at home or in a hospital. So let's say the opportunity to transmit the disease is limited to their family members. But about the symptomatic people, actually, the Chinese at the beginning said that they

didn't have any asymptomatic. They always claim that all positive individuals, if they are asymptomatic, they will eventually develop the disease, which is not what we see. So I think I'm surprised that the Chinese have missed the extent and the danger of asymptomatic people. So let me make sure I have this correctly. The viral load is roughly equivalent for symptomatic and asymptomatic people. And although the symptomatic shed more of the virus through, for example, coughing, that is at least partly offset by the fact that the asymptomatic are more social for the precise fact that they don't have symptoms.

So they're still going about living their lives, interacting with other people. Yeah, correct. Have you actually tried to quantify the R0 for the asymptomatic? It's a bit difficult because we don't have enough data because the asymptomatic we have only, for sure in transmission, we have only three now. We have only, on the second survey,

we have only three people that live with a symptomatic infected individual that got symptoms. So the data is a little bit thin on that. But having said that, of these eight, three came from asymptomatic, three came from family with people that had symptoms, and the other two we couldn't trace. So I don't think that there is much difference. I mean, the data doesn't allow to calculate exactly. There are not.

But on this, which is the most informative set of data so far available, it doesn't seem to be a huge difference. If you had to take a guess, Professor, would you say this disease is propelled mostly by super spreaders or mostly by the asymptomatic? I don't think well, the data involved doesn't suggest the presence of super spreader. You think it's more about the... No, also on the basis of the network of interaction, we don't have evidence of a super spreader. Well, occasionally there might be one or two people that infect

four or five individuals and maybe there are others that infect only one or two. But I I think from what we see in Vogue, we don't have a single or two individuals that are the main source of infection. The strategy that you designed in Vogue is broadly consistent with the strategy that's been implemented by countries like South Korea. It appears to involve three core components. Number one, mass testing testing including of the asymptomatic

number two contact tracing and number three enforced quarantine does that accurately describe the approach absolutely absolutely i mean i would add another element that you need to expand your hospital capability because you will have to face an increased number of people that are hospitalized and an increased number of beds in resuscitation units that are being occupied by these severe infections. Now currently Australia is doing quite well in terms of tests performed. This data isn't quite so recent. This is up to the 20th of March. But 113,615 tests had been performed by Australia, which at that point in time placed us fourth

in the world in terms of the total tests performed. And per capita, we came in third, just behind South Korea. Number one is United Arab Emirates. I believe in the last day or two, we've actually surpassed South Korea in tests performed per capita, but somebody can correct me if I'm wrong. However, at the moment in Australia, only the symptomatic can be tested my question for you professor should australia be copying vo's approach of testing for the asymptomatic and is there still time to implement the approach that was so successful in vo yeah of course you cannot test all the symptomatic people because they're

nobody has the ability to test I don't know 25 million people in life exactly those that live in Australia But it definitely the country like Australia has the capability to test Many many people around the single clusters This is what we are. Okay Yeah But if you have two three people in fact that they in aough, you should really lock down the borough and find everybody. Or even if the two, three cases are in the same apartment block

or let's say in the same neighborhood. So it's absolutely impossible to test the whole population, but what we mean when we say asymptomatic testing is we find the people with symptoms, then we trace their contacts, and then we test all of the contacts regardless of whether or not those contacts have symptoms. Correct. That's what we think. Right. Now, do you think the United States has reached the point where it's no longer possible to implement that strategy? Well, the United States, I think, also has another additional problem,

which now will become evident, that I think they have 40 million people that do not have access to health insurance. Now, these people tend not to go to the doctor unless they are very, very ill. So this will form a formidable reservoir of asymptomatic people or people infected with low level of symptoms.

And this will be a big, big problem to deal with. Professor, you mentioned four components to the strategy in Vaux, mass testing, contact tracing, enforced quarantine and scaling up ICU capacity at hospitals. Are any one of these components individually sufficient or do they all need to be implemented in combination? I think you need to implement in combination. I see with great sorrow all the effort that Lombardy has made

to scale up their hospital capacity, but nobody has ever won a battle by making a hospital. And an epidemic is a battle, and the battleground really is on the field, not on the hospital. Why do you think Asian governments have been more successful in getting the virus under control than Western governments thus far? Well, they tend to have a more autocratic regime. This means that in principle the people is more, I would say, well I could use the word obedient. They tend to do what they are told. And of course, the government, they have a lot of room to implement and measure their progressive limit of freedom.

So I think this is the answer, probably. And unfortunately, the limit of freedom is one of the tools that we have to fight the disease. Professor, people are going to listen to this podcast and they're going to say that Vaux is a small town of 3,300 people in the hills outside of Padua with only about one road leading into it. It's very easy to implement the strategy in Vaux that you implemented, but it doesn't mean that it's externally valid

or that it can be scaled up to whole countries. What do you say to those people well no i i in principle i i agree that is uh you can't scale to the whole country but you can identify spots and places that you can isolate around cases that that is what we advocate. You have four or five cases in your neighborhood, or this is where you have to look for the contact and for the others, because they are there for sure. Professor Mark Lipsitch wrote an article for Stat News on the 18th of March. He said, quote, in populations with good ascertainment of symptomatic cases, the number of infections is perhaps double what is observed. In well-tested countries, we can be nearly certain that no population has reached anywhere near half of its people

infected. That means that when each country lets up on control measures, transmission will increase, and the number of cases will grow again. End quote. How should we think about the prospect of further waves of the disease after the initial lockdown period? Well, this is a, again, this is an important point because after the lockdown people, in the lockdown time yeah and the lockdown time you have to use a metric to lift this measure no of course people may think well if we if we see that the case dramatically degrees maybe this is the right moment to start to be more lenient but I would disagree with that I think

the time where the cases start to decrease, you really need to be much more aggressive with active surveillance. Otherwise, you will likely to have a rebound. Professor, I'm all out of questions, but I just wanted to ask finally, how are you? Fine. So far, I'm okay of course this is a question that we ask every time ourselves yeah that's right well it's 11 44 p.m where you are in padua thank you so much for your time i'll let you get some rest now be well okay thank you very much i your time. I'll let you get some rest now. Be well. Okay. Thank you very much. I hope you enjoyed it. Okay. Bye. Ciao, ciao.

Thank you so much for listening. I hope you learned as much in that conversation as I did. For links and notes to everything discussed, you can find those on my website, www.josephnoelwalker.com. That's my full name, J-O-S-E-P-H-N-O-E-L-W-A-L-K-E-R.com. You can also find me on Twitter. My handle is at josephnwalker. Until next time, thank you for listening and be well. Ciao.