World-class epidemiologist on Greek coronavirus A-team studies challenges, possible second wave

Magiorkinis is studying the evolution of the virus in order to estimate whether antibodies developed during the first wave of the epidemic will be sufficiently active during a potential second wave.

By George Gilson

During Greece’s decade-long economic depression in which 25 percent of GDP was lost and the harsh austerity imposed by creditors broke the back of society, much was written about the biggest collateral damage wrought by the financial crisis.

The resulting brain drain led about 500,000 mostly young and educated Greeks to emigrate, a large percentage of which are expected to remain abroad even after economic normalcy returns at some as yet undetermined point in the future.

The mass exodus included thousands of well-trained doctors and medical professionals who found their niche in European and other countries where they landed well-paid jobs and gained recognition, something that Greece because of a variety of reasons never offered its doctors and scientists even long before the country’s economic collapse.

In this bleak terrain there have been bright exceptions albeit few who went against the tide to return to their homeland to continue their professional work and research and contribute to their country’s long and arduous road to reconstruction.

One such is Athens University Assistant Professor of Hygiene and Epidemiology Gkikas Magiorkinis.

Along with his post as a researcher and lecturer at Oxford (2012-2017) Magiorkinis gained international acclaim for his groundbreaking work on the evolutionary rate and global spread of Hepatitis C (which affects 130-180mn people worldwide) and is well known for his work on the spread of HIV as well.

His most important accomplishments are in the fields of the global epidemiology of and history of viruses, viral transmission and policy in drug users, and endogenous retroviruses. A stellar ten-page CV is packed with the top prizes in his field (including the European Commission, the European Council and the Academy of Athens) fellowships in top UK scientific societies, membership on the editorial boards of world-class scientific journals, and about 1.5mn euros in scientific research grants.

Today Magiorkinis sits on the 19-member scientific council – in which he was a staunch supporter of early closure of schools nationwide -that advises Prime Minister Kyriakos Mitsotakis and the government on the management of the coronavirus epidemic.

The government’s swift action on the advice of the committee in imposing restrictive measures and a lockdown and its success in rapidly slowing the transmission of coronavirus and flattening the curve – even as Italy and Spain suffered unspeakable tragedy -has earned Greece strong praise from the international media and scientific community.

Like all those who have reached the top of their fields on their merits, the soft-spoken scientist has an uncanny ability to explain the most complex and baffling scientific issues in a simple and comprehensible manner.

In a full-length interview with tovima.gr, in.gr, and tanea.gr, Magiorkinis touches on the huge challenges in containing the virus – regarding which he is focusing his research on asymptomatic carriers – tracking its behaviour, and exploring ways to defeat it.

What prompted you to leave a brilliant career at a major research university like Oxford and in the UK more broadly to return to Greece?
I completed my medical training at Athens University in February, 2010, and then joined the army for my obligatory service. Soon after my military service I took my first postdoctoral research post in Oxford in November 2010 funded by a Wellcome Trust Grant to Robert Belshaw.

I then took my first independently funded fellowship as a Marie Curie Research Fellow funded by the European Commission in April, 2012.

In August 2013 I received my first major independent funding as a Clinician Scientist Fellow funded by the MRC allowing me to start my own independent group, while at the same time I was a Consultant in Medical Virology at the Virus Reference Department, Colindale, London.

I moved back to Greece to take up a tenure-track Lecturer position in the Department of Hygiene, Epidemiology and Medical Statistics in May 2017.

You are one of the world’s well known epidemiologists. Could you tell us a bit about the research subjects that you have focused on and what have been the milestones in your research?

My research is classified into three categories. These are the global epidemiology of viruses and their history, viral transmission and policy in drug users, and endogenous retroviruses. Amongst the notable findings of my research are how HCV spread around the globe for which I received the Marie Curie Prize for the Most Promising Research Talent from the European Commission and the Prize for Medical Sciences from the Academy of Athens.

In addition I have conducted research on how an ancient retrovirus hidden in our genomes causes addiction.

What do you think the average person around the world today understands about what is going on with the coronavirus pandemic? How well do they understand it? Do they have an idea of where this is going?

I think that no one knows where this is going. Only a bunch of people can make some predictions. I think it depends on the part of the world and on the accuracy of the information they are getting from their government and if the media is accurate I think people are well-informed and they are worried.

Yet there are places like some parts of Russia for example where I think people do not know what is going on at all. I think the vast majority of the population of the planet does not really know what’s happening.

You are working with professor Richard Tedder on reserach regarding Covid-19 antibodies. Could you tell us a bit about that?

I am collaborating with Professor Richard Tedder from Imperial College on the development of methods evaluating antibody responses against SARS-CoV-2. The aims of this work is to study on the population level the immune responses as well as estimate the number of people that got infected with SARS-CoV-2, but also evaluate the antibodies against SARS-CoV-2 from patients that recovered.

The latter would help identify the best donors for convalescent plasma which can be used to support patients with severe Covid-19. My role on the project is to study the evolution of the virus and estimate whether antibodies developed during the first wave of the epidemic will be sufficiently active during a potential second wave.

You are on the 19-member scientific committee which as you told me previously takes decisions with a majority vote. What are the various fields of medical specialisation of the members and what have been the toughest decisions and dilemmas that the committee has faced?

Fields of medical specialisation include infectious disease specialists, microbiologists, and epidemiologists. I think the toughest decision has been the closure of schools as this decision affects a large part of the society and would eventually trigger more decisions to contain the epidemic. Luckily, these decisions were made on time

Do you think in some cases the available information and data is not being faithfully reported by governments?

I don’t think that people are hiding data in Europe. There were some concerns about what’s happening in China. There are also concerns about what is happening in Russia. I think there was an issue with communicating the strategy in the UK. I don’t think people were informed about the number of people that would die with the herd immunity strategy.

Did they in fact at first apply the herd immunity strategy?

There were people, mathematical modelers, saying that the impact was going to be severe and secondly that if they would go to a lockdown when they lift the lockdown the results would be the same but the economy would have major issues. So there were people saying let’s just get over with it and keep the economy safe. That was the main discussion that was going on. But no one ever told them what that actually meant in terms of the number of deaths and what the stress on the health system would be.

It has been reported that if countries took no measures then the global death toll would be about 1.8 million. Does that sound about right?

I would say even more but 1.8 million would mean that around 100 million people would get infected and I would say that is a conservative estimate. If 1.8 million would die [with no distancing measures] in three months that would be a tremendous number.

The Hong Kong flu in 1968 and 1969 killed an estimated one million people. How does Covid-19 differ from that and how was that crisis handled by the global community?

The most deadly pandemic was the Spanish flu that killed 50 million people in a couple of years. From 1918 until the late 1970’s we did not have anti-viral treatment and we did not have globalisation. Nevertheless, two million people in a couple of years is an entirely different story than two million people in three or four months. It has to do with how fast something happens. The dimension that we are using when we are speaking about mortality is how fast this happens and sometimes people don’t keep this in mind. You might get a billion deaths but if you have it in 100 years that’s a different thing than two million in two months.

One must keep in mind the time dimension, so when with the Spanish flu we had 50 million deaths in two years that was a hell of a lot. One million deaths in the pandemic of the late 1960s were actually over two years. Of course it’s a lot of people but it’s not like having two million deaths in two months.

What is the level of cooperation globally between researchers and scientists who are working on how to handle this right now?

I think this pandemic has the fastest data release that open source ever experienced, so the genome of the virus was released within the first ten days since the realisation of the pandemic and that was facilitated because there was already a culture of open source and data sharing in the scientific community that has been going on for at least three or four years.

It has matured a lot. We can also see people doing real-time analysis on the data that probably will be released later as research papers. So they are releasing papers at pre-print even if they are about to submit them as full papers in different journals, and then we have the journals releasing published peer-reviewed papers on open source. We are getting genetic data really, really fast. All of these studies are becoming part of the global scientific community. We have experienced the fastest data sharing, research sharing, and idea sharing and support than we have ever seen before.

That’s the positive side of globalisation. The negative side is the biological one as the virus moved extremely quickly to almost all countries on the planet. Is that rate of spread something that one would have ever expected before or is it a total surprise that it spread that quickly?

We had a similar situation back in 2003 with SARS and I recall my mentor Richard Tedder saying to the BBC at that time that the planet has become a global village and that a virus that starts in Asia becomes a problem in the developed world in countries like Canada. That is what happened with SARS. Around 800 people died. That virus, however, was not as transmissible. It was more lethal but less transmissible.

What determines the degree of transmissibility of a virus?

It has to do with the anatomical distribution of the target where the virus proliferates, whether the virus can proliferate in the eyes, the nose, and the mouth. It’s the upper respiratory tract that makes the virus more transmissible. If the virus needs to go deep into the lungs to proliferate then it has to travel all the way. It’s very difficult to go deep into the lungs, but if it is there it causes a very lethal result. So there’s an exchange between transmissibility and pathogenicity.

Right now coronavirus affects the upper respiratory tract. How probable is a mutation that would affect the lower respiratory tract?
It also affects the lower respiratory tract but to a lesser extent. If it evolves into becoming more lethal and if it proliferates only in the deep lung it will become less transmissible, so it is an evolutionary disadvantage for the virus to go deep into the lungs. Even if it happens it’s not selected by natural selection.

Why is this virus so strong and so far invincible? What biologically makes it so hard to beat?

There is one specific characteristic that epidemiologists fear and that is it resting quietly in the system. If you cannot identify someone as having it easily with standard medical practice then these people walk among us and transmit it freely and it is very difficult to isolate cases and to contain.

What about the cases that are being treated in hospital? Why is it so difficult to beat?

The fact is that with almost all viral infections unless you have an effective anti-viral treatment early on and it develops into pneumonia it’s difficult to treat later. It’s not that the virus is invincible or harder than influenza -it has the same difficulty as with influenza when things go wrong but with influenza we have an anti-viral treatment and if we provide it early on we get better results. We still get deaths from influenza. I’m just saying that for a small proportion of people it will go wrong and all the medical advances that we have now could not change that.

We have two processes going on right now – researchers trying to come up with an effective and targeted anti-viral treatment and clinical doctors who are trying combinations of pre-existing medicines. How are the two processes intertwined?

The anti-viral treatments that are being tested are forcive ones, however to get a mass production of them and know that we can use them in a large part of the population it will take time.

What medicines are being used now and what were they used for before this?

There was one that was designed for the Ebola virus – remdesivir – which is being put to clinical trials. It’s a very new drug that has not undergone trials before and they see that it has a result in RNA viruses so they said let’s go and do clinical trials for corona.

Doctor Anthony Fauci who advises the US government has projected it will take 12-18 months to develop a vaccine that is safe for humans. Does that sound about right to you?

Trials take a long time and that is the reason for the long delay until you have a market-produced vaccine and put it in global circulation. The difficulty is in the clinical trial. A volunteer will take a vaccine today and maybe one month later and this needs to be in an environment that has sufficient exposure to the coronavirus. At the same time, the same patient needs to be informed to take precautions for not getting exposed to the coronavirus because that would be unethical.

So depending on where the vaccinated volunteers are and how long it will take to have sufficient exposure to infected people in order to evaluate effectiveness between the vaccine and the placebo, this could take a lot of time. That’s why the guesstimates are between 12 and 18 months.

There has been a discussion that maybe the solution to shorten this time would be to have another type of trial where people get vaccinated but then they get exposed on purpose. This has happened with salmonella. There was a clinical trial for salmonella at Oxford where people were purposely getting exposed and also using placebo, so it has been tested before.

How does medical ethics view that?

Well for salmonella we have antibiotics and we actually minimise or eliminate the death rate. For a clinical trial like this we don’t have a sufficient anti-viral agent that we know could eliminate deaths for someone who was getting infected, so that would be unethical. I’m not sure if it is sufficiently ethical to do that.

Is self-isolation and distancing the only protection that people have right now?

The only protection that we have is standard hygiene, behaviour change by keeping a distance, and at the same time not to touching our face, mouth, nose, and eyes.

How does simple soap kill the virus?

Soap is used for all bugs, and only a couple of them are resistant, but almost all viruses are sensitive to soap because they are very fragile. The only thing the soap does is to remove the viruses from our skin and at the same time destroys the surrounding of the virus that is made of lipid. It both kills it and washes it away.

As a researcher in epidemiology, as far as this virus goes what is the problem you would most like to tackle and find a solution for?

The research question that I’m most interested in is how the virus spreads in the social network, which contacts are actually the mostdangerous and which people will transmit it. Some people will spread a lot and some not at all. How can we find these people who transmit a lot? We have coined such patients as super- srpeaders and theory predicts that if these patients get isolated, we can effectively control the epidemic. I am working on fast identification and isolation of Covid-19 super -spreaders.

Until now the vast majority of cases – but by no means exclusively – involve people let’s say over 60-years-old and people with serious underlying medical conditions. What is it that would change that and motivate younger people to take extra precautions when right now they see that very few of them are dying from it?

It’s the same problem that we find with every patient, especially the young ones throughout treatment. You get a young patient and you try to give them treatment. You can see that it’s very difficult unless they understand that it’s a matter of life or death. It’s very difficult to convince people to stop smoking and to stop drinking alcohol and of course it’s very difficult to convince people to stay home because this will save the lives other people. It’s a problem in medicine and the only way to approach it is through the social networks and television to try to convince them that this is their obligation to society but it’s very difficult.

Has Greece been doing a good job in the communications aspect of this?

I think the communication from the state and from other people has been very efficient. I don’t think there’s a person in Greece who hasn’t heard about the virus, what they need to do, why they should stay at home and so forth. Of course there are some minority populations like the Roma or people without shelter that are hard-to-reach populations. I think the state has been trying to communicate the message to them as well.

What about people in various countries who are uninsured and do not have access to healthcare, can’t that seriously undermine any containment effort?

You can’t have an epidemic policy without healthcare and that was the situation with China. You know China does not have a public health system. When the epidemic started the government picked up the tab and said that I’m going to pay for the hospitalisation of people with coronavirus. I think this is the only policy that can work. You cannot do anything else.

How is this pandemic affecting Africa? What is the spread there and the means to deal with it?

The fact is that we don’t know. People have been saying that there might not be a significant spread. The fact is that people in Africa have much more severe problems to cope with – HIV, malaria, cholera, sometimes a lack of clean water, and a high mortality rate in births. So they have a lot of other problems. My feeling is that it will cause stress but it will likely be less than the stress on the health system from diseases that they already have.

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