Not a board game
Tony Allen-Mills ,of London’s Sunday Times, speaks to scientists about the progression of Covid-19, the best response to it by different countries, and what a vaccine will mean.
Among the presents around Peter Openshaw’s Christmas tree 12 weeks ago was a strategy board game named Pandemic. Players take the roles of disease-fighting specialists seeking cures for plagues before they spin out of control. You win the game by ‘‘saving humanity’’.
A few days later the game turned real for Openshaw, 65, who is professor of experimental medicine at Imperial College London (ICL) and one of Britain’s foremost specialists on the behaviour of deadly viruses.
He had bought the Pandemic game for his son as a joke, but on checking Twitter after Christmas, he spotted a string of alarming messages about a mystery outbreak of viral pneumonia in the Chinese city of Wuhan.
Peter Horby, an Oxford University expert on infectious diseases, tweeted that the outbreak was ‘‘one to watch’’. Sir Jeremy Farrar, director of the Wellcome Trust research charity, added that ‘‘any cluster of severe respiratory infections (is) a real worry’’.
As luck would have it, Openshaw’s ICL research group was working at that moment on a question that would suddenly become central to the fight against Covid-19, the newly identified coronavirus disease that is rapidly turning into one of the most destructive health crises of the modern age.
‘‘Our main focus has been on trying to work out why people have such variable effects when struck by these viruses,’’ Openshaw said. ‘‘We have been infecting normal adult volunteers with different viruses, particularly the pandemic influenza and common cold viruses, trying to find out why some people are not affected at all, others have an infection but it’s not very symptomatic and some show clear symptoms of infection.’’
Within days, Openshaw was spending ‘‘all my waking and sleeping hours’’ gathering information on the new coronavirus. In addition to his ICL research work, he is one of the leading figures in a littleknown network of British epidemiologists who have been quietly preparing for another pandemic since the swine flu outbreak of 2009-10.
Set up with the help of the Wellcome Trust and the Medical Research Council, the group known as Isaric (International Severe Acute Respiratory and Emergency Infection Consortium) prepared what Openshaw described as ‘‘sleeping protocols’’ to ensure that researchers were ready to meet the challenge of any dangerous new virus.
A decade later that moment has arrived, the Isaric group has been activated and the full weight of British science is being brought to bear on the Pandemic board game challenge that no longer sounds quite so lighthearted: ‘‘Can you save humanity?’’
Last week Openshaw talked at length about the spread of Covid-19, the alarming behaviour it is displaying, the efforts of governments to contain it, the prospects for a vaccine and the mistakes we are in danger of making.
What is known about the new virus?
Openshaw’s first task was to build up a clinical portrait of
Covid-19. ‘‘What did this resemble? Was it behaving like flu or more like Sars [severe acute respiratory syndrome, caused by another coronavirus that emerged from China in
2003]?’’ he said. ‘‘What were its unique clinical characteristics? Why was it causing so many serious cases to appear in hospitals in Wuhan? Was it mostly affecting lungs? Why was there such a high mortality rate? Who was most at risk? All those questions became very pressing.’’
The search for answers was unexpectedly assisted by what some saw as a breakthrough in Chinese transparency. Unlike in the Sars pandemic, when detailed information was slow to emerge, Chinese scientists soon started sending data-rich reports to the world’s leading medical journals, The Lancet and the Journal of the American Medical Association.
‘‘They were producing articles within days,’’ said Openshaw. ‘‘Well written, detailed, and they didn’t seem to be holding back.’’
What the Chinese data revealed was not so encouraging. ‘‘It was immediately clear this was not a rapid illness,’’ said Openshaw. ‘‘Illness was developing in different stages and there was clearly a presymptomatic phase after exposure. It turns out to be about five days.
‘‘Then, once symptoms start, they often start gently or insidiously. People may develop a bit of a non-specific malaise and a cough, grumbling on for a week or so. It’s only then it becomes clear who is going to recover and who will be bitten hard by the next phase, characterised by inflammation of the lung, this viral pneumonia that seems to develop.’’
What worries scientists is that the human immune system may be contributing to that inflammation, instead of getting rid of it. And in a high proportion of cases requiring intensive care, the virus seems to affect other organs and systems.
‘‘Unusually this seems to affect the heart and maybe the blood vessels,’’ said Openshaw. ‘‘A proportion of people go on to get viral myocarditis [an inflammation of the heart muscle] and that seems to be an element in quite a portion of deaths. This particular virus goes on to cause mischief outside the respiratory system while continuing to cause inflammation in the lungs themselves.’’ All this helps explain why older people with underlying health conditions affecting the lungs or heart have emerged as the most at risk.
Who has done best in controlling the spread?
‘‘It has been very interesting to see the way in which different political systems have handled this type of outbreak,’’ said Openshaw.
‘‘With a very regulated society like China, where people are used to complying with government orders, you can imagine how it’s possible to knock a virus like this down. In societies where sociability is absolutely embedded, it’s more difficult.’’
Last year he visited Singapore, ‘‘a very authoritarian but quite science-based society’’, which responded to the Sars epidemic by building a state-ofthe-art, 330-bed National Centre for Infectious Diseases. ‘‘It was one of the most impressive
facilities I’ve ever visited.’’
The centre opened last year but remained largely empty until this year’s outbreak. Singapore had its first confirmed case on January 23, but managed to slow the spread, with a total of just 200 cases up to Friday night. Of these patients, 11 were in intensive care. No-one had died.
A combination of aggressive isolation of suspected cases, intensive tracing of their contacts and early social distancing measures saved a crowded island city-state from mayhem.
‘‘In our sort of system it’s impossible to imagine creating a whole hi-tech facility of empty hospital beds, just in case,’’ said Openshaw. ‘‘What they did in Singapore is incredible.’’
What does Italy’s experience tell us?
There are marked differences among scientists about the lessons to be learnt from Italy, which has resorted to mass quarantine and drastic social distancing measures to halt the spread of the virus.
Francois Balloux, professor of computational systems biology at University College London, believes the unprecedented quarantine of 16 million people in northern Italy – the worstaffected area – was ‘‘not sustainable in the long term’’. Mark Woolhouse, professor of infectious disease epidemiology at Edinburgh University, also questioned the month-long restrictions on movement.
‘‘What is the evidence that four weeks is the right duration? What happens if the . . . situation has not improved by April? Will the restrictions be extended? For how long is Italy willing to keep those restrictions in place? There is an important message here for any country imposing travel or movement restrictions to slow the spread: what is your exit strategy? And if the epidemic does not behave as hoped, what then?’’
Openshaw believes that ‘‘draconian’’ measures such as closing pubs, schools and universities and ordering people to work from home will certainly have an impact on the spread, ‘‘but it comes at a huge cost . . . the important thing for everyone to work out is how they as individuals should respond. I was meant to fly to Switzerland
. . . but decided against international travel and stayed at home in Devon.’’
Openshaw further tends to the view that Italy just got unlucky, in the same way as Toronto suffered a large outbreak of Sars traced to a single elderly Chinese woman.
‘‘There are events that forecasters call stochastic, meaning they depend on some random event it is impossible to predict on an individual basis,’’ he said. ‘‘It is not that every person who has the virus is infecting precisely 2.6 other people. Some are infecting 60 other people and others are infecting none. One person can have a massive impact on these transmission events.’’
Will a vaccine save us?
Perhaps the most alarming feature of Covid-19 has been the undisguised awe it has evoked in scientists studying its behaviour. Gabriel Leung, professor of public health medicine and dean of medicine at Hong Kong University, has described the virus’ ability to mutate and spread as ‘‘brilliant’’.
Openshaw said: ‘‘This pandemic has resulted from a single biological particle so small you couldn’t even see it with a conventional microscope. By itself it has managed to spread around the globe and cause huge impacts. We viruswatchers take our hats off to this one. It’s an extraordinary virus with immense potential, quite remarkable.’’
It may also prove much harder to defeat than the plague featured in the 1995 Hollywood blockbuster Outbreak, in which desperate scientists hunted for an infected monkey in order to obtain the vaccine that would save the world. ‘‘A cinematographic fantasy,’’ Openshaw chortled.
While the search continues for a possible animal host that may have transmitted Covid-19 to humans from a colony of Chinese bats, Openshaw admitted he was not concerned about whether it was a pangolin (one of several possible sources), a civet (linked to the Sars outbreak) or any other wild animal used in exotic gastronomy or traditional Chinese medicines. What matters to him is how the virus behaves in humans.
‘‘We know that for the four common cold viruses, immunity is partial and transient,’’ he said. ‘‘The fact that you’ve been exposed to one of these viruses doesn’t mean you can’t catch it again.’’
There is still no coronavirus vaccine, despite years of efforts to find one, and scientists remain far from certain that a vaccine generating antibodies intended to fight off disease is going to be effective in the case of Covid-19. ‘‘There are even hints that an antibody to coronaviruses in general may enhance disease,’’ Openshaw said. If the virus does not make you sick, the vaccine might make you sicker.
He pointed to past experiences with a proposed vaccine for dengue fever that had to be withdrawn after it was shown it could cause more disease. There is also a coronavirus infecting cats with feline infectious peritonitis – an abdominal inflammation. ‘‘The vaccine caused enhanced disease in cats,’’ said Openshaw.
‘‘All of this makes us a little bit worried,’’ he added. ‘‘Even when we do have a vaccine that induces immune responses, we don’t know yet that it is necessarily going to be protective. We hope so, but it’s not as obvious as it would be if this was ordinary influenza. These are very deep and complex questions that can’t be answered quickly and simply.’’