Wednesday, 18 March 2020

'Test, test, test' is the key to coronavirus epidemic control - the clear lesson from East Asia

How many people will die in the UK as a result of the COVID-19 pandemic? According to the scientists it will be between 20,000 and 500,000 depending very much on how we respond.

A team at Imperial College has produced a paper which this week has prompted the government to embark upon a range of new measures to stop the spread of the disease.

If we do nothing and just let the virus pass through the population unhindered – in the hope of producing so-called ‘herd immunity’ - then 81% of people would be infected and 510,000 would die from coronavirus by August.

If we adopt a mitigation strategy - trying to slow its spread to prevent a massive peak in cases that would overwhelm the NHS many time overs – we can expect 250,000 deaths.

But a suppression approach – breaking the chains of transmission in order to stop the epidemic in its tracks – would reduce total deaths to thousands or tens of thousands.  

The government has now concluded that suppression is the only viable line of approach. Their chief scientific adviser Patrick Vallance told a committee of lawmakers this week that 20,000 deaths would then be ‘a good outcome in terms of where we would hope to get to with this outbreak’.

Why has China done so much better than us?

But this raises a huge question. If 20,000 deaths is a ‘good outcome’, and the best we can hope to achieve, then why have there been only 3,000 deaths in China where the outbreak actually started?

On a population basis (the UK has 67 million people and China 1,435 million) the UK equivalent deaths to that in China would be just 140 had we handled it as successfully as them. 20,000 is over 140 times this figure.

So, what have the Chinese done differently? And what, by implication, have we failed to do?

The control of the spread of coronavirus in China is remarkable but real. Today’s figures show a total of 80,000 cases but only 10-20 new cases a day. There are still also 10-20 deaths a day from the virus in China but these are almost all people who were infected weeks ago. Things have tailed off massively.

But China has also achieved this fall-off much more quickly than other countries. 80,000 cases in China amounts to 56 cases per million population which is a better measure of how badly the virus has affected any given country.

By contrast Italy, with 31,000 cases to date, has 521 cases per million, almost ten times the China figure.

In fact, today on 18 March (and these figures are obviously increasing daily) there are 32 countries or territories with a higher density of cases than China. Some of these are small population states like Luxembourg, Andorra and San Marino, but others include Spain, Germany, France, Switzerland, Netherlands, Norway, Austria, Belgium and Denmark.

The two anomalies are the US and UK – today with 20 and 29 cases per million population respectively – but we know from the number of deaths alone in these two countries that the true number of those infected is much higher than this. Vallance said yesterday that a ‘reasonable ballpark’ current figure for the UK was 55,000 cases, not the 1,900 actually reported.

The reason the US and UK total case figures are so low is because we are doing so few tests for the virus. I’ll come back to that.

China’s remarkable success in controlling the virus is documented in the Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) dated 16-24 February. You can read the whole report here but there is an excellent summary here.

The diagram reproduced below from page 29 of the report (you can view it more easily here) shows the number of cases against time in China along with the major interventions made to try and slow the disease.

The outbreak was first announced on 30 December and the new coronavirus was isolated on 7 January and its gene sequence publicly shared on 10 January. The number of new cases per day peaked at around 3,000 just over two weeks later on 26 January but had fallen to fewer than 500 cases daily by 14 February.

A paper published on 16 March in Science shows that the virus first got away on the Chinese because they were unable to identify and isolate the very early cases.

They estimated that 86% of all infections were undocumented prior to the 23 January 2020 travel restrictions. The transmission rate of undocumented infections was only 55% of documented infections, presumably because those affected had less severe symptoms, yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases. These findings explain the initial rapid geographic spread of the virus.

However, after the initial stage China got quickly on top of the outbreak through a vigorous programme of widespread testing followed by isolation of those affected, backed up by travel restrictions.

Testing for coronavirus in China and the UK

China has a policy of meticulous case and contact identification for COVID-19. For example, in Wuhan more than 1,800 teams of epidemiologists, with a minimum of 5 people/team, traced tens of thousands of contacts a day. Contact follow up was painstaking, with a high percentage of identified close contacts completing medical observation. Between 1% and 5% of contacts were subsequently laboratory confirmed cases of COVID-19, depending on location.

But the effort outside of Wuhan was also huge. In Shenzhen, for example, the infected named 2,842 contact persons, all of whom were found, when testing was completed for 2,240 it was found that 2.8% of those had contracted the virus. 

Within weeks following the identification of the virus, a series of reliable and sensitive diagnostic tools were developed and deployed. By 23 February, there were ten kits for detection of COVID-19 approved in China by the NMPA and several other tests had been entered in the emergency approval procedure. Overall, producers have the capacity to produce and distribute as many as 1,650,000 tests/week.

In stark contrast, based on figures available on 13 March, the UK had carried out around 30,000 Covid-19 tests, at a median of 1,600 tests per day so far in March. 

The World Health Organization director-general, Tedros Adhanom Ghebreyesus, said this week that he had a simple message to countries on how to deal with the coronavirus outbreak sweeping the globe: ‘Test, test, test.’

Speaking during a news conference on Monday he urged countries to test more suspected cases, warning that they ‘cannot fight a fire blindfolded’. 

But fighting the fire blindfolded is essentially what the UK and US have been doing – simply because there are not enough testing kits. This was admitted by UK government adviser Professor Chris Whitty this week.

On 6 February, the World Health Organization said it had already shipped 250,000 tests to more than 70 laboratories around the world.

But as WHO shipped hundreds of thousands of tests, broader US testing struggled to begin. The US kits, developed by the CDC, were found not to be working as expected, which eventually required test kits to be re-manufactured. In fact, earlier this week it was reported that the US lags almost all developed countries in testing for the virus.

Whilst the abundance of testing kits in China meant that everyone with a fever or who had had contact with an infected person was tested, the shortage of testing kits in the UK has meant that tests are not even available for doctors on the frontline or for high-risk patients at risk. In fact, the only people being tested until very recently were those with severe symptoms admitted to hospital.

What this means is that those with less serious cases of COVID-19 have been able to roam free to spread disease, and frontline people (doctors and other health professionals), who are unwell but do not actually have the virus, are being unnecessarily quarantined for 14 days along with their families when they could be treating patients.

A pandemic out of control

It is now over two months since China initiated its control programme and countries seem now to be in two groups – those where the virus appears to be propagating largely out of control (mainly Western Europe) and those in East Asia where there has been success in getting on top of its spread.

The diagram (below) demonstrates this dramatically.

Cases (and deaths) in Europe and the US are spiraling out of control but in Singapore, Japan and Hong Kong – using more of a Chinese approach - the curve is considerably flattening over time.

Just today an article in Science attributed South Korea’s astounding success so far to the most expansive and well-organized testing program in the world, combined with extensive efforts to isolate infected people and trace and quarantine their contacts.

South Korea has tested more than 270,000 people, which amounts to more than 5,200 tests per million inhabitants. By contrast, the US has so far carried out 74 tests per 1 million inhabitants, data from the US Centers for Disease Control and Prevention show.

South Korea’s experience shows that ‘diagnostic capacity at scale is key to epidemic control,’ says Raina MacIntyre, an emerging infectious disease scholar at the University of New South Wales, Sydney.

Reports last week from Italy described doctors opting not even to assess high-risk patients, let alone tube and ventilate them, because they were simply overwhelmed by the numbers (see frightening twitter thread here and also Lancet paper from 13 March here). Spain is following closely but other countries including Germany, UK, Netherlands and Switzerland, are only a week or two behind.

It is a fundamental principle of medicine that there is no treatment without diagnosis. We need more testing kits rapidly deployed. It is incredible that even at this late stage we don’t really know who has the disease and who doesn’t.

There are already many types of testing kits available and capable of mass production (see also here). Can the UK government expedite the approval process as China so successfully did to bring them on stream?

Of course, all the other measures to prevent spread, which the UK has already implemented and with which we are well familiar, are absolutely necessary and right. And we need many more doctors, oxygen and ventilators to provide support for the rising tide of severe cases.

The figures for China are that 20% of all cases needed hospitalisation and oxygen often for weeks and 25% of these (5% overall) needed ventilation or ECMO. When we consider that the UK until recently only had 4,000 ventilators, 80% of which were already occupied, we can start to appreciate how serious this is.

But it is also clear that had we deployed more rigorous testing, contact tracing and isolation in the early stages of this pandemic we would not be in the position we are now.

We pride ourselves in the UK on both our standard of medicine and on the NHS. But we are lagging far behind those in China and other East Asian countries in our management of this crisis.

Whether it is too late to rectify this only time will tell. Will we end up in the UK with 20,000 deaths, 250,000 or 500,000?

What is clear is that many times more than 140 will die (the number of deaths the UK should have if equivalent to China on a population basis). That total will be passed in the next few days and advisors are predicting that new cases per day will not peak for another 10 to 14 weeks. The peak of the death rate will be two to three weeks after that.

It is clear that, as of this week, the UK government is now much better informed and pulling out all the stops to beat this challenge (helpful summary here). As we all work together we pray that these efforts will be successful and that the UK death toll is much closer to 20,000 than 500,000.

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