Coronavirus

Why developing an antibody test for coronavirus is almost as important as finding a vaccine

BY Jack Dickens | tweet jackfdickens   /  18 March 2020

It is a tool for combatting coronavirus COVID-19 which the British government’s Chief Scientific Adviser, Patrick Vallance, has described as a potential “game changer”. It would be “transformational”, said Chris Whitty, the government’s Chief Medical Adviser. No, they were not talking about a vaccine, although this would be the ultimate game changer – they were talking about what is known as an “antibody test”.

At the moment, the tests for coronavirus can only identify whether people are suffering from symptoms of the virus right now. But Public Health England are currently seeking to develop a new type of test that would also enable the UK’s health authorities to determine whether someone has had the virus while experiencing few or no symptoms.

Speaking at the Downing Street Press Conference on Monday this week, Vallance explained: “The absolutely key thing is…testing, and ramping up our ability to test – and in that, this ability to test who has had the disease rather than who has just got it now”.

Vallance added that the question of how many people have had COVID-19 and been asymptomatic is crucial. This is because it is the biggest unknown worldwide that would, as Vallance said, “completely change all sorts of things if we could get a handle on that number.”

In order to understand why developing an antibody test is so important, it is necessary to appreciate how the coronavirus spreads throughout the community.

When a person is infected with coronavirus, there is something known as the “incubation period” – that is the time it takes between a person becoming infected and experiencing symptoms. It is thought that this incubation period usually lasts for a period of 6 days, but it could last for up to 12 or 14 days.

A patient is believed to be at their most infectious when they begin to show symptoms. During this time, those who have contracted COVID-19 are most likely to infect others by excreting virus from the respiratory tract due to the cough associated with the disease.

Yet, according to Professor Dame Anne Johnson, Professor of Infectious Disease Epidemiology at UCL, while most infections are passed on from people who have symptoms, some may pass COVID-19 on when they have mild symptoms or just before they  display symptoms. This is not yet fully understood.

Those who are infected could be spreading the virus for as long as half a day before they realise they have the virus and self-isolate. Those who experience no symptoms will also continue spreading the virus in this way, without knowing that they are passing on COVID-19.

In other words, by the time a normal PCR test – which detects specific genetic material within the virus – can pick up evidence of the virus, a patient may have transmitted it by making contact with other people throughout the community.

When someone is infected, however, their body mounts an immune response and begins to produce antibodies to fight the infection. These antibodies, Dame Anne explains, will remain for a period of time – we do not yet know quite for how long.  They will possibly remain in a person’s blood for years and protect against future infection, but their strength may reduce over time.

This means that, if Public Health England were to develop a test kit that can test for antibodies rather than only for the COVID-19 virus, it would open up a number of possible avenues for the government’s policy response to the pandemic.

Such a test would empower the health authorities to better gauge the spread of the virus and slow this spread. It could help them to trace, test, and isolate new cases, and reduce transmission. And it would also help to free up much-needed manpower for public services at a vital time in the pandemic.

Tim Colbourn, Associate Professor of Global Health Epidemiology and Evaluation at UCL Institute for Global Health, told Reaction: “If people were able to know they have the virus while they are still asymptomatic then they could self-isolate before they feel unwell.”

The benefits do not stop there: if we know that a person has had the virus and recovered from it, there is good reason to believe that they will be immune, and no longer infectious. Colbourn said: “There is no reason to think they would not be (immune) as their immune systems will have successfully fought off the virus in order for them to recover.” Although, he hastens to add, immunity to coronavirus is still being researched by the experts. The length of time for which someone who has recovered from coronavirus has immunity is not yet fully understood.

But if someone has had COVID-19 and is no longer infectious, this would potentially allow those who know that they have had coronavirus to get on with their lives afterwards. People across the country who test positive on the antibody test would be able to see their elderly relatives and help them with their daily tasks.

Frontline staff in essential services such as the NHS, if they tested positive for antibodies, would not have to worry about catching and spreading the virus in care homes, hospitals, and other facilities. They could also work among vulnerable groups without fear of transmitting the disease, which is likely to be crucial as the virus reaches its peak. The UK, as with all other countries battling the virus, needs all the capacity that it can get.

Although, presumably, those who are immune would still have to observe very good personal hygiene and ensure that they did not pass on the virus in other ways, this really could be a game changer indeed.

In addition, this solution would have an important social and economic impact, helping to make the stifling conditions of social distancing less onerous and making the long-term commitment to social distancing easier to manage as a result.

As Vallance suggested – being “able to monitor this disease well” is key. Knowing who is infectious and being able to manage fluctuations in case numbers could lead to a period where the government “start relaxing measures again” as our understanding of “the effect of taking things off again” evolves.

Social distancing is part of the range of what are called “Non-Pharmaceutical Interventions” (NPIs). These are required to make sure that the resources of the NHS are not overwhelmed by the number of severe cases. NPIs include not only self-isolation and social distancing, but also the discouragement of large public gatherings and closing of schools introduced by Boris Johnson’s government this week.

The capacity not only to introduce NPIs but also to sustain them is going to be key to developing a long-term strategy for keeping COVID-19 under control.

Neil Ferguson, Professor of Mathematical Biology at Imperial College London, whose mathematical modelling encouraged the UK government to step-up its measures this week to suppress coronavirus, has noted the importance of the public uptake of NPIs. He made clear that the government’s plan to keep severe cases below the NHS’s capacity during the peak of the infection, if it is to work in reality as well as in theory, “depends critically on how people respond to their introduction”.

Ferguson also adds that “while experience in China and now South Korea show that suppression is possible in the short term, it remains to be seen whether it is possible in the long term”.

This week it has become clear that countries such as South Korea and Taiwan, who initially managed to curb and significantly reduce cases through a combination of very intensive testing for the virus, case isolation, and contact tracing, are now experiencing a spike in new cases. It may also take place in China, were a strict quarantine was enforced in Hubei Province.

This second wave has happened because, as these governments have relaxed their lockdown and NPI measures, imported infections from Europe – as students and family members returned home to escape the outbreak there – have re-introduced the infection. As a consequence, the virus has spread among the large proportion of populations who still lack immunity to COVID-19.

This will always be the danger, until a vaccine is developed, as Dame Anne explains, since “the problem with suppressing the virus…is that you suppress it, but then you keep on getting reintroductions and resurgence, and that seems like it may be happening, for example, in Korea. So, as soon as you let up the restrictions, you start getting more transmission.”

This presents a unique problem for policy-makers, because it makes it likely that NPIs will have to be imposed and relaxed in tides, acting as a pressure valve to control the flow of cases into public services.

“You  can try and let up the restrictions, but if you do start getting outbreaks you have to clamp down again. You then have a series of waves over really quite a large number of months”, Dame Anne said.

“How long can you go on doing that for? This is the really difficult thing to work out.”

This all matters because, as Ed Yong, Science Editor at the Atlantic Magazine, has outlined very clearly, we don’t yet know how long immunity against the novel coronavirus lasts for. And François Balloux, Director of UCL Genetics Institute, says that comparisons with other coronaviruses suggest that immunity could be relatively short-lived.

People infected with OC43 and HKU1, two other coronaviruses that regularly circulate among humans and cause common colds, stay immune for less than a year. But immunity against the first SARS virus from 2003 holds for much longer.

Ultimately, as Yong highlights, COVID-19 could take after either one of these extremes, while a recent research paper suggests that there could be anything from annual outbreaks to a decades-long quiet spell.

In short, we are in this for the long haul and having the knowledge at any one time, through antibody testing, of who has contracted the virus, who is infectious, and who is no longer infectious will be increasingly important. Given that a vaccine is still 12-18 months away, antibody testing provides the best means within our grasp to manage COVID-19. It will do so by allowing the authorities to continue monitoring the impact of a disease which may come in several waves.

From this perspective, antibody testing is as crucial to the response as eventually finding a vaccine will be. If the UK can get the right scale and strategy, rolling out rapid and remote antibody tests could make the difference between the crisis overwhelming NHS capacity and keeping case numbers under control.

What measures can the UK government now pursue to ensure that both conventional and antibody testing is rolled out across the country?

Martin Hibberd, Professor of Emerging Infectious Disease at the London School of Hygiene and Tropical Medicine, has said that the UK needs to increase its capacity both for PCR testing and accurate antibody testing.

This, he believes, would perhaps require a new, less central approach. This seems to accord with what Chris Whitty announced this week, that GP networks are being mobilised to survey and trace the spread of infection through the community, rather than only in hospitals.

Tim Colbourn says that the ideal strategy would be if “everyone got a coronavirus test kit posted through their letter box. Then the whole country could know whether they have it or not. If the test results were sent back on an app and stored with geolocation data, epidemiologists and public health authorities will know exactly where every case was and be able to intervene to stop spread.”

This is unlikely to happen in the current circumstances, he says, but argues that we need to move as close to this ideal response as we can, and as soon as possible.

The government certainly has been trying to “scale up testing” this week, as it races against time to get the NHS in battle order for the worst weeks and months of the crisis ahead.

Not only Public Health England, but private companies and academic researchers, are frantically trying to find ways to develop and produce large numbers of rapid and remote testing kits to aid the public and fight transmission. Scientists at the University of Oxford today announced that they have developed a super-sensitive rapid test for coronavirus which could give its user a result in under 30 minutes. The test, which detects viral RNA, would cut the testing time for a single case down from the 1.5-2 hours it usually takes to test using the current conventional testing kits and save valuable minutes, if not hours.

On Wednesday, the government announced that it was increasing conventional virus testing to 25,000 tests per day. The increased capacity is expected to be reached within about 4 weeks’ time. This would represent a significant step up from the 2,000 tests a day which the NHS is currently conducting, according to the Department for Health and Social Care.

The limited capacity means that those who are being targeted are mostly those with respiratory problems in hospitals. And as The Telegraph revealed today, the limited supply is causing many anxious Britons to turn to as yet unauthorised virus tests being provided by private companies.

Sources have told me that PHE is pulling out all the stops to draft in help from wherever it can, utilising its own lab facilities and increasingly considering how private sector companies can contribute to the national effort.

In all likelihood, based upon the experiences in South Korea and Iceland, where large numbers of virus test kits have been rapidly rolled out by the state in cooperation with private pharmaceutical and diagnostics companies, the private sector is going to have a key role to play in the coming months.

It has been reported that, as well as mobilising their 12 regional labs to produce testing kits, PHE is also checking private companies’ test kits in the hope of accrediting them and providing them with the ability to rapidly roll out new kits to boost capacity.

Meanwhile, Vallance said at today’s Downing Street press conference that PHE’s antibody test is “progressing very fast”, that they have a test “in house” and are now “looking at ways to get a much more widespread version of that out”.

All hands will be on deck – private and public – to meet the national emergency. It is going to be a challenge for government and business alike, and neither the state nor private enterprise can afford to fail. We are all of us facing the coming storm together.


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