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Why is it taking so long for health chiefs in Britain to approve antibody tests?

Coronavirus antibody tests which reveal exactly who has had the infection and is likely to be immune are said to be crucial for phasing countries out of lockdown.

Germany, Italy, Finland and the US have all launched large-scale antibody testing programmes in recent weeks as they look to get society up and running again.

South Korea – one of the few countries to flatten its curve without social restrictions -today became the latest country to scale up production of its antibody tests.

Boditech Med, based in Chuncheon, South Korea, is now manufacturing thousands of its iChroma COVID-19 antibody kits, which it claims are 96 per cent reliable.  

But the British Goverment has refused to approve any antibody test, claiming they give a ‘false positive’ too often (when they incorrectly tell people they are immune).

This is ‘dangerous’ because it might give people the false confidence to resume normal life and risk catching the bug, according to Chief Medical Officer Chris Whitty. 

The UK last months made a provisional order for 17.5million antibody tests from nine different companies, on the condition that they passed validation by Oxford University scientists. 

But researchers at the prestigious university found none of them were reliable enough to be rolled out to the masses.

Included in the 17.5million order were 2million tests from China that cost Britain a huge £16million. Officials are now scrambling to try to get that money back.

It comes as Swiss pharmaceutical giant Roche announced it would be launching a ‘highly specific’ antibody test by early May. 

Roche – one of the ‘big four’ diagnostics companies in the world – said it will be able to manufacture ‘double-digit millions’ of the devices by the end of June.    

While Roche did not specify how the tests will work, it is thought samples will need to be processed in a lab and will not be suitable for use at home.  

South Korea, one of the few countries to flatten its curve and not impose social restrictions, today became the latest country to scale up its production of antibody tests (shown)

Boditech Med, based in Chuncheon, South Korea, has started manufacturing thousands of its iChroma COVID-19 Ab kits, which it claims are 96 per cent reliable

Boditech Med, based in Chuncheon, South Korea, has started manufacturing thousands of its iChroma COVID-19 Ab kits, which it claims are 96 per cent reliable 

The proactive move comes as South Korea looks to eradicate the virus completely after reporting around just 20 new cases for the fourth day in a row

The proactive move comes as South Korea looks to eradicate the virus completely after reporting around just 20 new cases for the fourth day in a row

An at-home coronavirus antibody testing kit being sold in pharmacies in Germany. They are not regulated in the EU country yet but are being trialled on a large scale

An at-home coronavirus antibody testing kit being sold in pharmacies in Germany. They are not regulated in the EU country yet but are being trialled on a large scale

The Canea Schnelltest comes with a finger pricker, sterilising wipes and a small screening device

The Canea Schnelltest comes with a finger pricker, sterilising wipes and a small screening device

Essex-based firm Biosure has developed a DIY antibody test, but UK officials say it is not accurate enough. Biosure is now racing to make it reliable enough to pass validation

Essex-based firm Biosure has developed a DIY antibody test, but UK officials say it is not accurate enough. Biosure is now racing to make it reliable enough to pass validation

HOW DO ANTIBODY TESTS WORK, AND HOW ARE THEY DIFFERENT TO SWABS?

An antibody test detects if someone has previously had coronavirus and has since recovered, even if they are unaware they were infected. 

There are two different types of antibody tests – one which is done at home and takes a few minutes, and another which is posted to a lab to be analysed.

Both versions of the test are carried out using a finger pricker to extract a blood sample.   

People using the DIY home tests place their sample in a screening device which takes a few minutes to scour the blood for antibodies.

These are substances created and stored by the immune system when someone gets ill. 

If a person has COVID-19-specific antibodies, it means they have already defeated the virus and are likely to have gained some immunity to it.   

The antibody tests – also known as ‘serological tests’ – were described as a ‘game changer’ by Prime Minister Boris Johnson last month.

As well as painting a clear picture of who is safe to return to work, they are convenient and cheap.

WHAT IS AN ANTIBODY TEST, AND HOW IS IT DIFFERENT TO A PCR TEST? 

ANTIBODY TEST

An antibody test is one which tests whether someone’s immune system is equipped to fight a specific disease or infection.

When someone gets infected with a virus their immune system must work out how to fight it off and produce substances called antibodies.

These are extremely specific and are usually only able to tackle one strain of one virus. They are produced in a way which makes them able to latch onto that specific virus and destroy it.

For example, if someone catches COVID-19, they will develop COVID-19 antibodies for their body to use to fight it off.

The body then stores versions of these antibodies in the immune system so that if it comes into contact with that same virus again it will be able to fight it off straight away and probably avoid someone feeling any symptoms at all.

To test for these antibodies, medics or scientists can take a fluid sample from someone – usually blood – and mix it with part of the virus to see if there is a reaction between the two.

If there is a reaction, it means someone has the antibodies and their body knows how to fight off the infection – they are immune. If there is no reaction it means they have not had it yet.

PCR TEST

Antibody tests differ to a swab test, known as a PCR (polymerase chain reaction) test, which aims to pick up on active viruses currently in the bloodstream.

A PCR test works by a sample of someone’s genetic material – their RNA – being taken to lab and worked up in a full map of their DNA at the time of the test.

This DNA can then be scanned to find evidence of the virus’s DNA, which will be embroiled with the patient’s own if they are infected at the time.

The PCR test is more reliable but takes longer, while the antibody test is faster but more likely to produce an inaccurate result. It does not look for evidence of past infection. 

The devices cost between £6 and £20 and can be posted to people to be conducted from their own home.  

They work like a home pregnancy test, giving a ‘positive’ or ‘negative’ result within 10 to 15 minutes.  

Antibody tests differ to a swab test, known as a PCR (polymerase chain reaction) test, which the Government currently uses.

A PCR test can only tell whether a person currently has COVID-19 because it picks up on active viruses currently in the bloodstream.

Saliva samples have to be sent to a lab where scientists scan the DNA for evidence of the virus.

The PCR test is more reliable but takes longer – up to two days – while the antibody test is faster but more likely to produce an inaccurate result. 

WHY IS BRITAIN NOT MASS TRIALLING ANTIBODY TESTS?  

The Government promised weeks ago that they would be rolled out en-masse.

Britons were told they would be able to buy them from Amazon or Boots. 

But none have so far proved to be reliable enough for the public. 

The tests have only been trialled on 3,000 patients at the Defence Science and Technology Laboratory at Porton Down, near Salisbury.

By comparison, Germany is trialling the tests on tens of thousands of its population.

Last month, the UK Government ordered 3.5 million finger prick tests, mainly from Chinese manufacturers.

Later it announced it had placed provisional orders for 17.5 million tests from nine firms including some based in the UK.

Among them were two tests made by Chinese companies. Britain paid an estimated £16 million for them. 

But the deals were on the condition that they could pass reliability tests by scientists at Oxford University.

Researchers at the prestigious university did not approve any of them, meaning it could now be months before they are used in the UK, if at all. 

The tests were said to give ‘false positive’ results too often, meaning they incorrectly tells people they are immune.  

This might give people false confidence that they can’t catch the bug and put them at risk of infection. 

After being stung by the faulty Chinese antibody tests, the UK Government is said tonow be looking for ‘home grown’ devices made by British firms. 

Britain ‘paid £16m’ for two million coronavirus antibody tests from China that DON’T WORK 

Britain paid two Chinese companies an estimated £16 million for two million coronavirus antibody tests which officials then found were not accurate enough to be rolled out. 

The UK, along with every other country in the world, is still trying to find a test which can be mass produced which shows if someone has had the disease and now has immunity to it.

The government pounced on an early offer of potential tests produced in China with the New York Times reporting officials agreed to pay approximately $20 million to secure the home testing kits. 

However, when the antibody tests were put through their paces they were found not to be sufficiently accurate and as a result could not be used. 

Officials are now scrambling to try to get the money back. 

Downing Street today did not deny the claims but the Prime Minister’s Official Spokesman said he was not aware of the specific $20 million figure.

The spokesman said: ‘Where tests are shown not to have any prospect of working then we will seek to recover as much of the costs as we can.’ 

Officials have previously insisted that they had only purchased the minimum number of antibody test needed to conduct initial trials with full orders contingent on the kits actually working.        

But UK-based manufacturers are struggling to access blood samples of infected patients to trial their devices on. 

Essex-based Biosure said there was ‘a national shortage’ of samples.

It is now calling for blood donations from members of the public who were either diagnosed with, or were suspected of having, the virus.

A spokesperson told MailOnline: ‘We have discovered there is no current UK based bio-bank for confirmed positive COVID-19 blood samples.

‘We recognise the Government is under immense pressure with this global crisis, so for swift action we need to call to the nation for urgent support.

‘We are asking people to fill in an on-line questionnaire so we can build a database of people who have been diagnosed with COVID-19 and who would, if needed, be prepared to provide a small sample of their blood. 

‘People who fit the criteria will be contacted and sent a collection kit though the post, so that a blood sample could be self-collected at home and posted back for inclusion in our validations.’   

WHICH COUNTRIES ARE USING ANTIBODY TESTS ALREADY? 

No country has successfully implemented a nationwide antibody testing programme.

But the kits are being used alongside swab tests in South Korea, Germany, the US, Italy, Finland and China. 

Germany became the first in Europe to carry out large-scale coronavirus antibody testing last week.

The country launched three studies – one analysing blood donations, one involving  the country’s worst-hit areas and a representative study of the broader population. 

In the first, 15,000 samples will be taken every fortnight from blood donations. 

The second will look at blood samples taken from about 2,000 people. 

Preliminary results from these two projects are expected to be published in May.

In the third study, 15,000 people in 150 regions across Germany will be tested for antibodies. The research will begin next month.   

Pharmaceutical heavyweight Roche will launch antibody test next month 

Swiss pharmaceutical giant Roche announced it would be launching a ‘highly specific’ antibody test by early May.

Roche – one of the ‘big four’ diagnostics companies in the world – said it will be able to manufacture ‘double-digit millions’ of the devices by the end of June.

The test will launch in countries that accept the CE mark, a global standard.

Severin Schwan, the company’s chief executive, told the Financial Times the company ‘could easily get into the hundreds of millions’ in the following months.

Mr Schwan said the test was ‘highly specific’ but refused to elabroate as trials continue on patients. 

Dr Simon Clarke, associate professor in Cellular Microbiology, University of Reading, said: ‘This is a very interesting and potentially important advance in being able to diagnose who has been previously exposed to the coronavirus causing COVID-19, but I think the authorities in the UK would be wise to conduct independent evaluation, given how they’ve had their fingers burnt with other tests that they’ve purchased. 

‘Moreover, this test will require space and manpower in testing laboratories in addition to equipment already made by the manufacturer. It remains unclear how quickly laboratories that do not already have that particular instrument would be able to obtain them and at what cost.’

Finland has also announced a similar – but much smaller – antibody testing programme.

Finnish broadcaster Yle said the country will start testing 750 random blood samples every week. 

The US Centers for Disease Control (CDC) is also carrying out antibody testing.

It is analsying blood donations of Washington and New York City residents – two of the worst-hit regions in the States. 

A separate survey is looking at random samples of people across the country, and a third is studying health workers. 

In Italy, Giancarlo Maria Liumbruno, the director-general of the Italian National Blood Center, is said to be trying to roll out antibody tests within weeks.  

Mr Liumbruno said the country has more than 1.7 million blood donors the country could screen to see if they’ve had COVID-19.

Mr Liumbruno said he plans to use the antibodies to treat coronavirus sufferers.

Trials of this process have already started in some hospitals in Lombardy, Northern Italy – at the heart of the nation’s outbreak.

Plasma from patients who recovered and tested negative for at least two weeks is used on those still battling COVID-19.  

HOW ACCURATE DO THEY NEED TO BE TO WORK? 

There is not enough information on antibody tests to know for certain how accurate they need to be.

Early studies appear to show they give very few false negatives (meaning they rarely are wrong are determining if someone has never had the infection).

But UK officials are worried by how often the devices give false positive results.

Startling models from Imperial College London saw the Government change tack after scientists warned that up to 500,000 people could die without any action

Startling models from Imperial College London saw the Government change tack after scientists warned that up to 500,000 people could die without any action

Home testing kits could have ‘disastrous results’, experts warn 

Experts have warned that dishing out coronavirus tests to be conducted unsupervised at home could lead to ‘disastrous results’.

An NHS testing manager told the Health Service Journal (HSJ) people may take the tests at home when they develop symptoms and get misleading results.

Antibodies are not produced until between three and seven days after contracting the infection.

This could result in a person thinking they are safe to go out in the community when they are not.

The manager said: ‘However simple the test is, people will find ways of doing it wrong. The main issue is it’s an antibody test — that’s going to confuse people and cause problems.

‘There’s going to be a period of time, at least a couple of weeks, before people will [produce] an antibody response.

‘A member of the public will be showing symptoms and want to do a test [straight away], get a negative result and think they have not got the virus and there’s a risk they will go out and infect other people.

‘It’s going to cause a lot of confusion, but it’s going to make some companies a huge amount of money.’

This could give people false confidence that they are immune.

For this reason, England’s Chief Medical Officer Chris Whitty has described them as ‘dangerous’, saying a bad antibody test was worse than none at all. 

But some scientists say that, even if the tests are just 50 per cent accurate, they at least give officials a clearer picture of who is infected.

One top scientist, who wished to remain anonymous, told MailOnline: ‘Even if the sensitivity is not good enough to pick up every single instance, if you’re testing asymptomatic subjects (who otherwise you wouldn’t test at all) then anyone identified positive… is one more person identified and isolated. 

‘The safe method of testing – just a finger through a screen, or car window – and the level of protection that affords those carrying out the testing is also key. 

‘Way better than having to get up-close-and-personal to throat/mouth swab every person you want to test.’

WHY IS IT SO DIFFICULT TO MAKE A RELIABLE ONE?

The development of an antibody tests require some knowledge of the proteins that form the coat of the virus.

Viruses are made up of many proteins, called antigens, of which some are shared with other viruses. Only a few may be unique to the particular virus.

The proteins specific to the virus will trigger the production of antibodies that neutralise the virus, stopping it from replicating.

‘We have to figure out what part of the virus is going to be really specific for that virus,’ Dr Whittier, who heads up Columbia University and New York Presbyterian’s microbiology lab, told DailyMail.com.

Those sections of the viral protein coat must then be produced in the laboratory, using cell lines, to be tested in an immunoassay.

Scientists ‘take that protein, put it in the bottom of a plastic well and put the blood serum in it and see if there’s something that will stick to it,’ said Dr Whittier.

That ‘something’ would be the antibodies in the patients’ blood.  

Anna Petherick, a lecturer in public policy at University of Oxford, said immunoassays will form the basis of home testing kits for people who think they have had COVID-19.

Graph shows the UK's average daily coronavirus deaths for the previous seven days, based on official figures. The dip at the end shows the numbers falling for two days - the first drop since the crisis began. Although it could be a sign of numbers plateauing, Chris Whitty yesterday said he expected a rise in deaths today as officials catch up with a lag in reporting over Easter

Graph shows the UK’s average daily coronavirus deaths for the previous seven days, based on official figures. The dip at the end shows the numbers falling for two days – the first drop since the crisis began. Although it could be a sign of numbers plateauing, Chris Whitty yesterday said he expected a rise in deaths today as officials catch up with a lag in reporting over Easter

Major blow for home antibody tests as UK firm leading the race to develop them admits it doesn’t have enough blood samples

Hopes for at-home coronavirus antibody tests were dashed today as a firm leading the race to develop them admitted there are not enough blood samples of infected patients to draw from.

Manufacturers need the blood of coronavirus sufferers to test their device against. 

Essex-based firm Biosure said there was ‘a national shortage’ of samples and is now calling for blood donations from members of the public who were either diagnosed with, or were suspected of having, the virus.

A spokesperson said: ‘We have discovered there is no current UK based bio-bank for confirmed positive COVID-19 blood samples.

‘We recognise the Government is under immense pressure with this global crisis, so for swift action we need to call to the nation for urgent support.

‘We are asking people to fill in an on-line questionnaire so we can build a database of people who have been diagnosed with COVID-19 and who would, if needed, be prepared to provide a small sample of their blood.

‘If you would be interested in helping, please click here.

‘People who fit the criteria will be contacted and sent a collection kit though the post, so that a blood sample could be self-collected at home and posted back for inclusion in our validations.’ 

Biosure claims to have developed an at-home finger prick test that takes a quarter of an hour.

It works exactly like the firm’s HIV self test, which requires the user to take a drop of blood using a safety lancet.

Suspected patients then use BioSure’s pen device which absorbs the blood and is entered into a cartridge which scans the sample for COVID-19 antibodies. 

Sure’s HIV Self Test has been shown to be at least 99.7 per cent accurate.

But the coronavirus test is currently under review at PHE labs to trial its effectiveness.

It is believed to be in the running to secure a contract from the Government to make hundreds of thousands of them.  

‘But their development takes time,’ she explained in The Lancet.

‘Expressing the protein in the right structure is often the most difficult step.   

‘In a nonnative system, such as a bacterial cell, the complex protein structures can come out slightly deformed, enough to stop antibodies from recognising them as they would the original viral coat protein. 

‘There are also questions about which antigens (proteins) are best for this purpose. 

‘Some diagnostic developers are cagey about giving away too many details, although the viral spike protein is universally perceived as the obvious candidate.’

Various labs making antibody tests might not even be testing for exactly the same antibodies. 

Some tests may confuse antibodies produced in response to the virus that causes COVID-19 to those made for other coronaviruses. 

‘There are a lot of other coronaviruses, and the issue is you need to find what target is specific for this virus so it’s not going to cross-react,’ Dr Whittier said. 

Typically, finding the correct target would ‘take months or years, and we’re trying to do it in weeks to months,’ Dr Whittier said. 

‘We don’t know the specific antigens or targets to look for.

‘It seems to the lay public like it’s taking a super long time, but from a lab perspective it’s happening at lightning speed.’  

Labs are testing specific antigens by using the blood of patients who have been confirmed to have the infection. 

It will reveal if the antigen they have identified causes the antigens to stick. If it doesn’t, it is not accurate. 

‘At Columbia, we validated an antibody assay that was developed in Asia and tested lots of our [blood] serum that we had from patients and it turned out it was really specific – it only picked up SARS-CoV-2, which is good,’ said Dr Whittier. 

‘But it was only 50 per cent of patients who should have had antibodies.

‘So if it was positive, that was good, they definitely have antibodies’.

But if it was negative, ‘you might as well be flipping a coin’.

Needless to say, Columbia ditched that test. 

And with FDA guidelines relaxed in an effort to get more tests out more quickly, there’s less assurance that validation is done with a comprehensive sample of patients. 

Dr Whittier says that the package insert for one test she looked at said the company had only tested their test on about five patients. 

‘That’s crazy,’ she said. ‘Normally that would never happen, but in the middle of a pandemic, you’re allowed to push assays out because maybe perfect is the enemy of good.’ 

ANTIBODIES PROVIDE IMMUNITY – BUT HOW MUCH PROTECTION AND HOW LONG IT LASTS VARIES 

New Hampshire's test (pictured) looks for the presence of antibodies, but it may not tell what level of antibodies are in a person's blood, and scientists don't know how much is enough to offer protection from reinfection

New Hampshire’s test (pictured) looks for the presence of antibodies, but it may not tell what level of antibodies are in a person’s blood, and scientists don’t know how much is enough to offer protection from reinfection

When we contract an infection, the immune system goes to work creating specialized weapons against whatever invader we came into contact with, called antibodies. 

Once we’ve encountered a pathogen and develop antibodies to it, these proteins sound the alarm when the invader returns and neutralize it. 

But not all antibodies are created equal, and not everyone develops the same number of antibodies. 

For example, it’s well known that once you get chicken pox, you’re almost certainly immune to it and will never be infected again. 

That’s not true for antibodies against other pathogens. Immunity for other infections wears off relatively quickly. 

Flu is fairly well understood, but the virus has many strains which mutate readily. 

Antibodies produced against each variation of flu we encounter are quite specific to that unique infection. 

So when we come into contact with an evolved or different strain of flu the next season, the antibodies we developed the prior year don’t do us much good. 

That’s why flu vaccines are ‘recombinant’ – they’re made based on a combinations of several strains of flu, triggering the production of a variety of antibodies to block the strains scientists think we might making their way around the globe that year. 

The most common coronaviruses – those that cause seasonal colds – trigger fairly weak antibody responses, lasting only a couple of weeks, which is part of the reason you might get multiple colds in a single year. 

However, research on the new coronavirus’s closest relative – SARS – is somewhat more encouraging. By the second week after someone is infected, they’ve generated antibodies that seems to last an average of two years. 

But we simply don’t know how similarly antibodies for the virus that causes COVID-19 will behave because we’ve only known it existed for four months. 

WHAT DOES A POSITIVE CORONAVIRUS ANTIBODY TEST REALLY MEAN? EVEN THE EXPERTS DON’T KNOW… YET

Time and volume of people infected are two key crucial ingredients for an antibody test. They tell scientists how many antibodies are enough to make someone immune to reinfection, and how long that immunity lasts. 

And labs developing antibody tests have neither on their side. 

‘We can’t tell you that, because we don’t have a gold standard to compare it to,’ Dr Whittier said.

The FDA gave emergency use authorization to the first antibody test for coronavirus in the US on April 2 – less than two weeks ago. 

That’s about as long as scientists think that it takes for a patient to mount an antibody response to SARS-CoV-2. 

Dr Whittier said: ‘Twelve to 14 days is when most individuals are having an antibody response, but we don’t know if it’s protective, and we don’t know how long it lasts.’

Having the antibody test is the first step to answering those questions. But some people will develop antibodies more quickly than other, and some will develop greater quantities of antibodies than others. 

It will take following these people and testing them repeatedly to learn what the ‘gold standard’ for immunity is. 

What’s more, the first antibody tests only returned results about whether antibodies were present. They did not reveal what volume someone’s body had produced them. 

Now, labs are starting to produce ‘semi-quantitative’ tests, that can tell if someone has ‘a little antibody or a lot of antibody,’ Dr Whittier said. 

As more people are tested for levels of antibodies, not just their existence, epidemiologists can study what levels provide protection and for how long.

But for now, ‘we don’t know what we don’t know,’ Dr Whittier says.

Read more at DailyMail.co.uk