Health authorities in New York are today beginning to carry out coronavirus antibody tests to try and work out how many citizens have had COVID-19 already.
The blood tests, which look for signs of past infection, are considered by many to be key to lifting lockdown measures and controlling the virus’s spread in future.
The state, home to 19million, aims to test 14,000 random people – 2,000 a day – this week as it scales up efforts to get its outbreak under control.
New York has been devastated by the virus and has recorded more cases (243,000) than any country in the world and more than 17,000 people have died.
State governor Andrew Cuomo said yesterday the ‘aggressive’ testing effort will offer US officials ‘the first true picture’ of the scale of the coronavirus outbreak there.
In the UK, where Number 10’s slow uptake of testing remains a controversial topic, fewer than 4,300 tests have been carried out since they began this month.
Public Health England is believed to be carrying out all of its antibody testing in one laboratory in Wiltshire and to be shunning commercial tests in favour of its own.
Germany and Finland have all also begun antibody testing, while the Italian region of Lombardy plans to carry out 20,000 a day.
New York State governor Andrew Cuomo (pictured touring a science lab on Long Island, NY) said yesterday the ‘aggressive’ testing effort will offer US officials ‘the first true picture’ of the scale of the coronavirus outbreak there
When someone gets infected with a virus their immune system must work out how to fight it off and produce substances called antibodies.
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.
Mr Cuomo, giving a briefing on the situation in New York, said yesterday: ‘You could argue that we are past the plateau and we’re starting to descend, which would be very good news.’
But health experts say for places to emerge safely from lockdown and avoid second waves of infections, they must be able to do widespread testing.
Swab tests must be available to catch infected people before they spread the virus, and antibody tests must be used to evaluate how many people might have some natural immunity, reducing the risk of fast-spreading outbreaks.
Vice President Mike Pence said on Friday the US had the capacity to do a sufficient amount of testing for states to move into a phase one of reopening.
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.
Governors and state health officials, however, say there is nowhere near enough test kits and equipment available.
Mr Cuomo said in a briefing yesterday: ‘Any plan that is going to start to reopen the economy has to be based on data and that means it has to be based on testing,’ Politico reported.
‘You have all these scientists and all these experts who are basically trying to extrapolate from the data, but we don’t really know how many people were infected – how many people had coronavirus but self-resolved?
‘We don’t really know because we haven’t been able to do testing on that large a scale, but we’re going to start, and we’re going to start here in the state of New York with antibody testing.’
Antibody testing remains controversial in the UK because the Government insists it cannot find a commercial test good enough to use on the public.
The Department of Health bought 3.5million antibody testing kits but expert examination of them found they were not accurate enough to use.
Standards released by the Medicines and Healthcare products Regulatory Agency (MHRA) said antibody tests must be at least 98 per cent accurate.
The only commercial test to have been approved in the US – produced by a company called Cellex – is approximately 95 per cent accurate.
The UK last month 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.
The Department of Health set out antibody testing as its fourth pillar in its programme to understand the true size of the outbreak in Britain.
It said: ‘Robust population surveillance programmes are essential to understand the rate of infection, and how the virus is spreading across the country.
‘They help us to assess the impact of measures taken so far to contain the virus, to inform current and future actions, and to develop new tests and treatments.’
PHE said in guidance released on April 4 that it was in the process of analysing the first 800 samples collected.
It said PHE was in the process of scaling up its antibody testing programme to carry out around 5,000 per week.
Its end goal is to have up to 20,000 people who will be repeatedly tested over a 12-month period, to paint a clearer picture on the truth about immunity.
The most up-to-date DH figures, released yesterday, show 4,287 antibody tests have been carried out, including 377 on Saturday.
But the number of people actually tested will be lower because health bosses keep the samples sent to the Porton Down lab anonymised.
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.
Scientists say antibody tests will be crucial to building up herd immunity against the coronavirus, which may be the only long-term protection until a vaccine is made.
Herd immunity is a situation in which so many people have had a disease already and are protected from it that it cannot spread quickly through a community – those who are immune effectively create roadblocks against the disease.
It comes after the WHO warned there is no evidence to prove that people who have recovered from coronavirus will not catch it again.
The UN body warned world leaders against investing too heavily in the tests to show if a person has already had the virus, because they do not guarantee immunity.
WHAT ARE ANTIBODY TESTS? HOW DO THEY WORK? AND WHY HASN’T BRITAIN APPROVED ANY YET?
HOW DO ANTIBODY TESTS WORK, AND HOW ARE THEY DIFFERENT TO SWABS?
Scientists still don’t know if developing antibodies means lifelong immunity and whether tests will ever be accurate
Does everyone who has survived coronavirus develop antibodies?
When someone is exposed to coronavirus, the body begins making proteins known as antibodies which fight the infection.
If these antibodies can successfully contain the virus and stop it spreading within the body, symptoms will normally start to reduce in patients.
The immune system will then completely destroy all the virus in someone’s body – leaving them with no long-term health effects if all goes well.
Everyone who develops Covid-19 will produce these antibodies, but small amounts of the virus may remain in the body for a few days after they feel fully recovered – hence the importance of self-isolation.
Scientists are unclear whether developing antibodies means immunity will be lifelong – and they may only last an average of two years
Once someone has recovered from a viral infection, their body will retain cells known as lymphocytes in their system.
These effectively remember viruses the body has previously encountered, meaning it should quickly fight them off again.
This means your antibodies will probably stop the virus before it causes any noticeable symptoms – also known as ‘immunity’.
However, immunity can decrease over time for some viruses, which is why some people get revaccinated with ‘boosters’ which can prompt the immune system to make more antibodies.
The issue with Covid-19 is that because it is so new, scientists are currently unsure whether people who recover from the infection are immune to catching it again.
Furthermore, the World Health Organisation has warned there is limited evidence that coronavirus survivors were guaranteed future immunity to the disease.
Some early animal studies suggested that antibodies could block reinfection for at least two weeks.
But research on the new coronavirus’ closest relative – SARS – shows a patient generates antibodies that last an average of two years.
Tom Duszynski, an expert in epidemiology at Indiana University–Purdue University Indianapolis, said: ‘Doctors are finding antibodies in ill and recovered patients, and that indicates the development of immunity.
‘But the question remains how long that immunity will last. Other coronaviruses like SARS and MERS produce an immune response that will protect a person at least for a short time.
‘I would suspect the same is true of SARS-CoV-2 (the virus strain that causes Covid-19), but the research simply hasn’t been done yet to say so definitively.’
Once the test is developed, are they accurate enough to see people who have antibodies?
Guidelines from the US Centers for Disease Control and Prevention say that a person has recovered from Covid-19 when they have been fever-free without medication for three days in a row.
They must also show an improvement in other symptoms such as coughing and shortness of breath – as well as testing negative for the virus twice in two tests taken at least 24 hours apart.
As for the antibody test, government officials in the US and UK are yet to find one that is good enough for widespread use.
Columbia University expert Dr Susan Whittier has admitted it could take years to find a test which will be accurate enough, although scientists are trying to find a blood-based test within a few months.
The main issue is within identifying the exact antibodies produced by a body with a healthy immune system to fight the infection, which scientists are divided on.
This means antibody tests have been produced with various designs so far, some of which have failed to work with enough accuracy because they are not specific enough for SARS-CoV-2.
Viruses are made up of many proteins, called antigens, of which some are shared with other viruses – but only a few may be unique to Covid-19.
The proteins specific to the virus will trigger the production of antibodies that neutralise the virus, stopping it from replicating.
Dr Whittier said: ‘We have to figure out what part of the virus is going to be really specific for that virus.’
NHS England national medical director Professor Stephen Powis said today that officials ‘don’t have the perfect test for antibodies yet’, but the UK is working on one which will assess the real number of infections in the community.
He said: ‘What’s important now as we are a few weeks further on is actually getting the real number on infections in the community and that is best done by testing antibodies i.e. testing people who have caught the virus, and then developed an immune response and then have antibodies in their blood.
‘We are beginning to see some studies from other countries that are doing that, it’s not straightforward, firstly because the tests are still being worked out and we don’t have the perfect test for antibodies yet.
‘We don’t know how many people produce antibodies when they have the virus and when they produce it and how long they last for.
‘That’s the important information that will give us an actual figure that is much more closer to the number of infections.
‘That work is ongoing in the UK at the moment so we can have that information in the UK rather than relying on other countries.’
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.
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.
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.
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.
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.
‘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
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.
