Would you pay £300 for the test that tells if you’ve already had coronavirus?
IT’S A niggling question eating away at millions of Britons: was that wretched cough that lasted for most of February actually coronavirus? And if it was, might you have locked down your life for nothing? The answer lies in a simple test that looks for antibodies in the blood – proteins released by the immune system in response to the Covid-19 virus.
The theory is that if you’ve developed antibodies, the immune system is primed to fight the virus, and it’s highly unlikely you’ll get it again.
Such a test doesn’t tell you if you currently have it – a different test is used to diagnose active disease. But it will tell you if you’ve had it in the past.
And this has been deemed crucial from the very start of the pandemic – the key to establishing exactly how many have been infected.
The reason? Up to 80 per cent of those who get Covid19 suffer a mild illness or may not even realise they’ve had it – and diagnostic testing has, until recently, been limited to those ill enough to end up in hospital.
Just how prevalent Covid-19 really has been is still unknown. Last week, Public Health England backed a new antibody blood test developed by Swiss firm Roche, which officials hope might finally provide an answer. The manufacturers claim the test is almost 100 per cent accurate – and are in talks with NHS providers about distributing it across the country.
But scientists are cautious. Previous attempts to roll out such tests have proved disastrous. The initial misfire came in early April, when 3.5 million antibody test kits ordered for use by the Government were found to be useless. Studies showed that the tests were unable to differentiate between antibodies triggered by Covid-19 and those associated with the common cold.
A few weeks later, officials announced plans to distribute pregnancy-test style finger-prick tests to millions before some of those were found to be ‘insufficiently accurate’.
But at the same time, scores of private companies have begun offering similar DIY tests, costing up to £100. Some of the country’s biggest employers have even batch-bought the devices and are testing staff to get them back to work quickly and safely.
So do any of them work?
BROADLY speaking, there are two different types of antibody tests. The failed tests initially planned for use by the Government were so-called lateral flow immunoassay (LFI). They can be completed within minutes at home and look a bit like pregnancy kits.
The test must be taken about at least ten days after symptoms emerge, to allow time for antibodies to be produced.
Using a tiny needle, you prick your finger to draw blood, then place a droplet on a piece of blotting paper.
Built into the blotting paper are proteins called antigens. These antigens are targeted by antibodies released by the immune system deployed to fight the virus.
If antibodies are present in blood, they will bind to the antigens on the paper. A chemical is triggered, causing a blue line to emerge – an indicator of a positive result. Results are seen within ten minutes.
Yet several studies have found these tests to be unreliable – and for this reason, experts urge extreme caution. ‘A large quantity of antibodies needs to be produced by the body in order for these tests to detect them,’ says Dr Penny Ward, visiting professor in pharmaceutical medicine at King’s College London.
The concentration of antibodies found in the blood of those who have had Covid-19 is thought to vary – those who have had the worst symptoms have been found to have the highest numbers. However, those who have not had the disease as severely may have lower concentrations, and the LFI test may not pick these up.
‘These tests have a high false negative rate,’ warns Dr Ward.
Will Irving, professor of microbiology and infectious diseases at Nottingham University, adds: ‘In laboratories, we can add chemicals that help to pick up minuscule amounts of antibodies. You simply can’t do that with these tests.’
The second, more robust, method is a blood test carried out in clinics, which is considered the ‘gold standard’. Called an enzyme-linked immunosorbent assay, or ELISA, it involves taking about 10ml of blood, which is then spun in a machine to extract the antibody-rich blood serum. The serum is then placed on to plastic plates coated with specific coronavirus antigens. This too measures the number of antibodies that attach themselves to the antigens on the plate.
Unlike the LFI tests, only the blood serum – which carries the antibodies – is used, making it far easier to detect them.
The new antibody test approved for use last week, called the Elecsys, is a type of ELISA test. Blood samples taken at a GP surgery or specialist clinic are then analysed in a laboratory by scientists.
But what would a positive result actually mean?
The answer is not as straightforward as it might seem.
One UK clinic, Private Harley Street Clinic in London, is already offering its version of an ELISA blood test for a hefty price of £300.
Journalist Miranda Levy, 52, was one of the first Britons to take it. She was convinced that the rampant fever, persistent headaches and scratchy throat that plagued her in January, was, in fact, the coronavirus. ‘My boyfriend Hugo and I first became unwell during a holiday to the US,’ says Miranda, from Essex.
‘We flew to and from Nicaragua via New York, which must have been swarming with the virus at the time. My cough had finished by the time I got home a week later, but I didn’t feel right for weeks.
‘We didn’t think much of it until Covid-19 hit the headlines in March – and my boyfriend, who lives in America, was offered a free ELISA test as part of a research programme. It came back positive.’
When Miranda found a clinic offering the same test in the UK, she signed up immediately. But her results, which arrived last week, were negative.
‘I just thought, “How could that
be?” Hugo had had a slight fever in March – so mild, he hadn’t even mentioned it. Perhaps that was Covid-19? I was so disappointed – I wanted to feel like I had virusfighting superpowers too. But then I read articles suggesting a positive result may not mean a person is immune after all.’
Miranda’s doubts are justified. First of all, not all ELISA tests are created equally.
‘The technology works but each individual test varies in terms of accuracy,’ says Dr Ward. ‘There is currently no legislation that requires manufacturers to provide evidence to show their particular device works.
‘The test may have only been verified using animals or in petri dishes – not on humans.’
The same doubts apply to the new test backed by Public Health England – there is little detail about the research on which the accuracy claims are based.
‘Without seeing the study methods and the data, it’s impossible to verify these claims of accuracy,’ warns Prof Carl Heneghan, director of the Centre for Evidence-Based Medicine at Oxford University.
And Prof Irving adds: ‘Manufacturers might say their test is 99 per cent sensitive, based on 100 people with Covid-19.
‘But if all 100 of those people were very ill in hospital – producing large numbers of antibodies – then we’ve no idea if it will find antibodies in non-hospitalised patients with a mild illness who produce far less.’
A major trial run by Imperial
Healthcare Trust in London and the Department for Health hopes to fill this gap in information, by randomly distributing 100,000 of the newly approved antibody tests to people in the community.
But even if the test is 100 per cent accurate, what does it actually tell you?
‘For now, antibody tests can only tell you if you’ve had the virus, not if you’re definitely protected from reinfection,’ says Dr Ward. ‘We currently don’t know the level of antibody needed to grant immunity.’
Promisingly, studies from China suggest high levels of Covid-19 specific antibodies do appear to indicate immunity, or at least a less severe second infection. But how long immunity lasts is unknown, according to studies of previous coronaviruses. Survivors of SARS had protective antibodies for anything between three and 17 years, and they seemed to prevent reinfection. But a 2016 follow-up of MERS patients showed their protective antibodies lasted just three years.
Unlike the flu virus, which mutates and so can evade existing antibodies, mutations in the new coronavirus are rare.
But, as Dr Ward says, antibodies are only one small part of the puzzle when it comes to understanding Covid-19 immunity. ‘The immune system draws on several important modes of defence to guard us against reinfection,’ she says. Scientists are also investigating the role of a type of fighter cell, released in response to a virus, called a T-cell. Studies show these can remain for longer than antibodies – in recovered SARS patients they’ve been detected more than a decade later. ‘There’s a lot of research to do before we know what is needed to make someone immune from Covid-19,’ says Dr Ward. ‘It’s going to take years of studying people, the further away they get from the first infection.’
So, if there is no guarantee antibodies grant us immunity, why is the Government testing for them?
‘Antibody testing is crucial for understanding the spread of the disease and how deadly it is,’ says Dr Ward. ‘It may be that thousands of people in the community have come into contact with it but haven’t had symptoms. If this is the case, it would dramatically reduce the mortality rate.
‘We saw this in swine flu – only after subsequent antibody tests did we learn that, in many people, it was so harmless they didn’t even know they had it. It could be that we’re massively overestimating the mortality rate.’