Testing – Hope or Hype?

Some governments are putting all their bets on testing to help reopen their economies. This is why they are going to be very disappointed.

British Prime Minister Boris Johnson called them a ‘game changer’. Antibody tests have captured the world’s attention for their potential to help life return to normal by revealing who has been exposed, and might now be immune, to the new coronavirus.

So why are tests not the game changer that many people think they are? Are they Hope or Hype?

British Prime Minister Boris Johnson called them a ‘game changer’. Antibody tests have captured the world’s attention for their potential to help life return to normal by revealing who has been exposed, and might now be immune, to the new coronavirus.

Dozens of biotech companies and research laboratories have rushed to produce the blood tests. And governments around the world have bought millions of kits, in the hope that they could guide decisions on when to relax social-distancing measures and get people back to work. Some have even suggested that the tests could be used as an ‘immunity passport’, giving the owner clearance to interact with others again.

Many scientists share this enthusiasm. The immediate goal is a test that can tell healthcare and other essential workers whether they are still at risk of infection.

But as with most new technologies, there are signs that the promises of COVID-19 antibody tests have been oversold, and their challenges underestimated. Kits have flooded the market, but most aren’t accurate enough to confirm whether an individual has been exposed to the virus.

And even if tests are reliable, they can’t indicate whether someone is immune to reinfection. It will be quite a while before kits are as useful as hoped and hyped.

The UK government learnt about this the hard way after it ordered 3.5 million tests from several companies in late March, only to later discover that none of these tests performed well enough.

The old medical adage remains true – ‘No test is better than a bad test’.


When a virus invades the body, the immune system produces antibodies to fight it. Kits detect the presence of antibodies using components from the virus, known as antigens. Tests generally fall into one of two categories:

  • Lab tests that need to be processed by trained technicians and take about a day, and
  • Point-of-care tests that give rapid, on-the-spot results within 15 minutes to half an hour. Several companies, including Premier Biotech in the United States and China-based Autobio Diagnostics, offer point-of-care kits, which are designed to be used by health professionals to check if an individual has had the virus — but some companies market them for people to use at home.

The tests don’t detect the virus itself, so have limited use in diagnosing active infections. But in some countries, such as the United States and Australia, tests are being used in some cases to diagnose people who have suspected COVID-19, but who test negative on a standard PCR test.

Early studies in people who have recovered from COVID-19 have detected three kinds of SARS-CoV-2-specific antibody, and manufacturers and research institutes have developed tests that target these antibodies.

Who tests the tests?

One problem, however, is that most kits have not undergone rigorous testing to ensure they’re reliable. During a meeting at the UK Parliament’s House of Commons Science and Technology Select Committee on 8 April, Kathy Hall, the director of the testing strategy for COVID-19, said that no country appeared to have a validated antibody test that can accurately determine whether an individual has had COVID-19.

Kits need to be trialled on large groups of people to verify their accuracy: hundreds of people who have had COVID-19, and hundreds of people who haven’t, but so far, most test assessments have involved only some tens of individuals because they have been developed quickly.

It seems that many tests available now are not accurate enough at identifying people who have had the disease, a property called test sensitivity, and those who haven’t been infected, known as test specificity. A high-quality test should achieve 99% or more sensitivity and specificity. That means that testing should turn up only about 1 false positive and 1 false negative for every 100 true positive and true negative results.

But some commercial antibody tests have recorded specificities as low as 40% early in the infection.

Point-of-care tests are even less reliable than tests being used in labs, because they use a smaller sample of blood — typically from a finger prick — and are conducted in a less controlled environment than a lab, which can affect their performance. They should be used with caution.

Without reliable tests, we may end up doing more harm than good.

Timing of the test is critical

One unknown that affects both kinds of test is the interplay between timing and accuracy. If a test is done too soon after a person is infected and the body hasn’t had time to develop the antibodies the test is designed to detect, it could miss an infection. But scientists don’t yet know enough about the timing of the body’s immune responses to SARS-CoV-2 to say exactly when specific antibodies develop.

By contrast, false positives crop up if a test uses an antigen that doesn’t only target antibodies produced to fight SARS-CoV-2, and instead picks up antibodies for another pathogen as well. An analysis3 of EUROIMMUN’s antibody test found that although it detected SARS-CoV-2 antibodies in three people with COVID-19, it returned a positive result for two people with another coronavirus.

Ironing out all these issues takes time and involves trial and error, after all it took several years to develop antibody tests for HIV with more than 99% specificity.

Infection doesn’t equal immunity

Another big question surrounding antibody tests is the extent to which being infected with a pathogen confers immunity to reinfection. To have protective immunity, the body needs to produce a certain type of antibody, called a neutralizing antibody, which prevents the virus from entering cells.

But it’s not clear whether all people who have had COVID-19 develop these antibodies. An unpublished analysis4 of 175 people in China who had recovered from COVID-19 and had mild symptoms reported that 10 individuals produced no detectable neutralizing antibodies — even though some had high levels of binding antibodies. These people had been infected, but it’s unclear whether they have protective immunity.

So far, researchers say they have not seen any evidence that people can get reinfected with the virus, although there is anecdotal evidence that this has happened.

Even if it becomes clear that most people do develop neutralizing antibodies, most tests currently don’t detect them. And tests that do are more complex to develop and not widely available.

The fact that most antibody tests can’t detect neutralizing antibodies is also relevant because some politicians are pushing the idea that these tests be used to clear those with past COVID-19 infections to interact with others again, a so-called immunity passport. Researchers are trying to determine whether the antibodies detected by current kits can act as a proxy for protective immunity.

Another complicating factor for immunity passports is that antibody tests can’t rule out that a person is no longer infectious. A study published in Nature this month found that viral RNA declines slowly after antibodies are detected in the blood. The presence of viral RNA could mean that the person is still shedding infectious virus.

Despite the challenges, once reliable antibody tests are available, they could be important to understanding which groups of people have been infected and how to stop further spread. It’s just that they are not at that point yet, and so it is unwise to place too much importance on the results they give.