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, say health agencies. 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, says Smith. (A study1by researchers at Shenzhen Third People’s Hospital in China found that PCR tests did not always diagnose patients infected with the virus.)
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. For instance, the German biopharmaceutical company EUROIMMUN has developed a lab test that detects SARS-CoV-2-specific immunoglobulin G and immunoglobulin A.
Because of the ongoing emergency, the US Food and Drug Administration (FDA) has relaxed the rules that govern the use of such tests. It has authorized their use in laboratories and by health-care workers to diagnose active COVID-19 infection, with the disclaimer that they have not been reviewed by the FDA and that results should not be used as the sole basis for confirming that someone has the disease. Australia has also introduced similar emergency authorizations.
These measures are appropriate given the pandemic situation, says Smith. Antibody tests in people who might be actively infected can be an important part of managing patients at hospitals, and contact tracing, although the results need to be interpreted cautiously, he says.
Test the tests
One problem, however, is that most kits have not undergone rigorous testing to ensure they’re reliable, says Busch. 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, says Peter Collignon, a physician and laboratory microbiologist at Australian National University in Canberra. 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, adds Collignon. 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. In an analysis2 of 9 commercial tests available in Denmark, 3 lab-based tests had sensitivities ranging 67–93% and specificities of 93–100%. In the same study, five out of six point-of-care tests had sensitivities ranging 80–93%, and 80-100% specificity, but some kits were tested on fewer than 30 people. Testing was suspended for one kit. Overall, the sensitivity of all the tests improved over time, with the highest sensitivity recorded two weeks after symptoms first appeared. Some of these tests are also being used to test individuals in other countries, including Germany and Australia.
Point-of-care tests are even less reliable than tests being used in labs, adds Smith. This is 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, he says.
The WHO recommends that point-of-care tests only be used for research.
Without reliable tests, “we may end up doing more harm than good,” says Collignon.
Timing 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, says Smith. 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, says Collignon. It took several years to develop antibody tests for HIV with more than 99% specificity, he says.
Reference& Source information : https://www.nature.com/
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