In late March, the UK government announced the ordering of millions of home-based antibody tests and their planning to roll out the quick test to the public, in cooperation with Boots and Amazon.1 Thereafter, I wrote a blog post on introducing different types of test for SARS-CoV-2, which also compared the sensitivity and accuracy of the tests. I specifically pointed out that antibody tests, particularly the quick home-based antibody test, would have a much lower sensitivity and accuracy. Immediately the next day after the publication of the post, UK scientists who were involved in validating home testing kits said that no antibody test on the market has yet been shown to be sufficiently reliable.2 And the news in subsequent days was that the home-based antibody test will not be available in the UK in the coming few weeks, with the health secretary, Matt Hancock, saying that the tests are not yet "good enough".3,4
According to the news report, none of the antibody tests on the market have met the standards agreed with the Medicines and Healthcare products Regulatory Agency (HMRA). The Oxford group, which is responsible for assessing the tests, has characterised six different antibody tests and found that most failed to detect antibodies half the time, and the best spotted the immune cells only 70% of the time. If used at scale, the tests could leave millions of people who have immunity convinced they are still vulnerable to the infection. For the test to pass, the accuracy would have to be nearer 95%.3
In the same report, Professor Martin Hibberd from the London School of Hygiene and Tropical Medicine described that the finger-prick antibody tests are "traditionally very poor in terms of sensitivity and specificity". As I mentioned in my blog post, the low sensitivity is due to a tiny amount of blood being used. A false negative result would happen if the circulating antibody in the test sample is in low level; the poor specificity is due to the cross-reactivity which increases the chance of a false positive result. The monoclonal antibody raised against the target antibody wrongly recognizes another molecule which has high similar structural regions as the target. Therefore, the accuracy of the antibody test is largely dependent on how well the manufacturer raises and selects the antibody against the target. Unfortunately, those antibody tests available in the market "look very similar and probably come from the same factory in China," said Sir John Bell, a Regius professor of medicine at Oxford University. Due to the complexity of the work, a working antibody test with improved sensitivity and accuracy seems to be months away, or it's even possible that we won't get an antibody test that meets the standard.
On the basis of the finding of the quality of the tests and his experience, Prof Hibberd suggested "a centralised pathology lab antibody test" and that the UK government should drop the idea of making the finger-prick antibody test available to the public. Actually, the lab-based antibody test at Oxford University can distinguish positive and negative samples of blood with almost 100% accuracy.* The disadvantages are that blood needs to be taken from people, the whole test process takes much longer and involves much technical expertise.3
While the UK government is still struggling in validating the home-based antibody tests, Germany and the US have started carrying out a nationwide lab-based antibody test.5 The test project in Germany will be carried out jointly by three different universities, while the one in the US will be carried out by the CDC. With the references from other countries, it seems applicable for the UK government implementing a nationwide lab-based test which is more reliable than the home-based test.
*An antibody test, whatever a lab-based or a home-based finger-prick one, is basically an enzyme-linked immunosorbent assay (ELISA). However, a lab-based test has the advantage of being able to use a higher volume of blood sample, thus increasing the sensitivity of the test. Moreover, in the lab-based ELISA, washing steps are usually performed after the incubation of the test sample with the detection platform, which is mounted with detection agents. These washing steps can eliminate non-specific binding, and remove excessive components that can interfere with the assay, thus increasing the specificity of the assay. On the other hand, no adjustment can be done to improve the sensitivity and specificity of the home-based antibody test, due to the restriction of the setting.
References
1. "Coronavirus tests: UK to make 15 mins at-home kits available within weeks" The Independent, 25th March, 2020. https://www.independent.co.uk/news/uk/home-news/coronavirus-test-uk-kit-home-nhs-cases-symptoms-public-health-england-a9424741.html
2. "Coronavirus 'game changer' testing kits could be unreliable, UK scientists say" The Guardian, 5th April, 2020. https://www.theguardian.com/world/2020/apr/05/coronavirus-testing-kits-could-be-unreliable-uk-scientists-say
3. "UK government urged to abandon "poor" finger-prick antibody tests" The Guardian, 9th April, 2020. https://www.theguardian.com/world/2020/apr/09/uk-government-urged-to-abandon-poor-finger-prick-antibody-tests-coronavirus
4. "UK COVID-19 antibody tests not ready until May at earliest" The Guardian, 8th April, 2020. https://www.theguardian.com/society/2020/apr/08/uk-covid-19-antibody-tests-not-ready-until-may-at-earliest
5. "Germany to run Europe's first large-scale antibody test programme" Financial Times, 9th April, 2020. https://www.ft.com/content/fe211ec7-0ed4-4d36-9d83-14b639efb3ad
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