By Dr Claire Walker
Paid-up member of the Dream Team since 2013 (as discussed in a previous post, in her personal life most people call her Girlymicro Dream), token immunologist and occasional defector from the Immunology Mafia. Registered Clinical Scientist in Immunology with a background in genetics (PhD), microbiology and immunology (MSc), biological sciences (mBiolSci) and indecisiveness (everything else). Now a Senior Lecturer in Immunology at University of Lincoln.
A clinical immunologist’s thoughts on lateral flow antibody testing – this post follows on from Dr Dream’s awesome post on testing for the virus – concerns my thoughts on COVID-19 antibody testing by lateral flow technologies.
‘The LEDs on the top of the box turned on, one red, one green, beginning to flash in an alternating patter. The flashing slowed and finally stopped as the red light went out, leaving the green. Still clean.’
‘Feed’ by Mira Grant 2010 (see Newsflesh book review for some more on the series)
Whilst some days it might feel like the end of the world during the COVID19 Pandemic, we aren’t quite living through the zombie dystopian vision of the future described in Mira Grant’s Feedback trilogy. However, much like in the world envisioned in Feed, point of care testing has become part of many people’s lives. A friend recently received a lateral flow anti-SARS CoV-2 antibody test and sent me his result saying, “turns out I never had it, 80-90% confident”. It sounds like quite good odds, doesn’t it? If you happen to like gambling, and someone told you to bet on a horse with an 80-90% chance of winning, it’d be tempting to have a flutter. But when it comes to clinical testing, a 1 in 5 chance that that result is inaccurate is far less appealing.
What are the tests?
Antibody tests, unlike testing for the virus itself, detect the antibodies produced by our immune systems in response to infection. To envisage a lateral flow test, think about a pregnancy test. Instead of urine, a few drops of blood from a finger prick are mixed with a solution and applied to the device.
You then wait 10-15 minutes and the results can be read in the result window (image 2). There are many different versions of these tests out there, but the underlying principle is much the same. If you have the antibodies in your blood sample, they bind to viral proteins attached to gold particles. This forms an antibody-antigen-gold-particle complex which can be seen as the positive test line.
How good are the tests?
‘Confident’ isn’t a term we like to use in clinical science: we like the terms ‘sensitive’ and ‘specific’. We also like to use statistics to describe the sensitivity and specificity of a test. In the case of COVID-19, the sensitivity of the test is the proportion of people with COVID-19 that have a positive blood test. A test which is 100% sensitive means that all individuals with COVID-19 are correctly identified as having the disease. Conversely, specificity is the proportion of individuals without COVID that have a negative blood test. A test that is 100% specific means that all healthy individuals are correctly identified as not having COVID-19. It’s pretty hard for any clinical test to be this wonderful, but we are trying to get as close to this ideal as possible. The MHRA recommends these tests have a sensitivity of >98% and specificity of >98% (1). To date, none of the lateral flow assays to detect antibodies have met these criteria.
What are we using them for?
Testing for antibodies isn’t the same as testing for virus. A positive result means you were likely infected with COVID-19 in the past. This result should not be used to diagnose a current COVID-19 infection because it can take 1-3 weeks after infection for your body to make antibodies. We aren’t sure how long these antibodies are going to stick around either. Some viruses are very memorable to the immune system. Unfortunately, coronaviruses are pretty forgettable, and the ‘immunological memory’ – the antibodies against the SARS CoV-2 virus – may disappear in a matter of months. In the case of my friend, who took his antibody test in October to find out if he had COVID-19 in February, that negative result doesn’t mean very much.
This test only tells you that you’ve made antibodies to the virus, not how many are there and if they can stop reinfection. We don’t know if these antibodies are protective or if that makes you immune to the virus. You can also test positive for the virus and positive for antibodies at the same time, meaning you are still infectious. Best not to use the result to decide whether or not to visit Grandma.
The Bottom Line
Whilst I don’t love these tests for individual use, they are useful. By monitoring the prevalence of antibodies against SARS CoV-2 at a population level, we get a snapshot of what is happening in the country in the moment the test is taken. It tells us something about the antibody status of a community of individuals, helping to monitor the COVID-19 pandemic at a population level and more data will hopefully help immunologists better understand what on earth is going on with the immune response to this virus.
TLDR. Lateral flow tests for antibodies are best left for community studies and aren’t going to let you know if you had COVID-19 in January. You’ll just have to keep wondering.
Reference
- MHRA. Target product profile antibody tests to help determine if people have immunity to SARS-CoV-2, 2020. Available: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/883897/Target_Product_Profile_antibody_tests_to_help_determine_if_people_have_immunity_to_SARS-CoV-2_Version_2.pdf
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