Have you had a COVID test yet? Was it a lateral flow test or a PCR test?
Maybe you’re not sure which type of test you had – and for a lot of people, especially those who don’t work in science, perhaps it doesn’t seem important to know. However, the differences between types of tests being used has led to some confusion as to their usefulness and accuracy
Ever since the community testing pilot scheme was first launched back in November of 2020 here in Liverpool, I’ve been fielding questions from people about different sorts of COVID test. I thought it was might be useful to answer some of those questions here, as understanding how the tests work, and how they differ, is key to understanding the potential success of community testing.
The PCR test for SARS-CoV-2 is generally considered the “gold standard” when it comes to testing for COVID, which is why it is important to use it for symptomatic testing. If you had a test because you had symptoms, it would have been a PCR test.
PCR stands for Polymerase Chain Reaction. The test relies on the use of an enzyme called polymerase which usually exists in normal cells, doing useful things like helping to replicate DNA when we want to make a new cell.
In COVID testing, we use PCR to replicate genetic material belonging to the SARS-CoV-2 virus. Once you’ve taken your swab from the back of your throat and up your nose, the sample gets mixed up with some enzyme and a load of other ingredients designed to help the enzyme do its job, and we ask the enzyme to amplify the genetic material of SARS-CoV-2. Importantly we ask it to only amplify the genetic material of SARS-CoV-2.
Imagine the genetic material of SARS-CoV-2 is one half of a zip – the metal teeth down one side. The polymerase enzyme is like the slider, which you pull up to fasten each tooth to its pair. In the case of the PCR test, the enzyme fastens to one end of that genetic material, but rather than finding an existing part to pair it to, the enzyme creates a copy of the half we already have as it moves its way along, creating an entire sealed zip.
So now, we have our original piece of SARS-CoV-2 genetic material, and we have a copy of it, and the original and the copy are connected together. We use some heat to separate the two and then the enzyme can start all over again, making two new copies of the two halves. This process will keep going and going until we have enough copies of the genetic material to be detectable. This threshold of detection is especially useful because we can work out how quickly we reach the threshold – if we reach it really quickly, then we can assume there were already lots of copies of the SARS-CoV-2 genetic material for the enzyme to duplicate, which means the sample had a high viral load. If we reach the threshold really slowly, then there must not have been many copies of the SARS-CoV-2 material initially available, and so the sample had a low viral load.
That’s roughly how it works – but the important thing to understand is this: PCR is really specific (ie it only detects what we ask it to – in this case SARS-CoV-2); PCR is really sensitive (it can detect even very low levels of the virus because of this crucial amplification step); and PCR is pretty reliable (it doesn’t miss many cases of COVID).
PCR is also quite resource heavy – it takes time and expertise to run the test, and it requires special machinery and lab space as well as ingredients to help the enzyme do its job.
Enter the lateral flow test.
Lateral flow test
The lateral flow test is cheap, easy to implement and can be done pretty much anywhere. Test centres have popped up all over Liverpool, and in fact in local authorities across the country, in order to test as many people as possible as quickly as possible. While PCR testing gives you a result in 48 hours, lateral flow testing can give a result in less than an hour.
Lateral flow tests actually work very similarly to pregnancy tests. The idea is this: the SARS-CoV-2 virus is made of proteins, and we can use antibodies to detect proteins.
The lateral flow test contains a small cassette, which holds a piece of filter paper. The filter paper has a “conjugation zone” at the bottom where you apply the sample taken by swabbing the throat and nose.
The conjugation zone is loaded with antibodies which recognise proteins from SARS-CoV-2, and these antibodies are fused to a gold nanoparticle. Once the sample is loaded, the SARS-CoV-2 proteins bind to the antibody and start moving up the filter paper by lateral flow. First, they reach a test zone, where there are more antibodies which also recognise SARS-CoV-2 proteins. If the sample contains the virus, the proteins which are conjugated to the gold-antibody get trapped on the test zone, and because the gold is really concentrated, the zone turns pink (because gold nanoparticles are pink). Then, the sample continues to travel up the strip until it reaches a control zone. The control zone is loaded with an antibody which recognises the gold-antibody. Any of the gold-antibody which is not connected to SARS-CoV-2 protein gets trapped here and turns the control zone pink. This means the test worked as it was supposed to.
We therefore have three possible outcomes:
- The test zone is pink and the control zone is pink = the test worked and the sample was positive for COVID
- The test zone is blank and the control zone is pink = the test worked and the sample was negative for COVID
- The test zone is either pink or blank and the control zone is blank = the test did not work and should be repeated
Research shows that the lateral flow test is really specific (it only detects what we ask it to and does not lead to false positives) but the lateral flow test is not very sensitive. It struggles to detect low levels of virus. This means it is important to wait at least five days from exposure to COVID to take a lateral flow test, because in the first five days the viral load is quite low.
The lateral flow test is also a little unreliable.
Preliminary research from the University of Liverpool during the pilot scheme showed that the lateral flow test only detected 48.83% of the cases that PCR testing was able to detect (and the PCR test cannot detect 100% of cases).
But is this a problem?
The pros and cons of lateral flow testing
Lateral flow testing is only used for asymptomatic testing in the community. Before we introduced this community testing, you could only get tested for COVID if you had symptoms. Which means even if lateral flow testing detects less than 50% of all asymptomatic cases, it is still detecting more cases than we previously knew about. If all of those people it detects go on to self-isolate, then we are making a big dent on reducing transmission.
However, people who are tested using lateral flow testing and receive a negative result could still have COVID. The test misses over 50% of positive cases, giving them a false negative result. It is absolutely crucial that people who have had a negative lateral flow test result continue to social distance, continue to avoid mixing with other households indoors and continue to wear masks in public spaces and wash their hands frequently.
Lateral flow testing, although not as sensitive or reliable as PCR testing, is a reasonable testing strategy for reducing asymptomatic transmission if – and only if – people are aware of the limitations.
What lateral flow testing cannot be used for is to allow people to reduce their social distancing practices and return to “normal”. It cannot be used to permit stadiums and theatres to return to full capacity as long as all people are tested before entry. It cannot be used to allow you to visit your nana in a care home and breathe all over her or lick her face.
Lateral flow testing is a tool along the way to combatting the COVID-19 pandemic, but it is not, and was never designed to be, The Answer.