COVID-19: The tests

This article, written by CHT’s Chief Medical Officer Dr Ian Mann, addresses some of the most common questions we get about Covid testing and how it actually works. If you want to learn more about the virus itself, you might be interested in another article by Ian: COVID-19, the science.
 

What are the different types of Covid testing and how do they work?

A number of different tests are available for diagnosing people infected with COVID-19. The two dominant tests in use are Rapid Antigen testing (also referred to as ‘Lateral Flow testing’) and Polymerase Chain Reaction (PCR) testing. 

Rapid Antigen Tests (Lateral Flow tests) work by identifying protein fragments, or markers, from COVID-19. Scientists call lateral flow tests immunochromatographic assays. All that means is “a test which can give a visual result that is read by the naked eye”. The tests themselves use a strip of absorbent paper with some coloured particles and some antibodies that are impregnated on a layer in the test strip. When you take a sample from your throat and nose, whatever is on the back of your throat will end up on the swab. This then gets transferred, using a special liquid, from the swab onto the test strip. The liquid moves along the absorbent paper and if COVID-19 protein markers are present, they will bind to the antibodies that are fixed next to the positive line. If this binding happens colour particles get activated and you will see a line appear next to the "T" indicator. The other line on the test (normally by the "C" indicator) is called a control. It is there to check there isn’t anything wrong with the colour particles or the antibodies in the test.

PCR is method of testing that requires highly skilled people and expensive machines. PCR works by detecting DNA. The machine contains a reservoir of the building blocks for DNA. When a test sample swab is introduced to a small tube in the machine, it goes through a number of heating and cooling cycles to allow all the ingredients in the machine to make lots of copies of COVID-19, if it is present on the swab. This amplification of the amount of virus makes it much easier to know for sure if virus is present or not. If there is no virus present, there is nothing to amplify, and the sample comes back as a negative result. If there is even a small amount of COVID-19 DNA, PCR can amplify it and detect it—it is very sensitive.
 

Is a PCR or Lateral Flow test better?

One type of test is not ‘better’ than the other, they both have advantages and disadvantages.

The main differences between PCR and Rapid Antigen tests are speed, accuracy and cost. Rapid Antigen tests have the significant advantage of delivering a result in around 15-30 minutes. They are much cheaper and they can be done by anyone, anywhere. 

However, although Rapid Antigen tests are effective at picking up obvious positive results, if there is a low amount of the COVID-19 virus present—such as if you have just caught Covid, or if you are recovering from it, when you could still be infectious—Rapid Antigen tests may not be able to detect anything.

PCR tests have  the advantage of being able to detect the smallest amount of a virus and will identify some samples as being positive for COVID-19 that could not be detected by Rapid Antigen testing. This is why many countries will only accept negative PCR tests for entry. The downsides to PCR are that it takes several hours to get a result and requires expensive equipment with highly trained operators.

There are trade-offs between having answers faster but from tests that are less accurate versus slower test that is more accurate, so it depends on the situation which test is more helpful.
 

What is genomic testing?

A genomic PCR enables scientists to look deeper into the detected virus, to understand its exact structure. This enables public health authorities to track how the virus is mutating over time and identify new variants of COVID-19. This is particularly important given the possibility that new variants could be more infective, more dangerous, or resistant to current vaccines.

The quarantine tests and “Day 2 tests” required when someone enters the UK from abroad are all genomic tests. Normal PCR tests (and Test to Release tests) are not. This is why the tests are listed separately on our website, and also why entry tests are so important: it is so the Government can track which variants are coming into the UK.
 

What are pooled PCR tests? 

Pooled PCR tests are exactly the same as normal PCR tests, but some Covid testing companies group swabs from multiple patients together and test them in batches. They do this because it lowers the cost—since you only use one set of PCR ingredients for 5-10 patient swabs. 

There are two problems with pooling:

  • When samples are pooled, you could get a positive result if one of the other samples you are pooled with is positive.

  • There is also a higher chance that if you are positive, the result will come back incorrectly as negative, because of the high dilution in the process (pooled PCRs have a higher percentage of false negatives, see section below).

Either way, PCR test results are clearly less accurate if you do pooled testing. Pooling is legal, but we do not believe it is appropriate to sell people test results which by design may not reflect their health. As a result, we have never and will never pool PCR tests.


What do sensitivity and specificity mean?

You will likely have heard a lot of discussion around the words ‘sensitivity’ and ‘specificity’. These are scientific terms, which are not very user friendly. So, in clear English:
  • Sensitivity is the ability of a test to correctly identify patients with a disease.
  • Specificity is the ability of a test to correctly identify people without a disease.

The perfect test would have 100% sensitivity and 100% specificity, meaning that all of the people with a positive result really do have the disease, and all of the people with a negative result really don’t have the disease.
Unfortunately, no test is 100% perfect, and it is possible to get ‘false-positive’ results and ‘false-negative’ results. A false-positive result is when the result comes back as positive, but the person does not actually have the virus. A false-negative result is where the result comes back negative for COVID-19, but the person does have the virus.  High sensitivity test means that there are very few false negative test results and high specificity test means that there are very few false-positive results. 

Test designers usually have to make a trade off between sensitivity and specificity. For example, if you designed a test that decided if there were clouds in the sky and set it to only say “yes” if it was raining, you’d have very few false positives but that would come at the cost of a lot of false negatives.

In general, Lateral Flow test manufacturers are conservative and prefer to minimise false negatives as much as possible (for obvious reasons). When you see 99% specificity and 97% sensitivity of the Healgen Lateral Flow test on our website, this means that ~1 in 100 negative results are wrong, and ~3 in 100 positive results are wrong. This is calculated by comparing them with PCR test results. This doesn’t mean those test kits are faulty, or that the users or lab technicians have done something wrong—that’s just the how the tolerance levels have been set.

PCR tests are assumed to have >99% accuracy and are the ‘gold standard’ when it comes to Covid testing. 

Test results, they are not just negative or positive…

Positive or negative results are relatively easy to understand, with the caveats outlined in the previous paragraph. In PCR tests there are also two other possible results: inconclusive and rejected.

An inconclusive result mean that the test has run successfully and has picked up trace material of Covid 19, but not enough to conclusively say you had the virus when the test was done. This could happen because you were on the cusp of having the virus in a detectable amount, or because you have Covid 19 ‘leftovers’ after recovering from an infection. Inconclusive results are always re-run by our lab partners, to double check they are definitely inconclusive.

Rejected results are where there was insufficient (or no) DNA present on the PCR swab. This is normally down to not swabbing enough or not swabbing correctly, but that’s not the only reason. Some medications are also known to impact the concentration of DNA in saliva in a small number of patients.
 

Conclusion 

Testing remains a hugely important part of our fight against COVID-19. At CHT we take our responsibility to provide safe and effective testing very seriously.

If you would like to order a test (and are based in or around London), you can find details of our private Covid tests on our website.

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