COVID testing explainer 2: What is a false negative?

virus

I’ve seen a lot of comments on various Isle of Man facebook groups over the last few weeks where people are claiming their negative SARS-CoV-2 test result must be a “false negative”. So let’s delve into the testing and what “false negative” really means.

The first thing to know is that a SARS-CoV-2 PCR test result is reported as either:

  1. SARS-CoV-2 DETECTED
  2. SARS-CoV-2 NOT DETECTED

As you can see the lab doesn’t use the words “positive” or “negative”. When a PCR test is carried out, it either detects the virus or it doesn’t and that’s how the results are reported to your doctor.

This paper shows that infectiousness starts around 2.5 days before COVID-19 symptoms start and the peak viral load (the amount of virus) occurs about half a day before symptoms start. By the time you start to show symptoms (and therefore become eligible for a test through the IoM 111 line) there should be an awful lot of virus present at the back of your nose and throat for detection. Detectable (but possibly non-infectious) viral RNA also hangs around in there for at least two weeks and even up to a month. PCR testing helps to differentiate people with COVID-19 from people with colds and flu so that they can be contact traced and the spread of SARS-CoV-2 contained.

All PCR tests have something called a limit of detection which is the lowest number of copies of the virus that the test can detect. The test we use on the Isle of Man has a limit of detection of 10 copies of the virus, which is very sensitive.

np_swab

A possible weak point in SARS-CoV-2 testing is the swabbing. The nasopharyngeal swab that needs to be taken to collect the virus has to go really far back into the nose. It’s not very pleasant (but thankfully only takes a few seconds) and there’s the potential for a false negative result if the swab doesn’t collect enough cells. However, the testing we do on the Isle of Man actually takes this into consideration and tests the amount of human RNA present on the swab as well as the SARS-CoV-2 RNA. If the level of human RNA is below the threshold we established during our validation testing the result is reported as INSUFFICIENT SAMPLE and the patient is asked to have a new swab taken.

If we didn’t do the human RNA test then a small proportion of the low quality samples could be from patients with COVID-19 but could be reported as negative because the lack of material in the swab reduced the amount of virus below the limit of detection of the test. These would be false negatives and given the potential for a false negative person to spread the disease thinking they’ve had a negative test, we introduced the human RNA check on the Isle of Man to minimise the risk of false negatives as much as we possibly can.

So what does “false negative” really mean?

Well, there’s bit more to it than just that term and what most people assume it is. There are really four different terms to understand: true positive, true negative, false positive and false negative. 

positives-negatives

Let’s look at hypothetical Bob who was thought up by me and doesn’t exist in real life.

Bob has had a cough for a few months, sees the symptoms of COVID-19 on the news and decides to ring 111 for a test. He says the cough is new. The test result is “SARS-CoV-2 NOT DETECTED”. A few days later he gets infected with SARS-CoV-2 after a sneaky visit to his friend’s house during lockdown (bad Bob). At day 5 he becomes infectious and at day 7 he starts to show symptoms of COVID-19. He calls 111 for a second test and his result this time is “SARS-CoV-2 DETECTED”.

Bob assumes that his first test is a false negative and tells his mates on facebook that the test is rubbish.

But bad-boy Bob is wrong. His first test was a true negative and his second test was a true positive.

So no false negative for Bob.

As you can see, a real false negative is a patient who has COVID-19 disease but where the PCR test does not detect any SARS-CoV-2 virus (usually due to insufficient swabbing) rather than a true negative followed by a true positive. Despite the facebook rumours, real false negatives are actually pretty rare because of the human RNA test we carry out, the limit of detection and the known sensitivity of the test in patients with COVID-19 disease (99.4%).

So in conclusion, the likelihood is that if your test came back negative you had something else like a cold or the flu, not COVID-19.

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