Don’t go rushing to get a rapid coronavirus test! When it comes to detecting the SARS-Cov-2 virus, new studies show Abbott’s ID NOW rapid test works worse than the rest. If you have covid-y symptoms, you might think getting your test results quickly would ease some of your anxiety – one way or another, at least you’d know if you had it, right? Well, if you get negative results from one of those rapid tests, you still don’t *really* know – you could be one of the ~15% of infected people who these tests might miss! (Though if you get a positive result, you’ve almost certainly got it.) 

The other day I talked about how diagnostic test design is often a tug of war between sensitivity (being able to find all the infections) and specificity (not raising false alarms). I apparently should have added a third tugger – speed. Prioritize that and your test might not succeed… That coronavirus test that was the talk of the town for it’s speed (positive results in just 5 min, negative in 13) is now once again the talk of the town – for its inaccuracy, or more precisely, its (lack of) sensitivity. According to a Cleveland Clinic study led by Dr. Gary Procop (not yet published but reported by NPR) which tested 239 samples known to contain the virus using 5 different tests, the ID NOW test only “found it” in 85.2% of the samples. So, almost 15% of the samples gave false negatives. Not good! https://n.pr/2Y19JeW 

Really not good – to give you a better sense of what this means, imagine you test 1000 people, 800 of whom have the virus. In order to know how reliable a test is you need to know a few things. That 85.2% (0.852) is the test’s sensitivity (what is the probability the test will find the virus if it’s there). If a test had perfect sensitivity, it would never give a false negative. We also need to know the test’s specificity – this is the probability that the test will correctly say that the virus is NOT there when it is not there. If a test had perfect sensitivity, it would never give a false positive. They don’t say in this article the specificity, but usually it’s really good for these sorts of tests, so I will say 99.9%. 

As I work out in the figures, this means that 682 out of 800 infected people get the right result (true positive). The test misses 118 of them – those 118 were told they didn’t have the disease (false negatives) (and might not quarantine themselves, so they potentially go spread the disease more). 199 out of 200 uninfected people get the right result. Which means 1 person got a false positive – so they’re told they’re infected but they aren’t. In this case, if you get a positive result, there’s a 99.9% chance you have the disease. But if you get a negative result, there’s only a 62.8% chance you don’t (as explained in the figure and in more detail here: https://bit.ly/testterminology these “predictive values” depend on the proportion of people getting tested that have the disease (the way that I like to think about it is that you’re always going to have some false negatives, but the fewer the real negatives, the more likely any one negative result is to be false)

So, how do these false negatives arise?

These rapid tests work similarly to conventional Covid-19 tests in that (after making a DNA copy of the viral RNA in a Reverse Transcription step) they make lots and lots of copies of specific regions of the virus’ genetic blueprint (genome) and use fluorescent probes that bind to those copies and allow the machine to see if copies get made (which can only happen if there was viral genome there to copy). Conventional tests do this using Polymerase Chain Reaction (PCR), which involves lots of cycles of heating and cooling. The rapid test uses Isothermal Amplification, which uses a different method which makes copies without changing the temperature. Both techniques allow for exponential amplification, so the number of copies grows really fast. But there need to be enough copies there to start with or else the virus’ signal will just get lost in the noise. The starting number of virus bits, in jargon, has to be above the test’s Limit Of Detection (LOD). And, for these rapid tests, the LOD appears to too high, so a lot of patient samples fall below…

The tests have been found to really struggle when there isn’t much viral material in the starting sample. This can be common because they have to stick those swabs uncomfortably far up your nose and might not get a sample full of lots of viral particles. Additionally, sometimes, instead of sticking the swab straight in the machine, the doctor or technician sticks it in some transport fluid (nothing fancy – approved transport media include regular saline), swirls it around to let all the sample elute out of the swab, then tosses the swab, and stores this liquid. According to Abbott’s original guidelines, this should allow the sample to be stored for up to 8 hours at room temp, and 3 days if you stick it in the fridge. 

When reports started coming out about the tests giving false negatives, Abbott said that it was probably because the samples were getting too diluted when people were sticking them in the transport media instead of going straight from swab to machine. So they told people to only go swab to machine. This doesn’t seem to solve all the problems though – false negatives are still happening. 

Not to mention that this “gotta be straight from the swab” limitation causes additional problems. Unlike samples in transport media, samples on swab can only be stored for 2 hours at room temp or 24 hours in a fridge. And, even though each test is fast, these machines CAN ONLY RUN ONE TEST AT A TIME! (unlike conventional tests which are typically run lots at a time) So you can quickly see why results might not be so quick. And then they might not even be accurate! 

Sorry for this bit of a rant – if you want to learn more about the science behind these rapid tests, I go into more detail than you probably want to know here: https://bit.ly/2UVYiDt

You can find out more about the conventional tests and a bunch of other covid-19 related topics here: https://bit.ly/covid19bbresources 

And, pretty pretty please, STAY HOME IF YOU CAN! I know we all want to get out and speed up the opening up, but rapid isn’t always better! Especially when, if you go out unnecessarily, you don’t just risk your own life and that of others, and overwhelm the already overworked healthcare system, but you also extend this shutdown and/or make it more likely we’ll have to do it all over again. So please, stay home for those who can’t. Help everyone stay as healthy and happy as possible. Steps off soapbox…

more on topics mentioned (& others) #365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0

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