Q: Jennifer from Texas asks: Are there really false-positives from COVID tests? If so, how is it possible for a test to pick up something that is not there?
A: Yep, they exist.
High-profile false-positive COVID tests are making the news again after Michael Burton of the New Orleans Saints erroneously tested positive the day before a game against the Detroit Lions.
Two types of tests are commonly used to identify an active COVID-19 infection, and both of them can occasionally lead to a “false-positive” result, or a positive test result when there is actually no infection present. The two types of tests are
1. PCR tests 🧬, which detect itty bitty pieces of the virus’ genetic material, and
2. Antigen tests 🦠, which detect signature proteins on the outside of the virus. (Note: Don’t confuse antigen with antibody tests 🩸 ! That’s different.)
A PCR test works using a chemical reaction that matches genetic material collected in the sample to two fragments of genetic code that are totally unique to SARS-CoV-2. If there’s no match, the test is negative. If there’s a match on one fragment but not the other, the test is inconclusive and will usually be repeated, and if there is a match on both fragments, the test is positive.
Scientists think that false-positives in PCR tests happen most often because the bits of genetic code we are matching TO are very small fragments. Small remnants of the virus in the sample might match, even though they are not whole viruses and couldn’t infect anyone. So, bits of the virus are really there–but they’re not the whole virus any more.
You can imagine a sand castle that has crumbled. We are looking for grains of sand from that castle with a PCR test, but finding one doesn’t necessarily mean the sand castle is still intact.
An infected person is likely no longer able to get others sick about 10 days after their first symptoms appear, but they may still have little bits of inactive viral material in their body for quite some time. We’ve heard reports of people with positive PCR tests *months* after their symptoms have abated (shout out to Lu in Italy! Hang in there). This is likely due to inactive viral material still hanging around in the body after infection. Similarly, researchers studying one of the cruise ship outbreaks detected viral material on the ship 17 days after everyone disembarked, but it was likely just dried up little bits of virus that were no longer capable of causing an infection.
Another way false-positives happen in PCR tests is sample contamination. If a single viral particle happens to land in the sample as it moves through the air on its way to the test tube, you can get a false-positive.
Antigen tests give a positive result when they detect a particular protein on the surface of the virus, like a fingerprint. Antigen tests have some major advantages, including being fast and cheap. If you’ve ever had a rapid strep test, you’ve had an antigen test. And if you’ve ever had a positive rapid strep test, you know that the next thing they do is send your sample to a lab to be cultured–that’s a method of confirming the rapid test results. Antigen tests can return false-positives if they find a similar protein, if the sample is handled incorrectly, or if something goes wrong with the test chemicals.
How often does a false positive happen? Fewer than 1 in 100 PCR tests 🧬 is thought to be a false-positive–maybe as few as 1 in 500. This depends on the method used to process the test.
The false-positive rate for antigen tests 🦠 varies by manufacturer, but it’s in the range of 1 in 5 to 1 in 20. That sounds horrible, but it’s still useful when we are testing lots of people because on the whole, these tests will help us figure out where clusters of cases exist. A single person’s one-off test result should be interpreted with care, however. Because of the possibility of false-positives, people who test positive on an antigen test will typically get tested again with a more accurate PCR test to confirm before anyone panics.
The tests in wide circulation, though imperfect, still do a decent job of finding the people who are sick and separating them out from the people who are not *most of the time*. Testing is critical–but not the only tool–for managing the pandemic. (See our recent post about this here.
Both antigen tests and PCR tests also have false negatives, often arising from the test being administered early in the course of infection. That’s why when we get a negative test following a known exposure, we still need to quarantine for the remainder of a 14 day window after exposure. (We covered this recently too.)
The risk of false negatives and false positives are related to one another. We often have to trade off one for another, and having multiple types of testing where some have excellent sensitivity (ability to correctly identify someone who is infected) and others have better specificity (ability to correctly identify someone who is not infected) are both useful tools.
Finally: Even though false-positives on a PCR test are pretty rare, they can end up being a real problem in certain situations, and that problem is called low positive predictive value. This problem gets worse the more rare the disease is, because of denominators.
You can stop reading here if you don’t want to get into denominators.
Notice that the false-positive rate is not 1 in 100 *positive* tests. PCR tests will return a false-positive in 1 in 100 *total tests*. So the more you test, the more false-positives you will find. If there are very few people who are really positive in the group you’re testing, the ratio of real positives to false-positives gets ugly and you can end up with a problem. You can dork out about it here.