The COVID-19 Testing Conundrum: What Consumers Should Know About the Different Types of Tests

If you visit a pharmacy counter, you may see display racks of over-the-counter (OTC) COVID-19 tests for sale without a prescription. It’s tempting to pick up a package (some can be purchased for less than $10 per test) “just in case,” especially since most of the free testing sites have now closed and the idea of going to a local urgent care center can cause anxiety. The average consumer has many questions, such as “How reliable are the OTC tests?” “What test is best suited for individuals who have been vaccinated?” “Will OTC tests suffice for my upcoming travel needs?”

The situation is pretty confusing. Not all coronavirus tests are the same.  The coronavirus is made up of both proteins (the structural and functional parts of the virus) and RNA – the instruction set for making more virus. Mass testing sites, hospitals, and doctor’s offices typically use tests that detect viral RNA. If someone actually has the virus infecting them, these tests find it 80-90% of the time and are almost never “positive” when no virus is present.

As new variants emerge, laboratories can rapidly adapt their tests to remain as sensitive to new variants as they were to the old ones. Some of the tests you can buy in a drugstore are almost as good because they send your swab to a qualified laboratory for processing and testing. Some on-site testing can identify RNA and it might be important for you to know which tests are considered “molecular” identification methods.

In contrast, tests that promise results in less than an hour at home perform very differently than tests done in a certified laboratory. First, they typically detect coronavirus protein (not RNA) using techniques that are not as sensitive. Based on what the makers of the tests have told the FDA, these tests usually will fail to detect the virus in more than 15% of individuals who, in fact, have a positive RT-PCR test. These “rapid antigen” tests are more likely than RNA-based tests to report the COVID-19 causing virus is present when it is not (a so-called “false positive” result). These protein tests are also much less effective than RNA tests in finding the virus in people who do not have symptoms (are asymptomatic). Most seem to have about a 50/50 chance of finding the virus in asymptomatic people when it is there, conflicting with the data coming from the manufacturers of various tests suggest that some of them may be much better than that.  Some of these tests seem to be sensitive for detecting new variants, but there isn’t much information for others.

Knowing that different types of tests perform differently in specific situations, it is important to know what kind of test you are getting. Tests referred to as RT-PCR tests (or sometimes PCR, molecular, nucleic acid amplification test, or NAAT) are testing for the viral RNA. The RT-PCR tests are the more sensitive tests that rarely report the virus is present if it is not, and must be performed with special equipment, usually in a laboratory. Tests for the virus protein are referred to as antigen tests or antigen testing. If you have a test kit that provides rapid results in your own home, it is almost certainly an antigen test.

If you have been immunized using any of the vaccines (shots) available in the United States or Western Europe, today you are less likely to “catch” a symptomatic COVID-19 infection, and much less likely to die from it. The emergence of new variants, particularly the “delta” variant, may have made these shots less effective, though.  Many of these infections in vaccinated people are mild or asymptomatic, but any infected person – even someone who is vaccinated and has no symptoms -  can spread potentially fatal disease to someone who is especially vulnerable, such as a person in a nursing home or an unvaccinated adult or child.  Since new variants of this virus are likely to continue to appear until there are many fewer people being infected, it will be important to test for COVID-19 to see whether a person with symptoms is infected and how prevalent the COVID-19 infections are (particularly asymptomatic infection) within the community.

When does it make sense to use an “over the counter” antigen test?  It depends! If you are sick, and if the laboratory result won’t be back in the next day, a positive antigen test is a good reason to stay isolated until the test result comes back. Of course, staying isolated when you are sick is good advice for any infectious disease, but be careful! When there is not much COVID-19 illness present in your community, even the best of these tests, if positive, is more likely to be a “false positive” than “true positive.” When the rate of COVID-19 viral infection increases (as it has recently in most of the United States), then these tests will have many fewer “false positive” results, but the rate of “false negative” results will increase.  A negative result increases confidence that you are not infected with coronavirus. However, knowing the limitation of your test can help you avoid unnecessarily exposing others.

As “flu season” approaches this fall, you should remember that just because you do not have a coronavirus infection does not mean that you don’t have influenza (which kills tens of thousands of people each year) or another viral infection that can endanger vulnerable family members.  When you are sick, your doctor can send your specimen to a laboratory that tests for many infections that cannot be identified by any of the currently available over-the counter tests. Your doctor should always be your best source of advice for your particular situation.

Timothy J. O’Leary, MD, PhD
Member, AMP COVID Response (ACR) Steering Committee
Previous AMP President
Former Editor-in-Chief, Journal of Molecular Diagnostics (JMD)
Former Chief Research and Development Officer, Department of Veterans Affairs

Samuel K. Caughron, MD
Member, AMP COVID Response (ACR) Steering Committee
Chair, AMP Economic Affairs Committee (EAC)
President and CEO, MAWD Pathology Group