As a plethora of over-the-counter COVID tests come onto the market, causing both confusion and potentially false hope, laboratorians are in a unique position to educate friends, family members, and acquaintances about the critical differences between professional, laboratory-grade testing and at-home consumer tests.

By Timothy J. O’Leary, MD, PhD, and Samuel K. Caughron, MD

If you visit a pharmacy counter, you may see display racks filled with 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 some of the free testing sites have closed and the idea of going to a local urgent care center can cause anxiety. But with this OTC purchase come questions: “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?”

Cause for Confusion

The situation is pretty confusing. And to add to this confusion: Not every coronavirus test is 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.

Speed vs. Quality

In contrast, tests that promise results in less than an hour at home perform very differently than tests done in a certified laboratory. 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. The sensitivity issue is even worse in someone who doesn’t have any symptoms of COVID.  

These protein tests are also much less effective than RNA tests and most seem to have only about a 50/50 chance of finding the virus in asymptomatic people when it is there.  (That conclusion comes from data from independent studies and may conflict with the data coming from the manufacturers of the various tests who tend to suggest that they have a much higher sensitivity). Some of these tests seem to be adequate for detecting new variants, but there isn’t much information for others.  Finally, to make the tests even more challenging to use, “rapid antigen” tests are more likely than RNA-based tests to report the COVID-19 causing virus is present when in fact it is not (a so-called “false positive” result).

Knowing that various 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.

When does it make sense to use an OTC antigen test?  The short answer: 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 OTC 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 limitations of your test can help you avoid unnecessarily exposing others.

The Vaccination Factor

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. Many 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 else.  And that is especially problematic for the 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 determine whether a person with symptoms is infected and how prevalent the COVID-19 infections are (particularly asymptomatic infection) within the community.

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 on its own account) 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.

So what’s the best advice laboratorians can give to friends, family members, and acquaintances about COVID-19 or any potential infection?  Your doctor should always be your best source of advice for your particular situation. And if you do end up needing a COVID test, that OTC test may be an easy and quick option, but making sure it is backed up with a PCR based test will give you the greatest confidence in your final result.

About the Authors

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

This article was first published as an Association for Molecular Pathology blog post and is reprinted with permission.