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What’s The Difference Between A “Molecular” COVID Test And A “Antigen” COVID Test, And Does It Matter?

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There are two types of COVID-19 tests — diagnostic tests and antibody tests.  Let’s focus on diagnostic testing.  There are two types of diagnostic tests — molecular tests, such as PCR tests, that detect the tiniest bits of genetic code specific to SARS-CoV-2, and antigen tests that detect proteins that the virus produces, such as a specific protein on one of its namesake “corona” spikes.  Molecular tests are highly accurate but require trained healthcare workers, lots of PPE, lab technicians, specialized equipment, swabs and chemicals, and . . . time (for the test itself, and transport to the lab).  Antigen tests, once scaled up and distributed, are rapid, can be used in many different settings, are simple to perform, but are less sensitive than molecular tests.

Molecular tests  (AKA: nucleic acid amplification test (NAAT), PCR test, RT-PCR test)

How it works: A sample of mucus is typically taken from a person’s nose or throat (a few use saliva).  The sample is stored in a sterile tube or vial and then sent to a lab equipped with PCR (polymerase chain reaction) technology.  Trained lab technicians extract any genetic material and mix it with reagents (chemicals, primers and probes — some derived from the coronavirus itself) to greatly amplify viral genetic material if present.

How accurate is it: overall these are the most reliable tests and are the gold standard for accuracy.  However no test is perfect and some things can affect the test’s accuracy: you may have the virus, but the swab might not collect it from your nose or throat; the sample may be accidentally contaminated by the virus during collection or analysis; the sample may not be kept at the correct temperature prior to analysis; the reagents used during the PCR analysis may not work correctly.

How long it takes: Samples are sent to centralized labs for analysis, so it can take days, though results are coming back quicker as hospitals and regional health departments have PCR testing capacity in-house.  There are two rapid PCR tests, which can be run on specialized platforms already available in certain clinical sites across the U.S.  The fastest one, by Abbott Labs, can provide a result in less than 15 minutes, but several studies suggest this test can miss 10-15% of cases.  

Antigen Tests

How it works: Think of a rapid Strep test in a doctor’s office or an at-home pregnancy test.  A sample is typically taken from a person’s nose or throat and put onto a specially treated strip, which uses a color marker to indicate if coronavirus proteins are present.  

How accurate is it: While there is a wide range of accuracy between different tests, the majority of approved tests are giving results with increasingly consistent reliability.  However, at best they miss between 10-20% of cases.  Positive results, though, are quite accurate.  The shortcomings of antigen tests will soon be outweighed by their more accessible and quick turnaround times available at the “Point of Care,” i.e. doctor’s offices and screening centers.  Rapid antigen tests are most appropriate for those who have symptoms of COVID-19, where a positive antigen test can rapidly confirm infection with SARS-CoV-2.  They are less appropriate for asymptomatic screening (to “clear” someone to visit their at-risk elders), since they will miss 10-20% of true cases. 

How long it takes: As little as 15 minutes. 

(Sky Pittson, MD, Updated: November 3, 2020)