PCR, Antigen, and Antibody Tests: What is the Difference?

When you are tested for an infection, the laboratory can look for it in different ways. The three most common types of tests are PCR tests, antigen tests, and antibody tests. They are often used for the same infections, such as COVID-19, the flu, HIV, and hepatitis, but each one looks for a different thing. That difference is the reason two tests for the same infection can sometimes give results that seem to disagree.

This article explains what each of these tests looks for, what their results mean, and why the timing of a test matters, so you can make better sense of the results on your report. Throughout the article, the word microorganism (also called a microbe) refers to a living thing too small to see without a microscope, such as a virus or a bacterium.

What are these tests looking for?

The simplest way to tell these tests apart is to ask what each one is actually searching for.

A PCR test — looks for the microorganism’s genetic material, the molecular instructions (DNA or RNA) that are unique to it.
An antigen test — looks for pieces of the microorganism itself, usually proteins from its surface.
An antibody test — does not look for the microorganism at all. Instead, it looks for antibodies, which are proteins your immune system makes in response to an infection.

This is the key point: PCR and antigen tests look for the microorganism, so they tend to be positive when the microorganism is actually present. Antibody tests look for your body’s response, which can remain positive long after the microorganism is gone and can take time to appear after an infection begins.

PCR tests

PCR stands for polymerase chain reaction. It is a type of molecular test that detects the microorganism’s genetic material. Genetic material is the set of instructions, made of DNA or RNA, that every living thing carries. PCR tests are also called nucleic acid amplification tests, or NAATs, because they work by copying, or amplifying, any genetic material in the sample many times over. This amplification is what makes PCR so powerful: even a tiny amount of a microorganism can be copied enough times to be detected.

Because PCR detects the microorganism’s genetic material directly, a positive result usually indicates that the microorganism is present at the time of testing. PCR is used for COVID-19, hepatitis C (where it may be called an RNA test), and chlamydia and gonorrhea (where it may be called a NAAT), among many others. Results are usually reported as detected or not detected (sometimes written as positive or negative). For some infections, such as HIV or hepatitis, the report may also include a viral load, which is a measurement of how much genetic material is present.

The strengths and limitations of PCR are worth understanding:

Very sensitive and very specific — PCR rarely misses a true infection and rarely gives a false positive, so it is often used to confirm results from other tests.
Can stay positive after you recover — Because PCR detects genetic material rather than living microorganisms, it can remain positive for a time after you are no longer infected or contagious, as harmless leftover fragments are still detected.
Usually takes longer — PCR is often performed in a laboratory, so results may take longer than a rapid test, though rapid PCR machines are becoming more common.

Antigen tests

An antigen is a substance the immune system can recognize, and in this context, it means a piece of the microorganism, usually a protein from its surface. An antigen test looks for these pieces directly. Many of the fast tests you may have used belong to this group, including rapid home tests for COVID-19, rapid strep throat tests, and rapid flu tests.

Antigen tests are popular because they are fast, inexpensive, and can often be done at home or in a clinic without sending the sample to a laboratory. Results are usually reported simply as positive or negative.

The trade-off is in how reliable the result is:

A positive result is usually trustworthy — Antigen tests are good at correctly identifying the microorganism when there is enough of it, so a positive result is generally reliable.
A negative result is less certain — Antigen tests need a larger amount of the microorganism to turn positive than PCR does. This means they can miss an infection, especially when it is very early or very late, when only a small amount is present. For this reason, a negative antigen test is sometimes confirmed with a PCR test.

Antibody (serology) tests

An antibody test, also called serology, looks for antibodies in your blood. Antibodies are proteins your immune system makes to recognize and fight a specific microorganism. Because the body needs time to produce them, antibody tests do not detect the microorganism directly and are not used to find a brand-new infection. Instead, they show whether your immune system has responded to a microorganism, either now, in the past, or after a vaccine.

There are different types of antibodies, and the two most often mentioned on reports are IgM and IgG. In general, IgM tends to appear earlier in an infection, and IgG tends to appear later and last longer. (These are explained in more detail in a separate article on IgM and IgG.) Results are usually reported as reactive or non-reactive, or as positive or negative, and sometimes include a number called a titer that reflects the amount of antibody present.

A few points help make sense of an antibody result:

Antibodies take time to appear — There is a period early in an infection, before antibodies have developed, when an antibody test can be negative even though you are infected. This is called the window period.
A positive result has more than one possible meaning — Depending on the infection, a positive antibody test can mean a current infection, a past infection that has resolved, or immunity from a vaccine. Which of these applies depends on the specific infection and on the type of antibody found.
It may not show a current infection — Because antibodies can remain for months or years, a positive antibody test alone usually cannot tell you whether the microorganism is still present.

Why one test can be positive and another negative

Patients are often confused when two tests for the same infection seem to disagree. In most cases, this is not an error. It happens because the tests are looking for different things at different points in an infection. Here are the most common situations.

PCR positive, antigen negative — PCR can detect much smaller amounts of a microorganism than an antigen test can. Early in an infection, or when the viral load is low, PCR may be positive while the antigen test remains negative.
Antibody positive, PCR and antigen negative — This pattern usually points to a past infection or to immunity from a vaccine. Your body still carries the antibodies, but the microorganism itself is no longer present for detection.
PCR positive, antibody negative — This often means a very recent infection. The microorganism is present and detectable, but your immune system has not yet had time to make antibodies. This is the window period described above.
Antigen positive, PCR negative — This is less common. It can happen with a false positive antigen test, or because of differences in timing or in how the samples were collected. A PCR test is often used to sort out which result is correct.

How accurate are these tests?

No test is perfect, and two qualities describe how reliable a test is. Sensitivity is how well a test detects a true infection; a highly sensitive test rarely misses someone who is infected. Specificity is how well a test correctly excludes people who are not infected; a highly specific test rarely labels someone positive who is not infected. A false negative is a negative result in someone who actually has the infection, and a false positive is a positive result in someone who does not.

Timing is just as important as the type of test. Each test becomes reliable at a different point after exposure. PCR can usually detect an infection earlier, antigen tests need more of the microorganism to be present, and antibody tests become reliable only after the immune system has had time to respond. This is why your healthcare team pays attention to when you were exposed and when the sample was taken, and why a test is sometimes repeated after enough time has passed.

What happens after these tests

These tests describe what was found, and they inform the decisions you and your healthcare team make together rather than dictating a treatment on their own. A result is interpreted alongside your symptoms, your possible exposure, and the timing of the test.

Depending on the situation, the team may take different next steps. A negative antigen test may be confirmed with a more sensitive PCR test. A positive screening test, such as an antibody test for HIV, is usually confirmed with additional testing before a diagnosis is made. Some tests are deliberately combined to cover more than one stage of infection; the standard HIV test, for example, looks for both antigens and antibodies at the same time, so infections can be detected earlier. If a test was done too early to be reliable, it may be repeated after the window period has passed.

Questions to ask your doctor

Which type of test did I have, a PCR, an antigen, or an antibody test?
What exactly was this test looking for?
Does my result mean I have a current infection, a past infection, or immunity?
Could it be too early in the infection for this test to detect it?
If my rapid (antigen) test was negative, do I need a PCR test to be sure?
Should this result be confirmed with a different or repeat test?
Could this be a false positive or a false negative result?
How long after exposure does this test become reliable?
What do the words “detected,” “reactive,” or “positive” mean on my report?
Does a positive antibody result mean I am protected from getting this infection again?
Should my result be interpreted together with my symptoms and exposure history?
Who should I contact if I have questions about my results?