What is the difference between PCR, antigen and antibody COVID-19 tests?

COVID-19 testing is a vital part of the response to the COVID-19 pandemic.

Polymerase chain reaction (PCR) or molecular tests

Polymerase chain reaction (PCR) COVID-19 tests are the gold standard for detecting a COVID-19 infection.  PCR test detects the presence of viral RNA.  PCR or molecular tests are the most accurate tests for detecting a COVID-19 infection.  Laboratory technicians usually perform the test on written request from a healthcare provider.

This test is able to detect a COVID-19 infection even before the person becomes infectious and thus allows for early isolation.  The disadvantages of PCR tests are the financial cost compared to antigen tests, the longer time needed for test results to become available, and the need for highly professional staff to conduct the test.

A positive test result means you likely have COVID-19.  A negative test means you probably didn’t have COVID-19 at the time of the test.

What are antibodies and antigens?

An antigen is a substance capable of stimulating an immune response.  Antigens, are substances in your blood that trigger your body to fight infection.  Each antigen has distinct surface features, for example, the spike proteins found on the surface of the SARS-CoV-2 virus.

Antibodies are also called immunoglobulins (Ig).  An antibody is a Y-shaped protein produced by B cells of the immune system in response to exposure to antigens.  The tip of each Y-shaped arm contains antigen binding sites that bind to a specific portion of the antigen’s surface.  This binding helps to eliminate antigens from the body.

What is an antibody test?

An antibody test reveals if a person has already been exposed to an infection, by detecting antibodies in their blood or serum.  Antibody tests are not usually used to diagnose current infection as it takes the body some time to produce antibodies.

Data suggests that in the case of SARS-CoV-2, it takes the body at least 7 days to produce antibodies against the virus.  Data also shows that the COVID-19 IgM antibody production peaks around two weeks after infection, followed by the IgG antibody production peaking at three weeks.

What can COVID-19 antibody tests tell us?

Antibody tests can help us to track the spread of disease, giving a more accurate representation of the COVID-19 pandemic.  They can help to estimate how many people have already been infected with SARS-CoV-2 assessing herd immunity.

A test that distinguishes between IgM and IgG antibodies can also give information about the phase of infection, indicating how long ago the person was approximately infected with SARS-CoV-2.

Limitations of antibody tests

As with many other test methods, antibody test results are unfortunately not always correct.

A negative test result may occur if the test is taken too soon after infection before enough antibodies have been produced by the body or to late when the level of antibodies left in the blood falls below the detection limit of the test.  False positive test results could also occur due to cross-reactivity with other antibodies present, for example, as a result of previous infection with other coronaviruses.

Interpretation of results and what they mean warrants caution.  In the case of COVID-19, it is not yet known if a person’s own antibodies will protect them against re-infection from SARS-CoV-2, and if so, for how long this protection will last.  Data from studies shows that antibody levels begin to wane after two months.  This could mean that the window for which antibody testing can identify people who have been infected is relatively short, and therefore antibody test results will need to be interpreted with caution.

What are COVID-19 antigen tests and what can they tell us?

An antigen test reveals if a person is currently infected with a pathogen such as the SARS-CoV-2 virus.  Once the infection has gone, the antigen disappears.  Unlike nucleic acid-based tests, such as PCR, that detect the presence of genetic material (viral RNA), antigen tests detect bits of proteins on the surface of the virus called antigens.

Antigen tests are typically considered rapid, taking a few minutes to provide results.  Their advantage is their price, rapid result and the lower demands on the expertise of the staff.  There is no need to conduct the test in a laboratory.

Many antigen tests are authorized for emergency use.  They can be used to make a clinical diagnosis in symptomatic patients in the first five days of symptoms.  Antigen tests are used as screening tests for symptomatic patients early in illness, particularly where access to molecular tests is poor, when laboratories are swamped with test requests or where it takes a very long time to get results.  However, they aren’t currently recommended for screening asymptomatic populations.

Limitations of antigen tests

Antigen tests are less accurate (sensitive) than a PCR test.  Rapid antigen tests are most accurate when used within a few days of the start of symptoms or exposure to the virus, which is when the largest amount of virus is present in your body.

A positive test means you likely have COVID-19.  A negative test means you probably did not have COVID-19 at the time of the test or that the test was done to early when the viral load was below the detection limit of the test.  Because of this, if an antigen test is negative, your healthcare provider may order a PCR test to confirm the negative test result if you had been exposed to the virus (close contact).