Testing has become a vital part of the response to the COVID-19 pandemic. In addition to the gold standard PCR tests used to detect currently infected individuals, a number of alternative antigen and antibody tests are also in development. In this article, we take a look at the differences between these tests and what they can tell us.
What are antibodies and antigens?
An antigen is a molecule capable of stimulating an immune response. They may be proteins, polysaccharides, lipids or nucleic acids. Each antigen has distinct surface features that are recognized by the immune system.
SARS-CoV-2, the virus that causes COVID-19, has several known antigens, including its nucleocapsid phosphoprotein and spike glycoprotein, which are the visible protrusions on its surface.
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 (paratopes) that bind to a specific portion of the antigen’s surface (epitope). This binding helps to eliminate antigens from the body, either by direct neutralization or by “tagging” them for elimination by other arms of the immune system.
When infected with SARS-CoV-2, the body produces antibodies that bind specifically to the spike proteins and other antigens to help eliminate the virus. This binding can be harnessed to develop antibody and antigen-based diagnostic tests.
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. This can be done by a laboratory-based test such as an ELISA (enzyme-linked immunosorbent assay) or CIA (chemiluminescent immunoassay), or a point-of-care test based on lateral flow technology.
Antibody tests are not usually used to diagnose current infection as it takes the body some time to produce antibodies. During the period before the adaptive immune system kicks in, the fast-acting and non-specific innate immune response combats infection.
Data suggests that in the case of SARS-CoV-2, the IgM antibody response peaks around two weeks after infection, followed by the IgG antibody peak at three weeks.
What can 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, which can be important in assessing herd immunity.
A test which can distinguish between IgM and IgG could give information about the phase of infection, indicating how long ago the person was infected with SARS-CoV-2.
They could also help to identify those who should be prioritized for vaccinations when they become available, as well as potential donors for convalescent plasma therapy.
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 antibodies have been produced by the body. False positive test results could also occur due to cross-reactivity with antibodies present as a result of previous infection with other coronaviruses.
Interpretation of results and what they mean also 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, how long this protection will last. This means “immunity passports”, which have been suggested as a means of identifying immune individuals who are safe to return to work, are not currently recommended by the WHO.
Data from a recent study showed 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.
Are there any SARS-CoV-2 antibody tests currently available?
A number of antibody tests are currently available, including those developed by Roche, Beckman-Coulter, EUROIMMUN and Abbott.
A full list of tests granted FDA Emergency Use Authorization (EUA) can be found here.
What are 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, which detect the presence of genetic material, antigen tests detect proteins or glycans, such as the spike proteins found on the surface of the SARS-CoV-2 virus.
They can take longer to develop than molecular and antibody tests, as suitable antibodies for use in the assays must first be identified and produced, which can be a complex and time-consuming process. Accuracy can also be a problem, with antigen tests typically having a much lower sensitivity than PCR.
However, they usually provide test results rapidly, are relatively cheap, and can be more amenable to point-of-care use, which could make them more suitable for testing in the community and in remote regions.
Are there any SARS-CoV-2 antigen tests currently available?
Quidel has received EUA for its antigen test. There are a number of other antigen tests in development, including those developed by, OraSure, Iceni Diagnostics, and E25Bio.