Serology tests are used to determine whether a person had a past exposure to a pathogen. The tests look for antibodies, which can bind to the pathogen, that were formed as part of the immune response. COVID-19 serology tests look for antibodies that bind to specific SARS-CoV-2 proteins (antigen) on the virus, which are present if a person has been infected and recovered. These tests can be used to determine the prevalence of disease in a population, even after the infection has passed. Serology tests use blood samples, collected from either a blood draw from a person’s arm or finger stick. These tests are not used to diagnose active COVID-19, because they do not detect the virus itself, but evidence of the body’s fight against the virus. No currently available test can determine if a person is immune to reinfection by SARS-CoV-2 because it is unknown how long antibodies are likely to be protective and antibody levels typically wane over time.
Look for past SARS-CoV-2 infection by looking for specific antibodies that bind to the virus to provide evidence of the body’s fight against SARS-CoV-2
Require a blood draw or fingerstick in order to find antibodies in the blood
Identify antibodies formed to fight SARS-CoV-2 specific to that virus
Do not determine whether a person is immune to future reinfection
What types of serology tests are there and how do they work?
A variety of serology tests are available—all of which detect antibodies present in a person’s blood serum, which is the part of the blood that does not include red blood cells.
Qualitative serology tests provide a simple “yes” or “no” answer to whether a person was once infected with SARS-CoV-2. Rapid serology tests, typically lateral flow assays (LFAs), are qualitative and provide a positive/negative readout. From this type of test, a person can learn their “serostatus,” which is a commonly used term in public health to indicate whether a person is positive or negative for the antibodies of interest.
Quantitative serology tests, such as enzyme-linked immunosorbent assays (ELISAs) and chemiluminescent immunoassays (ChLIAs), provide more detailed information, such as levels of antibodies in a patient sample. Although knowing antibody levels may be interesting for research purposes, and has been used to determine whether a person is eligible to donate convalescent plasma, it is not necessary information for most individuals, as it should not change how people protect themselves and others against the virus. In fact, many of the US Food and Drug Administration emergency use authorizations for quantitative serology tests often stipulate that they should be used only to provide qualitative (“yes” or “no”) answers for patients.
The accuracy and performance of SARS-COV-2 serology tests vary greatly; quantitative tests are generally more accurate than qualitative tests, partially due to the detailed data generated.
Serology tests:
Detect antibodies in a person’s blood that bind to specific antigens on the SARS-CoV-2 virus
May be qualitative (yes/no, positive/negative) or quantitative (how many antibodies, how reactive)
Results returned to patients are usually qualitative (yes/no) instead of quantitative (high or low levels) because of potential for confusion or misinterpretation of results
Quantitative tests can be more accurate but are generally more useful for research purposes
Qualitative tests, like lateral flow assays, can be performed very quickly at the point-of-care
What kinds of serology tests are on the market?
Rapid serology test (RST): This is typically a qualitative (positive or negative) lateral flow assay that is small, portable, and can be used at point of care. These tests may use blood from a finger prick, saliva, or nasal swab fluids. RSTs are often similar to pregnancy tests, in that the test shows the user colored lines to indicate positive or negative results. In the context of COVID-19, these tests most frequently test for patient antibodies (IgG and IgM) or viral antigens. In some cases, it can be beneficial to measure baseline (before infection) of IgG and IgM titers.
Enzyme-linked immunosorbent assay (ELISA): This test can be qualitative or quantitative and is generally a lab-based test. These tests usually use whole blood, plasma, or serum samples from patients. The test relies on a plate that is coated with a viral protein of interest, such as Spike protein. Patient samples are then incubated with the protein, and if the patient has antibodies to the viral protein they bind together. The bound antibody–protein complex can then be detected with another wash of antibodies that produce a color or fluorescent-based readout. In the context of COVID-19, these tests most frequently test for patient antibodies (IgG and IgM).
Neutralization assay: This test relies on patient antibodies to prevent viral infection of cells in a lab setting. Neutralization assays can tell researchers if a patient has antibodies that are active and effective against the virus, even if they have already cleared the infection. These tests require whole blood, serum, or plasma samples from the patient. Neutralization assays depend on cell culture, a lab-based method of culturing cells that allow SARS-CoV-2 growth (like VeroE6 cells). When virus and cells are grown with decreasing concentrations of patient antibodies, researchers can visualize and quantify how many antibodies in the patient serum are able to block virus replication. This blocking action can happen through the antibody binding to an important cell entry protein on the virus, for example.
Chemiluminescent immunoassay: This test is typically quantitative, lab-based, and uses whole blood, plasma, or serum samples from patients. A variation of this test can use magnetic, protein-coated microparticles, known as a chemiluminescent microparticle immunoassay. The test relies on mixing patient samples with a known viral protein, buffer reagents, and specific enzyme-labeled antibodies that allow a light-based, luminescent read-out. Any antibodies in the patient sample that react to the viral protein will form a complex. Then, (secondary) enzyme-labeled antibodies are added that bind to these complexes. This binding induces a chemical reaction that produces light. The amount of light (radiance) emitted from each sample is then be used to calculate the number of antibodies present in a patient sample. This test can look for multiple types of antibodies, including IgG, IgM, and IgA.
Common types of serology assays:
Type of test
Time to results
What it tells us
Limitations
Figure
Rapid serology test
10-30 minutes
The presence or absence (qualitative) of antibodies against the virus present in patient serum.
The amount of antibodies in the patient serum, or if these antibodies are able to inhibit virus growth
