How can we know if someone has already contracted the novel coronavirus, especially if many are mild-to-asymptomatic? New antibody tests could have the answers.
Anxiety around the novel coronavirus, SARS-CoV-2, and the disease it causes, COVID-19, is on the rise as governments all over the world start locking down people, businesses and, in some cases, entire continents. The real severity of the situation is finally starting to sink and I, for one, am certainly feeling the worry creep in.
Much of this anxiety stems from the fact that people just don’t know if they have the virus or not at any given time. With the long incubation time of an average of five days, it could be almost a week before you know you’ve caught it and it’s contagious before symptoms even show. COVID-19 symptoms have a wide range of severity — essentially, from nothing to severe— and therefore leave many not even knowing if they’ve already had the disease and have been one of the lucky few to be asymptomatic (show no symptoms of the disease). Wouldn’t it be such a relief to know you’ve already had COVID-19 and therefore are no longer in danger, or no longer a danger to others? It sure would be for me.
However, a small light in these dark times is the recent news that a new antibody test has been developed in countries around the world that can test not if you currently have the novel coronavirus (we already have those tests) but if you’ve already had it. However, this news left many heads a cocked, asking “What even is an antibody test?”
Serology, Antibodies, and the Immune System
Serology is a term that has been injected into much of the media surrounding these new antibody tests. It means the study or examination of blood serum, usually in regards to the immune system. Which is exactly where we would want to look for signs of a previous SARS-CoV-2 infection.
When we are infected by a virus (or pathogenic bacteria), our immune system responds by producing antibodies from B cells, a type of white blood cell. These antibodies, which are large Y-shaped proteins, are designed to specifically bind to said infector. Antibodies bind to antigens, and are specific to the antigen. Antigens are a type of molecule presented on the surface of cells that enable the immune system to recognise native and non-native cells. For example, this is why if you have blood type A, you cannot receive a transfusion from someone with blood type B, as these refer to the antigens present on the red blood cells. In a person with blood type A, type B blood cells will be targeted by their immune system. This is also why blood type O-negative is a universal donor, as it has no antigens for the immune system to react to.
SARS-CoV-2 Antigen and Antibodies
The antigen on SARS-CoV-2 virions (virus particles) are the peplomers (also called spike proteins) on the outside of the virion capsid. These peplomers allow the virus to bind, fuse, and invade some of our cells. Research suggests that SARS-CoV-2, like SARS-CoV, binds to ACE2 receptors expressed on lung, heart, kidney and intestinal cells.
Once a virion has invaded a cell it then uses the cell’s own molecular machinery to replicate and release more virions. Within this replication process, some of the virus antigen is presented on our own cells, which can be identified by our immune system.
By binding to these antigens, our antibodies can help prevent the virus from binding and infecting our cells, restricting its ability to replicate and spread. Antibodies also mark virions, and our own infected cells presenting the virus antigen, for destruction by the immune system. This is the system by which our bodies fight these infections, by isolating virions and locking down infected cells. In a similar sense to how we humans are self-isolating infected people and locking down heavily infected communities and countries.
After the virus has been eradicated by our immune system, a small amount of these virus-specific antibodies remain in the blood. These aid in immediately suppressing a second infection. The presence of these antibodies are a kind of memory as to what pathogens we have been exposed to. Therefore, if a test shows the presence of SARS-CoV-2 antibodies, then the patient has previously been infected.
How Does the Antibody Test Work?
The current SARS-CoV-2 antibody tests — known as serology tests — in production all rely on the ELISA (enzyme-linked immunosorbent assay) system.
In short, an ELISA test relies on antigen-antibody binding. It is most likely that an indirect or sandwich ELISA will be used for such tests, as were used for the SARS-CoV outbreak of 2002–03.
An indirect ELISA test uses a plate that contains immobilised antigen. In this case, that antigen would be the SARS-CoV-2 peplomer. If a patient sample contains the SARS-CoV-2 antibodies, these will bind to the immobilised antigen. If present, the SARS-CoV-2 antibodies — now bound to the immobilized antigen — will recruit a secondary antibody which is bound to a reporter molecule (known as a secondary antibody conjugate). If positive for the SARS-CoV-2 antibody, the reporter molecule on the secondary antibody conjugate will initiate a visible colour change on the plate.
A sandwich ELISA test is much the same as an indirect ELISA test, except the antigen is first bound to an immobilised antibody on the surface of the plate.
This all may sound confusing but we are all very aware of this process perhaps without even knowing it, as ELISA is the method used in home pregnancy tests which use coloured bands to indicate a positive or negative result depending on the presence or absence of HCG (human chorionic gonadotropin) hormone in the sample (usually urine), respectively.
The SARS-CoV-2 antibody tests test for IgG (Immunoglobulin G) and IgM (Immunoglobulin M) antibodies. IgG antibodies are those Y-shaped antibodies we are more used to seeing depicted, and are the most abundant. IgM antibodies are those produced first by the immune system in response to an infection and only remain in the blood for a few weeks. The presence of IgG antibodies indicates a previous infection. The presence of both IgM and IgG antibodies indicate a very recent infection.
How Will an Antibody Test Help?
Being able to reliably confirm if a person has had COVID-19, especially if symptomless, would be a great help in more accurately tracking the spread of the virus and calculating how many cases are truly symptomless, along with allowing a more accurate mortality rate to be calculated. It could also be expected to enable people to safely socialise and go back to work, as well as not having to self-isolate again. This could see a modicum of normality return to many peoples’ lives.
On the other hand, finding large populations which have not yet been infected with SARS-CoV-2 would aid governments and healthcare in focussing on areas with high likelihood of an impending outbreak.
On a more individual note, knowing for sure if you have personally had, or not had, COVID-19 would go a long way to relieving some of the stress and anxiety that is palpable in communities across the world right now.
Further Reading
Chen, S., Lu, D., Zhang, M., Che, J., Yin, Z., Zhang, S., Zhang, W., Bo, X., Ding, Y. and Wang, S., 2005. Double-antigen sandwich ELISA for detection of antibodies to SARS-associated coronavirus in human serum. European Journal of Clinical Microbiology & Infectious Diseases, 24(8), 549–553.
Sciences, L., Biology, P., Center, P., Library, P., Methods, P. and ELISA, O. (2020). Overview of ELISA | Thermo Fisher Scientific — UK. [online] Thermofisher.com. Available at: https://www.thermofisher.com/uk/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/overview-elisa.html
Yan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y. and Zhou, Q., 2020. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science, p.eabb2762.
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