COVID-19

8. Antibody detection tests

An alternative approach to diagnosing infections is to look for a specific host response to infection, rather than detect the pathogen itself. The most common means of doing this is to measure antibodies in patient serum. The detection of (for example) SARS-CoV-2 antibodies does not indicate that a patient has ongoing infection, but rather that they have been exposed to the virus at some point in the past.

Indeed, it takes the body about 10 days to mount a measurable antibody response to an infection, which may mean antibodies are not detectable until the latter stages of illness. Once an infection is cleared, the level of antibodies in serum tends to decline over time, but can vary from person to person and is very dependent on the pathogen that provoked their production (humans respond to some pathogens with a much stronger antibody response than others).

 Because the production of antibodies in response to infection is delayed, tests measuring antibodies are not very useful for patient management. However, because antibodies persist for some time after infection, antibody assays are a valuable tool for infection surveillance – for example, quantifying what proportion of the population have been exposed to/infected with SARS-Cov2.

There is currently no one antibody assay that has been universally adopted for SARS-CoV-2 surveillance.  Different countries are using, to a greater or lesser extent, assays that have been developed by their national public health agencies and/or by private manufacturers. Most of the commercially-produced assays are “qualitative lateral flow immunochromatographic assays” – this format is akin to that commonly used to determine pregnancy and thus can be done easily by patients themselves (or at least at point-of-care) without the need for specialist equipment of technical training. This format makes it feasible for huge numbers of people to be tested. However, the sensitivity and specificity of these assays are currently considered inadequate by many; in particular, there is widespread concern about false negative results resulting from assays being unable to detect lower concentrations of antibodies in the sera of some recovered patients.

Viruses recognise and bind to target cells by the interaction of molecules on their surface, with those on the target cell. These are called “surface receptors” – and work a little like a lock and key: a virus can only invade a cell is its surface molecule (the key), matches the receptor (the lock) on the host cell. The SARS-CoV-2 key is the spike protein which matches the ACE2 receptor lock on target cells.  

After binding to target cells, virus particles enter the cell either by fusion of the lipid envelope with the host cell membrane (e.g. HIV) or receptor-mediated endocytosis (e.g. influenza virus or coronavirus), in which receptor binding triggers the cell to engulf the virus particle. Once inside the cell, the viral capsid dissolves, uncoating the viral genome, which can then be replicated. New viruses are now made by the host replication and synthesis machinery. Finally mature virus progeny exit the host cell. Enveloped viruses do this by budding, picking up a coating of lipids from the host cell membrane on the way out. Box 1 shows the size of virus particles, but also some of the surface receptors on coronaviruses and influenza virus.

Figure 3 A diagram, depicting the general trend of associated with a typical time-course of SARS-CoV-2 infection following infection. The initial peak of viraemia is detectable by either PCR or antigen-based methods. Following an assumed immune response, antibodies can instead be detected by serology, however the length of time these remain detectable for remains poorly understood.
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