From the blog post (linked to from Marginal Revolution): [...] [...]
From the blog post (linked to from Marginal Revolution):
The first issue in designing a serology test lies in the selection of the antigen. [...] Recombinant antigens are much easier to produce in bulk with the necessary consistency, but risk missing immune responses to other antigenic determinants on the virus.
[...] The next problem relates to the complexity of the human immune response: antibodies come in multiple isotypes, with an initial response of IgM followed by higher affinity IgG a week or two later. Even this over-simplifies what happens, because IgM-positive plasma cells also express IgD, but the levels of IgD vary almost 1,000-fold between individuals for reasons that we don’t properly understand. [...] IgD antibodies in the serum sample still bind to the recombinant antigen – and compete with the IgM and IgG also in the sample. The result is some very complex dilution curves (at best), or else a significant risk of false negatives.
[...] If you can dilute the sample a lot and still detect bound antibody, we say the individual has a high titre (or strong) response. If the signal disappears as the sample is diluted, that indicates progressively lower titre and hence weaker response. If we are trying to predict who is protected against re-infection with the virus, this titre information can be crucial.
Yet the competition between different isotypes can make titre estimates difficult or impossible. Sometimes the signal in the assay even INCREASES as the sample is diluted (because the low affinity competing IgD doesn’t bind at higher dilutions, revealing a higher affinity IgG response that was previously hidden).
[...]
But the challenges in designing the test, though not to be under-estimated, pale into insignificance compared to the challenge of interpreting the results.
At the simplest level, the question “how many people have been infected by the virus at any point in time?” is relatively straightforward. [...] But the real question we would like to address is “who has been infected by the virus and developed a productive immune response sufficient to ensure they will neither suffer symptomatic re-infection nor act as an asymptomatic carrier?”.
[...]
Running a serology test, however, doesn’t really answer that question. Do antibodies against different antigens all result in protective immunity? What titre for the immune response would be considered sufficient to confer such protection? Whatever cut-off in whichever assay is chosen, it seems certain some people will have a “positive” test but lack a neutralising (and therefore protective) immune response. But how many people? And which ones? Answering those questions will require clinical studies following a large cohort of people after testing for some considerable time.
From the blog post (linked to from Marginal Revolution):
[...]
[...]