May 4, 2020 | By


The following was contributed by Raj S Dattani:

As we close out another week in the COVID crisis, there has been increasing focus on testing and vaccines. One key biological aspect that is worthy of note is understanding what immunity and having an antibody really means. In Medicine when we say we understand a disease reasonably well that means we understand its “natural history”. This phrase means that we understand what happens without any intervention.

For most infectious diseases, we mount an antibody response which “neutralizes” the infection. What form (in terms of immunoglobulin class type), and what amount of antibody is required is determined through time-intensive study. The level/amount of neutralizing antibody required is known as the “correlate of protection” (i.e. the amount of antibody at which you are protected). It is this key piece of information we still do not have in empirical terms for COVID19. This affects both testing and vaccines.

We are reaching a point where antibody tests can detect with reasonable positive predictive value an antibody to COVID19, but without the correlate of protection data we don’t know what that really means. How much do you need to say you cannot get it again? Similarly, for vaccine trials we will definitely be able to detect whether an early trial has healthy volunteers developing an antibody response to COVID19, but we do not definitively know how much antibody response is required to say the person is protected. This is why for example the Oxford trial, though having an early read-out of antibody response due in a short period of weeks will require a prospective period of months (estimated to be September) for a cohort over time to demonstrate that people who received the vaccine have lower rates of infection and illness from COVID than those who did not receive the vaccine in order to really confirm it works.

So to my mind, as we scale up antibody testing (so called “serosurveys”) the interesting data-point will not just be how many people have “had it”, but the follow up data drilling into what levels of antibody response were mounted over time, and what different levels of antibody response really mean.