The facts about Anti-COVID antibody tests
There are several different types of antibodies , but we broadly think about immunoglobulin M as the acute antibody, generated at the point of first contact with the virus , and immunoglobulin G as the long-term antibody which usually remains detectable in the blood stream. But the mere presence of antibodies does not mean that those antibodies are protective.
There are two types of anti-coronavirus antibodies: a group that binds to the spike protein ( the crown part of the corona), and more importantly, a group that reacts to the receptor binding domain of the spike protein. The ability of the virus to bind to the receptor on a target cell surface (a receptor called ACE2) is the key that opens the door of your cells to infection. It is hoped that if there is an antibody that will shut down the virus, it will be one that blocks the ACE2 receptor binding mechanism.
It has been shown that compared with controls, IgG and IgM levels are higher among those who had recovered from COVID-19. As expected in this convalescent group, a bigger difference is seen in IgG compared with IgM. Experiments show that IgM antibodies go down over time as in any infective process but in the case of COVID about 20%-30% of people do not seem to have antibody titres significantly above controls. But broadly, the majority of people do make antibodies. However the key question here is are these neutralizing antibodies? Do they stop viral replication?
In order to find an answer to this question experiments were carried out to determine how much plasma you would need to shut the virus down by 50%; this is known as the "neutralizing titre" 50 (NT50). Results showed that 33% of post infected individuals tested had an NT50 of less than 50, which implies essentially no immunity to repeat infection; 79% had an NT50 less than 1000 — they may have partial immunity. Only two people out of all the people included in the study had an NT50 greater than 5000 meaning definite immunity. The conclusion was that higher overall antibody titres were associated with neutralizing ability but that only small number of the people tested could be considered to have true immunity.
Individuals who had been hospitalized for COVID-19 were more likely to have neutralizing antibodies than those who hadn't been hospitalized, suggesting that those with more severe illness are more likely to be immune in the future.
Overall, this is fairly concerning. Without neutralizing antibodies, an end to coronavirus transmission and the development of herd immunity seems very unlikely. In addition we are not sure if second infection is possible but at present there is no evidence that significant numbers of individuals have been proven to have cleared COVID-19 and then become re-infected. Experts think that even without high levels of neutralizing antibodies, if a second infection occurs it is likely to be less severe than the first.
There is a further note of optimism. The researchers have not stopped at simply measuring how many people had neutralizing antibodies. They have sequenced the genetic codes of 89 different anti-COVID antibodies to determine which specific antibodies were highly neutralizing. 52 have been identified that had some neutralizing ability and several of these that had potent neutralizing ability because they target specific amino acids on the receptor ACE2 receptor.
Most of the people in the experiments did have those highly neutralizing antibodies but they just were not the majority of antibodies being produced. This finding does suggest a pathway for the development of a successful vaccine. If most of us have the potential to produce these potent neutralizing antibodies then a vaccine designed to promote that particular antibody response could be highly successful.
It must also be remembered that effective immune systems are much more complex than a simple antigen meets antibody equation. There are dozens of other factors involved some of which have been responsible for the “cytokine storm” reactions seen in potentially lethal COVID infections. Amongst these factors are certain T cell lymphocytes. The vaccine being developed in Oxford seems to not only excite antibody responses but as a by product also stimulates certain T lymphocytes thus improving immune response. It also looks as though some post infected patients with low levels of neutralizing antibodies have active levels of lymphocytes and some people who have had no clinical symptoms of coronavirus infection nevertheless have the active T cells. This is another reason why a vaccine may be very effective even though antibody response may be unexciting and it is another area waiting for investigation.
Altogether, I believe that the huge amount of global scientific effort going into research on coronavirus immunity, vaccines and effective treatments, is going to come up with more and better solutions for us in future and the sooner the better. Nil desperandum!
A Cochrane review of 54 studies published in the BMJ which involved some 16,000 patients demonstrated the incidence of positive antibody tests at intervals after the start of symptoms :
- One week - 30%
- At two weeks - 72%
- Third week - 94%
Therefore the optimal time for COVID-19 antibody testing is three weeks after the first symptoms - if you can remember when and if you have had any. In line with what we know so far, the review is not able to say how long COVID-19 antibody positivity lasts nor comment on its relation to immunity.
Date posted: 06 July 2020
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