29 April 2020 Blog Post: COVID-19 Antibody Testing
We have used LabCorp as our commercial laboratory for many years now. They were the first laboratory with whom we were able to integrate our EMR into their clinical reporting systems, which was a critical step in reducing paperwork and receiving labs in a timely manner. We have been utilizing their expertise in the PCR identification of COVID-19 in respiratory samples since early March. They are now offering COVID-19 IgG antibody testing to the general public.
I have known for the past couple few weeks that they had been performing limited COVID-19 antibody testing targeting frontline healthcare workers. Beginning Monday April 27th, they have begun to offer IgG antibody testing more broadly to the general public. However, they are not including IgM and IgA testing at this time. IgG results will be reported not as a numeric measurement but instead as positive, negative or equivocal.
I have been critical of antibody testing efforts to date but in this instance LabCorp seems to have struck a conciliatory balance. They note that their testing modality has not been evaluated by the FDA, nor is it intended to diagnose disease, and has significant limitations in interpretation.
To contextualize the alphabet soup of IgM, IgA and IgG antibodies (and the relative importance of IgG compared to the other two in validating a person’s protection from subsequent infection), I’ll present a brief review of these antibodies. This is represented schematically in the figure below.
The first response to a new infection (and COVID-19 will be new to everybody) is an IgM response; I remember this by equating IgM with the words “iMmediate” and “iMmature”. It is our immune system’s “oh crap, what the hell is that?” response and begins around Day 7 post-infection. It is essentially a spider web of a molecule. IgM itself is constructed of five or six units hastily constructed in an attempt to simply trap a virus – you can see its general structure in the second figure.
IgG production begins around Day 14 post-infection. I think of it as the assassin of the immune system. If IgG were in a movie, Mark Wahlberg would play it (Will Ferrell would be a great IgM – somewhat goofy and lovable but not an action hero). You can see from the third figure that IgG is streamlined and efficient. It contains two identical heavy chains and two identical light chains. Its is the major immunoglobulin in blood and the central player in the immune response, keying the vital mechanisms that cells use to cope with microorganisms. Vaccines mostly mediate protection through the induction of highly specific IgG serum antibodies.
Notice that I have left out a discussion of IgA which is the principal antibody class found in respiratory passages and the gastrointestinal (GI) tract, as well as in saliva and tears. It is also found in the blood. Live oral or nasal vaccines, such as nasal infuenza, and cholera vaccines, induce an IgA response. A recent study of commercially available IgA tests for COVID-19 showed that these were of lower specificity (able to identify a true negative) than IgG assays (Okba et al., Erasmus Medical Center, Rotterdam, the Netherlands). Further, the precise role of IgA in natural infection is also less clear than that of IgG and IgM. While there is agreement that it plays an important role on body surfaces, whether or not it is critical to immunity remains unresolved. While some people who lack IgA suffer from recurrent sinus or GI infections, many exhibit no apparent issues whatsoever. So I would not think that IgA is a critical measurement in COVID-19 antibody testing.
So after all of this, what do I advise? I think IgG testing is a useful diagnostic tool and is now available from a reputable source. For those who have had a positive PCR nasal or throat swab and are now more than several weeks away from that test, it will be a clinically meaningful piece of information. For those that experienced a COVID-like illness and have recovered, it may also provide some clarity. For others without known disease or suspicious illness, its utility is less clear. Positive tests may be the result of past infection with non-COVID-19 coronavirus strains which account for up to 30% of seasonal ‘common’ colds. A negative test does not rule out prior infection.
As with most of COVID-19, we are all learning as we go along but it is a tremendous benefit to see such progress.
𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿
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