Where did all the antibodies go?

Where did all the antibodies go?

Did you think you had COVID-19? Did you have your antibodies checked? Did it come back negative? You would be one of the thousands of health care workers and the general population that faced this very confusing scenario.

What went wrong? The manufacturers of the antibody tests have told us they are highly accurate. Our experience seems to suggest otherwise. But this is not a failure of the test per se but rather the assumption that SARS-CoV-2 antibody production is durable.

A very recent paper published in JAMA has demonstrated why this assumption is wrong. While the numbers in the study were small, it provides a window into how the body reacts after SARS-CoV-2 infection.

The authors examined American healthcare workers in Nashville. Of 249 volunteers 19 (7.6%) had anti-SARS-CoV-2 antibodies detected at baseline. The blood test was repeated at 60 days. Only 8 (3.2%) still had measurable antibodies. 58% had become seronegative.

So it should come as no surprise that when the UK public and health care professionals were encouraged to have antibody testing in June that so many tests returned negative because for the majority the boat had been well and truly missed. If you had the infection in March or April it would already be more likely than not that your antibodies would be negative.

In truth, most of us gave up on antibody testing months ago, but these findings do raise important questions and provide answers for others.

The biggest concern in the public is if a lack of enduring antibodies makes re-infection more likely? This study cannot answer this question but it seems very unlikely. Despite being 9 months into this pandemic (arguably longer but that’s a topic for another blog) there have only been a handful of case reports of re-infection worldwide. Whether this is due to T cell-mediated immunity or B cell memory or some other mechanism entirely we don’t have the answers yet but something continues to protect a person after the disease.

And while we consider immunity, let’s think about it on a population rather than an individual one. Antibody rates in the population have been used to estimate the number of people that may have been infected. This study tells us that in these models rates of infection may have been underestimated. Indeed this fits with the lack of significant increases in early, hard-hit areas such as London compared to the relatively unexposed north.

And what about Long Covid? It is reassuring that current mortality rates in this second wave remain very low, but we will see many people with enduring sequelae secondary to this infection. While definitions and diagnostic criteria for Long Covid have yet to be agreed internationally, this data clearly shows that reliance on a positive test result, be it RT-PCR or antibody, is inappropriate (not to mention all those that never had the opportunity to be tested) and that Long Covid is very much a clinical diagnosis.

So great – if you’re within 2-3 weeks of your probable COVID infection and failed to get a swab despite refreshing the government website a hundred times then antibodies may be just the thing for you. Otherwise, forget the tests, use your clinical judgement, it all sounds very general practice to me.

Dr Neal Tucker
7th October 2020

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