What are COVID-19 antibody tests and why are so many failing……?

COVID-19 Antibody Test
  • Antibody blood proteins may be the key to knowing who has been infected with CORONA-19 virus.
  • They may also identify individuals who have immunity (protection) against viral infection.
  • Many assays for antibodies are currently available, but some don’t work and give false results.
  • Understanding the immune response to COVID-19 and how antibody assays work is crucial to comprehending the role of antibodies in managing the pandemic.

DISCLOSURE:

I have few areas of true expertise, but I have been an immunologist and designed these tests for over 40 years. I need to disclose that I am involved in evaluating COVID-19 test kits and making sure that they work. If the kits accurately identify COVID-19 antibodies, I may be involved in commercial activities to market them.

Tonight, I’m going to begin a three-part discussion of the most important topic in the news today; antibody tests for COVID-19. As you probably have heard, there has been much debate about blood assays looking for proteins (antibodies) that identify an individual who has been COVID-19 infected and then developed protective immunity. You probably have also read that the number of tests to identify COVID-19 antibodies has grown as fast as the pandemic itself! Many of these tests are not well designed or manufactured and are marketed by people who have no background in this type of testing. Some of these tests are being fraudulently sold despite not functioning.

To understand how COVID-19 antibody tests work and what use they are in following the pandemic, it is necessary to understand three different areas. Tonight, we will have a brief discussion of how COVID-19 infection causes an immune response that generates antibodies. I will also discuss the significance of what COVID-19 antibodies means. 

Tomorrow, I will focus on the antibody assays used in communities and by individuals, since large laboratories are unavailable to end users (and should know what they are doing!). The antibody tests are remarkable technology; it puts a complicated test that took hundreds of hours of laboratory work and places it in your hand. But these assays have technology that you need to understand to use them properly.

Finally, on Thursday evening I will discuss the problems with these assays and why they fail. I hope this last discussion gives appropriate caveats about why the technology has not been uniformly successful (and “buyer beware”).

So, whether you’re considering using a COVID-19 antibody assay on yourself, on your community, or even on an entire state, understanding what antibodies are and how they are measured will be crucial to making a rational decision. It’s a large and complex topic, which is why it will take three evenings to discuss. At the end I think it’s important that we all are educated consumers of these tests.

Part 1: How COVID-19 infection causes an immune response that generates antibodies, and the significance of COVID-19 antibodies. 

Your immune system is remarkable! It is the one part of your body that you can train to do different tasks. When you are confronted with a foreign material, like a virus, your immune system immediately recognizes it as foreign, walls it off to limit its access to your body, and then makes a response that specifically neutralizes the invader and allows you to return to health. No antibiotic or antiviral drug can cure you of an infection; drugs just slow down the infectious agent until your immune system can take over and clear it.

The Dendritic cell (in purple) presents the virus to the CD4 T cell (red). It then activates B cells (blue) to make antibody. So you cannot make antibody specific for COVID-19 without activating T cells.

The immune system specifically recognizes foreign materials. Specialized “presenting” cells show the foreign material to your lymphocytes. Whether this is a virus, bacteria, or toxin, this presentation to your lymphocytes mounts a specific Immune response. Lymphocytes that have receptors that recognize COVID proteins are preferentially stimulated and make both killer T cells and antibodies against the foreign invader. The killer T cells destroy your virally infected cells, removing the source of the virus, while the antibodies bind and neutralize free virus. This combination allows you to clear the virus and overcome the infection.

Blood components; plasma is the liquid component.

Antibodies are the proteins in the fluid component of the blood (plasma) that bind to and neutralize viruses. They are relatively easy to find because the plasma is easy to extract (by a finger prick or drawing blood through a needle) and test. In contrast, the cellular components of the immune response are located mainly in the lymph tissues (nodes) that are solid organs. These have to be surgically removed to be assayed. Most of us would not want a surgery just to sample our immunity to a virus! Fortunately, antibodies are not made without a cellular immune response, so finding COVID-19 antibodies is also a marker of a productive cellular immune response to the virus. 

When we look for COVID-19 antibodies in the blood, we’re looking for a sign that an individual has been infected and a productive immune response has occurred. This response necessarily involves both antibodies and cellular immunity. Almost every person who survives a viral infection has intact immunity to that virus. If immunity is incomplete, the virus replicates uncontrollably, and the person dies. No antiviral drug or antibiotic can cure you of an infection if you don’t have an intact immune system; these drugs simply slow down the infection until the immune system can clear the virus.

There has been much discussion about the failure of immunity in COVID-19 infection. This is greatly overstated; again, no person overcomes a COVID-19 infection without an effective immune response. It is possible that COVID immunity will not last long; maybe a year to 18 months. However, the individual had to make a productive immune response, or they would not have survived. In fact, some of the elderly people that died from this infection may have died because their immune system could not effectively respond to the virus.

Complex interactions of immune cells produce Killer T cells (CTL in red) that kill virally infected cells and B cells(green) that make antibody to neutralize free virus. Bottom line; the whole immune system needs to work to protect against a viral infection.

In summary, immunity to COVID-19 is important, and no one survives COVID-19 infection without productive immunity. Antibody presence is a long-lasting marker of productive immunity in the fluid component of the blood where it is easily accessed and tested. Identifying COVID-19 antibodies tells one sure thing: how many people have been infected with the virus. It may also tell us that those people have immunity that protects them from further infection, but that awaits definitive proof.

(to be continued) 

Published by jbakerjrblog

Immunologist, former Army MD, former head of allergy and clinical immunology at University of Michigan, vaccine developer and opinionated guy.

2 thoughts on “What are COVID-19 antibody tests and why are so many failing……?

  1. When I started my Internal Medicine residency many years ago, I remember getting revaccinated for MMR and getting the Hepatitis B vaccine, as well as reviewing my history vaccinations. It is one of a physician’s responsibilities in taking care of their health. Would it be reasonable for physicians, nurses and other Heath care workers to get tested for SARS-CoV-2? Certainly some asymptomatic individuals might pose a risk that is worth investigating.

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