COVID Serology

The immune system is a big complex machine.  Medicine tries to simplify the machine to make it understandable and to manipulate it to our advantage.  That’s why we measure antibody levels in the blood.  The measurement of antibody levels in the blood is called serology.  Serology doesn’t measure the whole immune system, but we do it because it’s easy, and it gives us an idea of what’s going on.  

Your immune system is stimulated by molecular structures that are not native to you.  You could say that your immune system is xenophobic, reacting against foreigners. And your immune system has a long memory.  Once stimulated, these memories allow your immune system to mount a defense quickly should that foreigner ever be encountered again. For many infectious agents, including SARS-CoV-2, this means the formation of antibodies which can be measured in your blood.

When you are infected by the virus, your immune system is exposed to all the molecules that make up that virus.  Your immune system can respond to any of those molecules, including one special molecule: the spike protein.  We need to understand what makes spike protein so special.

Contact between the spike protein on the SARS-CoV-2 virus and a cell inside the nose is the first step in the infection of our bodies by these tiny invaders.  The spike protein is like a key that unlocks the vault, giving the virus access the interior of the cell.  Once inside, the virus hijacks the cell machinery, converting it into a virus manufacturing plant.  Thousands of copies of the virus are pumped out which infect neighboring cells, and the process repeats.

Antibodies to spike protein are special because they are neutralizing antibodies.  Neutralizing antibodies get between the viral key and the cellular portals, acting like putty gumming up the keyholes.  That’s why code for spike protein is the active ingredient in mRNA vaccines, and that’s why we should be able to measure vaccine response with spike protein antibodies.  Other parts of the immune system are activated too, but these work after the virus has entered the body.  At least that’s the theory.

How well does all this work?  Imperfectly.

While vaccination may reduce the risk of future infection, it does not prevent it.  Breakthrough infections occur.  Maybe that’s because neutralization only happens when antibody levels are high enough.  Or maybe neutralizing antibody levels fade within months of vaccination.  Or maybe the small alterations in spike proteins of variants make vaccine-induced neutralizing antibodies less effective.  Or maybe it’s a combination of all these ideas.  We really don’t know.

And there’s the point.  We really don’t know.  We certainly don’t know enough to make universal vaccination the sole objective of our pandemic response.  Vaccination is a tool that can be used to keep people alive, but it should not become the primary goal.  Other theories need to be investigated to identify our best hope for survival.

For example, here’s a theory that should be investigated.  Based on what we know about the immune response, natural immunity from COVID-19 should be more durable, more protective, and better for our communities than vaccine.  Why?  Natural immunity exposes the immune system to many different molecules, not just spike protein, making it more likely to sustain emergence of new variants.  More durable immunity generates longer lasting herd immunity, reducing the size of subsequent disease spikes.  At least that’s the theory.

How well does it work?  We don’t really know.  

Although other nations have found wisdom in this theory, the CDC has not permitted us to try it.  Instead, the CDC stubbornly holds on to the universal vaccination idea, even vaccinating COVID survivors regardless of their antibody levels.

So how do we get out of this?  We need data.  We need answers to questions like what antibody levels indicate protective immunity?  How long does natural immunity last?  Is vaccine-induced immunity as protective natural immunity against variants?  Can antibody levels be too high?  What are the optimal antibody levels?  

That’s why I’m excited about the Texas CARES Survey.  This study sponsored by the UT Health Science Center at Houston, with testing by my friends and colleagues at Clinical Pathology Laboratories (CPL), promises to give us large cohort retrospective data on durability and magnitude of antibody responses after disease and/or vaccination, with matching outcomes.  Although the study has met its initial enrollment goals, check back for results and more opportunities to participate.

Why has it taken so long to ask these questions?