Are the Level of Antibodies Related to Immunity for COVID-19? Not Really.

In a great deal of the media coverage of COVID-19 (such as How an Ill-Fated Fishing Voyage Taught Us About COVID-19), we have seen a frequent and persistent confusion and misconception about the relationship between:

  • the level of antibodies detected in the blood of a person that has been exposed; and
  • the actual immunity to COVID-19 that person has – or has not – gained.

As Dr. Scott Halstead, Senior Science Advisor to Immunoprevention.org, put it:

Acquired immunity in humans differs for different types of organisms and from person to person. It is very complex and, honestly, we simply do not understand even the complexities we have identified. When you add in what it is we do not know, we are in very hot water. Anyone running around making claims about “protective” levels of antibodies for people that have been infected with COVID-19 is misunderstanding how acquired immunity – and antibodies – work.

There is no evidence from the SARS or MERS epidemics that humans experienced two different overt cases. SARS infections of animals result in protective immunity against disease. Indeed, most systemic virus infections result in solid protective immunity, usually life-long. Antibodies are simply a marker that a prior infection has occurred.  The titer of antibodies has nothing to do with “how protected” a previously infected individual is.  Immune protection against viral infections is a complex process and not just the effect of antibodies.

The protection afforded by passive transfer of antibodies – such as with Immunoglobulin and monoclonal antibodies – is a different story.

Dr. Scott Halstead, Immunoprevention.org

So, What’s the Difference?

To understand what and why of this difference, you need to understand the following concepts, and how they relate to your body’s ability to generate an immune response to a pathogen like COVID-19.

If you think of an infection like a fire, the job of your body’s immune system is to first detect the fire, and then put out the fire rapidly before it can get out of control and burn down the house.

Antibodies

Antibodies are one of your body’s natural defense systems against foreign attackers. Specifically, an antibody is a Y-shaped protein produced by B cells, which are part of the immune system. When your body detects foreign intruders (like bacteria or viruses), your immune system makes antibodies that recognizes them. These specific antibodies attach to the foreign intruders and target them for destruction.

Further Reading: All About Antibodies

Antibodies are the first responders – the firemen – of your immune system, which go directly to the flames (the virus) and direct the fire hoses and foam (white blood cells, etc.) to put them out.

Innate Immunity

The innate immune system is one of the two main immunity strategies found in vertebrates (the other being the adaptive immune system). The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms. The innate immune system performs many different functions that comprise your body’s first response, including recruiting immune cells to sites of infection, the identification and removal of antibody complexes, dead cells, and foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells. Crucially, it also activates the adaptive immune system through a process known as antigen presentation.

Further Reading: Wikipedia: Innate Immune System

Innate Immunity is the system in your body that responds first to a fire (the virus), without the firemen and additional tools like water and foam (white blood cells, etc.) needed to put out a big fire. It can also raise the alarm to trigger your adaptive immune response.

Adaptive / Acquired Immunity

The Adaptive Immune System, also referred as the Acquired Immune System, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminates pathogens by preventing their growth. Acquired immunity creates immunological memory after an initial response to a specific pathogen, and leads to an enhanced response to subsequent encounters with that pathogen. This process of acquired immunity is the basis of vaccination. Like the innate system, the acquired system includes both humoral immunity components and cell-mediated immunity components.

Further Reading: Wikipedia: Adaptive Immune System

Adaptive Immunity is the system in your body that remembers a virus. OK, here the fire analogy breaks down a bit, but you can think of it like installing a special kind of fire detector. It remembers and recognizes a virus you have been exposed to before, and very rapidly raises the alarm and marshals your body’s response by: (1) producing and sending antibodies (the firemen) to contain the fire; and (2) white cells and other mechanisms (the water and foam) to put it out.

Antibodies vs. Immunity

With that model in mind, the relationship between Antibodies and Immunity is much easier to understand. Your body will have a lot of antibodies to a virus either while you are actively fighting the infection and for a short period thereafter. This is when the firemen are needed to fight and put out the fire, and make sure it is out.

Once the fire is completely out, you don’t need the firemen to camp out in your neighborhood! They can go back to their stations and be ready for the next fire. Similarly, the antibodies to a particular virus will decrease rapidly over time after an infection. Therefore, counting how many antibodies someone has to COVID-19 several months after exposure will tell you very little about their immunity to it. It means they were exposed, and have some immunity. But how strong and lasting that immunity is depends on a variety of other factors involving your very complex Adaptive Immune System.

The good news is that the data so far from the dozens of trials of both vaccines and antibody-based drugs – as well as retroactive studies of exposures to controlled population groups on boats – have uniformly indicated that the body’s immune response to COVID-19 is both strong and lasting. This is still to be proven in the remainder of Phase 3 trials and beyond, but the signs are all good.

Counting antibodies to predict protection against COVID-19 is like counting firemen. Unless there is an active or recently extinguished fire, you will not find very many of them, and it won’t tell you how well you can put out the next fire.

Passive Immunity

Since we’ve come this far, it is worth also understanding Passive Immunity, since that is the key mechanism which makes antibody-based drugs effective.

Passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen (e.g. COVID-19) are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases.  Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.

Further Reading: Wikipedia: Passive Immunity

Passive Immunity is like sending in a whole troop of fireman instantly, who know exactly where to find the fire, contain it, and direct your bodies immune defenses (e.g. white blood cells) to put it out. For people that have weakened immune systems – the elderly and those with preexisting conditions – this can supplement or replace the fire stations that are either missing or ineffective.

This is why Passive Immunity with antibody-based drugs is so vitally important:

  1. for treatment, it can help the most with those population groups that are most vulnerable to COVID-19;
  2. for prevention, it can combat infections rapidly, stop disease before it happens, and reduce the window of transmission to others.

It’s like keeping a fire truck parked outside your front door!

And – a likely source of confusion in the media – unlike antibodies that are generated by the Adaptive Immune System, the count of these antibodies does indeed have a very direct correlation to the amount of protection you have. These are not naturally produced, so will decline over a few months, and need to be replenished with new treatments until a safe and effective vaccine is available.

Further Reading: How Antibodies Help Your Body Beat COVID-19

Are the Level of Antibodies Related to Immunity for COVID-19? Not Really.
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