COVID-19: Booster Doses – Part 1

The most recurring question I get is a variant (see what I did there?) of  “What about booster doses?”

A lot of complexity and potential for misunderstanding is built into that seemingly simple question. As my initial writing on this topic got longer and longer, I realized it was time for another 1980s style mini-series of blog posts. (Remember mini-series? They were such an ’80s phenomenon.) 

Anyway, today’s “Booster Doses – Part 1” will go over some of the basics of booster doses and review the use of additional doses (not boosters) in patients with compromised immune systems. Part 2 will be posted tomorrow and Part 3 the day after that.

So buckle up for your booster bonanza!

At the bottom of each part in this series you will find a link to some background posts that may be helpful, as well as a list of definitions.

What are booster doses? 

“Booster dose” is a very specific term. It does not merely refer to additional doses of a vaccine, but rather a booster dose refers to a dose with specific effects that is given after a “primary series” of a vaccine. Booster doses increase the quantity of antibodies produced by the body — and not just by a little. Instead of just an additive effect, booster doses typically have something akin to an exponential effect. 

Let’s say for simplicity’s sake a vaccine series causes the body to have a quantity of 100 antibodies, but after six months that amount goes down to 25 antibodies. A revaccination, or a simple “additional dose,” would only bring that number up to 100 or 125 antibodies. A true booster dose, however, would increase the antibodies to 500, 600, or more.

In addition, a booster dose not only increases the quantity of antibodies produced by the body, it also improves the quality of the antibodies. In basic terms, booster doses can produce antibodies that are better at their job than the first antibodies produced, which may be beneficial against future variants. And this may even be the case by using a booster with the same original spike protein genetic data. 

In other words, we may not need a booster dose targeting a specific COVID-19 variant to provide protection against that variant. After all, the original vaccine has maintained high rates of effectiveness against the variants that have emerged.

But wait, there’s more than just antibodies!

That’s right, booster doses often create not only antibodies, but also improved cellular immunity. It is nearly certain that without cell-mediated immunity (see definitions below), any protection against COVID-19 will be very short-lived. We need those cells to produce antibodies in the future, but more importantly to “remember” the virus, so that if you are exposed to the virus your immune system mounts a strong protective response.

Wait, you said “primary series.” What is that?

The primary series is simply the initial series of doses of a vaccine. Right now, we consider the two doses in the mRNA vaccine series to be the “primary series” and any additional doses to be booster doses. Although that is accurate, we should compare these vaccines to other vaccines for a fuller understanding.

Many vaccines require at least three doses, if not four or more. We don’t think any differently of vaccines that require three, four, or more doses because those vaccines have been around a while and the diseases they protect us from are just not that common anymore (think tetanus, polio, chicken pox, etc.). 

If we didn’t have a pandemic, and therefore didn’t need to move so quickly, we may have figured out that three or four doses of these mRNA vaccines is the ideal number. And we would consider such a schedule “normal.” But we don’t have the luxury of time to study multiple different vaccine schedules, so we have to give science some grace in this case. (I love using the words “science” and “grace” in the same sentence).

What about patients who don’t have decent immune systems? I heard they should get more doses?

The FDA authorized, and the CDC recommended, that patients with compromised immune systems should receive an additional dose of an mRNA vaccine. Note the phrase “additional dose.” For patients with truly compromised immune systems, these extra doses are not booster doses, because many of these people probably didn’t get a good (or possibly any) immune response to begin with. Essentially there was nothing to boost.

What patients “count” as having a compromised immune system?

I’ll start off by saying more people think they have a compromised immune system than actually do. The vast majority of people with acute and chronic diseases respond just as well to the COVID-19 vaccine (or any other vaccine) as those who are perfectly healthy. The CDC estimates that about 3% of the population have truly compromised immune systems. That may sound like a small percentage, but that is a large number of people.

You can assume a lack of protection from a COVID-19 vaccine for the following groups of people: those who are in active treatment for cancer (especially cancers like leukemia), those with organ transplants (although some patients whose transplant is years in the past may have only minimally suppressed immune systems), those with advanced HIV infection (far less common than it used to be), and those who take severely immunosuppressive medications (this is a long list).

There is a lot of gray area where patients should talk to their physician to determine how suppressed their immune system is. When in doubt I think it best to assume a sufficiently compromised immune system to warrant an additional dose of an mRNA vaccine.

When should patients with compromised immune systems get an additional dose?

Ideally patients with a compromised immune system should wait at least 28 days after their second dose of a COVID-19 vaccine before getting an additional dose. In addition, patients ideally would receive their COVID-19 vaccine doses at least two weeks prior to starting therapy that would compromise their immune system. Unfortunately ideal timing is not always possible. 

How many additional doses of an mRNA vaccine should patients with a compromised immune system receive?

Right now the recommendation is one additional dose. That additional dose will help protect many additional patients. The tricky and tragic part of a compromised immune system is that sometimes there are simply not enough doses to generate good protection. 

What other precautions should patients with a compromised immune system take?

1. Wear a mask in public, especially in indoor settings.
2. Be careful and cognizant with whom you are in close contact, and beg those who you are close with to get vaccinated.

Stay safe, and go make some lemonade.

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Past reading and definitions that may be helpful:

Please read this post for a somewhat in-depth description of how immunity prevents infection, disease, and contagiousness.

Please see this post to review some basic definitions. I’ve also pasted that list below along with some new definitions. (If you already know or remember these definitions, just skip to the next heading.)

COVID-19 infection. This is defined as, uh, well, infection with COVID-19. (You subscribe to this blog for that level of analysis, right?) This definition includes people who have “disease” as well as people with no symptoms.

Asymptomatic infection. People who are infected but who do not develop symptoms.

Incubation period. The average time from infection to onset of symptoms. For COVID-19 the average incubation period is about 5 days.

COVID-19 disease. A patient who is infected with COVID-19 and has symptoms of that infection (including anything from a low-grade fever all the way to severe pneumonia requiring mechanical ventilation).

Severe COVID-19 disease. There is no strict definition of the word “severe.” Obviously being hospitalized is an example of severe disease, and just having a minor cough is not severe. For purposes of this discussion, it is best not to quibble about definitions and use the term “severe” in its standard English meaning.

Infectious. A person who can spread COVID-19 to other people. Both those with asymptomatic infection and those with COVID-19 disease are infectious and can spread the virus. In general, people who never develop symptoms appear to be less infectious than those who eventually develop symptoms.

Carriers. We don’t really have COVID-19 “carriers.” A carrier usually refers to someone who is infected with a microorganism and carries that organism in their body for an extended period of time, like months. Bacteria provide the best example of “carriage.” Although we don’t know how long patients who have asymptomatic infection with COVID-19 have viable virus in their respiratory tract (and are therefore contagious), it’s probably no more than 10-14 days.

Antigen. The part of a virus or bacteria that causes your body to generate an immune response. Not all antigens are proteins, but many of the best ones are.

Antibody. A protein produced by the body that attacks pathogens like bacteria and viruses. Antibodies are produced either in response to infection or immunization.

Neutralizing antibodies. Antibodies that neutralize a pathogen (didn’t see that one coming, did ya?).

Cell-mediated immunity. Immunity that uses or requires cells. There are many different types of immune cells. Some cells directly kill pathogens (natural killer cells). Some cells produce antibodies (called B-cells). Some cells help other cells do their jobs (helper T-cells). Different infections may require different types of an immune response. The most protective and longest lasting types of immunity usually need both antibodies and cells.

Respiratory mucosa. The innermost lining of the mouth, nose, and the airway that extends all the way down to the lowest depths of the lungs. This lining is where COVID-19 infects the human body.

Sterilizing immunity. Immunity that prevents infection. 

Viremia. Viral replication in the blood. Although COVID-19 does not primarily infect the blood, there is some evidence that the virus can infiltrate the blood, which is likely how the virus spreads from the respiratory tract to other organs. The presence and the amount of viremia is associated with severe disease (not surprising).