Infectious disease expert Amesh Adalja has often been a voice of clarity and reason during this pandemic. In his latest blog post, he discusses Covid-19 Vaccine boosters. The punchline is: he does not think that most people need boosters on the current timeline indicated by the CDC. In this article, I review Adalja’s post and do my best to elaborate on his thinking. At the end, I provide a sample risk calculation using myself as an example. I hope that this helps you think through the issue of Covid-19 vaccine boosters in a methodical fashion.

First, to eliminate a common confusion, Dr. Adalja points out that the CDC’s current recommendation for a third dose of vaccine in immunocompromised people is not the same as the upcoming boosters for immunocompetent individuals. This distinction is important because the data used to recommend an additional dose of vaccine in immunocompromised patients is from immunocompromised patients. This data doesn’t apply to people with intact immune systems. Therefore, this distinction is important for public health recommendations, but also for individuals deciding whether or not to get a booster. We need to know which group we belong to so that we can understand which risks and benefits apply to us.

What has the CDC said about boosters? On August 18, 2021, the CDC and HHS said the following in a joint statement:

”The available data make very clear that protection against SARS-CoV-2 infection begins to decrease over time following the initial doses of vaccination, and in association with the dominance of the Delta variant, we are starting to see evidence of reduced protection against mild and moderate disease. Based on our latest assessment, the current protection against severe disease, hospitalization, and death could diminish in the months ahead, especially among those who are at higher risk or were vaccinated during the earlier phases of the vaccination rollout. For that reason, we conclude that a booster shot will be needed to maximize vaccine-induced protection and prolong its durability."

Despite the CDC’s rationale, Dr. Adalja is skeptical that it’s needed. He says, "There is marginal utility in the general healthy population getting booster vaccinations at an 8-month interval." However, he is careful to conclude his article with this statement, “There may come a time when boosters are needed and it’s important to be proactive and have streamlined approval and distribution pathways, but I don’t think that time is 8 months.”

Adalja makes several points in his blog post to explain why he doesn’t think boosters are needed yet for the ‘general healthy population.’

1. Waning antibody titers post-infection or immunization is expected and does not necessarily indicate lack of immunity (I explain this in more detail later in this article).
2. A so-called "breakthrough" infection of mild disease in an immunized person does not indicate vaccine failure because:
3. Vaccines are not and were not developed to prevent mild and moderate disease (though they may do so). They are instead intended to prevent severe disease, hospitalization, critical illness, and death.
4. Last, he questions the data sources the CDC and HHS have used to draw their conclusions, asserting that they are making an unwarranted leap from inapplicable data sources (I suggest reading his blog post if you want specifics on this point).

Should we listen to Adalja who says that a booster provides “marginal utility” or the CDC who says a booster is “needed to maximize vaccine-induced protection and prolong its durability.”

Neither of these generalizations is helpful in making a personal decision. To be fair, neither Adalja nor the CDC are intending to help individuals make these decisions. They are addressing the issue from a public health perspective. As foolish as I might be in making the effort, I’m going to try to indicate how you might make this decision for yourself.

The question we need to ask is simple: are we better off with or without a booster?

I think it’s helpful to unpack this question into more specific questions that we might have a chance at answering:

• What benefits do I stand to gain from a booster?
• What risks exist with and without a booster?
• What are the probabilities and magnitudes associated with each?

What benefits do I stand to gain from a booster?

To determine the benefits of a booster, we would need to know: i) that we have lost sufficient immunity to existing or potential Covid-19 variants such that infection would mean at least moderate or severe disease, not just mild infection, and ii) that a booster would be likely to prevent such morbidity or mortality.

What risks exist with and without a booster?

To determine the risk, we would need to know that the risks of a booster are less than the risk of infection without the booster. We would also need to know that a booster wouldn’t be more risky than the original vaccine series. We now know that the existing Covid-19 vaccines, while overwhelmingly safe, are not without risks [1, 2] including myocarditis, thromboembolic disease, and in rare cases, death.

What are the probabilities and magnitudes associated with each?

We need to have some rough idea of the probabilities of the questions above. With regard to magnitude, they’re fairly equal in this case. The worst case scenario with both Covid-19 infection and vaccine adverse events is critical illness and death. I suspect that deaths and critical illness from breakthrough infections will vastly outnumber those from vaccination.

Right now, we don’t have the ability to answer these questions with enough certainty. The data is not in.

So, what to do?

Despite the lack of information that is likely to persist for some time, I think we can still make a rough risk calculation based on age, health, Covid-19 infection and immunization history, risk tolerance, and lifestyle.

Here is an example of a qualitative risk calculation using myself as an example:

I’m a 35 year old man with no known medical problems. I’m in good metabolic health — I’m relatively lean and physically fit. To my knowledge, I’ve not been infected with Covid-19, but I did receive the two-series Pfizer-BioNTech vaccine series five months ago and had no adverse reactions that I’m aware of. I’ve been leading a fairly normal life for the past five months since vaccination – traveling, training martial arts in close-contact with others, and working in the emergency department where I wear an N95 mask into most rooms, but where I still might have exposures.

At this point, I think my likelihood of retaining immunity is very high. I also believe that my likelihood of developing severe disease if I contract Covid-19 is incredibly low given my age and health status. Therefore, I’m not motivated to receive a booster at this time. I’d rather wait to see more data.

What would change my mind?

If I were to find out that vaccine mediated immunity was insufficient to prevent severe disease even in young healthy people due to a new variant, and that a booster would likely protect me from this, I would be likely to change my mind.

If I had serologic evidence (a blood test), that I had little or no sign of immunity to Covid-19, I would be motivated to receive a booster.

Note: No such commercial test that proves Covid-19 immunity is available. You can get tested for antibodies whose presence is reassuring, but as I will indicate below, antibodies are not the only source of immunity and do not tell you with certainty whether or not you’re immune, or what will happen with a new exposure.

What else would change this risk calculation?

If I did not have regular exposure, if I was unhealthy in almost any way (overweight, obese, high blood pressure, diabetes, or any underlying vascular, heart, or lung problem), I would be more likely to want a booster as I’d be at much higher risk of severe disease.

This type of risk calculation is different for everyone. It’s useful to think through these different factors. It’s also useful to consider how you might feel in different circumstances. Nearly every unvaccinated Covid-19 patient that I’ve admitted to the hospital this month has volunteered that they deeply regretted not being vaccinated. I suggest playing out these scenarios in your head to see which are favorable to you and which are not.

In one discussion with a client of mine, I asked him: How would you feel if you didn’t get vaccinated and you ended up hospitalized or dead from Covid-19? Then I asked: How would you feel if you got vaccinated and you became ill or died from that? For most adults, the likelihood of the second is far lower than the first, but you have to answer these questions for yourself.

Ultimately, when it comes to tough decisions where life and death are at stake, I like to take a page out of Jocko’s book and be, as he puts it, “default aggressive.” If I thought the risks and benefits were a close call between taking and not taking the booster, I would choose to take it. I’d much rather be proactive and suffer for that, than be passive and let nature decide my fate.

Here are a few things you should know about the immune system that might help you interpret the often confusing discussions of immunity:

Immunity is not comprised merely of antibodies.

There are myriad other mechanisms by which the human body can fight pathogens like SARS-CoV-2. For instance, there are several different types and sub-types of immune cells that are involved in protecting you from infections.

There are different types of antibodies.

When people refer to "antibodies," they’re often referring to IgG antibodies, which are found predominantly in the blood and tissue, but not at the surface of mucous membranes. Most lab tests that look for the presence or absence of antibodies look for IgG. Contrast these antibodies with IgA antibodies. IgA is present at mucous membranes like the inside surfaces of the mouth, eyes, and nose. Covid-19 mRNA vaccines actually induce both IgA and IgG antibodies, but IgA are more short-lived.

Antibody levels in the blood naturally wane over time but your immune system has a memory.

This means that if you’re exposed to SARS-CoV-2 today, you may develop antibodies. The amount of these antibodies in your blood stream naturally goes down over time. Eventually, they may be undetectable. Nevertheless, your immune system likely retains a memory of these antibodies which can then be quickly manufactured when you’re exposed to SARS-CoV-2 again.

-Steve

Credits

Thank you to Ross England, MD, PhD who is currently a fellow with the Division of Infectious Diseases at the University of Pennsylvania and the Children’s Hospital of Philadelphia for reviewing this post and giving me his thoughtful feedback.

Thank you sincerely to Dr. Amesh Adalja for being a mind of reason and clarity during the pandemic.