Post-COVID: To Vaccinate or Not to Vaccinate? That is the Question.

With apologies to William Shakespeare for adapting a line from Hamlet to current day questions of great importance, I thought that I would address one of the most common questions I get about COVID. That question comes from those who know or believe that they previously had COVID as to whether they should get vaccinated. My answer is “definitely,” but I seldom have the opportunity to provide a detailed explanation as to why they should get vaccinated. So here goes.

First, a short primer on the immune response to infection with the SARS-CoV-2 virus that causes COVID-19 is in order. [Note: the following is greatly oversimplified, but intended for lay persons so that they can have a basic understanding of the science behind our recommendation that those previously infected with COVID still get vaccinated.]

There are essentially three arms of the immune system – the innate system (I have written previously about this, but for brevity and simplicity, I am not going to discuss this in detail for purposes of this blog post), the humoral system (this is where antibodies come into play) and the cellular system (this includes a range of specialized cells, but for our purposes, we will focus on so-called T-cells).

Various proteins on the surface of a virus can be recognized by the body as being “foreign” and therefore, something to be attacked when the virus enters our body through the nose, throat, lungs, gastrointestinal tract or other sites of entry. By now, most people are aware that for the SARS-CoV-2 virus, the spike protein is one of the most important proteins for the virus’ infectivity, but also for a target by our immune system and vaccines.

When exposed to SARS-CoV-2 and an infection results, our bodies will, in most cases (exceptions include persons who are immunocompromised), produce antibodies that will bind to various sites on the virus in an attempt to mark the virus for attack and destruction and to prevent the virus from being able to invade cells, such as the cells that line our lungs and blood vessels. To enter a cell, the virus needs to attach to a specific receptor on the lining of the cell, much the way that we need a specific key to open a looked door to allow us to enter a room. Not all, in fact, not even most, antibodies are effective in preventing the virus from attaching to the receptor on the cell because they have been developed in response to other proteins on the virus that are not involved in that binding. We have a special name for those antibodies that do bind to the specific site on the virus that then blocks the ability of the virus to attach to the receptor on the cell and gain entry into the cell – they are called neutralizing antibodies.

If you have not previously had COVID and you have not been vaccinated, then once you are exposed and infected by the SARS-CoV-2 virus, your innate immune system will try to hold the virus off for days (as much as 7 – 10) while your body produces antibodies to the virus. This is why vaccinated persons are so much better protected against the virus, because the vaccine causes us to already have these antibodies made and ready or able to produce them much faster than if we have never been vaccinated or exposed to the virus before. Thus, if vaccinated, we have much better chances of preventing these invading virus particles from entering our cells and causing damage, illness and more production of viruses and then more spread throughout our bodies. Most of those who have been previously infected will also have these antibodies ready to go, but I will discuss below why those who have been previously infected will still be better protected by also getting vaccinated.

Unfortunately, once the virus gets inside cells, antibodies no longer work against those virus particles and the virus takes control of the cell’s internal machinery to force it to produce more virus particles. [This is more than you want to know, but one of the reasons that the delta variant seems to be able to evade the immune system to an extent is that when the cell is forced to make more viruses, the viruses are then generally exported out of the cell to then spread to other cells, tissues and organs of the body, but when released outside of the cell, they are now vulnerable to these neutralizing antibodies. However, the delta variant can use another method by which newly produced virus particles spread directly from one cell to another contiguous cell, depriving antibodies of an opportunity to attack the brand-new virus.]

Once virus has entered cells, we have to rely on a different part of the immune system called the cellular immune system. These are specialized white blood cells. Some of these cells have the ability to identify cells that have been infected and kill the cells, which will stop the cell from producing more virus and often times kill the virus that is inside the cell. These cells are generally called T-cells, and more specifically, cytotoxic T-cells or CD8+ cells.

I think this is enough of a primer for us now to understand the science behind our recommendation that people who have previously had COVID still get vaccinated.

So, let’s look at 3 recent studies. The most recent one is “Antibody response to SARS-CoV-2 infection and BNT162b2 vaccine in Israel,” by Shapira et al posted July 8, 2021 as a preprint article, meaning that this has not yet been peer-reviewed and published in a medical journal. In this study, the authors examined 26,170 blood samples from persons in Israel between November of last year and March of this year. 8,078 of the samples were from persons who had positive tests for COVID, but were asymptomatic before the COVID vaccinations were available. 1,652 of the samples were from people recovering from symptomatic COVID infection. 3,516 samples were taken from people who were vaccinated with the Pfizer mRNA vaccine.

What the authors found was that vaccinated persons had the highest neutralizing antibody levels – nearly three times higher levels than those for persons recovering from COVID. 99.4 percent of the vaccinated individuals had detectable neutralizing antibodies six days or more following the second dose of the Pfizer vaccine, while only 75.7 percent of those recovering from COVID had detectable neutralizing antibody.

The next study is from last month, entitled, “Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose,” by Reynolds, et al, published in the journal Science. This study looked at vaccination (Pfizer) responses to a single dose of the two-dose regimen in health care workers in the UK in those who had not previously been infected and in those who had been infected with the original strain of the SARS-CoV-2 virus. They showed that 96 percent of those health care workers who had been previously infected developed a T-cell response to the spike protein as well as a neutralizing antibody response that was sufficient to provide protection against the alpha and beta variants. Only 70 percent of those health care workers who had not previously been infected developed a T-cell specific response. The T-cell response in those previously infected was 4-fold greater than that of those who had not been previously infected. We refer to the first dose of the mRNA vaccine as the prime and the second dose as the boost. It appears that for those previously infected with COVID, that infection serves as the equivalent of a prime and the first of the two-shot vaccine functions essentially as the boost.

The third study is from March and was also published in Science: “mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection,” by Stamatatos et al. The authors in that study found that persons who recovered from COVID had antibodies that routinely could neutralize the original form of the virus. However, the antibodies inconsistently neutralized the beta variant. However, a single dose of mRNA vaccine boosted neutralizing antibody titers against both original strain and the beta variant by up to a 1000-fold.

Therefore, we can conclude that persons who have recovered from COVID certainly do have some degree of immunity, but it is not as robust as the immunity derived from vaccination However, those who have recovered from COVID who then are subsequently vaccinated have even stronger immune responses compared to those who are vaccinated but did not have prior COVID infection.

Those who had COVID last year and are not vaccinated, likely do not have predictable immunity to all of the new variants, especially the delta variant that is now the predominant variant in the US. However, those who had prior COVID and have received the mRNA vaccine should have a high of protection against these variants.

So, if you have had COVID, so long as you have recovered from the initial illness, including those who have PASC (long-COVID), please get vaccinated ASAP if you have not already done so.