Why “Should You Get A COVID Booster?” Is The Wrong Question

Two weeks ago, the new COVID booster vaccines were released and the internet is full of articles titled “Should you get a COVID booster?“. This is the wrong question – the real question is “When should you get a COVID booster?”. We so want the COVID pandemic to be over and gone. Americans are returning to theaters and restaurants, houses of worship are full again, sporting events are sold out, and mask-wearers are a tiny minority at the grocery stores. But COVID is not going away.

For the past 3 years, there have been two peaks of case numbers every year – a large peak in January and a smaller peak in the summer. Data from the CDC this week indicates that the current 2023 summer peak is cresting and cases should begin to fall over the next few weeks (reported case numbers are unreliable but COVID hospitalizations, COVID deaths, and the percent of ER visits due to COVID are accurate measures). If history repeats itself, then we should have a break in cases for the next couple of months until they begin to rise again in the winter.

COVID is a moderately lethal infection – less lethal than Ebola but more lethal than influenza. Immunity is very effective in protecting you from dying of COVID but less effective from protecting you from catching a non-fatal COVID infection. There are two ways to get immunity – either by having a previous COVID infection or by getting a COVID vaccine (or both). On the whole, immunity from past infection is probably more effective than immunity from a vaccine. However, to get immunity from a past infection, you have to first survive the infection. There are a number of advantages to getting immunity from a vaccination compared to getting immunity from an actual COVID infection:

So far, 1,144,539 Americans have died from COVID and most of these were people who had no immunity to the virus and died from their first infection. To understand how our immune system fights COVID, let’s first take a look at the basics of the immune response to viruses.

How the immune system works

Viruses cannot reproduce on their own – they have to get inside of our cells and then hijack those cells’ RNA to produce new viruses. Our defense against viruses takes two forms: the innate immune system and the adaptive immune system. Innate immunity uses parts of the immune system that we are born with to fight any new infection. The innate immune system consists of interferons, natural killer lymphocytes, and macrophages. When a cell gets infected with a virus, that cell releases interferons that then signal natural killer cells to kill any other infected cell before it can produce more viruses. In addition to stopping the infection by killing infected cells, the innate immune system has macrophages that can eat and kill extracellular viruses before those viruses can infect other cells in the body. The innate immune system works whether or not a person has been previously infected with the same virus or has received a vaccine against that virus. Think of the innate immune system working on instinct. The adaptive immune system, on the other hand, can be thought of as working by learning. Of the two, the adaptive immune system is the more powerful.

The adaptive immune system learns from previous infection or vaccination so that when a person is exposed to a future infection, the adaptive immune system can be immediately activated against that virus. The adaptive immune system consists of T-lymphocytes, B-lymphocytes, and antibodies. When a person is first infected with a virus, T-lymphocytes become activated and then in turn activate B-lymphocytes to produce antibodies that are specifically directed against that particular virus. These antibodies are our immune system’s most important weapon against viruses and can defeat viral infections in four ways. First, antibodies can bind to the virus so that the virus cannot get into cells and thus prevent the virus from infecting cells. Second, when antibodies bind to a virus, it signals macrophages to eat and kill that virus. Third, when antibodies bind to an infected cell, they mark that cell for natural killer lymphocytes to kill that infected cell, thus preventing further viral replication. Fourth, when antibodies bind to infected cells, they activate the complement system to punch holes in that cell, thus killing it and preventing further viral replication. Antibodies last for about a month in the bloodstream and after an infection is resolved, the adaptive immune system cuts way back on new antibody production.

The innate immune system works immediately after an infection but it takes the adaptive immune system 1 – 3 weeks to ramp up antibody production after a new infection. However, the second time a person is infected with the same virus, that adaptive immune system can ramp up antibody production much faster, in a matter of days rather than weeks. This is because of memory T-lymphocytes and memory B-lymphocytes that have learned how to make antibodies against that particular virus. These memory cells cause antibodies to be produced much faster than during the first, initial infection with a virus.

Antibodies and COVID

Many people who are now getting infected with COVID are on their second or third infection. For most people, the second infection is not as severe as the first and the third infection is not as severe as the second. This is because the memory T-lymphocytes and memory B-lymphocytes allow the immune system to respond faster and more effectively against repeat infections. Multiple doses of vaccines do the same thing – with each vaccine dose, your body makes new antibodies against COVID variants covered by that vaccine booster and also trains your memory lymphocytes to ramp-up antibody production quickly if you are exposed to the virus in the future.

Because antibodies only have a lifespan of about a month, antibody levels fall after either an infection or a vaccination as the B-lymphocytes start to slow down antibody production. As a result, after vaccination, COVID antibody levels begin to fall after about 3 months. So, you are best protected against a future infection in the first 3 months after a COVID vaccine as well as in the first 3 months after a COVID infection. But what most people do not realize is that it is not just the antibody levels in the blood that protect against COVID infection but it is also the training of the memory T-lymphocytes and memory B-lymphocytes that protect against infection Those memory cells last many years and can sometimes last for a lifetime. We have blood tests that can measure antibody levels but we do not have blood tests that measure memory lymphocyte levels and consequently, this important effect of vaccination is often overlooked.

When you get a COVID mRNA vaccine, you produce antibodies against one small part of the COVID virus. On the other hand, when you get a COVID infection, you produce antibodies against many different parts of the COVID virus. For that reason, a COVID infection will stimulate stronger immunity against another future infection than vaccination does. But because the memory T-lymphocytes and memory B-lymphocytes learn from each exposure to a virus or to a vaccination, the more you stimulate those memory cells, the better they become at fighting infection. Also, because antibody levels eventually fall after a COVID infection, those antibody levels can be replenished if a person gets vaccinated several months after that infection. For these reasons, a COVID vaccination gives you good immunity, a COVID infection gives you better immunity, and a COVID infection plus a vaccination gives you the best immunity.

So, when should you get a COVID vaccine?

Early in the pandemic, the answer to this question was easy – everyone should get a COVID vaccine as soon as possible. However, now that most Americans have at least some degree of immunity from either previous vaccination, previous COVID infection, or both, the answer to the question is a bit more complicated. In order to get the maximum benefit from vaccination, the timing has to be individualized. And the key to individualization is the fact that antibody levels persist for about 3 months after infection or vaccination before those levels begin to drop off. So, here are my recommendations:

  • No previous vaccination or infection. These are people who are most likely to become severely ill or die if they get a COVID infection. They should get vaccinated immediately. Even if COVID case numbers in their community are low, it is not worth gambling with one’s life that they won’t be exposed to an asymptomatic person at the grocery store, at church, or at work.
  • Received an older COVID vaccine within the past 3 months. These people should wait until at least 3 months after their last vaccination. Their antibody levels are already high and it is better to wait until their antibody levels begin to fall before re-stimulating their adaptive immune system. However, given the anticipated January surge in COVID numbers, they should not wait long after that 3-month period.
  • Had a COVID infection in the past 3 months. These people should similarly wait until at least 3 months after their COVID infection. However, they should also get vaccinated before the anticipated winter surge in cases.
  • Previous vaccination more than 3 months ago and no previous infection. These people should time their vaccine to when they are most likely to be exposed to COVID. For the last 3 years, the winter peak of COVID cases has been in the first week of January. Assuming this year is similar, then get a new COVID vaccine now and by mid-November at the latest.
  • Previous vaccination more than 3 months ago and had a previous infection. Congratulations – these people already have the strongest immunity. But their immunity will be even stronger with a new COVID vaccine now or by mid-November at the latest.
  • Moderately or severely immunocompromised. Here is where things get a bit complicated. These people need more vaccine doses in order to be protected. If they have never been vaccinated, they should receive 3 doses of either the new Pfizer or the new Moderna COVID vaccine. If they have previously received 1 dose of either Pfizer or Moderna, then they should receive 2 doses of either of the new COVID vaccines. And if they have received 2 or more Pfizer or Moderna vaccinations in the past, they should receive 1 dose of either of the new COVID vaccines. If you are uncertain, it is better to err on the side of too many rather than too few doses for immunocompromised people.
  • Planning travel or large family get togethers over Thanksgiving or Christmas. Get a COVID vaccine now (or by the end of October at the latest) in order to ensure that you have protective antibody levels over the holidays. First, because it will protect you from getting infected while traveling and second, because you don’t want to get an infection just before your travel date and have to cancel your trip.

There are three COVID vaccines currently on the market. The Novovax protein subunit vaccine is based on the original strain of COVID and is only approved for primary vaccination in people who have never received any COVID vaccines; it is not available as a booster. Anyone who received the Novovax (or the no-longer available J&J vaccine) still needs to get one of the new mRNA vaccines since neither Novovax nor J&J covers the newly circulating COVID variant. The new Moderna and Pfizer mRNA vaccines are available for anyone for either primary vaccination or as a booster. The new Pfizer and Moderna vaccines are interchangeable so if you have previously received a Moderna vaccine, you can get either a Moderna or Pfizer booster and vice-versa.

The bottom line is that everyone should get a new COVID vaccination

Your body’s immune system is like your muscles – the more you train it the stronger it becomes. Vaccinations both keep your antibody levels high and train your immune system to make new antibodies rapidly and in large quantities. There are really no good reasons to not get vaccinated. Everyone should get vaccinated in the next 6 weeks to optimally protect themselves during the upcoming holidays and the anticipated upcoming winter surge in COVID numbers. The Moderna vaccine or the Pfizer vaccine – either one is fine, no matter what brand of vaccine you have received in the past.

And, oh by the way… get your other protective vaccinations, too. I got my influenza and pneumococcal vaccines together on September 1st and my RSV and new COVID vaccines together on September 18th. This was my 6th dose of a COVID vaccine since December 15, 2020. My immune system will be ready for whatever gets thrown at it this winter.

October 2, 2023

By James Allen, MD

I am a Professor Emeritus of Internal Medicine at the Ohio State University and former Medical Director of Ohio State University East Hospital