“You’re sick of hangin’ around and you’d like to travel
Get tired of travelin’, you want to settle down
I guess they can’t revoke your soul for tryin’
Get out of the door and light out and look all around”
Truckin’ (by the Grateful Dead, off the album American Beauty 1970)
Keep on Truckin’
I know…..it’s been awhile. Last blog, I said we were moving on….and we are. Not that you can go backwards in time anyway. And don’t start with some multiverse explanation while you are gearing up for the Dr. Strange movie.
Today’s topic will be about booster doses. Why consider one? Are they needed? Can they hurt? How many of these damn shots are we going to need? If you are looking for hardcore guidance from me today, you can stop reading now. What I seek to accomplish is to provide you enough information today to try to make the best decision you can for yourself.
The Grateful Dead performing Truckin’ live 1991.
What is a “Booster Vaccine?”
A “booster vaccine” is an additional dose of a vaccine that is required to either maintain or augment a response to a previously administered vaccine.
What is the difference between a second dose of a vaccine and a “booster” dose?
Often, with vaccines that require several doses in close temporal proximity, the initial doses are considered part of a “primary series” and not called boosters. For example, Pfizer’s Prevnar vaccine is administered at 2,4, and 6 months of age as part of their “primary series” with a “booster” at 12-15 months of age.
If, however, you go by definitions such as those on the NIH website, any second dose may be considered a “booster.”
Suffice it to say, this is arguing semantics. In keeping it simple, some vaccines need more than one dose. The subsequent doses vary in number and timing, depending on the illness and vaccine being discussed. For today’s purposes, the first two doses of vaccine to protect from Covid-19 will be considered primary series doses. Any subsequent doses will be considered “boosters,” and where appropriate will define whether it was a third or fourth or ninth dose.
Christian Guardino performing “Creep” on American Idol. Our homegrown talent killing it this year on Idol. While you all get to enjoy the incredible performances, you only get a glimmer on the show of the type of young man Christian is. Kind. Humble. Appreciative of the little things in life. So proud of you Christian, go win this thing!!!!
Click Here for American Idol Voting Instructions for Christian Guardino
When the vaccines first got rolled out, many were given the impression that you go and get your two doses of vaccine 3-4 weeks apart and simply put your concerns for Covid-19 contraction in the rearview mirror. If you got the J&J vaccine, it was to be a one shot wonder. This has led to much distrust and concern as the recommendations have changed. It is worth a quick mention as to why they changed, and in doing so help all understand why communication between providers and those they care for needs to improve.
Covid-19 vaccines were developed to a new pathogen during an active pandemic. This is different than the other vaccines in the modern era. Society was the recipient of a great gift of mRNA vaccine technology because the scientists that started working on the technology a decade ago never stopped and were able to apply it to the new pathogen. The safety studies for the vaccines were managed as with prior vaccines. Historically, no major side effects have ever been reported more than a few months after release of a vaccine. What lacked prior to licensing were studies for medium- to long-term efficacy (how well they work). The reason is that it would be morally reprehensible to not help people in the short-term, even if only the short-term, while one waited for longer efficacy studies to be conducted.
There is nothing wrong with saying “I don’t know” when there is no proper answer to give. When number of doses was initially discussed with the public it should have had a major caveat stating that need for future doses would be a matter of ongoing study. Fear that some would refuse two doses out of concern they would need a third is not informed consent, it is paternalism.
What determines if you need a booster?
Ultimately it comes down to realizing that folks are getting sick with something they were expecting to be protected against. For any vaccine to get approved for use, including those against Covid-19, they must demonstrate that they are preventing against a poor outcome, in a safe manner, and for a period of time. Comparing that data with ongoing data for those contracting Covid-19 provides the best way of assessing that immunity is lessening.
What your goal is also affects how you use the data to make decisions. Are you trying to prevent any infection? Infections with moderate symptoms? Hospitalizations? Death? My personal feeling is that I am fine with protection from long-term consequences and any outcome that does not permit me to sleep in my own bed. I don’t care if I get mild cold symptoms. This is a topic of dispute. Ultimately, as long as the data is available and the recommendations clearly state what the goals are, I think we can move along to other topics.
How did we know that we needed booster doses of Covid-19 vaccine?
Israel was early adopter of vaccines and keeps great data, as a large percentage of the population shares a common medical record system. About six months after the vaccine rollout (Israel uses the Pfizer vaccine), their data began to detect large numbers of people contracting the Delta variant. The response to identifying this trend in Israel was to add a third (booster) dose to the regimen. The Omicron variant again saw another surge in cases, including breakthroughs among individuals receiving third doses of vaccine. Israel began studying benefits of a four those as result.
Fun Fact: Obtaining good data in the United States on such scale is near impossible. Our EMR systems are derived from the Tower of Babel platform.
Ozzy performing “I Don’t Know” live in 1981. When they talk about people so talented that they may be aliens living amongst us, they are speaking about folks like Randy Rhoads. OMG. Sick!
There’s got to be a better way?
Do we really have to wait for catastrophe to befall a bunch of people before we can identify the need to boost?
Kinda sorta. It depends if the question is being asked on a population level or an individual level.
The best proxy at this time to use a marker for immunity to Covid-19 are neutralizing antibody titers. Before you starting checking the titers your doctor sent you for last week to see if you were immune or thinking you should go get some drawn, I am gonna burst your bubble. Those tests are not checking only for neutralizing antibodies. They measure anti-spike protein IgG antibodies in your serum that would only be present if either recovered from infection or vaccinated. Only a portion of these are neutralizing antibodies, and they are the only ones that matter.
Confused? On a population level, scientists can measure samples for neutralizing antibodies and provide some guidance for duration of immunity. For the individual, at this time, knowing whether you are personally immune is beyond the scope of currently commercially available technology. Checking your antibodies to make decisions as to whether to get vaccinated using today’s commercially available technology is near useless. It may be a smidge better attempting applied kinesiology though.
Are there studies looking at neutralizing antibodies and waning immunity?
Yes, there are studies. My goal as always is to educate without bias. As such, I will provide links to the articles I will discuss for you to read as well in original format. I will attempt to summarize a couple of articles to give you a flavor of what’s out there.
Study#1: Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months. Published in New England Journal of Medicine by Levin, et al (Dec 2021).
This study included nearly 5000 participants who were all health care workers in Israel. All were above 18 years of age and had no history of infection with Covid-19 prior to being vaccinated. All of the study participants had their anti-spike protein IgG antibodies measured. A smaller, higher risk subset of the participants also had neutralization assays performed (about 1250 participants) on their samples.
What the study found was that anti-spike protein IgG antibodies decreased significantly at a stable rate by six months. What was quite interesting, and getting back to the point of why the current commercial laboratory blood tests are not adequate, is that the neutralizing antibody titers dropped sooner, within the first 2-3 months. This was especially the case if you were older, male, or immunosuppressed.
Study #2: Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Published in Nature by Planas, et al (February 2022).
This study analyzed samples from 115 vaccine recipients and long-term convalescent individuals (infected awhile prior to study). Analysis consisted of neutralization assays against Covid-19 variants including Omicron. They conducted similar study using the commercially available monoclonal antibody treatments. The study found that antibodies from vaccine recipients or previously infected individuals and existing monoclonal therapies were ineffective at neutralizing the Omicron variant. This is not shocking as we all watched a few months ago tons of previously vaccinated individuals contracting the Omicron variant along with many folks that had the pleasure of getting Covid-19 again. The study included a small number of Pfizer third dose recipients. Those recipients did show much higher neutralizing antibody titers, and this does provide support for the ability to provide increased protection from a booster. Please note, this study is all in vitro and was not looking for infections in humans nor disease severity.
Don’t Let Me Down live on the Apple Studio rooftop. If you don’t know who the band is, time to get out from under that rock. And then go to a doctor. You have brain damage. It’s impossible for you not to know who they are.
The data in the prior section was all based on in vitro (“test-tube”) studies using serum from patients. In this section, we will take a quick glance at some studies that looked at data of actual infections in people that were vaccinated to assess benefits of “booster doses.”
Third Dose Data
Study #1: Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants. Published in JAMA by Accorsi, et al (January 2022)
This study was conducted in the United States. The patient population consisted of approximately 70,000 adults who sought care in December 2021 for Covid-19 like illness. Of those, nearly 23,500 were positive for Covid-19 (13,000 were Omicron variant, the remainder Delta variant). The data demonstrated significant protection from symptomatic disease in vaccinated individuals. There was increased protection in those receiving three doses of vaccine as compared with two doses as well. Protection was significantly better against the Delta variant relative to the Omicron variant. It is important to note that this study did not assess severity of disease, simply presence of symptoms. That being said, it would be very surprising for there to be less symptomatic cases in vaccinated individuals without similar findings among those getting severe disease.
Study #2: Protection of BNT162b2 Vaccine Booster agains Covid-19 in Israel. Published in New England Journal of Medicine by Bar-On et al. (October 2021)
This study looked at data in over 1 million adults above the age of 60 years in Israel who had their second dose of the Pfizer vaccine a minimum of 5 months prior. The study demonstrated a more than 10 fold improvement in preventing infection and a 20 fold improvement in preventing from severe disease in those receiving a third dose of vaccine. This study did not look at a long time period after the third dose, so assessing how long that “extra” protection lasts was not an end point. Still, even if brief, it demonstrates that you can provide additional protection to the most at risk in the population.
Study #3: Protection against Covid-19 by BNT162b2 Booster across Age Groups. Published in New England Journal of Medicine by Bar-On et al. (December 2021)
This study was similar in design to the prior Israeli study by the same primary author. This study however involved nearly 4.7 million people aged 16 and older. The vaccine demonstrated benefit at all ages for both protection from contracting the illness and having a less disease severity when contracted despite vaccination. If you drill into the data further though, you arrive at that place where decision making gets more difficult.
Using the data presented in Table 1, you can see that there were 60,778 cases of Covid-19 in the non-boosted population below the age of 50 years. Of these, 75 cases were severe, and three resulted in death. The boosted group suffered 3327 infections, four severe, and no deaths. The youth in the study were less likely to have had a booster dose and that does skew the numbers a bit. Those below 50 years of age compromised 63.8% of those in the non-booster group, but only 32.3% of those in the booster group. The reason is obvious, older folks at higher risk were more apt to volunteer to get that third dose. That being said, protection is demonstrated, but the number of severe cases prevented and deaths prevented is very low considering the scope of the study.
For those above 50 years of age, and as has been the case since day #1 with this illness, the story is very different. There were 22,703 infections in the non-boosted elder group, with 1096 severe cases and 295 deaths. The boosted group only suffered with 3844 infections, 171 severe cases, and 35 deaths. Looking at these numbers and knowing most were in fact boosted, if you are over 50 and not boosted, I think you may choose to reconsider.
Study #4: BNT162b2 Vaccine Booster and Mortality Due to Covid-19. Published in New England Journal of Medicine by Arbel at al. (December 2021)
This study was conducted in Israel with over 800,000 individuals above 50 years of age. The booster dose lessened the risk of death in this population by 90%. For clarity purposes again…IF YOU ARE OVER 50 YEARS OLD, HAVE NOT GOTTEN A THIRD DOSE, AND ARE NOT ON A DEATHWISH, YOU MIGHT WANT THAT THIRD DOSE ABOUT NOW.
Deep Purple. Space Truckin’ live in 1973. Killer!!!!
Fourth Dose Data
Was the third time the charm? Could you do better with four? I know y’all hate thinking about it, but fortunately for you, there are folks that try to prepare for all possible outcomes and are doing the studies for you regardless of whether you are in fact considering it.
Study #1: Protection by a Fourth Dose of BNT162b2 against Omicron in Israel. Published in New England Journal of Medicine by Bar-On et al. (April 2022)
This study analyzed data from 1.25 million Israeli adults 60 years of age or older, all of whom had received three prior doses of the Pfizer vaccine. Half of this population received a fourth dose of the Pfizer vaccine and were then compared with the three dose recipients as to their outcome. This study was conducted in January 2022, during winter season when Omicron was spreading like wildfire. The results demonstrated that those receiving a fourth dose had half the rate of confirmed infections and a third the rate of severe disease one month after administration.
The reason for the bold italics? To catch your attention of course. The study also looked at an eight-week time point. By that point, the protection from confirmed infection was negligible, at 1.1 infections in three dose recipients for every 1 infection in a four dose recipient. They reported no decrease from severe disease protection at a six-week time point. This distinction is very important. A major question going forward is “How long before protection from severe disease diminishes?”
Study #2: 4th Dose Covid mRNA Vaccines’ Immunogenicity & Efficacy Against Omicron VOC. Posted online at medRxiv by Regev-Yochay et al. (Feb 15th, 2022)
NOTE: This is an article available as a preprint and not yet peer reviewed.
This article summarizes a clinical trial in Israel assessing the safety and efficacy of a fourth dose of the Pfizer vaccine in adults 18 years and older. The trial was initially designed for the purposes of assessing how well the fourth dose triggered an immune response. Due to Omicron, the authors attempted to take a look at some end points to get some idea as to efficacy (disease prevention). Not surprisingly, it also showed decreased ability to protect from infection from the Omicron variant. I included this study for you today should you want to get a better feel of what goes on in the background as doctors and scientists work at trying to stay ahead of an infectious disease such as Covid.
More Christian Guardino for you today. He is performing again TONIGHT!
Thanks for Nothing Doc. WTF should I do?
You got a lot to think about. If you are older, immunocompromised, or have other risk factors making severe disease from Covid-19 more concerning for you, the data supporting at least a third dose is convincing. The lack of data supporting duration of benefit against severe disease with a fourth dose makes drawing strong conclusions there. It helps, but for how long? On the bright side, there does not appear to be a downside to receipt of the fourth dose.
If you are younger, it still may behoove you to get a third dose. True, you are not likely to end up with severe disease or taking that permanent nap. But it is clear that you are going to get some significant protection from it with respect to contracting the illness for several months at least. Less chance for long-Covid concern. Less school missed. Less work missed. Less chance of killing your grandparent. Downside. You may have a sore arm and feel like crap for a few days.
I would like to point out here that there was no data in children or teens in the studies presented today. They have not been performed as yet.
Parting Thoughts/Future Direction
I warn you now, this fall is going to get interesting. I expect that this illness will start to follow all prior coronaviruses with its seasonal predilection for later fall and winter. As we are seeing, there is a low level of disease out there now. Folks are less apt to get vaccinated or boosted during that time. As immunity wanes over the next several months entering the fall, we do run the risk of larger outbreaks.
In preparation the scientists are working on boosters that are more specific to Omicron and combined with prior doses of vaccine will hopefully provider broader immunity against newer emerging variants. Also awaiting studies on prevention of long-Covid, especially in younger individuals through vaccination.
What I hope is that the government and manufacturers are planning ahead and stockpiling medications that are helpful to treat those that fall ill and developing campaigns to get at minimum the higher risk folks a third if not fourth dose pending further data to prevent any poor outcomes on large scale. There is no excuse to not have all resources available to help during a resurgence two years into this pandemic.
Now, go enjoy your springtime. Mask free.
AND DON’T FORGET TO VOTE FOR CHRISTIAN GUARDINO. CLICK HERE TO DO SO.
Post authored by Jason Halegoua PhD, MD, MBA, FAAP. Jason is the founder of Peds First Pediatrics in 2009, and has been a practicing general pediatrician since completing residency at Schneider Children’s Hospital in 2004. In addition to earning his medical degree from the Medical College of Pennsylvania, Jason earned a PhD in Molecular Pathobiology for his work contributing to the understanding of the genetic regulation of immune responses to murine leukemia viruses from Hahnemann University in Philadelphia and an MBA in Finance from Hofstra University.