COVID Booster? But I Only Just Got Vaccinated!

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Three different vaccines to protect against COVID-19 have been either approved or authorized for emergency use in the U.S. And now the conversation has turned to booster doses for all three.

Booster shots are nothing new. After all, a flu “booster” is what is encouraged each and every year. When it comes to COVID-19, however, the back and forth and disconnect between the different government agencies may have left some confusion about who does and doesn’t need a booster.

After all, COVID vaccine studies show that even after a few months, efficacy is still higher than the original goal for the vaccine.

On this week’s episode, Ellie Murray, ScD, assistant professor of epidemiology at Boston University School of Public Health, joins us to help answer the question, do I really need another shot?

The following is an abridged transcript of her interview with “Track the Vax” host, Serena Marshall:

Marshall: So everyone gets their vaccine and you think you’re done for awhile, but we’re not even a year out, and we’re talking about boosters. What’s going on here?

Murray: A lot of this conversation was sparked by some data from Israel, which really rolled out their vaccination campaign very quickly early in the year, and then started to feel like they were seeing more COVID than they expected. They, at one point in the summer, said, okay, we’re done with masks, everything’s open. And then 10 days later, they instituted masks again, brought back more precautions because they saw COVID cases were going up.

There was a lot of concern that this meant the vaccine was not working as well as it was earlier in the year, but this is actually a really, really difficult question to answer scientifically, especially on this large population level, it’s one thing to, say, monitor one individual’s immune levels over time, in like a laboratory study, but thinking about what’s going on at the population level, it becomes really difficult.

Because it’s not just, did you get the first one and two doses of the vaccine, and compare to people who didn’t and what are they seeing with COVID. We have problems like, now compared to earlier in the year, we have the Delta variant, which is much more infectious. Compared to earlier in the year, we have less masking and we have schools open …

Marshall: People kind of going back to normal.

Murray: Exactly. So there’s behavioral changes, which means changes to your contact patterns, which means changes to your risk of infection. The Delta variant is more infectious, so that also means changes to your risk. And so it can be really difficult to tell, amongst all of that increased risk of COVID, is there also something going on with the vaccines?

Marshall: Let’s look at the data then. Is there something going on with the vaccine — is immunity waning? How long are you safe once vaccinated? Do we have answers to those questions, now that we have hundreds of millions of doses out?

Murray: Yeah. So we have a number of studies that tried to look at this in different populations, and many of these tried to look at pre-Delta and post-Delta periods to try to see if there was a trajectory. The ones that were done in the general population pretty much concluded that, for most people, nothing was really changing …

Marshall: Immunity wise. That sounds like a good thing.

Murray: Yeah. They make the inference about immunity by looking at what’s happening with infections, and in the best studies that have done this, they really actually focused on hospitalizations and those severe outcomes, because those are the ones that we know about from the trial. So we can kind of figure out, okay, is what we’re seeing now different from what we saw in the trials.

And so people with immunocompromised conditions, they do seem to be having more likely severe disease and hospitalization … after vaccination. So for those people, a third dose might be appropriate. And, a lot of people have suggested that we consider that more of a dose adjustment than a booster, really, because that’s a group that has a really hard time getting their body to respond fully to a vaccine.

Marshall: So when you say “dose adjustment,” the third shot is that — dose adjustment. And that’s why you use that term instead of the booster term, or is it a dose adjustment to those first two initial vaccines?

Murray: That third shot is just like giving them this extra dosing. And so thinking of it as, that third shot hopefully brings them up to where everyone else is. Rather than being sort of a booster that might need to happen on some recurrent timeframe or something like that.

Marshall: Okay. But the FDA didn’t approve the booster for just those who are immunocompromised. They approved it for a much broader swath of Americans. Those who are immunocompromised, those over the age of 65, those under the age of 65 who work in frontline positions. So what do we know about the efficacy of the vaccine and waning immunity in those populations?

Murray: Yeah. So this is where things get a lot harder to really be sure about. We have some studies looking at residents of nursing homes that suggest that maybe COVID infection was getting more common there. But this is actually a little bit tricky because, as I mentioned, the trials that we had initially looked at hospitalization and death as outcomes, they didn’t actually monitor everyone to see if you were getting infected or not.

And so we don’t really have a starting point value for infection to say, what is the efficacy against infection? And is that efficacy waning now? So yes, the efficacy against infection is lower than it is against hospitalization and death, but that’s almost sort of mathematically expected.

Marshall: I mean, we do know that the original efficacy data for Pfizer, for example, was, you know, in the high 80s, I think it was 88%. And then they said that it fell to the high 70s after 120 days. Is that normal? Is that to be expected? That seems to be the case with Moderna’s as well.

Murray: I’m not an immunologist, so I can’t really give the detail, but the one thing I do know for sure about the immune system is that it’s really complicated. And there are a lot of parts to the immune system, and there are pieces which respond rapidly and do that sort of active response.

And that’s a lot of where your symptoms are coming from when you get sick, or if you had a headache and felt feverish after you got the vaccine. It’s that sort of rapid immune response, recognizing the vaccine and kicking into gear. But then there’s longer-term components of the immune system, and there’s some evidence that some of those longer-term ones really fill a sort of more middle-term role and others fill a really longer-term role. And so what we may be seeing is just a sort of shift from that sort of middle-term to longer-term immunity.

Marshall: Which is why that rate of effectiveness seems to drop a little bit.

Murray: Right. And so what we’re seeing [with] hospitalization and death is that the effectiveness is remaining really high. And, I think before we had the trial results, you know, everyone was hoping for something along the lines of 60% effective.

Marshall: Yeah, that’s what I was wondering. Cause I think we said at the beginning, when we started this podcast way back when, they were hoping for 50%, 60%, that would be a gold standard. And we were in the 90s, and so dropping to the 80s doesn’t seem like that big of a deal.

Murray: It’s tricky for a number of reasons, right? The vaccine effectiveness when we think about it has to do with how much are people who got vaccinated getting infected or getting sick compared to people who didn’t get vaccinated. And some of that’s going to be related to the vaccine.

But if you imagine a situation where everyone who didn’t get vaccinated stayed home, and so had no contacts, but people who did get vaccinated, went out and did stuff, it might be possible to make it look like the vaccine almost really does nothing for you because the people who are unvaccinated are totally protected if they stay home.

And so there’s this component to, are people who are vaccinated and unvaccinated taking the same behavior. And this is, I think, what the CDC and the White House said in February and March about the types of behaviors people who are vaccinated could engage in; it’s really important to figure out whether or not what we’re seeing is biological waning of effectiveness or something to do with the actions we’re taking. Because people who are unvaccinated, a lot of them seem to still be doing pretty much the same sort of things that they were doing before the vaccines were available, with the exception of the under-12 group who are now in school and they weren’t last year.

But vaccinated people, a lot of them have changed their behaviors quite a bit. They may be going to work in person or they may be eating in restaurants or cafes. Even at 95%, which is amazing effectiveness, no vaccine is perfect. And so if you increase your risk behaviors, there’s a potential to have more infections just from that, even without waning of the vaccine.

So that’s not to say that there’s not necessarily waning. It’s typical for vaccines to wane. And at some point, certainly, we would expect waning. But whether that’s really what we’re seeing in the data is a little bit of a challenge to tease out.

Marshall: Okay. So what does the data say that led the FDA to then authorize it for a broader group of individuals? Let’s maybe start with the Pfizer data, because there is a lot of confusion, I think, around that disconnect from the CDC advisory committee and what the FDA ultimately did. So let’s start with Pfizer’s data on what led to this disconnect and what led to the decision.

Murray: Yeah. So the U.S. data that we have, the CDC, when they were talking about it in August, September, they were really relying on three major studies done in the U.S. One was a nursing home population and possibly there is waning of protection against infection with some of the caveats I’ve talked about.

And then the other two were looking at — there was one in New York State and there was one more generally across the U.S., and both of those seemed to show that protection against severe disease was holding pretty constant. But there were a couple of signals that maybe needed more investigation.

One was the people with immunocompromised conditions. Definitely it looked like there was something going on there. And then one of the studies also showed a possibility that maybe the vaccines were less effective in the sort of working-age population, that 18 to 49 population. And why that’s important, I think, for the decision that came up is that’s the sort of age group of a lot of people who are working in nursing homes or healthcare settings. Maybe not necessarily doctors, but frontline workers. And so these people who are in these higher-risk, caretaking occupations kind of fall into that group.

And so I think that there was some concern that it may look lower in that group because they were vaccinated earlier, and it’s already waned because they were high-risk workers, and so they’re seeing some waning and that’s why we’re seeing a little bit more hospitalization in that group.

Or it could be, that’s also the age group who started going out to restaurants and whose kids have started going back to school.

Marshall: Whose behavior has changed the most.

Murray: Exactly. So it’s this sort of question of, which thing do you think is driving that signal, combined with is that signal real? So from the U.S. data, there’s almost more questions than answers.

Marshall: Yeah, it sounds like it. Have any of those questions been answered when it comes to Moderna’s data and the decision there to allow boosters?

Murray: Uh…

Marshall: That pause and laugh tells me probably not.

Murray: Not really. A big part of that is that it’s really, really hard to answer those questions without having a core group of people that you’ve followed and monitored for the whole time, and that’s not really something we’ve been doing a lot of.

Marshall: So, I’m still a little bit confused though, Ellie, because it sounds like the efficacy of these vaccines is still very high. Now it was waning, but still way higher than what we had hoped the vaccines would be last year. So why issue a booster recommendation? Why not just leave it as is and continue working on getting more people vaccinated?

Murray: Yeah. So I think here there’s a couple of things that probably drove this decision and I’m not necessarily privy to all the conversations about it, so I can’t say for sure. But, one piece is that we have continued to see data from Israel that seems to suggest that the vaccines are not doing as well as they had expected.

Marshall: Once these human behaviors started again?

Murray: Right. And so, again, it’s really hard to tease these things out. But the differences that they were seeing in Israel are much starker. So they were seeing, you know, values dropping down. They were estimating things at 60% — much bigger than even the sort of possible signals we were seeing in the U.S. data. And so there was concern that because Israel rolled out their vaccine much quicker that this indicated what’s coming down the pipeline for us here in the U.S.

Marshall: They’re trying to get ahead of it, which makes sense. But what about those of us who are in that cohort that are 18 to 65 who are not frontline workers?

Murray: So, I think the way that you get COVID is that you get exposed to someone that has COVID, and so your risk is going to be partly around what your personal susceptibility is in terms of how much immunity you have, but it’s also gonna be partly around the actions you take. And so if you are someone who is in a frontline position, who has to be working really closely with people, you’re in a nursing home or something …

Marshall: They’re exposed to COVID possibility more often.

Murray: Right, and you’re in this very close contact with a lot of people, where you can’t necessarily manage things, then your best bet is to maximize your personal immunity to keep yourself as minimally as susceptible as possible. But for the rest of us, it’s actually probably more useful for us to just reduce the chances that we come into casual contact with someone who is infectious.

And so there are ways that we can do that. One is by encouraging those people in our lives who are not yet vaccinated to get vaccinated. If you have people in your life who are unvaccinated but eligible, and you can get them to get vaccinated, that is the best thing you can do for your own personal safety against infection, because unvaccinated people are going to be much more likely to transmit to you than a vaccinated person.

Marshall: But what about all of those people who are in that cohort that have kids who can’t get vaccinated?

Murray: Right. So then the next question is, okay, can we find ways to protect ourselves in other ways? So we know that people who are vaccinated, even without the booster, they’re not transmitting as much as people who are unvaccinated. So there’s less concern that the parents who are vaccinated will transmit to an unvaccinated child than there is the other way around.

So an unvaccinated child who got sick could transmit to a vaccinated parent. Similarly, an unvaccinated child might transmit to a vaccinated teacher, but that’s less likely than if the teacher is also unvaccinated. But an unvaccinated teacher could be a much bigger risk to an unvaccinated child than a vaccinated teacher.

So things like vaccine mandates for teachers and other school personnel are one way we kind of help build a firewall around our under-12 group.

Marshall: So it sounds like if, you’re in that group, you’re not in contact with a lot of COVID patients that you, for the most part, would be safe continuing to, you know, hand wash, mask, etc.

So let’s talk about those who do need boosters a little bit deeper here, Ellie. Let’s look at those who got a J&J or an adenovirus vector vaccine, and now we’re learning they are also recommending, in those subpopulations, to get a booster. Should they get another adenovirus vector booster, or switch over and get a different one, a Pfizer or an mRNA one to be more broad?

Murray: We’re getting some indications that mixing and matching might actually be a better way of going about vaccinating — that it might have more of an impact. Possibly just because you’re giving your body — you can think of the vaccine as like, you’re giving it a picture, a warning label — lookout for that and if you see this, attack it!

And so giving it different vaccines could be kind of giving it pictures from different angles and maybe can get a better sense of what that virus looks like. But, I think, it’s also true that there are people who chose the Johnson & Johnson vaccine for reasons that were … I don’t want to downplay. People may have chosen it because they felt more comfortable with a vaccine that relied on a technique that’s been used in many other vaccines.

Marshall: For some, though, too, it was just easier to get. One and done is what the thought process was.

Murray: Right. So if you’re in the one and done situation, then any booster you might as well, you know, the first booster you can get is the best booster you can get. If you’re in the booster-eligible groups, and you’re just looking to get a booster — all the boosters are just one shot.

Marshall: If you only want to get it once and not have to do another booster in another period of time, is it better to get the mRNA vaccine booster or just stick with the shot that you have? And does it work the opposite way? Is it better for someone who had an mRNA one to get an adenovirus vector vaccine?

Murray: I don’t think that we have good information on getting an adenovirus vector vaccine following an mRNA vaccine. So I’m not sure I can answer that one.

I think in terms of, will there be another booster down the road? I think that really is going to depend on how we as a society kind of agree to view the vaccines.

In February, March, there was this kind of push that if you’re vaccinated, you can just pretend that the pandemic is over. And all we need to do is vaccinate everyone and everything will be fine. But the Delta variant is so much more transmissible that even if we got 100% of people vaccinated with a vaccine that’s 95% effective, we wouldn’t necessarily be able to completely get rid of COVID, the Delta variant.

Marshall: I’m glad you brought up the Delta variant again, because it just brings me to a bigger question here, which is, should we be focused on getting boosters for those who’ve already been vaccinated or putting more effort into convincing or encouraging those who are not vaccinated to get the first dose, or even looking at what the WHO chief said — that the increasing use of boosters as “immoral, unfair, and unjust. And it has to stop.”

Murray: So I think there are a lot of opinions here. My view is that depending on who you are, you’re going to have different goals, right?

Individuals may have the goal of maximizing their own personal health. In which case, if there’s someone who’s going to be in contact with COVID patients or someone who’s in one of these high-risk groups, getting a booster could potentially help them maximize their individual health.

It’s also true that wearing a higher-quality, tighter-fitting mask and keeping their distance more and opening windows, all of those things that worked before we had vaccines are still going to work. So those are also things you can do to maximize your own personal health.

If you’re thinking about public health, if you’re thinking about how long does this pandemic go on? You need to think in a slightly different way. You need to think about, how do we minimize the number of people in the population who are infectious and maximize the number of people who have some level of immunity. And so long as the average level of immunity of the people who are immune is higher than the proportion of people that have immunity, we’re better served by getting more people immune. So, basically, if the vaccines worked 80%, if they were 80% effective, then until we have 80% of people vaccinated, we should always be trying to get more people vaccinated than to move those 80% people up to 90%.

Marshall: Ellie, one other question on this is, what about those who had COVID? They fall outside or inside, I guess, one of those cohorts that it’s recommended for. Does the booster act differently for them, or since they’ve had COVID and then gotten two shots, they’re already at that three mark and don’t need a booster?

Murray: That’s a really good question. I don’t think that we have a concrete answer to that. We do have some studies sort of tracking the immune responses of people post-infection, and those studies do suggest that the immunity post infections doesn’t last as long as post vaccine, and it’s maybe not as strong as post vaccine.

So, certainly, if you haven’t gotten any vaccine yet, but you did get infected, you’re better off getting a vaccine then relying on that natural infection. Whether that kind of exempts you from a booster, I don’t think we have a good answer for that.

Marshall: I mean, we’re seeing data, though, that even shows that there are now more Americans getting a third COVID shot than who are going for and trying to get their first. And we’re not even talking about other countries and shouldn’t the focus then be on those other countries, getting them vaccines so we don’t have another variant that perhaps could evade the vaccines we do have?

Murray: And this is where the public health thinking really comes in because just getting unvaccinated Americans vaccinated will help everyone in America, and also getting unvaccinated people around the world vaccinated will help everyone in America and everyone around the world.

And, so, if we really want to be done with this pandemic, we need to get everyone everywhere vaccinated as quickly as possible. Even if we could just bring everyone up to 20% immune, that would be better than having one small group of people who are really immune, in terms of controlling the virus.

And, as you say, just because we don’t have a variant that has evaded the vaccine yet doesn’t mean we couldn’t have one. And the more unvaccinated people there are, the more potential there is for COVID to circulate. And the more COVID circulates, the more potential there is for new variants to arise. And, right now, we don’t have a variant that is able to escape the vaccine …

Marshall: But, we don’t know what the future holds.

Murray: Exactly, we don’t know what the future holds.

Marshall: Okay. Well, all things we will continue to be watching, as this is no doubt going away anytime soon.