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Boosters have been approved for most Americans. Should you get one? And which one? Andy Larsen gives answers.

What the science says about Pfizer, Moderna and Johnson & Johnson vaccines.

We’re officially in the booster shot era.

A few weeks ago, the Centers for Disease Control and Prevention approved a Food and Drug Administration authorization of Pfizer booster shots for a segment of the population that previously received two doses of the Pfizer vaccine at least six months ago.

This past week, the FDA and CDC authorized booster shots for those who had originally received the Moderna and Johnson & Johnson vaccines.

To make your options a bit more flexible, but also a little more confusing, the FDA also opened the door to so-called mix-and-match vaccines. In other words, if you got one vaccine months ago, you can get a different one for your booster now.

So in this article, let’s first present to you the data that the FDA’s advisory panel used in voting on this decision, and then answer the obvious questions you have: Who should get a booster? How much of a difference will it make? And, of course, what kind of booster shot should you get?

If you’re in a hurry, and would like to skip down to the answers to those questions without spending time on the science in the middle of this article, I officially give you permission.

The science

First, let’s talk about the evidence that the FDA used.

A study recently was released containing data from a huge swath of the population: the 2.7% of Americans who are tracked by the Veterans Health Administration. Researchers found that vaccine protection decreased from 91.9% in March to 53.9% in August across all vaccines and that there were differences in which vaccines saw the largest declines.

The results of a Veterans Health Administration study on vaccine efficacy over time, which is clearly decreasing. Janssen refers to the medical company that created the vaccine Johnson & Johnson distributes.(https://www.medrxiv.org/content/10.1101/2021.10.13.21264966v1.full.pdf)

Worst of all, the highest reduction seemed to be with the Johnson & Johnson vaccine. It conferred nearly zero protection against infection in the VHA group by August. It’s now October, so it’s probably reasonable to expect that protection has slinked somewhat lower in the past couple of months for the other vaccines as well.

How about hospitalizations? Because hospitalizations are less frequent, it’s harder to get a good sample size to make beautiful graphs like the one above, where it’s obvious to see a declining efficacy. But a CDC study of data in nine states found that the vaccine’s protection against hospitalization between June and August remained at 92% for the Moderna vaccine, but had fallen to 77% for the Pfizer vaccine, and 65% for the Johnson & Johnson shot.

So what kind of protection do you get from getting that booster dose? We can look to Israel, the first country to recommend boosters for its population, for answers. Once again, we’ll break it up into two categories: How well do the boosters prevent infections, and how well do they prevent hospitalizations?

In general, the boosters made it between eight and 18 times less likely that someone was infected in Israel, when compared to the vaccinated-but-not-boosted population. For those most at risk, those 60 and older, the vaccine reduced the risk of infections twelvefold.

Results from Israel's booster protection study — the rightmost column indicates how much less likely someone with a booster is to be infected than someone without a booster. (https://www.medrxiv.org/content/10.1101/2021.10.13.21264966v1.full.pdf)

How about hospitalizations? Well, the news was even better there. Those with the booster dose saw 18- to 22-fold reductions in hospitalizations when compared to those who had been vaccinated, but not boosted. In other words, if protection against hospitalization had fallen to the 77% estimated above, the booster dose raised it back up to about 99% protection.

Those with the booster shot were about 18-22 times less likely to be hospitalized than those without the booster shot. (https://www.medrxiv.org/content/10.1101/2021.10.13.21264966v1.full.pdf)

That’s pretty good. But, in Israel, the only shot really used was Pfizer’s. What about here in America, where Moderna, Pfizer and Johnson & Johnson were all used?

Scientists have long known about the potential benefits of mixing and matching different types of vaccines to create longer-lasting and stronger immunity. Essentially, the problem with giving additional doses of the same vaccine is that the body has already learned how to handle it: “Hey, you already taught me how to deal with that,” you might imagine your immune system saying. A differently formulated vaccine, on the other hand, might provoke more well-rounded immunity.

Nor is mixing and matching typically problematic. You don’t know the brand of the flu vaccine you get every year, for example.

A federally funded study of the various options looked to investigate the various mix-and-match possibilities. To do so, researchers found 450 fully vaccinated people — 150 had received the Moderna vaccine, 150 the Pfizer vaccine and 150 the J&J shot. They then split those groups up into three, and gave each a booster shot of one of the three vaccines — thereby creating nine groups of 50 people each of all of the possible vaccine combinations.

Finally, they presented the test subjects with a harmless “pseudovirus” that matches the shape of the coronavirus, and averaged out how well the immune system neutralized the “threat.”

This is perhaps the most complicated study figure I’ve ever shown in a Tribune coronavirus column, but it’s a worthwhile one to understand. There are a lot of numbers and lines and boxes here. Ready? Here goes:

(https://www.fda.gov/media/153128/download)

This is the 23rd slide of the presentation the study group gave to the FDA this week. Each of the nine boxes, spread out like tic-tac-toe, represents the nine groups of about 50 people each — “mRNA-1273″ is Moderna, “Ad26.COV2.S” is Johnson & Johnson, and “BNT162b2″ is Pfizer. Each of those boxes contains two plots: how well the immune system neutralized the virus before getting the booster, and how well the immune system neutralized the virus 15 days later.

The blue number for each, GMT, stands for “Geometric Mean Titer” — essentially an index of how effective the neutralization was on average across the participants. Then the red number represents the improved ratio. Just how much more effective was the neutralization after the booster?

As you can see, boosting any vaccine with any other vaccine is always, at least, helpful in neutralizing the virus.

The data doesn’t have enough statistical significance to sufficiently conclude that one booster strategy is better than another, necessarily, and people who were dosed with Johnson & Johnson originally were, on average, dosed later than the Pfizer vaccinations, for example.

But in this small sample, which represents some of the best evidence we have at the moment, it’s not clear that using Johnson & Johnson as a booster is ever optimal. Those who were boosting with Johnson & Johnson saw worse virus neutralization than those boosting with either Pfizer or Moderna, no matter what their initial vaccine choice was.

Indeed, boosting with another dose of the Moderna vaccine saw the highest neutralization numbers. Now, it gets even more complicated. In this study, participants were dosed with 100 micrograms of the Moderna vaccine, whereas the booster dose approved by the FDA is only 50 micrograms. Would we see similar numbers with the smaller booster? It’s hard to know — and it’s definitely something to study moving forward.

Finally, the study also looked at the percentage of participants who experienced side effects. No related serious adverse effects were reported among those who got the booster, though four of the 450 total participants did have responses deemed as “significant.” Three of the four boosted with Johnson & Johnson.

Most suffered the same kind of mild effects as people experience with the first two doses. Here’s the same tic-tac-toe style chart, showing what percentage of participants experienced what kind of side effects:

Side effect profiles for the various mix-and-match strategies. (https://www.fda.gov/media/153128/download)

There’s widespread similarity between the side effects here, with some differences that aren’t enough to be statistically significant.

The quick answers to your questions

OK, so with all of that prep work of understanding out of the way, here are the answers to your booster questions from the beginning of the article:

Who should get a booster?

If you got the Johnson & Johnson shot, you are eligible for a booster as long as you got it at least two months ago, no matter who you are. Given the far lower efficacy of that vaccine, you should get a booster when you can.

If you got the Pfizer or Moderna vaccines, you are eligible for a booster if you had your second dose six months ago and are at high risk for severe disease. What does that mean? It’s if you fall into any of these categories:

• If you are over 65.

• If you are high risk due to health issues. This includes overweight folks — anyone with a body mass index of 25 or above. I just went to the scale, and I’m 6 feet and 209 pounds as I write this article. That means I have a BMI of about 28; so overweight — about 74% of Americans are overweight or obese. It also includes diabetics, smokers, pregnant women, people with substance addiction, heart, lung, or kidney issues, and a number of other health conditions.

• If you are at high risk because of where you live or where you work. First responders, teachers, manufacturing workers, prisoners and prison guards, bus drivers, and restaurant, food and grocery store workers are all listed as examples by the CDC, but any job with significant interaction with high numbers of people with unknown vaccination status would qualify.

In short, nearly everyone is eligible, unless you’re young, skinny and work a relatively solitary job.

Should you get the booster shot if you’re eligible? In short, if protecting yourself from being infected is important to you, either for your own health or for those who are high risk around you, get the booster.

If infection doesn’t scare you but hospitalization does, I would consider whether you got Pfizer or Moderna originally — if you got Moderna, you likely have better protection currently than the Pfizer folks. If you consider decent protection against infection and quite good protection against hospitalization sufficient for your needs, and the nonmonetary costs of getting the booster are high (getting to a clinic, potentially missing work for a day as side effects occur, etc.), then there’s an argument for skipping the booster.

There’s also a very solid argument for skipping the booster if you were previously infected with symptomatic COVID and already vaccinated.

How much of a difference will the booster make?

In general, it looks like it makes a big difference, improving your protection to 95% levels against infection and 99% protection against hospitalization.

People with a booster shot are about 10 times more likely to avoid infection than those who were vaccinated but not boosted, though the exact number varies somewhat by age.

People with a booster shot are about 20 times more likely to avoid hospitalization than those who were vaccinated but not boosted.

What booster shot should I get?

Thanks to the FDA’s decision to allow mixing and matching, you may even have a choice in which kind of booster dose you get. We have limited evidence on this topic, but here are early hints from the evidence we do have.

If you had Johnson & Johnson for your first dose, I would recommend switching to Pfizer or Moderna for your second dose. People with that dosing scheme showed improved virus neutralization compared to those who stuck with J&J in the limited data we have.

If you had Pfizer, it’s a bit of a personal preference at this point. Again, the limited data we have shows somewhat increased neutralization when switching to Moderna, but those with Pfizer were slightly less likely to have some annoying but still mild side effects (like chills, headache and joint pain) in the hours after.

If you had Moderna, first of all, congratulations. Boosting with Pfizer or Moderna showed a similar neutralization profile, but switching to Pfizer seemed to slightly reduce the risks of annoying but still mild side effects in the hours after the shot.

I can’t see a lot of a reason to ever get a second dose of Johnson & Johnson, to be honest. It’s better than nothing, but there are better options available to you.

Andy Larsen is The Salt Lake Tribune’s data columnist. You can reach him at alarsen@sltrib.com.