Should I get a COVID-19 booster?

Scientists continue to debate the pluses and minuses of extra doses of vaccine

On 12 September, a vaccine advisory group to the Centers for Disease Control and Prevention (CDC) once again will wrestle with the question of who in the United States should receive a booster shot to protect against COVID-19.

As several new variants and an uptick in COVID-19 hospitalization fuel concerns among some health officials and the public, three companies have made new COVID-19 vaccines that can be used as a booster (or as primary doses for the unvaccinated). The Food and Drug Administration (FDA) is expected to approve at least one of these latest iterations before Tuesday’s meeting of CDC’s Advisory Committee on Immunization Practices, which will address the question of who should receive it, and the panel’s discussion promises to be complicated.

Science spoke with clinicians, vaccine researchers, and biostatisticians about how they view the value of these latest shots. Several cautioned against falling into extremist camps—boosters are worthless or everyone must get boosters. “I just want people to have tempered expectations,” says Natalie Dean, a biostatistician at Emory University who specializes in evaluating vaccines. “There is room for reasonable debate about how much added value there is for a young, healthy person.” Two years ago, with the pandemic raging and vaccines dramatically cutting serious illness and death, there was little doubt about their value for everyone. Now, Dean says, “We’re in a very different situation than we were a few years ago.”

What is the new booster?

All FDA approved or authorized vaccines to date rely on introducing the spike protein of SARS-CoV-2 into a person—either via messenger RNA (mRNA) encoding it or the protein directly—to generate antibodies and immune cells targeting the coronavirus. But spike keeps changing as the virus evolves so the Pfizer/BioNTech collaboration, Moderna, and Novavax have new shots delivering the spike from XBB 1.5, a variant of SARS-CoV-2 that was predominant at the time the companies formulated the latest vaccines but has since been eclipsed by other related mutants. The XBB family all derived from the Omicron variant that has dominated globally since November 2021, so the hope is the XBB 1.5 spike will confer protection against currently circulating strains.

Will the latest variants dodge the immune responses triggered by the new boosters?

Not the viruses now in widespread circulation. The two most common variants in the U.S. today, EG.5 and FL 1.51, accounted for about 35% of the infections in the 2 weeks preceding 3 September. Both descended from the XBB 1.5 strain now in circulation. Pfizer and BioNTech, Moderna, and Novavax have all issued press releases that say their new formulations trigger strong antibody responses against the XBB descendants.

A variant dubbed BA.2.86 has not yet spread far, but has received intense attention because it has an unusually high number of mutations in spike that, in theory, could allow it to dodge antibodies more effectively. “This one has become the scary variant du jour,” says immunologist John Moore of Weill Cornell Medicine. But a lab led by Dan Barouch of the Beth Israel Deaconess Medical Center and two others now have reported laboratory studies that suggest BA.2.86 doesn’t transmit well and remains susceptible to antibodies triggered by other XBB variants.

How much protection can I expect from a booster?

The worth of boosters depends on how you slice the (imperfect) data. When COVID-19 vaccines closely match the strain in circulation, as happened during the initial trials and in the first few months after they went into use, the shots can powerfully reduce cases of mild illness and, in some cases, prevent transmission altogether. Some evidence suggests the vaccines can also lower the risk of Long Covid. But all of these positive outcomes are bonuses.

The main goal of the vaccines is to prevent severe disease, hospitalization, and death, and the data show the boosters clearly help—for a time. An analysis published in the 26 May Morbidity and Mortality Weekly Report looked at people in seven states since the bivalent booster became available in September 2022. It gauged vaccine effectiveness by comparing rates of COVID-19–linked hospitalization and critical illness (intensive care unit admission or death) in adults who had received this booster versus those who had not. In people who were not immunocompromised, the booster provided 62% and 69% protection against hospitalization and critical illness, respectively, for the first 59 days. But the immunity quickly waned to just under 50% for both between 60 and 119 days. Although protection against critical illness remained the same out to 179 days, it plummeted to 24% for hospitalization. The median age of the boosted group was 76 years old.

What if I have immunity from earlier infections?

“The vast majority of the U.S. population has been both vaccinated and infected, possibly multiple times,” Barouch says.

He and other vaccine researchers suspect that hybrid immunity may now be playing a large role in protecting people. “Despite the majority of people not getting boosted, severe disease remain very low,” he points out. So if you’ve had, say, a booster shot in the past year and then COVID-19, another booster may not offer you much extra protection against severe disease.

Do we really know enough about the value of boosters?

The CDC study was what is known as an observational, retrospective analysis to gauge effectiveness. The gold standard of clinical evidence for a vaccine is a randomized, controlled trial (RCT) that prospectively tracks people after they get immunized and measures efficacy.

“We know there can be substantial issues with observational studies,” Dean says. But RCTs would require large numbers of participants, likely followed for many months, and cost a pretty penny. “Who is paying for the trial?” she asks. “The company, the government?”

And by the time an RCT had results, the variants in circulation also likely would have changed. “Despite the limitations of observational studies, we probably do have a good ‘order-of-magnitude’ sense of the relative effectiveness” of boosters, Dean concludes. Countries also don’t conduct RCTs of the annual flu shots because the influenza virus shifts too fast; health officials make an educated guess as to what strain to use and hope for the best, and then conduct retrospective effectiveness studies to assess how well the vaccines worked.

Should I get a booster if I’m at higher risk of severe disease?

Everyone Science spoke with said yes, if you are elderly, immunocompromised, or have medical conditions that make you particularly susceptible to harm from the virus. “For people who are at high risk of severe disease, I think the answer is pretty simple and largely noncontroversial: A 4- to 6-month period of protection has a meaningful clinical benefit,”  Barouch says. “It’s clear that that population benefits from a boost and probably more than one boost for the year.”

What are the downsides of a recommendation to boost all ages?

It could cause confusion, and for some, the risks could outweigh potential benefits.

Paul Offit, a pediatrician at Children’s Hospital of Philadelphia who sits on FDA’s own vaccine advisory group, has strongly opposed the broad recommendation for previous boosters and says it makes even less sense now. “The goal of the vaccine is to prevent severe illness,” he says, stressing that many people wrongly expect the shots to prevent mild disease or even transmission. “You can’t ask people to get a vaccine if you’re trying to prevent serious illness and there’s no clear evidence that you are at risk of serious illness.”

Offit, who is 72, already had COVID-19 once and is in good health, did not receive the bivalent booster himself and doesn’t plan to get the new one. “I think I have hybrid immunity and clearly hybrid immunity is best.” He says it comes down to the data. “If [CDC is] going to make that broad recommendation, show me why that is,” he says. “Take healthy 12- to 17-year-olds who have already gotten three doses of vaccine or two doses and natural infection. Are they getting hospitalized?”

He notes that the mRNA vaccines made by the Pfizer/BioNTech collaboration and Moderna also have a risk of causing a heart condition called myocarditis. It is rare and often quickly resolves itself, but, he says, “this is a real side effect.” There are also even rarer vaccine side effects that scientists are still trying to understand.

Jennifer Nuzzo, an epidemiologist who heads the Pandemic Center at Brown University, favors a recommendation that “laser targets” the populations that will benefit most from the boosters. “When you equate 20-year-olds with 65-year-olds that gives 65-year-olds a different idea of what’s necessary,” Nuzzo says, explaining that the elderly may not realize that shots are especially important for them. “Lumping everyone into one category for boosters may wind up leaving the most vulnerable behind.” She also worries that a broad recommendation can feed the fire of people who discount the value of boosters. “Some people have hijacked the booster debate, saying, ‘These same people think 10-year-olds should get boosted.’”

What are the upsides of a broad recommendation?

It might encourage more people to get boosters, and the benefits for people who are the least vulnerable, even if modest, might still outweigh the risks. “Acceptability, feasibility, clarity, and simplicity are the dominant issues,” says William Schaffner, an infectious disease specialist at Vanderbilt University. “I hope we make it as acceptable as possible. Don’t think about it, just get it.”

Schaffner, medical director of the National Foundation for Infectious Diseases, stresses that SARS-CoV-2 can cause serious illness for every age group, even in people who do not have risk factors. “We ought to open up this accordion and make it as similar to the flu vaccine as possible,” he says. “The more we make it a social norm for everyone to do, perhaps we will get beyond some of this vaccine ennui, vaccine hesitancy, and the political aspects that still surround these decisions.”

Could a booster protect me from Long Covid?

Some evidence suggests vaccination may offer incremental protection against the “postacute sequalae” of SARS-CoV-2 infection, which can include everything from subsequent heart attacks months later to the chronic, lingering symptoms of what is known as Long Covid. The largest study to address Long Covid prevention and vaccination looked at more than 30,000 people who sought care through the Veterans Health Administration and became infected after being immunized. The analysis compared them with millions of uninfected controls who were both vaccinated and unvaccinated. Vaccination before infection reduced the risk of Long Covid by about 15%, the researchers reported in the July 2022 issue of Nature Medicine. “Long Covid is not one thing,” cautions the lead author, Ziyad Al-Aly, a clinical epidemiologist at Washington University in St. Louis. “That risk reduction varies by organ system, and it has the most effect on lung and coagulation problems with blood clotting.”

But Al-Aly does not think Long Covid is needed to tilt the scales on the booster decision. “Even when you don’t factor in Long Covid, I’d still advocate for vaccines for all,” he says.

If I get a booster could that potentially protect others?

Possibly, but not for a long period. A booster might lower the amount of virus in people who do become infected, reducing what they shed. “You might want to time that booster so that you have that peak level of protection when you’re going to see your elderly relatives,” Nuzzo suggests.

What’s the bottom line?

Vaccine experts agree that booster shots will help the most vulnerable, but there’s little consensus about who else will benefit from them. “I know that some of my colleagues have different opinions, and they’re trying to be as thoughtful as I am,” Schaffner says. “I don’t think there’s one easy, correct, best answer.” And whatever the recommendations, people will have to decide for themselves whether they want another boost.

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