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Who should get a 4th COVID-19 shot?


A health care worker prepares a COVID-19 vaccine in Jackson, Ala., Oct. 5, 2021. Several studies have found that while mRNA booster shots have been successful at preventing hospitalization and death, their effectiveness against infections is waning.

By Knvul Sheikh


As coronavirus case counts continue to plummet across the United States, people’s immunity may be declining, too. Several studies have found that although mRNA booster shots have been successful at preventing hospitalization and death, their effectiveness against infections is waning.


It’s no wonder, then, that late last week, Moderna sought emergency use authorization from the Food and Drug Administration for a second booster shot for all adults. The company’s request came just days after Pfizer and BioNTech filed for emergency authorization for a second booster of its coronavirus vaccine for people 65 and older.


Moderna said that its much broader request would give the Centers for Disease Control and Prevention, as well as health care providers, more flexibility in determining who would benefit most from getting an additional booster shot and when.


Scientists and physicians are sharply divided over this. “I don’t think everybody should get another booster right now,” said Dr. Yvonne Maldonado, a pediatric infectious diseases physician at Stanford University. “But I don’t see any reason why we shouldn’t start to review the data that is available.”


Who is currently eligible for a fourth vaccine dose?


As of now, the only people authorized for a fourth dose are those with weakened immune systems. This includes teenagers and adults who have had organ or stem cell transplants, who are undergoing chemotherapy for cancer, who have advanced or untreated HIV, or who are on immune-suppressing drugs.


It’s hard to predict how soon — or if — the FDA might authorize a second booster (or fourth dose) for all adults. The agency is expected to convene an advisory committee next month to discuss the issue. And although experts say it’s reasonable that the committee might move swiftly on Pfizer’s application for older adults, it is unclear if Moderna’s more sweeping request will get the green light.


“We know that people over the age of 65, even when vaccinated, have a higher risk of dying than people under the age of 65,” said Dr. Carlos del Rio, an infectious disease specialist at Emory University. “That gets lowered significantly if people get boosted.”


One reason older adults may benefit from an additional booster shot is because as the immune system ages, it tends to weaken and does not produce the same quantity or quality of antibodies as it did when it was younger. On top of that, older adults often have other medical conditions that take up the body’s attention, putting them at higher risk of severe disease, said Dr. Christian Gaebler, an immunology researcher at Rockefeller University in New York City. “Diabetes, hypertension, obesity and chronic kidney disease are all risk factors for severe COVID,” he said. “And we know that these usually manifest in older age.”


In their justification for seeking second boosters for people 65 and older, Pfizer and BioNTech relied heavily on evidence from two studies conducted in Israel that suggested that people who had received fourth shots were less likely to become infected with the virus compared with those who had received three doses.


In one study, published on a preprint server in February, scientists reviewed the health records of about 1.1 million people older than 60 who had received a fourth dose and compared them with those who had received just three doses. They found that the rate of confirmed infections, as well as that of severe illness, was lower in people who had gotten their fourth shot.


The second study, published Wednesday in The New England Journal of Medicine, looked at Israeli health care workers of all ages and found that both Pfizer’s and Moderna’s fourth shots bolstered antibody levels, although they were not very good at preventing infection.


Experts, however, cautioned that the available data is still preliminary and has not yet shown how long the benefits of a fourth dose will last.


If the shots are authorized for seniors, how should they think about timing them?


Experts tracking COVID-19 are careful not to give specific advice on when to get a fourth dose when the safety and efficacy data are still limited.


If another surge is just around the corner, for instance, seniors may benefit from getting an extra shot as soon as it’s authorized. But if the next wave doesn’t occur until the summer or even the fall, getting a booster now could backfire because the recipients’ immunity might start to wane by the time they need protection the most. Current vaccines are based on the original strain of the coronavirus, so getting a booster now may also do little to protect against future variants.


“It would be great if we knew exactly when the next wave was going to be so we could vaccinate people beforehand,” said Dr. Amy Sherman, an infectious disease physician at Brigham and Women’s Hospital in Boston. “But I think we’re not quite at the point where we know a clear seasonality, and we know the exact tempo and dynamics of COVID and newer variants.”


That being said, if a fourth shot is authorized for adults older than 65, and it has already been several months since they got their first booster, “I would start thinking about whether I need a booster now,” del Rio said.


What does this mean for everyone else?


For people younger than 65, who are otherwise healthy, most experts agree that three doses are most likely enough for now. Those in their 20s and 30s who have already received three shots of the vaccine, for instance, will see only marginal benefits in protection from an additional shot, Gaebler said.


“Fourth doses might turn out to be advisable,” he said, “but at this point, I think the focus should be on administering third doses.”


Del Rio agreed. “I’m more concerned about the millions of Americans who are not vaccinated or are only partially vaccinated,” he said. “That, to me, is where we need to put our major focus.” Getting more people vaccinated, nationally and globally, could potentially have a bigger effect on reducing virus transmission and curtailing new variants so that everyone can return to normal life, del Rio said.


And there is hope that better vaccines and treatments are on the way. Pfizer and Moderna are testing new omicron-specific versions of the COVID-19 booster. And other researchers are investigating vaccines that boost mucosal immunity in the nose, as well as protein-based shots that may be better at protecting against the coronavirus in the future.


“We have to really think carefully about our vaccine strategies,” Sherman said. “We have to think as a society about what our goal is with repeated boosters and vaccines because none of our existing vaccines completely prevent transmission or prevent all disease. And so at what point are we comfortable with asymptomatic or mild infection in the population while still being able to protect those who are vulnerable?”

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