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COVID-19: Who needs a second booster?
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Rosemary Pitrone

On March 29, the CDC updated its guidance to recommend additional COVID-19 booster shots for some individuals. Emory epidemiologists Dr. Jodie Guest and Dr. Carlos del Rio teamed up to discuss who is now eligible for a second booster, potential risks and benefits of a fourth dose, and whether to mix and match booster shots.

On March 29, the Centers for Disease Control and Prevention (CDC) announced changes to its recommendations for COVID-19 booster shots among certain individuals. The changes followed a decision by the U.S. Food and Drug Administration to authorize a fourth dose, or second booster, of the Pfizer and Moderna COVID-19 vaccines for older individuals and those who are immunocompromised.

To discuss the updated guidance, Jodie Guest, PhD, professor and vice chair of the department of epidemiology at Emory’s Rollins School of Public Health, teamed up with Carlos del Rio, MD, distinguished professor of medicine, epidemiology and global health and executive associate dean of Emory University School of Medicine at Grady Health System. They answer questions about who should receive a second booster, potential risks and benefits of a fourth dose, and whether to “mix and match” boosters.

Their conversation is part of an online video series hosted by Guest, who also leads the Emory COVID-19 Outbreak Response Team, answering questions related to the COVID-19 pandemic.

Q: Who is eligible for a second booster?

A: Based on the new CDC guidance, certain immunocompromised individuals and people over the age of 50 who received their first COVID-19 booster dose at least four months ago are now eligible for another mRNA booster — either Pfizer or Moderna — to increase their protection against severe disease from COVID-19.

Additionally, adults who received a primary vaccine and booster dose of the Johnson & Johnson COVID-19 vaccine at least four months ago may now receive a second booster dose using an mRNA COVID-19 vaccine.

Q: Who is eligible for the first booster?

Eligibility for the first booster has not changed. Individuals ages 12 and older who have completed a two-dose vaccination series of the Pfizer vaccine remain eligible for their first booster dose at least five months after completing their primary vaccination series.

Adults who completed a two-dose vaccination series of the Moderna vaccine remain eligible for their first booster at least five months after completing their primary vaccination series, and adults who received a Johnson & Johnson vaccine remain eligible for a booster at least two months after their first shot.

“If you've only been vaccinated and you haven't been boosted, you should get boosted, because there's clear evidence that three doses is way better than two doses,” del Rio says.

“My concern is the millions of Americans who have yet to be vaccinated,” he adds. “If you haven't yet been vaccinated, I'm very concerned about you, because it is time to get vaccinated now.”

Q: Does the second booster prevent severe disease, hospitalization and death due to COVID-19?

A: In its updated recommendations, the CDC highlighted the particular importance of second boosters for individuals over the age of 65 and those over the age of 50 with underlying medical conditions that put them at greater risk for severe disease and death due to COVID-19.

“We're trying to be proactive and prevent something from happening, as opposed to catching up,” del Rio says. “There is science to support giving a booster to people who are immunocompromised, and there is also science for giving a fourth dose to people who are over the age of 60.”

del Rio cites data from Israel showing that mortality in individuals between the ages of 60 and 100 who received a fourth dose and acquired COVID-19 infection was around 50-60% lower than among individuals who had only received one booster.

“So, in that population a fourth dose makes a lot of sense,” he says. “Again, the outcomes we want to avoid with these vaccines are severe disease, death and hospitalizations.”

There are no known safety issues associated with a fourth dose in healthy individuals under the age of 60, but del Rio suggests the benefit of a second booster in this population may be limited. He has not seen evidence to indicate that a fourth dose provides extra protection against severe disease and death in this population.

“When you look at the studies looking at three versus four doses, it shows that it looks about the same” among healthy individuals under the age of 60, del Rio says. “You may get a little bit of protection against infection, but that little bit of protection against infection goes away, wanes, within eight to 12 weeks.”

Q: Should you receive a second booster if you already had COVID-19?

A: Individuals who previously had COVID-19 do have some protection against the virus. Immune protection is even stronger among individuals who had COVID-19 and are vaccinated and boosted.

“We saw more of the breakthrough infections with Omicron than we've seen with any other variant,” Guest says. “It's important to recognize that boosters really do help [with immunity].”

del Rio suggests that most individuals who recently had a breakthrough COVID-19 infection can wait before getting a second booster if they are otherwise healthy.

“If you're under the age of 60, you've been vaccinated and boosted, and in addition to that you were infected because you got Omicron or you got Delta, you’ve got the best protection ever,” he says. “As a friend said, ‘You don't need to run to your booster, you can walk to your booster.’”

Q: How do immunocompromised individuals benefit from an additional booster?

A: People with immunocompromising conditions may not mount the same immune response to vaccines as people who are not immunocompromised. Guest says that additional doses of mRNA vaccines can help ensure these individuals receive the “maximum benefit” possible from the vaccine.

del Rio explains that this specific category of patients includes individuals undergoing cancer chemotherapy, organ transplant recipients or those who are receiving immunosuppressive drugs that impact the immune system.

In some cases, these patients may not respond to vaccines at all. “For those individuals, we have Evusheld, a monoclonal antibody that you can get for prevention that’s an infusion every six months,” del Rio says. He recommends that these patients talk to their doctors when considering either Evusheld or an additional dose of vaccine for protection against COVID-19.

Q: Does a second booster increase protection against COVID-19 infection?

A: In addition to preventing severe disease and death, Guest says studies from Israel have shown that a fourth dose can increase protection against COVID-19 infection in individuals over the age of 60.

“This fourth dose does reduce the rate of infection by about two times and reduces the rate of severe disease about four times” among this population, she says. “The fourth dose is not giving quite the additional level of protection that we saw with the first booster — the third dose — but it is still increasing the prevention that we see.”

Guest also notes that preventing infection through vaccination helps prevent long-term conditions related to COVID-19.

“The best way to prevent long COVID is to be vaccinated and the best way to prevent long COVID is to not get COVID,” del Rio adds.

Q: When is the best time to receive the second booster?

A: del Rio is aware that some people hope to align their booster shots with plans such as travel that may put them at higher risk for exposure to COVID-19.

“I tell people that’s a little bit like trying to time the stock market,” del Rio says. “It just doesn’t work. If you’re going to get a booster, if you’re four months out, just go ahead and get it, but continue thinking, ‘I can still get infected.’”

“In the last week, I've heard about at least a dozen people who have gotten infected,” he continues. “They're all doing fine, but if you're over the age of 50, my advice is: if you get infected, try to get diagnosed quickly, try to start on one of the drugs that is out there for the outpatient management of COVID, because they do make a difference.”

He adds that the newly released website is a great resource for locating COVID-19 testing, treatments and vaccines.

Q: Will individuals who receive a second booster now need another booster in the fall?

A: “There are some studies happening right now trying to understand if we need a booster in the fall, and what the booster is going to be,” del Rio says. “Is it going to be the booster with the vaccines we have? Will Omicron be here to stay, because it's so transmissible, and maybe we need an Omicron-specific booster? A lot of those studies are happening, and I think they're going to inform decision making, hopefully, for the fall.”

“My advice is: if you're over the age of 60 and you are more than four months away from your boost, get a fourth dose now,” he continues. Receiving a booster now will not preclude these individuals from receiving a potential fifth dose in the fall, should that be recommended.

For healthy individuals under the age of 60, del Rio does not currently see a need for a fourth dose because there are no data to show that it provides additional protection against severe disease, hospitalization or death compared to a third dose in that population.

“I think it's important for us to remember how incredibly well our vaccines are still working, especially if you've gotten that first boost [after the primary series of mRNA vaccinations],” Guest adds. “They are really still working extremely well.”

Q: Does it matter which mRNA vaccine an individual receives for the second booster?

A: There are no risks or benefits to “mixing and matching” COVID-19 vaccines. For example, an individual who received Moderna’s vaccine for their first three doses may receive Pfizer’s vaccine for their fourth dose.

“The mix and match study that was done, and Emory was one of the sites, shows really no benefit and no risk,” del Rio says. “While it may be fun to mix, the reality is: get the booster that's out there, get the vaccine that you can find, whether it's Pfizer or Moderna. Your immune system really doesn't know the difference.”

“I've never had anybody go to the drugstore and say, ‘I want to get the flu shot, but I want to get the Pfizer one or I want to get the Sanofi one,’” he adds. “You just go and get your flu shot. And you need to think about it that way. If the FDA has approved the vaccine, it’s a good vaccine.”

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