War Fourth shot of COVID-19 vaccine may help immunocompromised but might not be needed for everyone

War Fourth shot of COVID-19 vaccine may help immunocompromised but might not be needed for everyone


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Evidence supports giving a fourth dose of COVID-19 vaccine to people with weakened immune systems, but it’s not clear whether fourth shots make sense for healthy Americans.

A third dose of the Pfizer-BioNTech or Moderna vaccine has been extremely effective at preventing severe disease from the omicron variant, which accounts for virtually all the COVID-19 infections in the USA.

Nervous people wonder if they need an additional dose and when that should be.

The Centers for Disease Control and Prevention authorized a fourth dose at least five months after a third for people with immunocompromised conditions – such as transplant recipients, cancer patients receiving certain treatments and people on certain medications.

The CDC has not said whether or when it would consider allowing healthy people to get a fourth shot, nor has the Food and Drug Administration considered authorizing one.

Dr. Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia, has long argued that two doses are enough to protect against severe disease and death in people with healthy immune systems.

US COVID-19 map: Tracking cases and deaths

He said he’s not against a third shot in healthy people because data shows it provides better protection against omicron. Unlike a disease such as measles, respiratory viruses simply can’t be eliminated by vaccines, he said – all they can do is reduce the risk of severe outcomes. 

To limit severe disease, the best approach would be to get more people vaccinated, he said, not worry about giving four or more doses to people who are largely protected.

“We’re focusing on the wrong group,” Offit said. “If you really want to have an impact on this pandemic, vaccinate the unvaccinated.”

Israel, alone in the world, started providing fourth doses to health care workers and people over 60 to provide additional protection at least for some time, although an early study showed it might not boost antibody levels enough to prevent mild disease.

The data on a fourth dose for healthy people remains thin, British epidemiologist Jonathan Sterne told The Lancet Respiratory Medicine, although an Israeli Health Ministry advisory panel recommended last week that all Israeli adults should be eligible for a fourth dose at least five months after a third.

“Fourth doses are mainly being done on a precautionary basis; we have very little evidence of their effect either from studies of immune function or from observational studies of clinical events,” said Sterne, a professor of medical statistics and epidemiology at the University of Bristol.

War Who benefits from extra doses?

People with compromised immune systems seem to benefit from extra doses, whether a third, fourth, or maybe even more.

“One of the things we’re learning is that there is some truth to the old adage ‘if at first you don’t succeed, try, try again,’” said Dorry Segev, a transplant surgeon, professor and epidemiologist at Johns Hopkins in Baltimore.

In most of the immunocompromised people he’s studied, Segev found that each additional dose increased the likelihood that they got a protective response from a vaccine.

“There are people who were negative after (dose) two who start to show something after three, or who were negative after three who start to show something after four,” he said. “Something is happening in these immune systems that we might not see above the surface but that’s happening beneath the surface.”

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Monday, the National Institutes of Health announced it was awarding Segev a $40 million grant to study whether giving kidney and liver transplant patients a fourth dose alone is the right approach or whether there’s a way to modulate a person’s immunosuppressive medication in addition to vaccination to see if there’s a more effective way to build immunity. 

“We don’t have enough data to say whether it is safe enough and more effective enough to merit doing things like changing immunosuppressive medications in transplant patients,” Segev said, but it probably makes sense in people with autoimmune disease.

Anyone who is immunosuppressed and wants additional shots should join a clinical trial, he said. 

Segev said he would like to see the Food and Drug Administration permit doctors to prescribe additional doses to patients if they think they’re needed.

“We know it’s safe,” he said. “If I think that my transplant patient needs a fourth dose, it’s time for me to be able to prescribe that.”

War For the healthy, data on 4th dose unclear

Two doses of vaccine provide protection against severe disease, but immunity against any infection with COVID-19 is likely to fade, even after a fourth dose, said Dr. Justin Zaghi, chief medical officer at Heal, a primary care and home health care service.

“There’s some data suggesting there is a value to a fourth dose; however, what we know based on our experience of a third dose is that immunity will likely wane, and it won’t be a perfect match for the omicron variant,” Zaghi said.

It’s too early to know how many doses will provide long-term protection against severe disease and death, but Zaghi said he’d like to see subsequent shots targeted to specific variants, such as omicron.

The way experts try to match flu vaccines to the three or four circulating strains, so COVID-19 vaccines could be matched to whatever variant is circulating, he said. Like the flu, the matchup won’t always be perfect, but because original COVID-19 vaccines work against omicron, there’s probably enough overlap among variants to at least allow vaccines to prevent severe disease and death, he said.

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In trials announced this week, Pfizer and its collaborator BioNTech will test an omicron-specific booster in people who’ve had three shots of the companies’ original vaccine. Moderna said it is also developing an omicron-specific vaccine.

When thinking about subsequent shots, people need to consider the goal of vaccination, said Dr. Daniel Kuritzkes, chief of the division of infectious diseases at Brigham and Women’s Hospital in Boston.

To prevent every case of COVID-19 would require an endless round of shots and would never be fully effective, he said. 

China, Australia and New Zealand, trying to prevent every infection, have severely limited the movements of their citizens – locking people in their homes for weeks in China, he said – and they still see infections.

Providing basic vaccination for most people and tolerating mild infections in people with healthy immune systems will be a better approach long-term than an endless cycle of variant-specific boosters, he suggested. 

“It’s unrealistic to believe any kind of vaccine is going to prevent mild symptomatic disease forever,” Kuritzkes said. “Current vaccines are continuing to do an outstanding job of protecting people against severe disease and dying.”

Contact Karen Weintraub at kweintraub@usatoday.com 

Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.

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