Nation/World

Boost now? Boost later? Tricky calculation for a fourth coronavirus shot.

Bill and Rudi Weissinger remain COVID-cautious. They’ve had three shots of the Moderna coronavirus vaccine. They wear masks at the grocery store and avoid large gatherings. When Bill recently offered a friend a fist-bump rather than a handshake, the friend said, “Oh, still?” Yes is the answer, and most of their friends in Friday Harbor, Wash. - an island community - are similarly vigilant.

The Weissingers want to get another booster shot. They’re in their mid-70s and eligible. But they also plan to travel to France later this year. Boost now? Boost later?

“Our fear is if we get the booster now, it will have faded by then,” Bill says.

“We definitely believe in the boosters. We are not anti-vaxxers. Give me any shot you can,” Rudi says.

Most Americans aren’t trying to time their next booster for an overseas vacation, and many people in low-wage jobs and crowded multigenerational households are far more exposed than the Weissingers are. But their uncertainty about a fourth shot reflects the widespread confusion about boosters - who exactly should get them, and when, and why - that has dogged the government’s vaccination campaign.

Even highly informed consumers of pandemic news may struggle to sift through the latest government guidance and newest scientific studies. And even at this stage in the crisis, they may be unclear on what additional boosters can and can’t do.

Public health officials who authorized a second booster shot last month for people 50 and older and for immunocompromised people 12 and older have insisted it’s a stopgap, aimed primarily at keeping the most vulnerable people out of the hospital or the cemetery. A second booster appears to add to protection against severe illness in people 60 and older but offers only a modest, temporary shield against infection.

[Should I still wear a mask in public? A guide to help you decide.]

The booster issue reveals some tension between public health priorities and individual interests. The disease experts worry about epidemic waves that can overwhelm the health-care system. To a doctor, a vaccine has worked fine if it keeps a person out of the hospital, with just a mild to moderate case - which can mean anything from a few sniffles to a miserable week in bed utterly flattened by the virus. Many people, though, don’t want that bad week - with the attendant risk of long COVID - and will do anything to keep it off their calendar.

“I think the expectations [from] the first performance of the vaccines is that it is possible to be completely protected against infection, or any small cough even,” Hanneke Schuitemaker, head of viral vaccine development and translational medicine at Janssen, a division of Johnson & Johnson, said at a recent forum held by the New York Academy of Sciences.

The reality is that a person who is up to date on vaccination is very unlikely to wind up in the hospital, although the virus may still be able to break through the initial line of immune defense and generate sickness.

“You may have sort of a common cold, but your immune system will deal with it and prevent severe disease,” Schuitemaker said.

Even as many people rush to get a fourth shot, many others still haven’t received their third, second or first. Despite clear evidence that a third shot can save lives and better protect people, more than 90 million eligible people in the United States haven’t rolled up their sleeves for their first booster. Booster uptake has been higher among White people than in communities of color.

Medical advisers to the federal government have debated the necessity and ethics of a fourth shot given that there are higher public health priorities, including reaching unvaccinated communities and ensuring wider global access to vaccines. But in their late March authorization, federal agencies said people 50 and older could get an additional booster it they are at least four months past their previous shot.

Strikingly, the agencies did not clearly recommend that booster for everyone who is eligible, and federal officials’ advice varies.

Rochelle Walensky, director of the Centers for Disease Control and Prevention, said people 65 and older and those 50 and older with underlying medical conditions are most likely to benefit. Ashish Jha, White House COVID-19 response coordinator, told “Fox News Sunday” the data were “pretty compelling” for people older than 60 to get a second booster. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said on MSNBC that people older than 50 should get a fourth shot.

Data from Israel, which offered fourth shots to people 60 and older during the omicron surge, show that the additional shot increases protection against severe illness and death compared with a third shot. But against infections - most of which are officially deemed “mild” - a fourth shot provided only a modest and brief increase in protection, peaking at four weeks after the booster dose and dropping back to the baseline after eight weeks.

“[T]hese findings suggest that protection against confirmed infection wanes quickly,” the researchers concluded.

“I was shocked,” said Robert M. Wachter, chair of the department of medicine at the University of California at San Francisco. He said he thought the additional protection against infection from the fourth shot would mirror that of the third rather than be so brief.

If the fourth shot offers a relatively brief window of higher protection, he said, timing that booster according to plans - a wedding, a family reunion, visiting an elderly relative, a vacation - seems reasonable. But it’s not an easy calculation, he said, because there are so many factors in the equation.

“There’s no perfect plan. You’re weighing risks, benefits, uncertainties, your own personal circumstance,” Wachter said. “I do this for a living, and I get a headache when I try to think this through.”

Risk analysis is not the strong suit of most people. Guidance from the CDC about the risk of infection has not always been clarifying. The risk on any given day depends a great deal on the current level of community transmission, but that data may not be easily found or interpreted and could be out of date.

And the virus itself is not a fixed entity. The omicron variant is more transmissible than earlier forms of the virus, and there is now a growing roster of omicron subvariants, including BA.2, which are more transmissible yet. As it mutates, the virus has become more evasive of the human immune system.

The result is that an individual’s risk analysis - is it safe, on this day, with this level of community transmission of this latest omicron subvariant on the prowl, to dine indoors at a restaurant? - is thoroughly contaminated with guesswork, wishful thinking and/or fear.

There is no simple test of an individual’s protection. There isn’t a line in the sand - what experts call a “correlate of immunity” - that means someone is immune or not immune, or is or isn’t likely to end up in a hospital bed.

Antibodies may have become the public face of the immune system, to the detriment of public understanding. Antibodies naturally drop after most vaccinations, but protection against the worst outcomes clearly persists longer, because of the multifaceted way immunity works.

T cells provide a layer of immune defense and stick around in the body for at least six months, with only modest erosion. Memory B cells persist and kick into action to churn out virus-fighting antibodies through what is called a “recall response.”

Neutralizing antibodies wane naturally - the body doesn’t want to arm itself endlessly with battalions of defenders against a hypothetical invader - and in the case of COVID, they wane more quickly than some disease experts had hoped two years ago.

The boosters authorized to date are identical to the first vaccines. Those shots were designed to deal with the original Wuhan strain of the coronavirus, which has since evolved into an array of slippery variants.

This confusion about the goal of vaccination - and thus when shots should be considered to be failing - even extends to the experts as they debate the long-term booster strategy for the public.

“At what point will we say the vaccine isn’t working well enough?” asked H. Cody Meissner, a pediatric infectious-diseases specialist at Tufts Medical Center in Boston at a recent federal advisory committee meeting.

“What is enough? What is our expectation?” CDC official Amanda Cohn asked. “Given that our effectiveness against hospitalization in immunocompetent individuals is over 80% - and that’s in older adults and persons with chronic medical conditions - I think we may have to accept that level of protection and then use other alternative ways to protect individuals with therapeutics and other measures.”

Vaccine expert Paul A. Offit at Children’s Hospital of Philadelphia argues that it was a mistake to call mild and asymptomatic infections “breakthroughs.” The immunity mustered by current vaccines is not expected to protect against all infections.

“The term ‘breakthrough,’ which implies failure, created unrealistic expectations and led to the adoption of a zero-tolerance strategy for this virus,” Offit wrote in a recent perspective piece in the New England Journal of Medicine.

The decision about when, whether and who to boost has also been complicated by imperfect data. A widely quoted CDC study showed that protection against severe illness from three shots waned over four months, from 91% to 78%.

What was lost in the messaging was that those who had been vaccinated for more than four months in that study were primarily people with poorly functioning immune systems, who typically respond less well to vaccination. When the data was instead limited to people with functioning immune systems, there was little evidence that protection against hospitalization was waning, even among people 65 and older, according to data presented by Ruth Link-Gelles, part of the CDC’s Epidemiology Task Force at a federal advisory committee meeting this month.

The Food and Drug Administration’s decision on boosters came amid skepticism from some vocal members of the scientific community, who would like to see more data showing it is necessary.

“We’re very much on board with the idea that we simply can’t be boosting people as frequently as we are, and I’m the first to acknowledge that this additional fourth booster dose that was authorized was a stopgap measure,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said at a meeting where experts debated future boosters.

The debate appears likely to continue this week when a CDC advisory committee meets to discuss who should get an additional booster. Breaking with typical CDC practice, Walensky did not wait for that advisory committee to weigh in before issuing guidance supporting the extra booster for people 50 and older.

The FDA is also developing strategies for the rest of the year and trying to decide under what circumstances the vaccines should be modified to deal with variants. Vaccine companies are testing alternative formulas and delivery systems.

The booster debate comes as many scientists say that what the world needs are vaccines that would provide a broader blanket of immunity to respond to whatever the virus evolves into.

“Instead of more boosts of the same original thing, I think we need to use a better vaccine,” said Erica Saphire, president and CEO of the La Jolla Institute for Immunology.

Kristian Andersen, an immunologist at Scripps Research, has contended that people need to be boosted every six months or so.

“We just need to realize that immunity, unfortunately, wanes pretty quickly,” Andersen said. “We don’t want that to be true. We want lifelong immunity. We want measles-type immunity.”

He said that is wishful thinking at the moment.

“Our default assumption should be that we need to broaden immunity. If we don’t, the virus will bypass immunity even more than it has already with omicron. . . . But we’re not planning for that,” Andersen said. “Our entire response to this has been based on equal measure hope and wishful thinking, and that continues to this day.”

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The Washington Post’s Lena H. Sun contributed to this report.

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