FOCUS: Fourth COVID Vaccine Offers Relatively Little Benefit. Do We Need It?

Long-awaited data is in: A fourth dose of the coronavirus vaccine reduces the risk of getting severely ill.

But triple-vaccinated people already are so well protected from hospitalization that a fourth dose offers relatively little real-world benefit, experts say.

The second booster drops the risk from exceedingly small to … even smaller. But is that enough for the U.S. to launch another ambitious round of immunizations?

“For the majority of healthy younger adults, I don’t believe a fourth vaccine makes sense,” said Dr. Warner Greene of the Gladstone Institutes in San Francisco. “Three doses provides strong protection from hospitalization and death — these are the numbers that count, not the number of infections.”

Israel was one of the first countries to vaccinate its population and carried out the world’s first booster campaign.

Faced with signs of declining protection, in early January it began offering fourth doses to older and immunocompromised people and to health care workers. Other countries — including the U.S., Chile, Cambodia, Denmark and Sweden — also are beginning to offer fourth doses to specific groups.

The analysis of that Israeli effort came earlier this month. It reports a fivefold boost in antibody levels. More important, high-risk people who received a fourth dose of COVID-19 vaccine were three times more resistant to serious illness than triple-vaccinated people in the same age group, according to a team from the Israel’s Technion, Ministry of Health and others.

“A threefold drop sounds like a lot, and so the decision to take a remarkably safe booster may feel like a slam-dunk,” said infectious disease expert Dr. Bob Wachter, chair of UC San Francisco Department of Internal Medicine.

But for an individual person, the benefit is very modest, Wachter said.

The fourth shot reduced the odds of severe illness in high-risk Israelis from about 1 in 21,936 to 1 in 75,460.

In other words, many people need to be boosted again in order to prevent one additional case of severe illness. That’s a lot of effort for marginal reward.

The payoff is even smaller for younger and healthier people, because their odds of severe illness are less.

And there’s a global equity issue. Because protection from boosters appears to be short-lived, rolling out endless doses — potentially at the expense of immunizing unvaccinated people in low-income nations — is not a reasonable long-term approach, according to the World Health Organization.

In a January statement, WHO asserted that “a vaccination strategy based on repeated booster doses of the original vaccine composition is unlikely to be appropriate or sustainable.”

“I don’t think it’ll be absolutely crucial for young, immunocompetent, healthy individuals,” said Gladstone’s Nadia Roan. The current shots are still doing a very good job at protecting us against severe COVID-19 likely due in part to their ability to trigger the immune system’s memory, killing infected cells, she said.

To be sure, there may be advantages for some individuals.

So far, only moderately and severely immunocompromised Americans are eligible for a fourth shot. The CDC said that this group could receive the additional booster five months after their third dose. About 2.7% of U.S. adults, or about 7 million adults, are considered immunocompromised.

“Giving a fourth shot only makes sense in the context of severe immunosuppression,” said Greene. These patients “need all the help that they get.”

But for the rest of us, repeated booster doses of our existing vaccines offer only diminishing returns in terms of protection against future strains, Greene said.

Both Moderna and Pfizer have started clinical trials of a booster shot that specifically targets the omicron variant. Pfizer expects initial results from its trials in the first half of this year. Moderna has not provided a timetable. Both companies are suggesting that a second round of boosting could come to the U.S. later this year.

“Assuming omicron is an acceleration to the endemic phase, I still believe we’re going to need boosters in the fall of 2022 and forward,” Moderna CEO Stéphane Bancel said at an investor conference

Pfizer‘s chief scientific officer Mikael Dolsten said another boost will be needed “if omicron is present in March, because it’s very evasive for the immune system. And then we need to roll into annual campaigns.”

But other scientists think it might not be worthwhile because omicron could vanish before regulators can finalize the vaccines.

And there’s no guarantee that the next variant will be like omicron. While new strains of the flu typically emerge from the previous year’s strain — easing vaccine development — the behavior of the COVID-19 virus isn’t as predictable. The highly mutated omicron variant, for example, came out of left field.

What’s needed, especially for the most vulnerable, is a combination booster with broadened power — a vaccine that targets both delta and omicron variants, Greene said.

“I wouldn’t want to get boosted a fourth time with the current vaccine,” said Greene. “But I would be first in line to get boosted with an omicron- and delta-like vaccine.”