Is It Time for Yet Another COVID Booster?

Kathleen Doheny

February 17, 2022

Is it time to get an additional COVID booster shot?

The first COVID booster shot is now in the rear-view mirror for millions of Americans —for the 28% who got it, at least — but new data finds its effectiveness waning after about 4 months. The Centers for Disease Control and Prevention (CDC) has already recommended boosters for immunocompromised people.

So, is the next logical step another booster for every other adult?

The consensus among public health officials seems to be: Not so fast.

At the White House COVID-19 briefing Wednesday, chief White House medical advisor Anthony Fauci, MD, focused on the question of the hour. Citing data, he said that "a single booster shot continues to provide high level protection against severe disease caused by Omicron" in people who are not immunocompromised.

According to CDC research, cited by Fauci, vaccine effectiveness after two doses of the mRNA vaccine drops to 58% after 4-5 months. After a booster dose, the vaccine is initially 91% effective at preventing hospitalizations, but that drops to 78% at months 4 to 5. "Nonetheless, the level of 78 [%] is still a good protective area," Fauci said.

"The future requirement for an additional boost or a fourth shot for mRNA or a third shot for J&J is being very carefully monitored in real time," he said, adding that recommendations will be updated as needed and if needed as the data evolves.

Wait on the Data

Other public health officials and agencies echo Fauci's advice: Wait on the data.

"At this time, CDC does not have a recommendation for a fourth dose/second booster dose for most Americans," said Scott Pauley, a CDC spokesperson, referring only to people who are not immunocompromised.

In a statement issued January 11, the World Health Organization (WHO) said that "a vaccination strategy based on repeated booster doses of the original vaccine composition is unlikely to be appropriate or sustainable." In discouraging the repeated booster strategy, the WHO cited factors such as the need for global equity in access to vaccines and the evolution of the virus, with the emergence of variants.

"There is no data to support the generalized use of a fourth dose of the vaccine beyond the immunocompromised," said Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins Center for Health Security. "In fact, there is data to suggest diminishing returns with fourth doses."

In a preprint study posted this week, researchers from Sheba Medical Center in Israel followed 274 healthcare workers after a fourth dose of either the Moderna or the Pfizer vaccine. They found the booster restored antibody levels to the same peak levels following the third dose, but was not effective in preventing mild or asymptomatic Omicron infections.

Breakthrough infections were common. The researchers concluded that their results suggest the urgency of "next-generation vaccine development."

Considering the Pandemic Trajectory

Decisions about second booster recommendations demand evaluating the big picture, said William Schaffner, MD, infectious disease specialist at Vanderbilt University Medical Center in Nashville. At the moment, he said, hospitalizations are down, and "even deaths, a lagging indicator," are declining, although not to the same degree in all parts of the country. Even so, he said, the trends are going in the right direction.

At the White House COVID-19 press briefing Wednesday, CDC director Rochelle Walensky, MD, said federal officials are "cautiously optimistic about the trajectory we are on," noting that the current 7-day daily average of cases is about 147,000, down about 40% from the previous week. Hospital admissions, at 9500 a day, have declined about 28%, and the 7-day average of daily deaths are about 2200, a decreased of about 9% from the prior week.

The hope, Schaffner said, is that this combination of the Omicron spread, with many having natural immunity from that infection, along with vaccination, will produce a sustained reduction of cases. "If that is the case, we don't need a booster anytime soon."

However, that scenario also assumes we don't see a new variant of concern, he said.

Then, "as we move from pandemic to endemic, we will be able to determine at what interval a booster will be necessary and what the composition [of it] will be," Schaffner said. For now, however, "I don't think a fourth dose — a second booster — is in the cards in the near-term future [for those not immunocompromised], if everything goes the way it has been going."

"What you can’t see is that all my fingers are crossed," he added.

Booster Goals

It's difficult to give definitive answers about boosters for the general population without sufficient data yet, agreed Alejandro Balazs, PhD, a virologist and principal investigator at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard.

The critical question: "Are we trying to stop transmission or just severe disease?"

Adalja agreed: "If the goal is protection against serious disease, hospitalization and death, targeting the boosting of high-risk populations [but not others] makes sense as the standard regimens are holding up in the general population."

Even as antibody levels decline after vaccinations, your memory T-cell and B-cell response may endure, making it possible to fight the virus, Balazs said. "The antibodies can prevent the infection from establishing itself."

However, if antibody levels decline, and you get infected, your immunological memory response is ready to go. "That is probably contributing to less disease even after antibody levels have faded," he said.

Booost Now, Data Later?

Despite the lack of data, doctors say their patients are asking now about second boosters. "At this point in time, it is impossible to predict whether additional booster doses will be needed for healthy people,'' said Aaron Glatt, MD, chief of infectious diseases at Mount Sinai South Nassau in Oceanside, New York.

Could premature boosting by healthy people have a downside? "I don't see any immediate harm [to that]," Schaffner said. "However, I'm not so sure about the benefit."

"The one harm is hypothetical," Adalja said, "and it is that continuing to boost with first-generation vaccines directed against the ancestral strain of the virus may blunt the ability of the immune system to fully respond to new variants, a phenomenon called original antigenic sin."

Another solution: "There are studies underway to see if there could be a universal vaccine," Glatt said. "These are very exciting prospects but are not yet clinical realities."

Schaffner, Glatt, Balazs, and Adalja have disclosed no relevant financial relationships.

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