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Real-world data from the U.K. showed that efficacy of a third dose of a COVID-19 vaccine waned significantly at the 10-week mark, leaving boosted individuals at risk of infection with Omicron.

In a December 23 vaccine efficacy against symptomatic infection generally fell to around 40% some 2.5 months after a booster dose.

Meaghan Kall, a PhD candidate and an epidemiologist at the HSA, that this effect "is not seen with Delta."

For its analysis, the agency assessed 147,597 Delta cases and 68,489 Omicron cases from November 27 to December 17.

It found that for those with a Pfizer primary series and booster, efficacy against symptomatic disease was 70% immediately after the third dose but fell to 45% at 10 weeks or longer.

Those who had a Pfizer primary series but a Moderna booster saw protection against symptomatic disease hover around 70% to 75% for up to 9 weeks post-boost.

For those with a primary series of AstraZeneca, efficacy peaked at 60%, 2 to 4 weeks after either a Pfizer or Moderna booster, then fell to 35% with Pfizer and 45% with Moderna by around 10 weeks.

The report didn't include data on vaccine efficacy against severe disease, including hospitalization and death, because the number of Omicron cases admitted to the hospital following a positive test was too small to create an estimate, , of HSA.

Still, "based on experience with previous variants, we do expect [vaccine efficacy] against the more severe outcomes such as hospitalization to be substantially higher than [vaccine efficacy] against symptomatic infection," Kirsebom noted.

Data from Israel also has suggested waning efficacy after a booster dose, though that country's data pertain to the Delta variant. Last week, the expert panel advising the Israeli government recommended a fourth vaccine dose given at least 4 months after a third shot for certain groups: those ages 60 and up, immunocompromised people, and healthcare workers.

Data from the Israeli advisory committee showed a doubling in the rate of infection with Delta among people ages 60 and up within 4 or 5 months of the third shot, but it did not offer specific numbers. There was no clear indication of reduced efficacy against severe disease, according to the news report.

Peter Hotez, MD, PhD, of Baylor College of Medicine in Houston, has been advocating for a fourth shot of a COVID-19 vaccine for U.S. healthcare workers, who were among the first to receive their booster doses . They are about to face a substantial increase in exposure risk due to the Omicron wave, leading Hotez to write in a that "We must take quick action to prevent instability in our health system. If there are data to support its safety and impact, an emergency fourth shot might be offered to those healthcare workers now several months out from their booster shot. Doing so could reduce the risk of breakthrough symptomatic infection and keep these individuals on the job."

The HSA report did offer some good news -- additional confirmation of other early findings of reduced illness severity with Omicron. It found about a 60% reduced risk of hospital admission with Omicron compared with Delta (HR 0.38, 95% CI 0.30-0.50) based on 70 hospital admissions with Omicron and 3,884 with Delta.

A separate put infection severity in the lowest-risk "green" category based on these findings and three other analyses:

• An showed about a 45% reduced risk of hospitalization
• An showed about a 70% reduced risk of hospitalization
• An showed about an 80% reduced risk of hospitalization

Kall cautioned that the findings have low confidence because these are early analyses with small numbers of hospitalizations, limited follow-up time, minimal adjustment for previous infection, and limited spread into the most vulnerable age group.

Still, "very good news, and needed after many weeks of doomsday predictions. This will significantly cut the number of expected hospitalizations & deaths."

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