By Molly Walker

Rates of confirmed Omicron-related COVID infection and severe disease were lower after a fourth dose of the Pfizer-BioNTech vaccine, according to real-world data from Israel, although protection against confirmed infection seemed short-lived.

Among adults ages 60 and up, the adjusted rate of confirmed infection 4 weeks after the fourth dose was twice as low compared to those who received three doses (171 vs 340 cases per 100,000 person-days), reported Yair Goldberg, PhD, of Technion-Israel Institute of Technology in Haifa, and colleagues.

Moreover, the adjusted rate of severe illness after 4 weeks was three times lower in the four-dose group (1.6 vs 5.5 per 100,000 person-days), they wrote.

Adjusted rates of both infection and severe disease were both higher in a third "internal control" group, who received a fourth vaccine dose only 3 to 7 days earlier (308 and 3.6 cases per 100,000 person-days, respectively), they noted.

However, Goldberg and colleagues added that from week 5 onward, the rate ratio for confirmed infection began to decline, with the adjusted rate of infection 8 weeks after the fourth dose being "very similar to those in the control groups."

The authors concluded that a fourth dose provided "only short-term protection and a modest absolute benefit," for confirmed infection, but that it did increase protection against severe disease. They highlighted that "protection against severe illness did not appear to decrease by the sixth week after receipt of the fourth dose," but acknowledged that "More follow-up is needed in order to evaluate the protection of the fourth dose against severe illness over longer periods."

In January, Israeli authorities approved a fourth dose of Pfizer vaccine for adults ages 60 and up, high-risk populations, and healthcare workers, 4 months after a third dose, they noted. FDA recently authorized a second booster dose of Pfizer or Moderna vaccine for adults, ages 50 and up, and those with immunocompromising conditions, in part using real-world Israeli data as the basis for their decision.

Goldberg's group examined data on adults ages 60 and older who received three doses of Pfizer at least 4 months prior to the end of the study. The study period was defined as January 10 to March 2 for confirmed infection, and until February 18 for severe disease. The four-dose group completed their fourth dose at least 8 days prior to infection or severe COVID, they said.

Overall, 1,252,331 adults were included in the study, with 623,355 receiving four doses of vaccine and 628,976 not receiving four doses of vaccine. The aggregated four-dose group and internal control group had more person-days over age 80 (about 25% apiece vs 16.2%).

At 4 weeks, the adjusted rate of confirmed infection in the four-dose group was lower by a factor of 2.0 (95% CI 1.9-2.1) versus the three-dose group and lower by a factor of 1.8 (95% CI 1.7-1.9) versus the internal control group.

For severe disease at 4 weeks, the adjusted rate differences were 3.9 fewer cases per 100,000 person-days (95% CI 3.4-4.5) versus the three-dose group and 2.1 fewer cases per 100,000 person-days (95% CI 1.4-3.0) versus the internal control group.

Limitations to the data include unmeasured confounders, such as behavioral differences between adults who chose to receive the fourth dose and those who did not. Pre-existing conditions could have affected risk for severe disease, and the authors added they did not adjust for those as this information is not available in the national database. Different COVID treatment may have also affected the results, they noted.