Fourth Dose of Pfizer Vaccine vs Omicron — Real-world data show less infection and severity, but long-term benefit less clear

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 in the New England Journal of Medicine.

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." ...