4th shot of COVID vax: To jab or not?

Having a fourth dose of COVID-19 vaccine (ie, second booster dose) substantially protects against severe illness in face of the Omicron variant, compared with only three doses of vaccine that were given more than 4 months earlier, according to data from the Israeli Ministry of Health database.

Protection against severe illness was sustained throughout the study period of up to 6 weeks, the researchers highlighted, even though protection against infection appeared to wane at 4 weeks after the fourth vaccine dose.

“More follow-up is needed in order to evaluate the protection of the fourth dose against severe illness over longer periods,” said the researchers.

The analysis was based on data of 1,252,331 individuals aged ≥60 years in Israel who were eligible for the fourth dose of COVID-19 vaccine at a time when the Omicron variant was the predominant circulating strain. [N Engl J Med 2022;386:1712-1720]

Overall, the unadjusted rate of severe COVID-19 cases (adjudicated 8 days after the fourth dose) was 1.5 per 100,000 person-days in the four-dose group compared with 3.9 per 100,000 person-days in the three-dose group. The researchers also compared the results with an internal control group — comprising people who received a fourth dose 3 to 7 days earlier — for whom the rate was 4.2 per 100,000 person-days.

Using the quasi-Poisson analysis, the adjusted rate of severe COVID-19 cases was lower in the four-dose group, at 4 weeks after the fourth dose, by a factor of 3.5 (95 percent confidence interval [CI], 2.7–4.6) when compared with the three-dose group and by a factor of 2.3 (95 percent CI, 1.7–3.3) when compared with the internal control group.

For the number of confirmed infections, the unadjusted rate was similarly lower in the four-dose group than the three-dose group and the internal control group (177 vs 361 and 388 per 100,000 person-days, respectively).

This corresponded with an adjusted rate of confirmed infection that was lower in the four-dose group, at 4 weeks after the fourth dose, by a factor of 2.0 (95 percent CI, 1.9–2.1) when compared with the three-dose group and by a factor of 1.8 (95 percent CI, 1.7–1.9) when compared with the internal control group, based on the quasi-Poisson analysis.

“[The results indicate that] a fourth dose provides added short-term protection against confirmed infections and severe illness caused by the Omicron variant,” said the researchers.

“Comparing the rate ratio over time since the fourth dose suggests that the protection against confirmed infection with the Omicron variant reaches a maximum in the fourth week after vaccination, after which the rate ratio decreases to approximately 1.1 by the eighth week,” the researchers reported. “These findings suggest that protection against confirmed infection wanes quickly.”

“[In contrast,] protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose,” they pointed out.

As information on coexisting conditions were not captured in the database, the researchers acknowledged that the analysis did not adjust for this risk factor, which might have influenced the results for severe illness. Other residual confounder included potential behavioural differences between people who had received the fourth shot and those who did not.