Lower risk of SARS-CoV-2 after booster dose

Receipt of a booster dose of the BNT162b2 mRNA vaccine is tied to a reduced risk of testing positive for SARS-CoV-2, according to results of a study from Israel.

“[W]e found that a third dose of the mRNA vaccine BNT162b2 provided additional protection against detected SARS-CoV-2 infection,” said the authors.

“Across the test-negative and matched case-control analyses, we estimated an 83 to 87 percent reduction in the odds of testing positive for SARS-CoV-2 after at least 2 weeks following receipt of the booster compared with receiving two doses … This reduction comes on top of the reduction in the risk conferred by the first two doses.”

Participants in this retrospective, case-control study were 306,710 individuals aged ≥40 years enrolled in the database of Maccabi Healthcare Services, an Israeli healthcare maintenance organization. The researchers used data collected between March 1, 2020 and October 4, 2021, with the analyses focused on the period following August 1, 2021 (study period) when the BNT162b2 mRNA vaccine booster programme was initiated in a national campaign. All participants had received either two* (mean age 53 years, 57.3 percent female) or three doses (mean age 59 years, 53.4 percent female) of the BNT162b2 vaccine and did not have PCR-confirmed SARS-CoV-2 before follow-up began.

Of the 500,232 PCR tests carried out during the study period, 227,380 and 272,852 were done in individuals who had received two and three doses of BNT162b2, respectively.

Among those who had received two vaccine doses, 6.6 percent (n=14,989) had positive PCR results, compared with 1.8 percent (n=4,941) who received three doses.

The percentage of patients with a positive test following receipt of the booster dose was greatest at 0–6 days post-booster dose (6.0 percent), and reduced over time (3.0, 1.1, 1.0, and 0.7 percent at 7–13, 14–20, 21–27, and 28–65 days after the booster dose).

At 28–65 days following receipt of the third dose, the odds of testing positive for SARS-CoV-2 was reduced by 86 percent among those who received the third dose compared with those who received two doses (odds ratio [OR], 0.14, 95 percent confidence interval [CI], 0.13–0.15). [JAMA Intern Med 2021;doi:10.1001/jamainternmed.2021.7382]

The odds of testing positive for SARS-CoV-2 reduced with time since receipt of the booster dose, beginning with a 12 percent reduction at days 0–6 following the booster dose (OR, 0.88, 95 percent CI, 0.83–0.92), to a 58 percent reduced risk at days 7–13 (OR, 0.42, 95 percent CI, 0.39–0.44), to an 85 percent reduced risk at days 14–20 and 21–27 (OR, 0.15, 95 percent CI, 0.14–0.17 for both timepoints).

“Because it takes time for the booster to induce an immune response, a measure of effectiveness was not expected in the first week after receipt of the booster,” the authors said.

Additional analysis showed that the risk of hospitalization was reduced by 92–97 percent 14 days following receipt of the booster dose compared with those who had only received two doses. The measure of effectiveness of the booster dose was 87 percent at 0–6 days post-vaccination.

“However, these results should be interpreted with caution because a reduction in the odds of hospitalization was already evident in the first week after receipt of the booster when an effect would not be expected,” the authors pointed out.

What does this tell us?

“[W]e showed an association between receipt of the booster dose and a reduction in the odds of testing positive for SARS-CoV-2, potentially counteracting waning immunity in the short term,” the authors said.

However, they acknowledged the limitations posed by the short-term follow-up. Additionally, the booster doses were administered when the delta variant was the predominant circulating SARS-CoV-2 strain in Israel, limiting the generalizability of the findings to other strains.

“The total benefit of the vaccine programme will depend on the long-term effectiveness of the first two doses of the vaccine against infection and severe disease,” they said. The booster dose may be able to restore some of the benefits which will reduce with declining effectiveness of the first two doses, though waning effectiveness of the booster dose requires assessing, they concluded.