Odds of Testing Positive for SARS-CoV-2 After 3 vs 2 mRNA Vaccine Doses

 Tal Patalon, MD^1,2; Sivan Gazit, MD, MA^1,2; Virginia E. Pitzer, ScD^3,4; et al

doi:10.1001/jamainternmed.2021.7382

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Key Points

Question  What is the additional reduction in the odds of infection with SARS-CoV-2 in people receiving a third dose (booster) of the BNT162b2 (Pfizer-BioNTech) vaccine compared with those receiving 2 doses?

Findings  In this case-control study that included 306 710 Israeli adults 40 years and older, there was an estimated significant reduction in the odds of SARS-CoV-2 infection within a few weeks of receiving the booster compared with receiving just the 2 primary doses. Those receiving the booster also had lower odds of hospitalization.

Meaning  The findings of this study suggest that the waning of vaccine-induced protection against SARS-CoV-2 infection seems to be counteracted in the short-term by a third dose and further monitoring is needed to determine the duration of immunity following the booster.

Abstract

Importance  With the evidence of waning immunity of the mRNA vaccine BNT162b2 (Pfizer-BioNTech), a nationwide third-dose (booster) vaccination campaign was initiated in Israel during August 2021; other countries have begun to administer a booster shot as well.

Objective  To evaluate the initial short-term additional benefit of a 3-dose vs a 2-dose regimen against infection of SARS-CoV-2.

Design, Setting, and Participants  This preliminary retrospective case-control study used 2 complementary approaches: a test-negative design and a matched case-control design. Participants were included from the national centralized database of Maccabi Healthcare Services, an Israeli healthcare maintenance organization covering 2.5 million members. Data were collected between March 1, 2020, and October 4, 2021, and analyses focused on the period from August 1, 2021, to October 4, 2021, because the booster dose was widely administered from August 1 onward.

Exposures  Either 2 doses or 3 doses of the BNT162b2 vaccine.

Main Outcomes and Measures  The reduction in the odds of a positive SARS-CoV-2 polymerase chain reaction (PCR) test at different time intervals following receipt of the booster dose (0-6, 7-13, 14-20, 21-27, and 28-65 days) compared with receiving only 2 doses.

Results  The study population included 306 710 members of Maccabi Healthcare Services who were 40 years and older (55% female) and received either 2 or 3 doses of the BNT162b2 vaccine and did not have a positive PCR test result for SARS-CoV-2 prior to the start of the follow-up period. During this period, there were 500 232 PCR tests performed, 227 380 among those who received 2 doses and 272 852 among those who received 3 doses, with 14 989 (6.6%) and 4941 (1.8%) positive test results in each group, respectively. Comparing those who received a booster and those who received 2 doses, there was an estimated odds ratio of 0.14 (95% CI, 0.13-0.15) 28 to 65 days following receipt of the booster (86% reduction in the odds of testing positive for SARS-CoV-2).

Conclusion and Relevance  Previous studies have demonstrated that vaccine-derived protection against SARS-CoV-2 wanes over time. In this case-control analysis, we 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. Further monitoring of data from this population is needed to determine the duration of immunity following the booster.

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2786890