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Association of a Third Dose of BNT162b2 Vaccine With Incidence of SARS-CoV-2 Infection Among Health Care Workers in Israel

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To identify the key insights or developments described in this article
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Key Points

Question  What is the association between immunization with a third (booster) dose of BNT162b2 vaccine (Pfizer-BioNTech) and the incidence of SARS-CoV-2 infection among immunocompetent health care workers?

Findings  In this cohort study of 1928 health care workers in Israel who were previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was significantly associated with lower risk of SARS-CoV-2 infection during a median of 39 days of follow-up (adjusted hazard ratio, 0.07).

Meaning  Among health care workers previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was significantly associated with a lower rate of SARS-CoV-2 infection in short-term follow-up.

Abstract

Importance  Administration of a BNT162b2 booster dose (Pfizer-BioNTech) to fully vaccinated individuals aged 60 years and older was significantly associated with lower risk of SARS-CoV-2 infection and severe illness. Data are lacking on the effectiveness of booster doses for younger individuals and health care workers.

Objective  To estimate the association of a BNT162b2 booster dose with SARS-CoV-2 infections among health care workers who were previously vaccinated with a 2-dose series of BNT162b2.

Design, Setting, and Participants  This was a prospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. The study cohort included 1928 immunocompetent health care workers who were previously vaccinated with a 2-dose series of BNT162b2, and had enrolled between August 8 and 19, 2021, with final follow-up reported through September 20, 2021. Screening for SARS-CoV-2 infection was performed every 14 days. Anti–spike protein receptor binding domain IgG titers were determined at baseline and 1 month after enrollment. Cox regression with time-dependent analysis was used to estimate hazard ratios of SARS-CoV-2 infection between booster-immunized status and 2-dose vaccinated (booster-nonimmunized) status.

Exposures  Vaccination with a booster dose of BNT162b2 vaccine.

Main Outcomes and Measures  The primary outcome was SARS-CoV-2 infection, as confirmed by reverse transcriptase–polymerase chain reaction.

Results  Among 1928 participants, the median age was 44 years (IQR, 36-52 years) and 1381 were women (71.6%). Participants completed the 2-dose vaccination series a median of 210 days (IQR, 205-213 days) before study enrollment. A total of 1650 participants (85.6%) received the booster dose. During a median follow-up of 39 days (IQR, 35-41 days), SARS-CoV-2 infection occurred in 44 participants (incidence rate, 60.2 per 100 000 person-days); 31 (70.5%) were symptomatic. Five SARS-CoV-2 infections occurred in booster-immunized participants and 39 in booster-nonimmunized participants (incidence rate, 12.8 vs 116 per 100 000 person-days, respectively). In a time-dependent Cox regression analysis, the adjusted hazard ratio of SARS-CoV-2 infection for booster-immunized vs booster-nonimmunized participants was 0.07 (95% CI, 0.02-0.20).

Conclusions and Relevance  Among health care workers at a single center in Israel who were previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was associated with a significantly lower rate of SARS-CoV-2 infection over a median of 39 days of follow-up. Ongoing surveillance is required to assess durability of the findings.

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Article Information

Corresponding Author: Oryan Henig, MD, Department of Infectious Diseases and Infection Control, Tel Aviv Sourasky Medical Center, Weizmann 6, Tel Aviv, Israel 6423906 (oryanh@tlvmc.gov.il).

Accepted for Publication: December 12, 2021.

Published Online: January 10, 2022. doi:10.1001/jama.2021.23641

Author Contributions: Drs Spitzer and Angel had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Spitzer and Angel contributed equally to the work.

Concept and design: A. Spitzer, Angel, Marudi, Zeltser, Saiag, Goldshmidt, Stark, Gamzu, Feigin, Mizrahi, Yakubovsky, Elkayam, Eviatar, Itzhaki-Alfia, Sprecher, Ben-Ami, Henig.

Acquisition, analysis, or interpretation of data: A. Spitzer, Angel, Marudi, Goldshmidt, Goldiner, Halutz, Slobodkin, Amrami, Elbaz, Furman, Bronstein, Chikly, Eshkol, Furer, Mayer, Meijer, Melloul, Yakubovsky, Rosenberg, Safir, L. Spitzer, Taleb, Elkayam, Silberman, Elalouf, Levinson, Pozyuchenko, Sprecher, Ben-Ami, Henig.

Drafting of the manuscript: A. Spitzer, Angel, Marudi, Saiag, Goldshmidt, Halutz, Slobodkin, Feigin, Elbaz, Furman, Bronstein, Chikly, Mayer, Yakubovsky, Safir, Levinson, Pozyuchenko, Ben -mi, Henig.

Critical revision of the manuscript for important intellectual content: A. Spitzer, Angel, Zeltser, Goldshmidt, Goldiner, Stark, Gamzu, Amrami, Eshkol, Furer, Meijer, Melloul, Mizrahi, Yakubovsky, Rosenberg, L. Spitzer, Taleb, Elkayam, Silberman, Eviatar, Elalouf, Levinson, Itzhaki-Alfia, Sprecher, Ben-Ami.

Statistical analysis: A. Spitzer, Angel, Eshkol, Yakubovsky.

Obtained funding: Goldshmidt, Halutz, Yakubovsky.

Administrative, technical, or material support: Angel, Marudi, Zeltser, Saiag, Goldshmidt, Goldiner, Stark, Halutz, Slobodkin, Amrami, Feigin, Bronstein, Eshkol, Mayer, Meijer, Melloul, Yakubovsky, Safir, L. Spitzer, Taleb, Elkayam, Silberman, Elalouf, Levinson, Pozyuchenko, Itzhaki-Alfia, Sprecher.

Supervision: Zeltser, Goldshmidt, Gamzu, Slobodkin, Mizrahi, Yakubovsky, Elkayam, Levinson, Sprecher, Henig.

Conflict of Interest Disclosures: Dr Angel reported receiving grants from Pfizer outside the submitted work. Dr Goldshmidt reported receiving reagents for the serology tests from Siemens during the conduct of the study. Dr Ben-Ami reported receiving personal fees from Pfizer, Gilead, Teva, and Merck outside the submitted work. No other disclosures were reported.

Funding/Support: The study was funded by the Tel Aviv Sourasky Medical Center. Anti–S1-RBD serology laboratory assays were funded and provided by Siemens. Dr A. Spitzer is partially supported by the Israeli Council for Higher Education via the Weizmann Data Science Research Center, and by a research grant from the estate of Tully and Michele Plesser.

Role of the Funder/Sponsor: Siemens did not have a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the hospital’s employees and students for their participation in the study. We also thank Shabi Shamlo, MA, Lital Zand, MA, Lihi Turgeman, MBA, Avi Ben-Zaken, BSc, ME, Ettie Oziel, BA, Eti Amzel, Tzvi Gregory Avishai, BPharm, MHA, Tanya Grossman, BSc, and Alona Green, MBA, Tel Aviv Sourasky Medical Center, for their administrative assistance and support throughout the study. None of these contributors received compensation for their role in the study.

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