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. 2022 Jan 25;327(4):341-349.
doi: 10.1001/jama.2021.23641.

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

Avishay Spitzer  1   2   3 , Yoel Angel  2   4   5 , Or Marudi  2 , David Zeltser  2   6 , Esther Saiag  2   7 , Hanoch Goldshmidt  2   8 , Ilana Goldiner  2   8 , Moshe Stark  2   8 , Ora Halutz  2   8 , Ronni Gamzu  2   9 , Marina Slobodkin  2   10 , Nadav Amrami  2   10 , Eugene Feigin  2   10 , Meital Elbaz  2   11 , Moran Furman  2   12 , Yotam Bronstein  2   10 , Amanda Chikly  2   11 , Anna Eshkol  2   12 , Victoria Furer  2   13 , Talia Mayer  2   12 , Suzy Meijer  2   11 , Ariel Melloul  2   10 , Michal Mizrahi  2   10 , Michal Yakubovsky  2   11 , Dana Rosenberg  2   13 , Ari Safir  2   12 , Liron Spitzer  2   12 , Eyal Taleb  2   12 , Ori Elkayam  2   13 , Adi Silberman  2   13 , Tali Eviatar  2   13 , Ofir Elalouf  2   13 , Tal Levinson  2   11 , Katia Pozyuchenko  14 , Ayelet Itzhaki-Alfia  2   14 , Eli Sprecher  2   12   15 , Ronen Ben-Ami  2   11 , Oryan Henig  2   11
Affiliations

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

Avishay Spitzer et al. JAMA. .

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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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Study Population of Vaccinated Health Care Workers
BNT162b2 vaccine is manufactured by Pfizer-BioNTech.
Figure 2.
Figure 2.. Study Participants by Receipt of Booster Vaccination and Incidence of SARS-CoV-2 Infection
A, Cumulative incidence of SARS-CoV-2 infection among booster-immunized and nonimmunized participants throughout the study period. B, Number of booster-immunized and booster-nonimmunized participants at each point throughout the study period. Participants were considered booster immunized 7 days or more after receipt of the booster dose. SARS-CoV-2–confirmed cases were censored on the day of positive result.
Figure 3.
Figure 3.. Distribution of Serology Values Obtained Within 5 Days of Booster
Follow-up anti–spike protein receptor-binding domain (anti–S1-RBD) IgG titers for participants who were tested 0 to 4 days after receipt of the booster dose (n = 29). Among participants who received the booster dose and were tested 5 days or more after its receipt (n = 966), 98.6% (952/966) had reached the maximal anti–S1-RBD IgG level measurable by the assay used (100 index values).
Figure 4.
Figure 4.. Breakthrough Infections in Vaccinated Participants Who Did Not Receive a Booster
Cumulative fraction of the number of booster nonrecipients (n = 278) and SARS-CoV-2-positive individuals (via polymerase chain reaction [PCR] testing) within this group (n = 34) across the range of baseline anti–spike protein receptor-binding domain (anti–S1-RBD) IgG levels. This group of participants was further divided into 3 groups based on the 3 distinct incline segments of the PCR-positive curve (marked by the vertical lines). Incidence rates per 100 000 person-days in the first (≤7 index values), second (7-14 index values), and third (>14 index values) segments are shown.
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Comment in

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