Association of Receipt of the Fourth BNT162b2 Dose With Omicron Infection and COVID-19 Hospitalizations Among Residents of Long-term Care Facilities

Abstract

Importance: The administration of a fourth BNT162b2 COVID-19 vaccine dose was approved in Israel in December 2021 for individuals 60 years or older who were vaccinated with a third dose 4 months previously or earlier to control the substantial surge of the SARS-CoV-2 Omicron variant. Nonetheless, the association between receipt of the fourth dose and protection against infection remains elusive.

Objective: To determine the association of the fourth BNT162b2 dose with protection against SARS-CoV-2-related infections, hospitalizations, and deaths during the Omicron surge in long-term care facility (LTCF) residents.

Design, setting, and participants: This prospective cohort study was conducted in Israel between January 10 and March 31, 2022 and included LTCF residents 60 years or older.

Exposures: Vaccination with the fourth dose of BNT162b2 vs 3 doses that were administered 4 months previously or earlier.

Main outcomes and measures: Cumulative incidences of SARS-CoV-2 infections, hospitalizations, and deaths during the Omicron surge. The follow-up was initiated more than 7 days after receipt of the fourth dose, which was matched to the follow-up initiation date of those who had received 3 doses of vaccine in each facility. We obtained hazard ratios and 95% confidence intervals from multivariable Cox regression models.

Results: The data of 43 775 residents (mean [SD] age, 80.1 [9.4] years; 29 679 women [67.8%]) were analyzed, of whom 24 088 (55.0%) and 19 687 (45.0%) received the fourth and third dose (4 months previously or earlier), respectively. The median follow-up time was 73 days (4-dose group: IQR, 6 days; 3-dose group: IQR, 56 days). More than 7 days postvaccination with the fourth dose, SARS-CoV-2 infection was detected among 4058 fourth-dose vs 4370 third-dose recipients (cumulative incidence, 17.6% vs 24.9%). The corresponding incidences of hospitalizations for mild-to-moderate COVID-19, severe illness, and mortality were 0.9% and 2.8%, 0.5% and 1.5%, and 0.2% and 0.5%, respectively. The adjusted protections were 34% (95% CI, 30%-37%), 64% (95% CI, 56%-71%), and 67% (95% CI, 57%-75%) against overall infection, hospitalizations for mild-to-moderate illness, and severe illness, respectively, and 72% (95% CI, 57%-83%) against related deaths.

Conclusions and relevance: The results of this cohort study suggest that receipt of a fourth BNT162b2 dose conferred high protection against COVID-19 hospitalizations and deaths among LTCF residents during a substantial Omicron variant surge, but protection was modest against infection. These findings are relevant to the control of COVID-19 pandemic globally, especially among the population of LTCFs.

Figure 1.. Flowchart of Selection of Study Groups

During step 1, we excluded from the analysis very small facilities that had fewer than 10 residents per facility, resulting in the exclusion of 975 residents from 292 very small facilities. The mean number of residents per facility before the exclusion of these facilities was 96 (median, 37 residents) and after the exclusion of these facilities was 132 (median, 80 residents).

Figure 2.. Cumulative Incidence of the Study End Points by Study Group

Shaded lines represent 95% CIs. The follow-up began more than 7 days after vaccination with the fourth dose and a matching facility-specific starting follow-up date for the recipients of the 3 doses. P values were obtained by the log-rank test.

Figure 3.. Adjusted Association of BNT162b2 Fourth Dose Vaccination With Protection Against Omicron

Adjusted association (filled circles) and 95% CIs (error bars) of the administration of a fourth dose of BNT162b2 vaccine with protection against overall SARS-CoV-2 infection, COVID-19 hospitalizations, and related deaths at 7 days (A) and 14 days (B) after vaccination compared with vaccination with 3 doses four months previously or earlier.