Six-Month Effectiveness of BNT162B2 mRNA COVID-19 Vaccine in a Large US Integrated Health System: A Retrospective Cohort Study

Background: Vaccine effectiveness (VE) studies have not differentiated the impact of Delta from potential waning immunity on recent observed reductions in effectiveness against SARS-CoV-2 infections. We evaluated overall and variant-specific effectiveness of BNT162b2 against SARS-CoV-2 infections and COVID-19-related hospitalizations by time since vaccination among members of a large US healthcare system. Methods: In this retrospective cohort study, we analyzed electronic health records from Kaiser Permanente Southern California (KPSC) between Dec 14, 2020 – Aug 8, 2021 to assess BNT162b2 VE against SARS-CoV-2 infections and COVID-19-related hospitalization. Effectiveness calculations were based on hazards ratios from adjusted Cox models. Findings: For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95%CI: 72‒74) and against COVID-19-related hospitalizations was 90% (89‒92). Effectiveness against infections declined from 88% (86‒89) during the first month after full vaccination to 47% (43‒51) after ≥5 months. Among sequenced infections, VE against Delta was lower compared to VE against other variants (75% [71‒78] vs 91% [88‒92]). VE against Delta infections was high during the first month after full vaccination (93% [85‒97]) but declined to 53% [39‒65] at ≥4 months. VE against hospitalization for Delta for all ages was high overall (93%). Interpretation: Our results confirm high effectiveness of BNT162b2 against hospitalizations through roughly six months after being fully vaccinated, even in the face of widespread dissemination of Delta. Reductions in effectiveness against SARS-CoV-2 infections over time are likely primarily due to waning rather than Delta escaping vaccine protection. Trial Registration: NCT04848584 Funding: Pfizer Inc. Declaration of Interest: JMZ, SG, KP, FJA, LJ, and JMM are employees of and hold stock and/or stock options in Pfizer Inc. TBF holds stock in Pfizer Inc. SYT received research support from Pfizer during the conduct of this study. All other authors report no conflicts. Ethical Approval: The study protocol was reviewed and approved by the KPSC institutional review board, which waived requirement for informed consent (IRB#12816).