BNT162b2 Effectiveness and Durability Against BA.1 and BA.2 Hospital and Emergency Department Admissions in a Large US Health System: A Test-Negative Design

Abstract

Background: The SARS-CoV-2 omicron (B.1.1.529 BA.1) lineage was first detected in late November 2021 and has been associated with lower vaccine effectiveness compared to previous variants of concern. By March of 2022, BA.1 was replaced by sub-lineage BA.2 in the United States. As new SARS-CoV-2 variants evolve, it is critical to continually assess vaccine performance. We compared vaccine effectiveness (VE) and durability of BNT162b2 against hospital and emergency department (ED) admission for BA.1 and BA.2.

Methods: Using a test-negative design, we analyzed electronic health records from members ≥18 years of age at Kaiser Permanente Southern California from Dec 27, 2021 through June 4, 2022. Variant-specific VE was calculated among those admitted to the hospital and ED (without subsequent hospitalization) with acute respiratory infection (ARI) and tested for SARS-CoV-2 via polymerase chain reaction using odds ratios from adjusted logistic regression models.

Findings: Analyses were conducted for 16,994 encounters, including 7435 BA.1 and 1056 BA.2 hospital and ED admissions, respectively. In adjusted analyses, after only two doses the overall effectiveness against hospitalization and ED admission for BA.1 were 40% (95%CI: 27–50) and 29% (18–38), respectively, and were 56% (31–72) and 16% (-5–33) against BA.2. After three doses, effectiveness against BA.1 hospitalization was 80% (74–84), and 74% (69–78) for ED admission <3 months after the third dose and was 76% (69–82) and 65% (56–73) against these same two endpoints, respectively, at ≥3 months. Against BA.2, effectiveness was 74% (47–87) for hospitalization and 59% (40–72) for ED admission at <3 months after the third dose and 70% (53–81) and 5 (-21–25) against these same two endpoints, respectively, at ≥3 months.

Interpretation: Two doses of BNT162b2 provided only limited protection against BA.1- and BA.2-related hospital and ED admission, which underscores the need for booster doses against omicron. While three doses of current vaccines continue to offer high levels of protection (>70%) against BA.1- and BA.2-related hospitalization, variant adapted vaccines are likely needed to improve protection against less severe endpoints like ED admission, especially for BA.2.

Trial Registration: This study was registered with ClinicalTrials.gov, NCT04848584.

Funding Pfizer Inc.

Declaration of Interest: SRV, LJ, LP, and JMM are employees of and hold stock and/or stock options in Pfizer Inc. SYT, JMS, VH, FX, and BA received research support from Pfizer during the conduct of this study that was paid directly to KPSC. BA received research support for work unrelated to this study provided by Pfizer, Moderna, Dynavax, Seqirus, GlaxoSmithKline and Genentech. JMS received research support from ALK, Inc., Dynavax, and Novavax for work unrelated to this study. SYT received research support from Genentech for work unrelated to this study.

Ethical Approval: The study was approved by the KPSC Institutional Review Board, which granted a waiver of informed consent.

Keywords: BA.2, BA.1, omicron, effectiveness, BNT162b2, SARS-CoV-2, COVID-19, United States, test-negative, Kaiser Permanente, real-world