Pfizer-BioNTech COVID-19 Vaccine Effectiveness Study - Kaiser Permanente Southern California

Inclusion Criteria for Test Negative Design

• KPSC patients eligible to receive BNT162b2 who are admitted to the hospital (primaryobjective and some secondary objectives) with acute respiratory infection (ARI;International Classification of Diseases (ICD) codes) after 14 December 2020 (dateof first vaccinations at KPSC), and who receive a PCR test for SARS-CoV-2.

• For secondary objectives estimating VE against ED admission, the TND will includeKPSC patients eligible to receive BNT162b2 who present to the ED with ARI after 14December 2020, and who receive a PCR test for SARS-CoV-2.

• We will include membership requirement of 1 year prior to index date, which isdefined as the date of hospitalization or ED admission (allowing 31-dayadministrative gap), to facilitate accurate capture of comorbid conditions.

Inclusion Criteria for Cohort Design-

• All KPSC members as of 14 December 2020 (date of first Pfizer vaccination at KPSC)eligible to receive BNT162b2.

• For the cohort study, patients must have at least 1 year of membership (allowing 31-day administrative gap) prior to 14 December 2020 (index date, date vaccinationsfirst began at KPSC) to facilitate accurate capture of comorbid conditions.

Exclusion Criteria Test Negative Design Patients who receive only another newly licensed or investigational SARS-CoV-2 vaccine or COVID-19 prophylactic agent other than Pfizer's COVID-19 vaccine prior to hospitalization (or ED, for secondary objective) will be excluded from the study population When estimating VE for BNT162b2 vaccination, patients receiving another newly licensed or investigational SARS-CoV-2 vaccine or COVID-19 prophylactic agent other than Pfizer's COVID-19 vaccine prior to hospitalization or ED will be excluded from the analysis. Patients will also be excluded if the index date is within certain time windows from vaccination date, outlined further in the exposure section below.

Exclusion Criteria for Cohort Design There will be no exclusion criteria for the cohort design, however patients will be censored for receiving any other newly licensed or investigational SARS-CoV-2 vaccine or COVID-19 prophylactic agent other than Pfizer's COVID-19 vaccine

XBB.1.5-adapted monovalent vaccine eligibility analyses:

Inclusion Criteria:

• KPSC membership for a minimum of 1 year prior to index date, allowing a 30-day gapin membership to allow for delays in renewal. Participants <1 year did not have amembership requirement.≥6 months of age as of index date

• Admitted to the hospital or had an encounter in the ED, UC, or OP setting with adiagnosis of acute respiratory infection (ARI; defined based on InternationalClassification of Diseases (ICD) codes listed in Appendix Table 1) after 25September 2023

• Received a SARS-CoV-2 PCR or rapid antigen test

Exclusion criteria:

• Individuals who received a non-Pfizer-BioNTech XBB.1.5-adapted monovalent vaccine

• Individuals with an index event <14 days after vaccination with Pfizer-BioNTechXBB.1.5-adapted monovalent vaccine

• Individuals receiving a mRNA bivalent BA4.5 booster ≤ 8 weeks (≤ 56 days) sincereceiving last wild type dose

• Individuals with <28 days between a second and subsequent wild type dose

• Individuals receiving a XBB.1.5-adapted monovalent vaccine ≤ 8 weeks (≤ 56 days)since receiving a mRNA bivalent BA4.5 booster

• Individuals receiving oral COVID-19 antiviral OP treatments within 30 days of indexevent (will be excluded for primary analysis, but included in sensitivity analyses)