There will be a large retrospective database study using two parallel study designs: a test-negative case-control design and a retrospective cohort design. Exploratory analyses of VE estimates by strain type will be conducted.

Outcomes in addition to hospitalization to be assessed include COVID-19-associated ED admissions, ICU admissions, outpatient visits, and death.

To assess VE, we propose a large retrospective database study using two parallel study designs: a test-negative case-control design and a retrospective cohort design. The test-negative design (TND) will assess VE against COVID-19 hospitalization (primary endpoint) and emergency department (ED) admission.

The retrospective cohort analysis will assess VE against COVID-19 hospitalization (primary), ICU admission, death, ED admission, and outpatient disease (with no subsequent hospitalization within 14 days). We will further conduct exploratory analyses of VE estimates by strain type.

Results

Findings Between Dec 14, 2020, and Aug 8, 2021, of 4,920,549 individuals assessed for eligibility, we included 3,436,957 (median age 45 years [IQR 29–61]; 1 799395 [52·4%] female and 1 637394 [47·6%] male). For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95% CI 72–74) and against COVID-19-related hospital admissions was 90% (89–92). Effectiveness against infections declined from 88% (95% CI 86–89) during the first month after full vaccination to 47% (43–51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85–97]) but declined to 53% [39–65] after 4 months. Effectiveness against other (non-delta) variants the first month after full vaccination was also high at 97% (95% CI 95–99), but waned to 67% (45–80) at 4–5 months. Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84–96]) up to 6 months.

Interpretation

Our results provide support for the high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably due to waning immunity with time rather than the delta variant escaping vaccine protection