COVID-19 vaccine effectiveness against SARS-CoV-2 infection during the Delta period, a nationwide study adjusting for chance of exposure, the Netherlands, July to December 2021

Background: Differential SARS-CoV-2 exposure between vaccinated and unvaccinated individuals may confound vaccine effectiveness (VE) estimates. Aim: We conducted a test-negative case-control study to determine VE against SARS-CoV-2 infection and the presence of confounding by SARS-CoV-2 exposure. Methods: We included adults tested for SARS-CoV-2 at community facilities between 4 July and 8 December 2021 (circulation period of the Delta variant). The VE against SARS-CoV-2 infection after primary vaccination with an mRNA (Comirnaty or Spikevax) or vector-based vaccine (Vaxzevria or Janssen) was calculated using logistic regression adjusting for age, sex and calendar week (Model 1). We additionally adjusted for comor-bidity and education level (Model 2) and SARS-CoV-2 exposure (number of close contacts, visiting busy locations, household size, face mask wearing, contact with SARS-CoV-2 case; Model 3). We stratified by age, vaccine type and time since vaccination. Results: VE against infection (Model 3) was 64% (95% CI: 50-73), only slightly lower than in Models 1 (68%; 95% CI: 58-76) and 2 (67%; 95% CI: 56-75). Estimates strati-fied by age group, vaccine and time since vaccination remained similar: mRNA VE (Model 3) among people >= 50 years decreased significantly (p = 0.01) from 81% (95% CI: 66-91) at < 120 days to 61% (95% CI: 22-80) at >= 120 days after vaccination. It decreased from 83% to 59% in Model 1 and from 81% to 56% in Model 2. Conclusion: SARS-CoV-2 exposure did not majorly con-found the estimated COVID-19 VE against infection, suggesting that VE can be estimated accurately using routinely collected data without exposure information.