Projeto S: A Stepped-Wedge Randomized Trial to Assess CoronaVac Effectiveness in Serrana, Brazil

Abstract

Background: A stepped-wedge trial is an approach for assessing vaccine effectiveness in the real world. By the end of the study, all participants could receive the intervention, eliminating the ethical dilemma of placebo, especially during a pandemic. Methods: We evaluated the effectiveness of CoronaVac in Serrana, Brazil, amid an uncontrolled community Covid-19 epidemic using a stepped-wedge randomized trial. The city was separated into 25 subareas, divided into four groups, and randomized to receive CoronaVac in a two-dose scheme with a four-week interval. Intervention was initiated in each group with a one-week interval. The primary endpoint was the incidence of symptomatic cases in fully immunized individuals. The secondary endpoints were Covid-19-related hospitalizations and deaths and incidence according to immunization coverage. Findings: The study occurred during epidemiological weeks 6 to 19 in 2021. Up to 27,406 participants received the first dose of the study vaccine, corresponding to 81·3% of the adults and 60·9% of the urban population. Among fully immunized individuals, the vaccine effectiveness was 80·5 (95% CI, 75·1 to 84·7) for preventing symptomatic Covid-19 cases, 95% (95% CI, 86·9 to 98·1) and 94·9% (95% CI, 76·4 to 98·9) for preventing Covid-19-related hospitalizations and deaths, respectively. There was a significant indirect protective effect in unvaccinated people when 52% of the adult population was fully vaccinated. The Gamma variant was dominant during the study. Interpretation: CoronaVac effectively prevented symptomatic Covid-19 cases and protected against severe disease and death during Gamma variant circulation. Unvaccinated individuals benefited from high vaccine coverage levels. Trial Registration: This study was registered with (ClinicalTrials.gov Identifier, NCT04747821) Funding: Fundacao Butantan and Sao Paulo Research Foundation (FAPESP). Declaration of Interest: MCB, BMC, GJV, NNF, PMMG, RH, BALF, and RTC received research funding from Butantan Institute during the conduct of this study. RP, MTRPC, APB, JPS, and ROP were employees of Butantan Institute during the conduct of this study. HAB, EGP, GGP, SCSV and DC are employees of Butantan Institute. All other authors declare no competing interests Ethical Approval: The study was reviewed and approved by the Ethics Committee of the Clinical Hospital, Ribeirao Preto Medical School, University of Sao Paulo (CAAE 42390621.1.0000.5440).