Change in COVID-19 risk over time following vaccination with CoronaVac: A test-negative case-control study
Authors: Hitchings Matt D.T. , Ranzani Otavio T. , Lind Margaret L. , Dorion Murilo , D’Agostini Tatiana Lang , de Paula Regiane Cardoso , de Paula Olivia Ferreira Pereira , de Moura Villela Edlaine Faria , Scaramuzzini Torres Mario Sergio , de Oliveira Silvano Barbosa , Schulz Wade , Almiron Maria , Said Rodrigo , de Oliveira Roberto Dias , da Silva Patricia Vieira , de Araújo Wildo Navegantes , Gorinchteyn Jean Carlo , Dean Natalie E. , Andrews Jason R. , Cummings Derek A.T. , Ko Albert I. , Croda Julio 
Published: December 2021

AbstractObjectiveTo estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech) in São Paulo state, Brazil.DesignTest negative case-control study.SettingCommunity testing for covid-19 in São Paulo state, Brazil.ParticipantsAdults aged 18-120 years who were residents of São Paulo state, without a previous laboratory-confirmed covid-19 infection, who received only two doses of CoronaVac, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 30 September 2021.Main outcome measuresRT-PCR-confirmed symptomatic covid-19 and associated hospital admissions and deaths. Cases were pair-matched to test-negative controls by age (in 5-year bands), municipality of residence, healthcare worker (HCW) status, and date of RT-PCR test (±3 days). Conditional logistic regression was adjusted for sex, number of covid-19-associated comorbidities, race, and previous acute respiratory infection.ResultsFrom 137,820 eligible individuals, 37,929 cases with symptomatic covid-19 and 25,756 test-negative controls with covid-19 symptoms were formed into 37,929 matched pairs. Adjusted odds ratios of symptomatic covid-19 increased with time since series completion, and this increase was greater in younger individuals, and among HCWs compared to non-HCWs. Adjusted odds ratios of covid-19 hospitalisation or death were significantly increased from 98 days since series completion, compared to individuals vaccinated 14-41 days previously: 1.40 (95% confidence interval 1.09 to 1.79) from 98-125 days, 1.55 (1.16 to 2.07) from 126-153 days, 1.56 (1.12 to 2.18) from 154-181 days, and 2.12 (1.39-3.22) from 182 days.ConclusionsIn the general population of São Paulo state, Brazil, an increase in odds of moderate and severe covid-19 outcomes was observed over time following primary series completion with CoronaVac.What is already known on this topic-The effectiveness of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech) against moderate and severe covid-19 has been demonstrated in clinical trials and observational studies.-Observational studies have suggested that effectiveness of other covid-19 vaccines appears to decrease over time, prompting many countries to deploy additional doses for individuals who have completed their primary series.-There is currently no evidence for change in the rate of breakthrough infection in individuals who have received a primary series of CoronaVac.What this study adds-In individuals receiving two doses of CoronaVac, the odds of symptomatic covid-19 increased over time since series completion.-Larger increases in covid-19 odds were observed in individuals aged 18-40, and in healthcare workers compared to non-healthcare workers.-Odds of covid-19 hospitalisation or death increased over time since series completion, but to a lesser extent.