Change in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study

• Type of Material: Article
• Authors: Matt DT Hitchings, University of Florida; Otavio Ranzani, Barcelona Institute for Global Health; Margaret L Lind, Yale School of Public Health; Murilo Dorion, Yale School of Public Health; Tatiana Lang D'Agostini, São Paulo State Department of Health; Regiane Cardoso de Paula, São Paulo State Department of Health; Olivia Ferreira Pereira de Paula, São Paulo State Department of Health; Edlaine Faira de Moura Villela, São Paulo State Department of Health; Mario Sergio Scaramuzzini Torres, Municipal Health Secretary of Manaus; Silvano Barbosa de Oliveira, Pan American Health Organization; Wade Schulz, Yale University; Maria Almiron, Pan American Health Organization; Rodrigo Said, Pan American Health Organization; Roberto Dias de Oliveira, State University of Mato Grosso do Sul; Patricia Vieira da Silva, Universidade Federal de Mato Grosso do Sul - UFMS; Wildo Navegantes de Araújo, Pan American Health Organization, Brasília; Jean C Gorinchteyn, Health Secretariat of the State of São Paulo; Natalie Dean, Emory University; Jason R Andrews, Stanford University; Derek AT Cummings, University of Florida; Albert I Ko, Yale School of Public Health; Julio Croda, Yale School of Public Health
• Language: English
• Date: 2022-06-14
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/bmj-2022-070102
• Title of Journal or Parent Work: BMJ-BRITISH MEDICAL JOURNAL
• Volume: 377
• Start Page: e070102
• End Page: e070102
• Grant/Funding Information: This work was supported by grant R01-AI139761 from the National Institute for Allergy and Infectious Diseases to NED and the Sendas Family and Beatrice Kleinberg Neuwirth Funds to AIK. JC is supported by the Oswaldo Cruz Foundation (Edital Covid-19 – resposta rápida: 48111668950485). OTR is funded by a Sara Borrell fellowship (CD19/00110) from the Instituto de Salud Carlos III. OTR acknowledges support from the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa 2019-2023 Program and from the Generalitat de Catalunya through the CERCA Program. All funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The Health Secretary of State of São Paulo and PRODESP reviewed the data and findings of the study, but the academic authors retained editorial control. OTR, MDTH, and JC had full access to de-identified data in the study, and OTR and MDTH verified the data; all authors approved the final version of the manuscript for publication.
• Keywords: Life Sciences & Biomedicine; Science & Technology; SCOTLAND; Medicine, General & Internal; HOSPITAL ADMISSIONS; General & Internal Medicine
• Research Categories: Biology, Biostatistics; Health Sciences, Epidemiology

Abstract

Objective: To estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine CoronaVac (Sinovac Biotech) in Sao Paulo State, Brazil. Design: Test negative case-control study. Setting: Community testing for covid-19 in Sao Paulo State, Brazil. Participants: Adults aged ≥18 years who were residents of Sao Paulo state, had received two doses of CoronaVac, did not have a laboratory confirmed SARS-CoV-2 infection before vaccination, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 14 December 2021. Cases were matched to test negative controls by age (in 5 year bands), municipality of residence, healthcare worker status, and epidemiological week of RT-PCR test. Main outcome measures: RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. Conditional logistic regression was adjusted for sex, number of covid-19 associated comorbidities, race, and previous acute respiratory illness. Results: From 202 741 eligible people, 52 170 cases with symptomatic covid-19 and 69 115 test negative controls with covid-19 symptoms were formed into 43 257 matched sets. Adjusted odds ratios of symptomatic covid-19 increased with time since completion of the vaccination series. The increase in odds was greater in younger people and among healthcare workers, although sensitivity analyses suggested that this was in part due to bias. In addition, the adjusted odds ratios of covid-19 related hospital admission or death significantly increased with time compared with the odds 14-41 days after series completion: from 1.25 (95% confidence interval 1.04 to 1.51) at 70-97 days up to 1.94 (1.41 to 2.67) from 182 days onwards. Conclusions: Significant increases in the risk of moderate and severe covid-19 outcomes occurred three months after primary vaccination with CoronaVac among people aged 65 and older. These findings provide supportive evidence for the implementation of vaccine boosters in these populations who received this inactivated vaccine. Studies of waning should include analyses designed to uncover common biases.