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. 2022 Jun 13:377:e070102.
doi: 10.1136/bmj-2022-070102.

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

Matt D T Hitchings  1 , Otavio T Ranzani  2   3 , Margaret L Lind  4 , Murilo Dorion  4 , Tatiana Lang D'Agostini  5 , Regiane Cardoso de Paula  5 , Olivia Ferreira Pereira de Paula  5 , Edlaine Faria de Moura Villela  5 , Mario Sergio Scaramuzzini Torres  6 , Silvano Barbosa de Oliveira  7   8 , Wade Schulz  9 , Maria Almiron  7 , Rodrigo Said  7 , Roberto Dias de Oliveira  10 , Patricia Vieira da Silva  11 , Wildo Navegantes de Araújo  7   8   12 , Jean Carlo Gorinchteyn  13 , Natalie E Dean  14 , Jason R Andrews  15   16 , Derek A T Cummings  17   18   16 , Albert I Ko  4   19   16 , Julio Croda  4   11   20   16
Affiliations

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

Matt D T Hitchings et al. BMJ. .

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 São Paulo State, Brazil.

Design: Test negative case-control study.

Setting: Community testing for covid-19 in São Paulo State, Brazil.

Participants: Adults aged ≥18 years who were residents of São 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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Allergy and Infectious Diseases and from the Sendas Family and Beatrice Kleinberg Neuwirth Funds; MDTH and DATC report a contract from Merck (to the University of Florida) for research unrelated to this manuscript; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Flowchart of study population and case and control selection. RT-PCR=reverse transcription polymerase chain reaction
Fig 2
Fig 2
Distribution of second dose timing by age group in matched cases and controls, stacked by healthcare worker (HCW) status
Fig 3
Fig 3
Odds ratio of symptomatic polymerase chain reaction confirmed covid-19 disease against days since vaccination, relative to 14-41 days from vaccination, by age group and healthcare worker (HCW) status
Fig 4
Fig 4
Odds ratio of polymerase chain reaction confirmed covid-19 related hospital admission or death for days since vaccination, relative to 14-41 days from vaccination
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