Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil

Srinivasa Vittal Katikireddi, Thiago Cerqueira-Silva, Eleftheria Vasileiou, Chris Robertson, Sarah Amele, Jiafeng Pan, Bob Taylor, Viviane Boaventura, Guilherme Loureiro Werneck, Renzo Flores-Ortiz, Utkarsh Agrawal, Annemarie B. Docherty, Colin McCowan, Jim McMenamin, Emily Moore, Lewis D. Ritchie, Igor Rudan, Syed Ahmar Shah, Ting Shi, Colin R. SimpsonMauricio L. Barreto, Vinicius de Araujo Oliveira, Manoel Barral-Netto, Aziz Sheikh*

*Corresponding author for this work

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Abstract

Background: Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants—especially delta (B.1.617.2)—is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon). Methods: In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2–3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs. Findings: 1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54–2·62) at 10–11 weeks, 3·01 (2·26–3·99) at 14–15 weeks, and 5·43 (4·00–7·38) at 18–19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01–2·61) at 10–11 weeks, 3·10 (2·63–3·64) at 14–15 weeks, and 4·71 (3·83–5·78) at 18–19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7–87·0) at 2–3 weeks, to 75·9% (72·9–78·6) at 14–15 weeks, and 63·7% (59·6–67·4) at 18–19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4–87·3) at 2–3 weeks, to 59·7% (54·6–64·2) at 14–15 weeks, and 42·2% (32·4–50·6) at 18–19 weeks. Interpretation: We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19. Funding: UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. Translation: For the Portuguese translation of the abstract see Supplementary Materials section.

Original languageEnglish
Pages (from-to)25-35
Number of pages11
JournalThe Lancet
Volume399
Issue number10319
Early online date20 Dec 2021
DOIs
Publication statusPublished - 1 Jan 2022

Bibliographical note

Funding Information:
This study is part of the EAVE II project. EAVE II is funded by the MRC (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). Additional support has been provided through Public Health Scotland and Scottish Government Director General Health and Social Care. The original EAVE project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (11/46/23). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the UK government. The Brazilian component is part of the Fiocruz VigiVac project on continuous digital evaluation of the national anti-COVID-19 immunisation programme. SVK and SA acknowledge funding from an NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the MRC (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). This partnership between Brazil and Scotland was established through funding from the NIHR (GHRG /16/137/99) using UK aid from the UK Government to support global health research. This study was partially supported by a donation from the Fazer o Bem Faz Bem programme. The authors thank DATASUS for its excellent work in providing unidentified databases. GLW, MLB, and MB-N are research fellows from the Brazilian National Research Council. GLW acknowledges funding from FAPERJ (Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro; E-26/210.180/2020). We thank Dave Kelly from Albasoft (Inverness, UK) for his support with making primary care data available; Wendy Inglis-Humphrey, Vicky Hammersley, and Laura Brook (University of Edinburgh, Edinburgh, UK); and Pam McVeigh, Amanda Burridge, and Afshin Dastafshan (Public Health Scotland, Glasgow, UK) for their support with project management and administration.

Funding Information:
SVK is a member of the UK Government's Scientific Advisory Group on Emergencies subgroup on ethnicity, the Cabinet Office's International Best Practice Advisory Group, and was co-chair of the Scottish Government's Expert Reference Group on Ethnicity and COVID-19. CR reports grants from the Medical Research Council (MRC) and Public Health Scotland, during the conduct of the study, and is a member of the Scottish Government Chief Medical Officer's COVID-19 Advisory Group, Scientific Pandemic Influenza Group on Modelling, and Medicines and Healthcare products Regulatory Agency Vaccine Benefit and Risk Working Group. AS is a member of the Scottish Government Chief Medical Officer's COVID-19 Advisory Group and its Standing Committee on Pandemics; he is also a member of the UK Government's New and Emerging Respiratory Virus Threats Risk Stratification Subgroup and a member of AstraZeneca's Thrombotic Thrombocytopenic Taskforce. All roles are unremunerated. VdAO, VB, MLB, and MB-N are employees of Fiocruz, a federal public institution, which manufactures Vaxzevria in Brazil, through a full technology transfer agreement with AstraZeneca. Fiocruz allocates all its manufactured products to the Ministry of Health for the public health service use. All other authors declare no competing interests.

Funding Information:
This study is part of the EAVE II project. EAVE II is funded by the MRC (MC_PC_19075) with the support of BREATHE?The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). Additional support has been provided through Public Health Scotland and Scottish Government Director General Health and Social Care. The original EAVE project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (11/46/23). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the UK government. The Brazilian component is part of the Fiocruz VigiVac project on continuous digital evaluation of the national anti-COVID-19 immunisation programme. SVK and SA acknowledge funding from an NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the MRC (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). This partnership between Brazil and Scotland was established through funding from the NIHR (GHRG /16/137/99) using UK aid from the UK Government to support global health research. This study was partially supported by a donation from the Fazer o Bem Faz Bem programme. The authors thank DATASUS for its excellent work in providing unidentified databases. GLW, MLB, and MB-N are research fellows from the Brazilian National Research Council. GLW acknowledges funding from FAPERJ (Funda??o Carlos Chagas Filho de Amparo ? Pesquisa do Estado do Rio de Janeiro; E-26/210.180/2020). We thank Dave Kelly from Albasoft (Inverness, UK) for his support with making primary care data available; Wendy Inglis-Humphrey, Vicky Hammersley, and Laura Brook (University of Edinburgh, Edinburgh, UK); and Pam McVeigh, Amanda Burridge, and Afshin Dastafshan (Public Health Scotland, Glasgow, UK) for their support with project management and administration.

Publisher Copyright:
© 2022 The author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Data Availability Statement

A data dictionary covering the datasets used in this study can be found at https://github.com/EAVE-II/EAVE-II-data-dictionary. All statistical code used in this study is publicly available at https://github.com/EAVE-II/Covid-VE. The data used in this study are sensitive and will not be made publicly available.

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