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Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study

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Michela Antonelli, Rose S Penfold, Jordi Merino, Carole H Sudre, Erika Molteni, Sarah Berry, Liane S Canas, Mark S Graham, Kerstin Klaser, Marc Modat, Benjamin Murray, Eric Kerfoot, Liyuan Chen, Jie Deng, Marc F Österdahl, Nathan J Cheetham, David A Drew, Long H Nguyen, Joan Capdevila Pujol, Christina Hu & 10 more Somesh Selvachandran, Lorenzo Polidori, Anna May, Jonathan Wolf, Andrew T Chan, Alexander Hammers, Emma L Duncan, Tim D Spector, Sebastien Ourselin, Claire J Steves

Original languageEnglish
Pages (from-to)43-55
Number of pages13
JournalThe Lancet infectious diseases
Volume22
Issue number1
Early online date22 Dec 2021
DOIs
E-pub ahead of print22 Dec 2021
PublishedJan 2022

Bibliographical note

Funding Information: ZOE provided in-kind support for all aspects of building, running, and supporting the app and service to all users worldwide. This work was supported by the UK Department of Health via the NIHR Comprehensive Biomedical Research Centre Award (COV-LT-0009) to Guy's and St Thomas' NHS Foundation Trust (in partnership with King's College London and King's College Hospital NHS Foundation Trust) and a grant to ZOE, and by the Wellcome Engineering and Physical Sciences Research Council Centre for Medical Engineering at King's College London (WT 203148/Z/16/Z). This work was further supported by the UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value-Based Healthcare. Investigators also received support from the Wellcome Flagship Programme (WT213038/Z/18/Z and WT212904/Z/18/Z), the Medical Research Council, the British Heart Foundation, the Alzheimer's Society (AS-JF-17–011), the EU, the NIHR, the Chronic Disease Research Foundation, and the NIHR-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust (in partnership with King's College London). SO was supported by the French Government through the 3IA Côte d'Azur Investments in the Future project managed by the National Research Agency (reference number ANR-19-P3IA-0002). ATC was supported by a Stuart and Suzanne Steele Massachusetts General Hospital Research Scholar Award and by the M Schwartz and L Schwartz award from the Massachusetts Consortium on Pathogen Readiness. JM was partially supported by the European Commission Horizon 2020 programme (H2020-MSCA-IF-2015–703787). This work was also supported by the National Core Studies, an initiative funded by UK Research and Innovation, the NIHR, and the Health and Safety Executive. The COVID-19 Longitudinal Health and Wellbeing National Core Study was funded by the Medical Research Council (MC_PC_20030). We thank Kate Tilling for helpful discussions on study design. Funding Information: JW, AM, LP, CH, SS, and JCP report being employees of ZOE during the conduct of the study. JM reports grants from the European Commission and National Institutes of Health, and has served as a co-investigator on an unrelated nutrition trial sponsored by ZOE. ATC reports grants from the Massachusetts Consortium on Pathogen Readiness during the conduct of the study, and personal fees from Bayer Pharma, Pfizer, and Boehringer Ingelheim, outside the submitted work. DAD reports grants from the National Institutes of Health, the Massachusetts Consortium on Pathogen Readiness, and the American Gastroenterological Association during the conduct of the study, and has served as a co-investigator on an unrelated nutrition trial sponsored by ZOE. LHN reports grants from the National Institutes of Health, the American Gastroenterological Association, and the Crohn's and Colitis Foundation. CHS reports grants from the Alzheimer's Society during the conduct of the study. EM reports a grant from the Medical Research Council during the conduct of the study. CJS reports grants from the Chronic Disease Research Foundation, the Medical Research Council, the Wellcome Trust, and the National Institute for Health Research (NIHR) during the conduct of the study. SO reports grants from the Wellcome Trust, UK Research and Innovation, and the Chronic Disease Research Foundation during the conduct of the study. ELD reports receiving grants from the Chronic Disease Research Foundation during the conduct of the study. TDS reports being a consultant for ZOE during the conduct of the study. All other authors declare no competing interests. Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

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Abstract

BACKGROUND: COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness.

METHODS: This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status.

FINDINGS: Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50-2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01-1·23; p=0·039). Individuals without obesity (BMI <30 kg/m2) had lower odds of infection following their first vaccine dose (OR 0·84, 95% CI 0·75-0·94; p=0·0030). For the disease profile analysis, 3825 users from cases 1 were included in cases 3 and 906 users from cases 2 were included in cases 4. Vaccination (compared with no vaccination) was associated with reduced odds of hospitalisation or having more than five symptoms in the first week of illness following the first or second dose, and long-duration (≥28 days) symptoms following the second dose. Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older.

INTERPRETATION: To minimise SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated, and might have implications for strategies such as booster vaccinations.

FUNDING: ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, and the Alzheimer's Society.

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