Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies
- King's College London, United Kingdom
- University of Cambridge, United Kingdom
- University College London, United Kingdom
- University of Glasgow, United Kingdom
- University of Leicester, United Kingdom
- University of Bristol, United Kingdom
Abstract
Background: SARS-CoV-2 antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts.
Methods: Samples were collected from 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N = 4,256; ALSPAC, N = 4,622), and in TwinsUK only in November 2021-January 2022 (N = 3,575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables.
Results: Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had 3-fold greater odds of SARS-CoV-2 infection over the next six to nine months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK 'Shielded Patient List' had consistently greater odds (2- to 4-fold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations.
Conclusions: These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies.
Funding: Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing - National Core Study (LHW-NCS) HMT/UKRI/MRC (MC_PC_20030 & MC_PC_20059). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant COV-LT-0009). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC.
Data availability
Data from all analyses presented in figures and tables herein are tabulated and available as a supplementary spreadsheet file. Original antibody test data are available within the UK Longitudinal Linkage Collaboration upon application (see https://ukllc.ac.uk/apply/). UK LLC houses COVID-19 related datasets from over 20 UK longitudinal population studies (see https://ukllc.ac.uk/datasets/). Original TwinsUK data are available to researchers on application. Access to original TwinsUK data is managed by the TwinsUK Resource Executive Committee (see https://twinsuk.ac.uk/resources-for-researchers/access-our-data/) and access to original ALSPAC data via an online proposal system (see http://www.bristol.ac.uk/media-library/sites/alspac/documents/researchers/data-access/ALSPAC_Access_Policy.pdf). This is to ensure privacy and protect against misuse. ALSPAC study data were collected and managed using REDCap electronic data capture tools hosted at the University of Bristol. REDCap (Research Electronic Data Capture) is a secure, web-based software platform designed to support data capture for research studies (doi:10.1016/J.JBI.2008.08.010). The study website contains details of all the data that is available through a fully searchable data dictionary and variable search tool on the study website (http://www.bristol.ac.uk/alspac/researchers/our-data/). Analysis code will be made openly available via GitHub at: https://github.com/nathan-cheetham.
Article and author information
Author details
Olivia KL Hamilton
Charis Bridger Staatz
Daniel Major-Smith
Funding
NIHR (COV-LT-0009)
- Nathan J Cheetham
- Milla Kibble
- Andrew Wong
- Richard J Silverwood
- Anika Knuppel
- Dylan M Williams
- Olivia KL Hamilton
- Srinivasa Vittal Katikireddi
- George B Ploubidis
- Ellen J Thompson
- Ruth CE Bowyer
- Maria Paz Garcia
- Nishi chaturvedi
- Nicholas J Timpson
- Claire J Steves
NIHR Bristol Biomedical Research Centre (BRC-1215-2001)
- Nicholas J Timpson
MRC Integrative Epidemiology Unit (MC_UU_00011/1)
- Nicholas J Timpson
Medical Research Council (MR/W021315/1)
- Milla Kibble
NRS (SCAF/15/02)
- Srinivasa Vittal Katikireddi
Medical Research Council (MC_UU_00022/2)
- Srinivasa Vittal Katikireddi
Scottish Government Chief Scientist Office (SPHSU17)
- Olivia KL Hamilton
- Srinivasa Vittal Katikireddi
Medical Research Council (MC_UU_12017/11)
- Olivia KL Hamilton
Medical Research Council (MC_UU_00022/3)
- Olivia KL Hamilton
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The ethics statements for each of the longitudinal studies involved in this study are outlined below. TwinsUK: All waves of TwinsUK have received ethical approval associated with TwinsUK Biobank (19/NW/0187), TwinsUK (EC04/015) or Healthy Ageing Twin Study (H.A.T.S) (07/H0802/84) studies from HRA/NHS Research Ethics Committees. The TwinsUK Resource Executive Committee (TREC) oversees management, data sharing and collaborations involving the TwinsUK registry (for further details see https://twinsuk.ac.uk/resources-forresearchers/access-our-data/), in consultation with the TwinsUK Volunteer Advisory Panel (VAP) where needed. ALSPAC: Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time. Consent for biological samples has been collected in accordance with the Human Tissue Act (2004). USoc: The University of Essex Ethics Committee has approved all data collection for the Understanding Society main study and COVID-19 web and telephone surveys (ETH1920-1271). The March 2021 web survey was reviewed and ethics approval granted by the NHS Health Research Authority, London - City & East Research Ethics Committee (reference 21/HRA/0644). No additional ethical approval was necessary for this secondary data analysis. 1958 NCDS, 1970 BCS70, Next Steps, MCS: The most recent sweeps of 1958 NCDS, 1970 BCS, Next Steps and MCS have all been granted ethical approval by the National Health Service (NHS) Research Ethics Committee and all participants have given informed consent. ELSA: Waves 1-9 of ELSA were approved by the London Multicentre Research Ethics Committee (approval number MREC/01/2/91),and the COVID-19 sub-study was approved by the University College London Research Ethics Committee (0017/003). All participants provided informed consent. 1946 NSHD: Ethical approval for the study was obtained from the NHS Research Ethics Committee (19/LO/1774). All participants provided informed consent. SABRE: Ethical approval for the study was obtained from the NHS Research Ethics Committee (19/LO/1774). All participants provided informed consent. EXCEED: The original EXCEED study was approved by the Leicester Central Research Ethics Committee (Ref: 13/EM/0226). Substantial amendments have been approved by the same Research Ethics Committee for the collection of new data relating to the COVID-19 pandemic, including the COVID-19 questionnaires and antibody testing.
Copyright
© 2023, Cheetham et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies
eLife 12:e80428.
https://doi.org/10.7554/eLife.80428
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Background: The role of circulating metabolites on child development is understudied. We investigated associations between children's serum metabolome and early childhood development (ECD).
Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children's milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥ 1. The interaction between significant metabolites and the child's age was tested.
Results: Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child's nutritional status, diet quality, and infant age. Cresol sulfate (β = -0.07; adjusted-p < 0.001), hippuric acid (β = -0.06; adjusted-p < 0.001), phenylacetylglutamine (β = -0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = -0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged -1 SD: β = -0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (-1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).
Conclusion: Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding: Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
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