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.
Reviewing Editor
- Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States
Publication history
- Received: May 20, 2022
- Accepted: December 22, 2022
- Accepted Manuscript published: January 24, 2023 (version 1)
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
Further reading
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- Epidemiology and Global Health
Background: In contrast to most of the world, the cervical cancer screening programme continued in Denmark throughout the COVID-19 pandemic. We examined the cervical cancer screening participation during the pandemic in Denmark.
Methods: We included all women aged 23-64 years old invited to participate in cervical cancer screening from 2015-2021 as registered in the Cervical Cancer Screening Database combined with population-wide registries. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of cervical cancer screening participation within 90, 180 and 365 days since invitation during the pandemic in comparison with the previous years adjusting for age, year and month of invitation.
Results: Altogether, 2,220,000 invited women (in 1,466,353 individuals) were included in the study. Before the pandemic, 36% of invited women participated in screening within 90 days, 54% participated within 180 days and 65% participated within 365 days. At the start of the pandemic, participation in cervical cancer screening within 90 days was lower (pre-lockdown PR=0.58; 95% CI: 0.56-0.59 and 1st lockdown PR=0.76; 95% CI: 0.75-0.77) compared with the previous years. A reduction in participation within 180 days was also seen during pre-lockdown (PR=0.89; 95% CI: 0.88-0.90) and 1st lockdown (PR=0.92; 95% CI: 0.91-0.93). Allowing for 365 days to participation, only a slight reduction (3%) in participation was seen with slightly lower participation in some groups (immigrants, low education and low income).
Conclusions: The overall participation in cervical cancer screening was reduced during the early phase of the pandemic. However, the decline almost diminished with longer follow-up time.
Funding: The study was funded by the Danish Cancer Society Scientific Committee (grant number R321-A17417) and the Danish regions.
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- Epidemiology and Global Health
Against a backdrop ofwidespread global transmission, a number of countries have successfully brought large outbreaks of COVID-19 under control and maintained near-elimination status. A key element of epidemic response is the tracking of disease transmissibility in near real-time. During major out-breaks, the effective reproduction number can be estimated froma time-series of case, hospitalisation or death counts. In low or zero incidence settings, knowing the potential for the virus to spread is a response priority. Absence of case data means that this potential cannot be estimated directly. We present a semi-mechanisticmodelling framework that draws on time-series of both behavioural data and case data (when disease activity is present) to estimate the transmissibility of SARS-CoV-2 fromperiods of high to low- or zero- case incidence, with a coherent transition in interpretation across the changing epidemiological situations. Of note, during periods of epidemic activity, our analysis recovers the effective reproduction number, while during periods of low- or zero- case incidence, it provides an estimate of transmission risk. This enables tracking and planning of progress towards the control of large outbreaks, maintenance of virus suppression, and monitoring the risk posed by re-introduction of the virus. We demonstrate the value of our methods by reporting on their use throughout 2020 in Australia, where they have become a central component of the national COVID-19 response.
