REACT-2 Round 5: increasing prevalence of SARS-CoV-2 antibodies demonstrate impact of the second wave and of vaccine roll-out in England

  1. Helen Ward
  2. Graham Cooke
  3. Matthew Whitaker
  4. Rozlyn Redd
  5. Oliver Eales
  6. Jonathan C Brown
  7. Katharine Collet
  8. Emily Cooper
  9. Anna Daunt
  10. Kathryn Jones
  11. Maya Moshe
  12. Michelle Willicombe
  13. Sophie Day
  14. Christina Atchison
  15. Ara Darzi
  16. Christl A Donnelly
  17. Steven Riley
  18. Deborah Ashby
  19. Wendy S Barclay
  20. Paul Elliott

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Abstract

Background

England has experienced high rates of SARS-CoV-2 infection during the COVID-19 pandemic, affecting in particular minority ethnic groups and more deprived communities. A vaccination programme began in England in December 2020, with priority given to administering the first dose to the largest number of older individuals, healthcare and care home workers.

Methods

A cross-sectional community survey in England undertaken between 26 January and 8 February 2021 as the fifth round of the REal-time Assessment of Community Transmission-2 (REACT-2) programme. Participants completed questionnaires, including demographic details and clinical and COVID-19 vaccination histories, and self-administered a lateral flow immunoassay (LFIA) test to detect IgG against SARS-CoV-2 spike protein. There were sufficient numbers of participants to analyse antibody positivity after 21 days from vaccination with the PfizerBioNTech but not the AstraZeneca/Oxford vaccine which was introduced slightly later.

Results

The survey comprised 172,099 people, with valid IgG antibody results from 155,172. The overall prevalence of antibodies (weighted to be representative of the population of England and adjusted for test sensitivity and specificity) in England was 13.9% (95% CI 13.7, 14.1) overall, 37.9% (37.2, 38.7) in vaccinated and 9.8% (9.6, 10.0) in unvaccinated people. The prevalence of antibodies (weighted) in unvaccinated people was highest in London at 16.9% (16.3, 17.5), and higher in people of Black (22.4%, 20.8, 24.1) and Asian (20.0%, 19.0, 21.0) ethnicity compared to white (8.5%, 8.3, 8.7) people. The uptake of vaccination by age was highest in those aged 80 years or older (93.5%). Vaccine confidence was high with 92.0% (91.9, 92.1) of people saying that they had accepted or intended to accept the offer. Vaccine confidence varied by age and ethnicity, with lower confidence in young people and those of Black ethnicity. Particular concerns were identified around pregnancy, fertility and allergies. In 971 individuals who received two doses of the Pfizer-BioNTech vaccine, the proportion testing positive was high across all age groups. Following a single dose of Pfizer-BioNTech vaccine after 21 days or more, 84.1% (82.2, 85.9) of people under 60 years tested positive (unadjusted) with a decreasing trend with increasing age, but high responses to a single dose in those with confirmed or suspected prior COVID at 90.1% (87.2, 92.4) across all age groups.

Conclusions

There is uneven distribution of SARS-CoV-2 antibodies in the population with a higher burden in key workers and some minority ethnic groups, similar to the pattern in the first wave. Confidence in the vaccine programme is high overall although it was lower in some of the higher prevalence groups which suggests the need for improved communication about specific perceived risks. Two doses of Pfizer-BioNTech vaccine, or a single dose following previous infection, confers high levels of antibody positivity across all ages. Further work is needed to understand the relationship between antibody positivity, clinical outcomes such as hospitalisation, and transmission.

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  1. ScreenIT

    SciScore for 10.1101/2021.02.26.21252512: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: We obtained research ethics approval from the South Central-Berkshire B Research Ethics Committee (IRAS ID: 283787), and MHRA approval for use of the LFIA for research purposes only.
    RandomizationTests were sent to named individuals randomly selected from the National Health Service (NHS) patient list that includes anyone registered with a General Practitioner in England and covers almost the entire population.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    (13) The LFIA has a clinical sensitivity on finger-prick blood (self-read) for IgG antibodies following natural infection estimated at 84.4% (70.5, 93.5) in RT-PCR confirmed cases in healthcare workers, and specificity 98.6% (97.1, 99.4) in
    IgG
    suggested: None
    Participants were tested for antibodies to SARS-CoV-2 spike (anti-S) protein using the Abbott IgG Quant II chemiluminescent immunoassay (threshold value for positivity 50 AU/ml).
    anti-S
    suggested: None
    Serological testing: Serum was tested for antibodies to nucleocapsid protein (anti-NP) using the Abbott Architect SARS-CoV-2 IgG 2 step chemiluminescent immunoassay (CMIA) according to manufacturer’s instructions.
    anti-NP
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    In vitro live virus neutralisation assay: The ability of sera to neutralise SARS-CoV-2 virus was assessed by neutralisation assay on Vero cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Sera were serially diluted in OptiPRO SFM (Life Technologies) and incubated for 1h at RT with 100 TCID50/well of SARS-CoV-2/England/IC19/2020 and transferred to 96-well plates pre-seeded with Vero-E6 cells.
    Vero-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Serological testing: Serum was tested for antibodies to nucleocapsid protein (anti-NP) using the Abbott Architect SARS-CoV-2 IgG 2 step chemiluminescent immunoassay (CMIA) according to manufacturer’s instructions.
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    Statistical Analysis: Statistical analysis was conducted using Prism 9.0 (GraphPad Software Inc.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are a number of limitations to this study. While the use of self-administered lateral flow tests for population surveillance allows the rapid evaluation of large numbers of individuals in a cost-effective manner, these LFIA assays are generally less sensitive than laboratory assays.(12) In addition, they provide a threshold reading rather than a quantitative assessment of antibody response. As such, the estimates of antibody positivity here are likely to be lower than those obtained on laboratory platforms and it is unclear the extent to which antibody positivity, including from LFIA, correlates with protective immunity. However, we demonstrate that the detection of antibody on the test used correlates well with a threshold for neutralisation of live virus in in vitro assays. In addition, both Pfizer-BioNTech(25) and AstraZeneca/Oxford(26) vaccines generate antibody and T cell mediated immune responses such that vaccinated individuals may have T cell mediated protection even if antibody responses are not detected. LFIA tests may also be subject to errors when used at home, although we have found good usability in earlier work including in older people.(13) However, it is possible that poorer visual acuity in older people affects the ability to read the test result if there is a faint line. It is a high priority to establish the relationship between antibody positivity and the subsequent risk of hospitalisation and/or death. Initial data from a cohort of UK healthcare wo...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.02.26.21252512v1 on medRxiv