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Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults

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In this article, a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England was conducted, where 161,537 adults completed questionnaires and self-administered lateral flow immunoassay (LFIA) tests for immunoglobulin-based self-testing.
Abstract
Background REACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England. Methods We contacted a random sample of the population by sending a letter to named individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to perform the test at home and complete a questionnaire, including reporting of their test result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for IgG against SARS-CoV-2 between 27 October and 10 November 2020. Results The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9% (24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at 9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2% (4.0-4.3). Interpretation The second wave of infection in England is apparent in increasing antibody prevalence, particularly in younger people, students, and in the Northern Regions. By late October a large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first and early second wave.

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1
Increasing SARS-CoV-2 antibody prevalence in England at the start of the second
wave: REACT-2 Round 4 cross-sectional study in 160,000 adults
Helen Ward PhD
1,2,3,4
, Christina Atchison PhD
1
, Matt Whitaker MSc
1
, Christl A Donnelly
ScD
1,2,5
, Steven Riley PhD
1,2
, Deborah Ashby PhD
1
, Ara Darzi PhD
4,6
, Wendy S Barclay
PhD
7
, Graham Cooke PhD
3,4,7
,
Paul Elliott PhD
1,3,4,8,9,10
for the REACT study team.
All listed authors made substantial contributions to the conception or design of the work; or the acquisition, analysis, or
interpretation of data for the work; AND drafting the work or revising it critically for important intellectual content; AND final
approval of the version to be published; AND agreement to be accountable for all aspects of the work in ensuring that questions
related to the accuracy or integrity of any part of the work areappropriately investigated and resolved.
1
School of Public Health, Imperial College London, UK
2
MRC Centre for Global infectious Disease Analysis and Abdul Latif Jameel Institute for
Disease and Emergency Analytics, Imperial College London, UK
3
Imperial College Healthcare NHS Trust, UK
4
National Institute for Health Research Imperial
Biomedical Research Centre, UK
5
Department of Statistics, University of Oxford, UK
6
Institute of Global Health Innovation at Imperial College London, UK
7
Department of Infectious Disease, Imperial College London, UK
8
MRC Centre for Environment and Health, School of Public Health, Imperial College
London, UK
9
Health Data Research (HDR) UK London at Imperial College London, UK
10
UK Dementia Research Institute at Imperial College London, UK
Corresponding authors: Prof Helen Ward, h.ward@imperial.ac.uk
, +44 20 75 94 33 03; Prof
Paul Elliott, p.elliott@imperial.ac.uk
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted July 22, 2021. ; https://doi.org/10.1101/2021.07.21.21260926doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

2
Abstract
Background: REACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2
antibodies in the community in England.
Methods: We contacted a random sample of the population by sending a letter to named
individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a
lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to
perform the test at home and complete a questionnaire, including reporting of their test
result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for
IgG against SARS-CoV-2 between 27 October and 10 November 2020.
Results: The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This
was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9%
(24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which
increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students,
(adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most
in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West
from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at
9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest
prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and
African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2%
(4.0-4.3).
Interpretation: The second wave of infection in England is apparent in increasing antibody
prevalence, particularly in younger people, students, and in the Northern Regions. By late
October a large proportion of the population remained susceptible to SARS-CoV-2 infection
in England based on naturally acquired immunity from the first and early second wave.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted July 22, 2021. ; https://doi.org/10.1101/2021.07.21.21260926doi: medRxiv preprint

3
Introduction
Repeated prevalence surveys of SARS-CoV-2 antibodies can provide information on the
distribution of infection within the population.[1,2] Antibody prevalence will change over time
dependent on the incidence of infection, uptake of vaccination and waning of detectable
antibody levels in those previously infected. England had a large first wave of COVID-19 in
March and April 2020, leading to high mortality,[3] and significant morbidity for those with
long COVID.[4] There was a national lockdown with the closure of schools, universities,
hospitality, all but essential retail, and advice to work from home and avoid non-essential
travel from late March with relaxations starting in May which led to a sustained reduction in
cases and deaths until the second wave started in late August.[5]
We previously reported antibody positivity based on a self-administered lateral flow
immunoassay (LFIA) test from a representative survey of 105,000 individuals during June
and July 2020 where we found an overall prevalence, weighted to the adult population of
England, of 6.0%.[6] Over two subsequent rounds of study in August and September 2020
we observed a decline in positivity to 4.4% which we attribute to waning antibody levels.[7]
Here we report the prevalence of detectable antibody in a further round in October to
November 2020 as part of the REal-time assessment of Community Transmission -2
(REACT-2) programme.[8]
Methods
The REACT study protocol has been published.[8] Briefly, we included non-overlapping
community samples from the adult population 18 years and older, using a self-administered
questionnaire and LFIA test at home (Table 1).[6,8] Invitations were sent to named
individuals randomly selected from the National Health Service (NHS) patient list which
includes anyone registered with a General Practitioner (primary care physician) in England,
covering almost the entire population. We aimed for a sample size of 150,000 in round 4 to
obtain prevalence estimates for the 315 local authorities in England. Registration was closed
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted July 22, 2021. ; https://doi.org/10.1101/2021.07.21.21260926doi: medRxiv preprint

4
after 200,721 people signed up, which was 36% of those invited registered; 169,927
completed a survey and 161,537 (29% of those invited, 80% of those registered) provided a
valid (IgG positive or negative) antibody result (Supplementary Table S1). Those who
registered were posted a self-administered point-of-care LFIA test (Fortress Diagnostics,
Northern Ireland) with written and video instructions. The assay uses the S1 subunit
(including RBD). The sensitivity of finger-prick blood (self-read) for IgG antibodies was
84.4% (70.5, 93.5) in RT-PCR confirmed cases in healthcare workers, and specificity 98.6%
(97.1, 99.4) in pre-pandemic sera.[9] Participants completed a short registration
questionnaire (online/telephone) and a further survey upon completion of their self-test.
Survey instruments are available on the study website:
(https://www.imperial.ac.uk/medicine/research-and-impact/groups/react-study/
).
The prevalence from each round was calculated as the proportion of individuals reporting a
valid test result with a positive IgG result, adjusted for test performance,[10] and weighted at
national level for age, sex, region, ethnicity and deprivation to the adult population of
England.[6] Index of Multiple Deprivation 2019 (IMD) was used as a measure of relative
deprivation, based on seven domains at a small local area level across England (income,
employment, education, health, crime, barriers to housing and services, and living
environment).[11] Epidemic curves were constructed retrospectively using information from
participants with a positive antibody test who reported date of onset for a confirmed or
possible case of COVID-19, i.e. excluding those who were asymptomatic and for whom date
of onset was unknown. Logistic regression models were developed for prevalence by key
covariates, and adjusted for age, sex and region, and additionally for ethnicity, deprivation,
household size and occupation. We used complete case analysis without
imputation. Confidence intervals for the changes in prevalence were calculated using a
normal approximation to the sampling distribution of a difference in prevalences.[12]
Data were analysed using the statistical package R version 4.0.0.[13]
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted July 22, 2021. ; https://doi.org/10.1101/2021.07.21.21260926doi: medRxiv preprint

5
We obtained research ethics approval from the South Central-Berkshire B Research Ethics
Committee (IRAS ID: 283787), and Medicines and Healthcare products Regulatory Agency
approval for use of the LFIA for research purposes only. A REACT Public Advisory Group
provides input into the design and conduct of the research.
Results
Results were available from 161,537 people tested between 27 October and 10 November
2020. Over half of these test results were submitted in the first three days, i.e. by 29
October. The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This
was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9%
(24.0-29.9). The results over the first 4 rounds show the highest prevalence in the first round
in June, declining over the next 2 rounds and then increasing again by the end of October
(Table 1).
Figure 1(a) is a reconstructed epidemic curve, based on date of onset reported by those with
positive antibody tests who reported a confirmed or suspected case of COVID-19, with each
round shown. It clearly shows that, from all rounds, most of the cases were from the first
wave in March and April 2020; it also shows the start of the second wave becoming
apparent in early September in the plot from round 4. The shaded area is where there will be
under-ascertainment of cases as this IgG antibody test is validated for detection 21 or more
days post onset.[9] Figure 1(b) shows the same reconstruction by age group, and
demonstrates a marked increase from early September in those aged 18 to 24, with slower
and slightly later increases in older age groups.
The characteristics of the early second wave are suggested by the relative changes in
prevalence between rounds 3 and 4 in different groups. The largest increase by age was in
the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-
7.2) to 9.9% (9.3-10.4), in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1%
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted July 22, 2021. ; https://doi.org/10.1101/2021.07.21.21260926doi: medRxiv preprint

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References
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Q1. What contributions have the authors mentioned in the paper "Increasing sars-cov-2 antibody prevalence in england at the start of the second wave: react-2 round 4 cross-sectional study in 160,000 adults" ?

In this paper, the authors report the prevalence of detectable antibody in a further round in October to November 2020 as part of the REal-time assessment of Community Transmission -2 ( REACT-2 ) programme.