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medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020.

The copyright holder for this preprint


(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

High prevalence of SARS-CoV-2 antibodies in


care homes affected by COVID-19;
prospective cohort study, England

Shamez N Ladhani, MRCPCH(UK),1,2 Anna Jeffery-Smith, BMBCh,3 Monika Patel, BSc,3 Roshni

Janarthanan, MBBS,4 Jonathan Fok, FFPH,4 Emma Crawley-Boevey, MFPH, 4 Amoolya Vusirikala,

MPH,4 Elena Fernandez, BSc.,4 Marina Sanchez Perez, MPH,4 Suzanne Tang, MPH,4 Kate Dun-

Campbell, MRCGP,4 Edward Wynne- Evans, FFPH,4 Anita Bell, FFPH,4 Bharat Patel, FRCPath,4 Zahin

Amin-Chowdhury, BSc,1 Felicity Aiano, MPH,1 Karthik Paranthaman, FFPH,5 Thomas Ma, MSc,5 Maria

Saavedra-Campos, MSc,5 Joanna Ellis, PhD,3 Meera Chand, FRCPath,6 Kevin Brown, FRCPath,3 Mary E

Ramsay, FFPH,1 Susan Hopkins,6 Nandini Shetty, FRCPath,3 J. Yimmy Chow, FFPH,4 Robin Gopal, PhD,3

Maria Zambon, FRCPath.3

1 Immunisation and Countermeasures Division, Public Health England, London, UK


2 Paediatric Infectious Diseases Research Group, St. George’s University of London, UK
3 Virus Reference department, Public Health England, London, UK
4 London Health Protection team, National Infection Service, Public Health England, London, UK
5 Field Service, National Infection Service, Public Health England
6 Antimicrobial Resistance and Hospital Acquired Infection Department, Public Health England,
London, UK

Corresponding author: Dr Shamez Ladhani, the Immunisation and Countermeasures Division, Public

Health England, 61 Colindale Avenue, London NW9 5EQ, United Kingdom. Email:

[email protected]

NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

1
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

ABSTRACT

Background: We investigated six London care homes experiencing a COVID-19 outbreak and found

very high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up

serological analysis in these care homes five weeks later.

Methods: Residents and staff had a convalescent blood sample for SARS-CoV-2 antibody levels and

neutralising antibodies by SARS-COV-2 RT-PCR five weeks after the primary COVID-19 outbreak

investigation.

Results :

Of the 518 residents and staff in the initial investigation, 208/241 (86.3%) surviving residents and

186/254 (73.2%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive

residents and staff were antibody positive five weeks later, whether symptomatic (residents 35/35,

100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.1%).

Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates

(residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic RT-PCR negative individuals

(residents 62/92, 67.3%; staff 95/143, 66.4%). Neutralising antibody was present in 118/132 (89.4%)

seropositive individuals and was not associated with age or symptoms. Ten residents (10/108, 9.3%)

remained RT-PCR positive, but with lower RT-PCR cycle threshold values; all 7 tested were

seropositive. New infections were detected in three residents and one staff member.

Conclusions

RT-PCR testing for SARS-CoV-2 significantly underestimates the true extent of an outbreak in

institutional settings. Elderly frail residents and younger healthier staff were equally able to mount

robust and neutralizing antibody responses to SARS-CoV-2. More than two-thirds of residents and

staff members had detectable antibodies against SARS-CoV-2 irrespective of their nasal swab RT-PCR

positivity or symptoms status.

2
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Introduction

Nursing and residential homes have been disproportionally affected by COVID-19 with high rates of

hospitalisations and deaths among residents because of their advanced age and underlying

comorbidities.1,2 In England, the first cases of imported COVID-19 cases were confirmed in late

January 2020 with autochthonous transmission established by early March 2020. Cases peaked in

mid-April before declining as a consequence of intense control measures.3 London, England, was one

of the most affected cities and large outbreaks associated with high case fatality rates (CFR) among

residents were reported in London care homes.3

During 10-13 April 2020, we investigated six London care homes reporting a suspected or confirmed

COVID-19 outbreak to Public Health England (PHE).4 We found that 105 (40%) of 264 residents and

52 (21%) of staff had confirmed SARS-CoV-2, with half of both groups remaining asymptomatic

throughout the surveillance period.4 Mass serological testing can help uncover the true extent of an

outbreak within the care home setting,5 and potentially inform staff allocation and cohorting

practices. Neutralising antibodies, in addition, may provide evidence for protection against

reinfection, especially among the older residents who may not reliably mount an adequate

protective response despite antibody production because of immunosenescence.6,7 As part of

follow-up investigations, the residents and staff in the six care homes experiencing a COVID-19

outbreak were followed-up with a repeat nasal swab and a blood sample five weeks after the initial

investigations. The study aimed to estimate SARS-CoV-2 seropositivity and neutralising antibodies in

care home residents and staff of care homes experiencing a COVID-19 outbreak and assess any

association with age, symptoms and SARS-CoV-2 RT-PCR positivity.

3
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Methods

The enhanced outbreak investigation initiated in April 2020 included six nursing and residential

homes of different sizes, providing care for 43-100 residents with 14-130 staff per care home, with a

confirmed COVID-19 outbreak.4 During the initial investigation, nasal swabs were taken for SARS-

CoV-2 RT-PCR for all residents and staff working in the care home at the time. Infection control

measures were reinforced and all SARS-CoV-2 RT-PCR positive individuals were isolated. All tested

participants were followed up for any symptoms during the two weeks before, at the time of testing

and for two weeks after the test.4

Follow-up investigation involved a repeat nasal swab and a blood sample from all participants five

weeks after the initial RT-PCR testing. Consent was obtained by care home managers from staff

members and residents or their next of kin as appropriate. Testing began on the week of May 18,

2020. Care home staff took nasal swabs for residents and submitted their own samples by self-

swabbing with appropriate instructions. Care home nurses took blood samples from residents and

their colleagues, with external phlebotomists assisting two care homes with sampling. It was not

appropriate or possible to involve patients or the public in the design, or conduct, or reporting, or

dissemination plans of our research

SARS-CoV-2 antibody testing

SARS-CoV-2 Infected virus lysate assay: Native virus antigen ELISA was modified from a previously

described MERS-CoV assay.8 Microplate bound detergent extracted lysates of SARS-CoV-2 (isolate

England/02/2020) infected Vero E6 cells and uninfected cells were reacted with a serial dilution of

convalescent serum obtained from participants in an indirect ELISA format. Virus lysates contained a

mixture of viral proteins expressed in Vero E6 cells, including viral nucleocapsid and spike proteins.

Microneutralisation assay and neutralising antibody titre.

4
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

SARS-CoV-2 (isolate England/02/2020) specific neutralising antibody levels were measured using a

modification of the WHO influenza microneutralisation methodology.9 Briefly, 200 TCID 50 of virus

was incubated with serial dilutions of serum from participants, after which a suspension of Vero E6

cells were added. After 22 hours, cells were fixed and in-cell SARS-CoV-2 nucleoprotein (NP)

expression determined by ELISA. The virus neutralising antibody titre was determined as the serum

concentration that that inhibited 50% SARS-CoV-2 NP expression. All work was undertaken in a BSL-3

laboratory.

SARS-CoV-2 PCR

Nucleic acid was extracted from samples and analysed by a real-time reverse transcription (RT) PCR

assay targeting a conserved region of the open reading frame (ORF1ab) gene of SARS CoV-2,

together with detection of an assay internal control to monitor the extraction and RT-PCR processes.

This assay used the primers and probe sequences made public by CDC China

(http://ivdc.chinacdc.cn/kyjz/202001/t20200121_211337.html) and required 5μL RNA in a total RT-

PCR reaction volume of 25μL. Reverse transcription and PCR amplification was performed on an

Applied Biosystems 7500 FAST system.

Statistical analysis

Descriptive analyses were performed. Data that did not follow a normal distribution were described

as medians with interquartile ranges and compared using the Mann Whitney U test. Antibody

concentrations were presented as ELISA index values with medians and 95% confidence intervals

(95% CI). Antibody concentrations above the index value of 0.5 were considered positive. Median

antibody concentrations were compared using Kruskal-Wallis with Dunn’s multiple comparisons test

adjustment. Categorical variables were described as proportions and compared using chi squared or

Fishers Exact test as appropriate. Data were analysed using Stata version 15.0 (Statcorp, Tx) and

GraphPad Prism.

5
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

RESULTS

Seropositivity

Of the original 518 residents and staff involved in the initial care home outbreak investigation during

10-13 April 2020, 394 (76.1%) consented for follow-up investigations at median of 36 days (range,

30-45 days) (Figure 1). SARS-CoV-2 seropositivity for the cohort was 77.9% (95%CI, 73.6-81.7%;

Table 1, Figure 2a ). Seropositivity was associated with being symptomatic and SARS-CoV-2 RT-PCR

nasal swab positive during at the initial test, but not with gender, age or being a resident or staff

member (Table 1, Figure 2).

Residents

Twenty-one of the 264 residents tested in the initial investigations died within two weeks and two

others died prior to follow-up testing. Thus, 186 of the remaining 241 residents who consented to

SARS-CoV-2 antibody testing and 81.2% (151/186) were seropositive. Of the 35 residents who had

been symptomatic during the outbreak and were PCR-positive during the initial testing period, all

were SARS-CoV-2 antibody positive (Figure 1, Figure 2c). At the same time, 97% (32/33) of residents

who were PCR-positive but remained asymptomatic throughout the outbreak were also SARS-CoV-2

antibody positive (Figure 1, Figure 2c). Of the 118 residents who had tested PCR-negative initially,

85.2% (23/27) of those who had been symptomatic during the outbreak were SARS-CoV-2 antibody

positive and 67.0% (61/91) of residents who remained asymptomatic (Figure 1, Figure 2c).

Staff

Among the 254 staff members involved in the initial investigation, 208 consented to additional

investigations and 75.0% (156/208) were seropositive (Figure 2a). All 22 staff members who were

SARS-CoV-2 RT-PCR positive at initial testing and symptomatic during the outbreak were positive for

SARS-CoV-2 antibodies, as were 95.5% (21/22) of RT-PCR positive asymptomatic staff (Figure 1,

Figure 2c ). There were 201 staff members who were SARS-CoV-2 RT-PCR negative and 25 went on to

develop COVID-19 compatible symptoms during the follow-up period; of the21 staff tested, 18

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medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

(85.7%) were SARS-CoV-2 antibody positive. The remaining 176 SARS-CoV-2 PCR negative staff

members were asymptomatic throughout the surveillance period and, of the 143 tested, 95 (66.4%)

were SARS-CoV-2 antibody positive (Figure 1, Figure 2c).

SARS-CoV-2 Antibody seropositivity and index values

There was no association between SARS-CoV-2 seropositivity and age (Chi-square test, P=0.31)

(Figure 3, left panel). Among SARS-CoV-2 antibody positive individuals, there was no significant

difference in median index value between the those who had been PCR positive or negative at initial

testing (Figure 3, right panel). There was no association between median SARS-CoV-2 antibody index

value and symptom status, PCR status or gender (data not shown). Six individuals had equivocal

SARS-CoV-2 antibody index values; all were asymptomatic throughout the surveillance period and

were SARS-CoV-2 RT-PCR negative on nasal swabs at both timepoints.

Neutralising antibodies

Neutralising antibodies were detected in 89.4% (118/132) of seropositive individuals. There was no

association between the detection of SARS-CoV-2 neutralising antibodies and age, sex, symptom

status or PCR status (Figures 4a-c, data not shown). There was a trend toward increasing neutralising

antibody titre with age (Figure 4d).

Nasal Swab RT-PCR

All consenting residents and staff had a repeat nasal swab at the time of blood sampling. Thirteen

residents were SARS-CoV-2 RT-PCR positive, including 10 who had been SARS-CoV-2 RT-PCR positive

at an interval of 36-45 days previously, although SARS-CoV-2 RT-PCR Ct values were significantly

lower at follow-up (Figure 5). Of these ten, 7 also had serum samples taken and all were

seropositive (Table 2). Four residents became SARS-CoV-2 RT-PCR positive at follow-up and were

seropositive (Figure 1); all remained asymptomatic. None of the SARS-CoV-2 RT-PCR positive staff at

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medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

the initial visit were positive on repeat testing. A previously SARS-CoV-2 RT-PCR negative staff

member who was asymptomatic throughout the surveillance period became positive on repeat

testing, with a Ct value of 35.6; this staff member was also seropositive for SARS-CoV-2 antibodies.

DISCUSSION

In six London care homes experiencing a COVID-19 outbreak at the peak of the pandemic, 81.2% of

surviving residents and 75.0% of staff were SARS-CoV-2 antibody positive five weeks after the initial

outbreak investigation. These rates are far higher than any other cohort including frontline

healthcare workers managing patients with confirmed COVID-19 in hospitals.10-12 Almost all residents

and staff who were SARS-CoV-2 RT-PCR positive on nasal swab at initial testing developed SARS-CoV-

2 antibodies, irrespective of whether they were symptomatic at any point during the outbreak. High

seropositivity rates were also observed for symptomatic residents and staff even if they had a

previously negative SARS-CoV-2 RT-PCR test. The serological investigation emphasises the extent to

which SARS CoV-2 can penetrate vulnerable communities in closed settings, and the

underestimation of exposure through point prevalence estimates using RT-PCR from nasal swabs.

The lowest seroprevalence was observed in residents and staff who remained asymptomatic

throughout the outbreak and who were SARS-CoV-2 RT-PCR negative on both testing visits but, even

in this cohort, more than two-thirds were positive for SARS-CoV-2 antibodies. In this cohort, SARS-

CoV-2 antibody levels were not associated with age, sex, presence of symptoms, PCR-positivity or

resident/staff status.

There are now sensitive and specific serological assays, such as the one used in this investigation

based on using native viral antigens derived from infected cells.13 Overall, a recent systematic review

estimated that serological tests had 30% sensitivity for SARS-CoV-2 antibodies during the first week

after symptom onset, rising to 72% in the second week, 91% in the third week and 96% up to 5

weeks later.14 The finding that almost all residents and staff with confirmed COVID-19 through nasal

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medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

swab SARS-CoV-2 RT-PCR – irrespective of whether they were ever experienced symptoms during

the outbreak – is reassuring and validates the use of our serological assay as a measure of past

exposure. The very high seropositivity rates among symptomatic but RT-PCR negative residents and

staff suggests that their original illness was also most likely due to COVID-19 and highlights the

sensitivity limitations of single point nasal swabbing for diagnosis and the narrow window of SARS-

CoV-2 detection in infected individuals, and significantly underestimated exposure to SARS-CoV-2 in

these outbreak settings.15 The very high seropositivity of 75.0% among care home staff compared to

17-44% of patient-facing healthcare workers is staggering.10,11 A possible explanation may be more

prolonged and intense exposure to the virus because of level of care required by the residents.2,15 In

our initial investigations, we also found evidence of transmission between staff members in care

homes, highlighting the importance of maintaining infection control practices for all contact,

including those between staff, whilst on care home premises.8 Despite reinforcement of infection

control measures at the outset, one further staff member and three residents became infected with

SARS-CoV-2 at follow-up. Residents and staff who were SARS-CoV-2 RT-PCR positive at follow-up all

had high Ct values, consistent with non-viable virus at the time of testing,4 and were also SARS-CoV-

2 antibody positive. Further studies are needed to assess whether the presence of SARS-CoV-2

antibodies, including neutralising antibodies, are protective against re-infection and, if so, the

duration of protection. Questions also remain as to whether antibody concentrations provide a

useful measure of protection in infected individuals.16

Notable, too in this study, was the observation that SARS-CoV-2 antibody levels were similar among

symptomatic and asymptomatic residents and staff across the care homes, which contrasts with

recent reports suggesting that higher antibody levels and persistence were achieved in patients with

more severe disease compared to those with mild disease or asymptomatic infection.12 The high

fatality rates among residents across the six care homes, particularly affecting those who had been

symptomatic and SARS CoV-2 RT-PCR positive indicates that that the cohort described here is more

9
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

representative of milder illness and depleted of individuals who suffered the most severe outcomes

of infection.4 We also found that 90% of seropositive staff and residents had neutralising antibody

responses, with no significant differences in neutralising antibody levels between by age, sex,

symptom status or staff/resident status. There was a trend towards increasing neutralising antibody

titres with increasing age (Figure 4c) but this was not statistically significant. These findings of such

robust antibody responses in surviving care home residents, especially when compared to younger,

healthier staff members with similar exposure risks to SARS-CoV-2, are novel and may play an

important part in future recommendations for infection control practices and vaccination against

SARS-CoV-2.

Several key questions relating to this novel pandemic remain to be answered and are particularly

relevant to this highly vulnerable population and setting. In particular, it is not known whether SARS-

CoV-2 antibodies are protective against re-infection.16 We identified a small number of residents

who were still RT-PCR positive up to five weeks later; all had detectable antibodies, including some

with neutralising antibodies at the time of the persistent virus detection.17 The RT-PCR Ct values

were consistent with non-live virus in all residents and staff members who were RT-PCR positive on

nasal swab at follow-up. The prolonged nasal swab RT-PCR positivity in a proportion of residents and

staff is consistent with a recent large healthcare worker study where up to a quarter were still RT-

PCR positive up to six weeks later, highlighting yet another limitation of our understanding of the

kinetics of viral replication and immune responses COVID-19.18,19

The strengths of our investigations include the extensive and robust epidemiological, virological and

serological testing of residents and staff across six London care homes experiencing large outbreaks

of COVID-19, the broad age ranges involved, the daily follow-up after initial testing and the high

uptake for retesting five weeks later. The data collected have provided a wealth of information on

SARS-CoV-2 infection, transmission and antibody responses in a high-risk care setting involving a

very vulnerable cohort. A limitation is that the care homes were already in the middle of the

10
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

outbreak. Consequently, some residents had already developed COVID-19 and some had died of

their infection. Another limitation was that we did not obtain blood samples for antibody testing at

the first visit, which could have provided additional useful information on antibody kinetics in a large

cohort of elderly residents and younger staff members. The lower nasal swab positivity during the

initial investigations compared to the antibody results five weeks later reflects the limited sensitivity

of test, the quality of sampling, the stage of infection at the time of testing and the gene targets

used by different RT-PCR assays.20 Some of these limitations could potentially have been mitigated

by repeated swabbing at different time points.

In conclusion, almost all residents and staff with confirmed SARS-CoV-2 infection had detectable

antibodies five weeks later, irrespective of whether they were ever symptomatic or remained

asymptomatic throughout the outbreak. Additionally, a high proportion of those who were

symptomatic but SARS-CoV-2 RT-PCR negative were also seropositive. SARS-CoV-2 antibody levels

were not associated with age, sex, PCR positivity, symptomatic/asymptomatic or resident/staff

status. Our findings demonstrate the older and vulnerable residents are able to mount a robust

antibody response to SARS-CoV-2 that is similar to younger and healthier staff members. Further

studies are needed to determine whether SARS-CoV-2 antibodies protect against re-infection and, if

so, the duration of protection.

Ethics approval : The research protocol was approved by the PHE Research Ethics and Governance

Group (REGG Ref: NR0204, 07 May 2020).

Role of the funding source : This study was funded by Public Health England as part of the COVID-19

response. The authors had sole responsibility for the study design, data collection, data analysis,

data interpretation, and writing of the report. The authors are all employed by Public Health

England, the study funder, which is a public body — an executive agency of the Department of

11
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

Health. The corresponding author had full access to all the data in the study and final responsibility

for the decision to submit for publication.

Acknowledgements : The authors are very grateful to the care home managers, their staff and the

residents for their willingness to support the investigation, along with the staff in the immunisation

and countermeasures division, PHE Operations, the virus reference department, the London

Coronavirus Response Cell and Field Services for their help and support with the investigation.

Conflicts of interest : none

Author Contribution : SNL, JYC and MZ conceived and designed the study; all authors contributed to

the analysis and interpretation of the data, and commented on the manuscript prior to submission

License statement:

“The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of

all authors, a worldwide licence to the Publishers and its licensees in perpetuity, in all forms, formats

and media (whether known now or created in the future), to i) publish, reproduce, distribute, display

and store the Contribution, ii) translate the Contribution into other languages, create adaptations,

reprints, include within collections and create summaries, extracts and/or, abstracts of the

Contribution, iii) create any other derivative work(s) based on the Contribution, iv) to exploit all

subsidiary rights in the Contribution, v) the inclusion of electronic links from the Contribution to third

party material where-ever it may be located; and, vi) licence any third party to do any or all of the

above."

Dissemination declaration : we have provided the overall findings of the study to the participating

care homes

Data Sharing: there are additional data for sharing

12
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

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medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY-NC-ND 4.0 International license .

n % total Seropositive (n) (%) 95% CI


Overall 394 100 307 77.9 73.6 - 81.7
Sex
Male 95 24.1 73 76.8 67.4 - 84.2
Female 299 75.9 234 78.3 73.2 - 82.6
p value 0.781
Age group
19-39 62 15.7 46 74.2 62.1 – 83.5
40-59 117 29.7 91 77.8 69.4 – 84.4
60-79 68 17.3 49 72.1 60.4 – 81.3
>80 147 37.3 121 82.3 75.4 – 87.6
p value 0.312
Residents and Staff

Residents 186 47.2 151 81.2 75.0 - 86.2


Staff 208 52.8 156 75.0 68.7 - 80.4
p value 0.151
Symptoms at any time during first test period
Symptomatic 105 26.6 98 93.3 86.9 - 96.7
Asymptomatic 289 73.4 209 72.3 66.9 - 77.2
p value <0.00011
First round PCR results
1st PCR + 112 28.4 110 98.2 93.7 - 99.7
1st PCR - 285 72.3 197 69.1 63.5 - 74.2
p value <0.00011

Table 1:Demographics of care homes cohort and seropositivity by group: percentage and 95%
confidence intervals shown. Statistical analysis using 1Fisher’s exact test and 2Chi square test of
proportions, p values as shown.

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medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
FIGURE 1.

It is made available under a CC-BY-NC-ND 4.0 International license .


Figure 1. Flow diagram of residents and staff in 6 London care homes experiencing a COVID-19 outbreak during the pandemic who consented to follow-up
testing including blood sampling for SARS-CoV-2 antibodies four to six weeks later. ‘Ever-symptomatic’ indicates that symptoms were experienced at some
point during the follow-up period.
*Four individuals in this group became SARS-CoV-2 PCR positive at follow-up RT-PCR testing conducted simultaneously with SARS-CoV-2 antibody testing.

16
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
FIGURE 2.

It is made available under a CC-BY-NC-ND 4.0 International license .


Figure 2. Proportion of indicated study populations with positive (maroon), equivocal (yellow) or negative (green) native viral antigen lysate assay. a)
Seroconversion for all cohort and staff and resident sub groups. b) Seroconversion by sex for whole cohort. c) Seroconversion by acute RT-PCR result and
presence of symptoms for residents and staff. All N = 394; Staff N= 208; Residents N= 186.

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medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
FIGURE 3.

It is made available under a CC-BY-NC-ND 4.0 International license .


Figure 3. Age group analysis native viral antigen lysate assay. Left panel: Seroconversion percentage by age group for whole cohort, N=394. Right panel:
Native viral antigen assay index value for seropositive individuals by initial RT-PCR status and age group, N=307. Bars indicate median and 95% confidence
interval. Dashed line indicates assay positive cut-off. Statistical analysis using Chi square test of proportion and Kruskal-Wallis with Dunn’s multiple
comparisons test, no significant difference.

18
medRxiv preprint doi: https://doi.org/10.1101/2020.08.10.20171413.this version posted August 12, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
FIGURE 4.

It is made available under a CC-BY-NC-ND 4.0 International license .


Figure 4. Virus neutralising antibody titre analysis. a) Virus neutralising positive and negative percentage by age group for whole cohort. N=132 b) Virus
neutralisation titre by sex. Bars indicate median and 95% confidence interval. c) Virus neutralisation titre by symptom status during the initial testing
period. Bars indicate median and 95% confidence interval. d) Virus neutralisation titre by age group. Box and whisker plot with bars indicating full range of
results. N=118. Statistical analysis a) chi-square test, no significant difference; b and c) Mann-Whitney U Test; d) Kruskal Wallis with Dunn’s multiple
comparisons test adjustment, no significant difference.

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