COVID-19: Healthcare Worker Bioresource: Immune Protection and Pathogenesis in SARS-CoV-2
Conditions: Health Care Worker Patient Transmission, Coronavirus, Coronavirus Infections, Immunological Abnormality
Sponsor: University College, London

 
 
ID: 130852. 
Study: COVID-19: Healthcare Worker 
Bioresource: Immune Protection and 
Pathogenesis in SARS-CoV-2. 
NCT Number: 04318314. 
Document Date: 21/09/2020. 
Title of document: Full study protocol updated – 
Amendment 4 
 

 
 
 
 
COVID-19 consortium (COVIDsortium): Healthcare worker Bioresource and 
preliminary analysis: Immune Protection and Pathogenesis in SARS-CoV-2  
A study from the COVID-19 Research Strategy Oversight Group UCLH, plus Barts Hospital and 
Royal Free London NHS Foundation Trust.  
V1.4:   21/09/2020 (current). Previous versions are available at weblink.   
  
Professor James Moon 
Chief Investigator 
Barts Hospital and UCL Institute of Cardiovascular Science. 
james.moon1@nhs.net 
Professor Mahdad Noursadeghi 
Basic Science Lead 
UCL Infection & Immunity, Cruciform Building 
m.noursadeghi@ucl.ac.uk 
Dr Gabriella Captur 
Royal Free London NHS Foundation Trust; gabriella.captur@nhs.net 
Professor Steffen Petersen 
Barts Hospital and William Harvey Research Institute, Queen Mary 
University of London; s.e.petersen@qmul.ac.uk 
Dr Thomas Treibel 
Principle Investigator, Barts 
Barts Hospital and UCL Institute of Cardiovascular Science. 
Thomas.Treibel@nhs.net 
Dr Charlotte Manisty 
Principle Investigator, Barts 
Barts Heart Centre and UCL Institute of Cardiovascular Science. 
c.manisty@ucl.ac.uk 
Professor Ben O’Brien 
Clinical Director Perioperative Medicine (including Intensive Care); 
Barts Heart Centre and Department of Translational Medicine and 
Therapeutics, QMUL. ben.obrien@nhs.net 
Professor Hugh Montgomery 
Centre for Human Health and Performance and Whittington Hospital 
h.montgomery@ucl.ac.uk 
 

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Additional writing group: Dr Rhodri Davies, Dr Joao Augusto, Dr Katia Menacho, Dr Anish Bhuva, 
Mervyn Adiapen, Dr Sophie Welch, Maudrian Burton, Ruth Bowles, Jessry Veerapen, Dr Marianna 
Fontana, Dr Hibba Kurdi  
1st Review group: Dr Dan Davis, (DELPHIC COVID-19), Elena Halouni and Catherine Houlihan 
(SAFER), Alun Hughes/Reecha Sofat (UCL and UCLH COVID-19 research strategy group), Riyas Patel 
(Barts Peer review), Dr Heinke Kunst (Blizard institute, respiratory QMUL/Barts)     
 
 

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1. Abstract 
 
 
Modelling repurposed from pandemic influenza is currently informing all strategies for SARS-
CoV-2 and the disease COVID-19.  A customized disease specific understanding will be 
important to understand subsequent disease waves, vaccine development and therapeutics. For 
this reason, ISARIC (the International Severe Acute Respiratory and Emerging Infection 
Consortium) was set up in advance. This focuses on hospitalised and convalescent serum 
samples to understand severe illness and associated immune response. 
 
However, many subjects are seroconverting with mild or even subclinical disease.  Information 
is needed about subclinical infection, the significance of baseline immune status and the earliest 
immune changes that may occur in mild disease to compare with those of SARS-CoV-2. There 
is also a need to understand the vulnerability and response to COVID-19 of the NHS workforce 
of healthcare workers (HCWs). HCWs present a cohort with likely higher exposure and 
seroconversion rates than the general population, but who can be followed up with potential for 
serial testing enabling an insight into early disease and markers of risk for disease severity. 
 
We have set up “COVID-19: Healthcare worker Bioresource: Immune Protection and 
Pathogenesis in SARS-CoV-2” (Figure 1). This urgent fieldwork aims to secure significant 
(n=1000) sampling of healthcare workers (demographics, swabs, blood sampling) at baseline, 
and weekly whilst they are well and attending work, with acute sampling (if hospitalised, via 
ISARIC, if their admission hospital is part of the ISARIC network) and convalescent samples 
post illness. We will also collect samples at 6 and 12 months from baseline to assess for 
persistence/ decay of immune protection.  These will be used to address specific questions 
around the impact of baseline immune function, the earliest immune responses to infection, and 
the biology of those who get non-hospitalized disease for local research and as a national 
resource. A subset of participants will be invited to undertake in depth analysis of specific 
subsets of circulating immune cells that contribute to the immune response to the virus.   
  
The proposal links directly with other ongoing ISARIC and community COVID projects sampling 
in children and the older age population.  
 
Figure 1. Study design 
 

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2. Aims and Objectives 
- To swiftly create the bioresource to understand baseline host factors and early responses that 
determine protection and pathogenesis in SARS-CoV-2 infection across NHS HCWs.  
- to assess genetic influences on disease severity following infection with COVID-19 infection 
 
Hypothesis 
- Baseline immune status and early immune responses during subclinical phase of infection and 
including the pauci-symptomatic and seroconverters will mechanistically determine clinical 
outcomes in NHS HCWs. 
Primary objective 
Identify baseline and early immune responses that predict incident disease stratified by time 
interval to disease in NHS HCWs. 
Secondary objectives 
Identify immune responses that predict seroconversion in disease free NHS HCWs. 
Identify genetic determinants of disease severity following infection with SARS CoV-2.  
 
3. Links to other affiliated projects                                                     
This study substantially uses existing infrastructure:  Recruits into this study who are 
subsequently suspected to have COVID-19 can be co-recruited into ISARIC using ISARIC 
Ethics Ref: 13/SC/0149 (Oxford C Research Ethics Committee, UK CRN /CPMS ID 14152 IRAS 
ID126600 for acute samples and data collection. Sampling can be delivered via existing 
research personnel from furloughed projects (CLRN nurses, research fellows, Barts 
Bioresource). Convalescent sampling will be via an otherwise inactive Clinical Trials unit.  It 
links to 3 additional healthy cohort multi-time point surveillance projects: 
- DELPHIC COVID-19 substudy (n=1000 healthy asymptomatic in Camden via the MRC Unit for 
Lifelong Health and Ageing at UCL): Ethics Ref: 13/SC/0149 (Oxford C Research Ethics 
Committee), UK CRN /CPMS ID 14152. IRAS ID126600 
- SARS-CoV-2 Acquisition in Frontline Health Care Workers– Evaluation to Inform Response 
(SAFER) Study– submitted to HRA. This study focuses on healthcare worker behavior, risk 
perception and attitudes, correlating with subclinical virology and serology (monthly) as a 
seroconversion endpoint, rather than early immune responses)- PI Dr Eleni Nastouli/Dr 
Catherine Houlihan. 
4. Methods                                                      

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The proposed study is a prospective observational cohort design which will be carried out 
across three different trusts: Barts Health NHS Trust (St Bartholomew’s Hospital, The Royal 
London Hospital, Whipps Cross Hospital and Newham Hospital and NHS Nightingale), Royal 
Free London NHS Foundation Trust (Royal Free Hospital) and University College London 
Hospitals NHS Foundation Trust (UCLH). 
Participants will be asymptomatic front-facing HCWs who are involved with delivery of patient 
care in different areas of the corresponding hospitals above. 
a) Study participants 
We anticipate 1000 HCWs recruited from NHS trusts. Recruitment will be by hospital email, 
posters (Appendix 1), staff huddles, training session and participant information leaflets 
(Appendix 2).  We consider “walk-in” centres to assess likelihood of participation. It will be 
important to ensure there is no coercion/social pressure on staff to participate. 
All individuals will be working in the NHS Trusts listed above during the study period will be 
invited to participate (including nurses, doctors, health care assistants, pharmacists, ward clerk). 
We will also include participants who are redeployed to the NHS frontline and are working in 
clinical areas from other sectors due to the Coronavirus pandemic including: army workers, 
porters, cleaners, ambulance paramedics, etc.    
Participation will be voluntary and there will be no remuneration. Members of the research team 
will attend the above mentioned clinical areas to invite eligible staff to enroll. Verbal and written 
information will be provided to eligible staff, which includes a study participant information sheet 
(Appendix 2). The following personal information will be requested: name of the participants, 
phone number, date of birth, email, home address and NHS number (confirmed from the 
former). Eligible staff will have an opportunity to discuss any details further with the research 
team prior to enrolment.  
At the time of the original consent, participants were made aware that no clinical results will be 
available during the study. Since then, virus testing capacity has been expanded and antibody 
testing has been rolled out across NHS trusts. After consultation with participants, our sponsor 
(UCL) as well as the clinical and research leadership of our study sites, we would like to 
disclose all clinically-relevant validated diagnostic virus PCR and SARS-CoV-2 serology results 
to participants.   
 
On the 22nd of May 2020, we obtained written permission from the Chair of the research ethics 
committee Oxford A; see appendix) to offer participants the opportunity to receive results 
available at the time (the first five weeks of the study in the first 400 participants) and to ask if 
they wished occupational health to be informed (see email in Appendix 6). All participants were 
contacted on 22nd May 2020. To date >60% of participants requested access to their previous 
results.  
 
In this substantial amendment (#2; 08/06/2020), we will therefore offer participants the 
disclosure of results that: 

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a) have potential specific implications for participant health and well-being (as per initial ethics 
consent form) based on current knowledge. 
b) use validated diagnostic test platforms.   
For the sake of clarity, this means disclosure of SARS-CoV-2 antibody testing done with 
commercial assays in a diagnostically accredited laboratory; virus PCR results. Non-disclosure: 
assays performed solely in non-clinical / research setting - for example saliva test development 
results, experimental neutralising antibody results, transcriptomics results, non-approved 
micronutrient assays, pathogen genome sequencing, B or T cell characterisation results. 
All results disclosed will be provided in writing (NHS email) when they become available and 
accompanied by written clinical advice. 
Should we achieve a position where PCR results are anticipated to be available within 8 days of 
sampling, then participants will be informed at their follow-up visit prior to nasal swab sampling 
that this is possible, and that any positive results available within 8 days will be disclosed to the 
participant and occupational health (due to local infection control risks). This is in line with other 
recent HCW studies during COVID-19 (Rivett et al 2020). If the participant has concerns about 
potential occupational health involvement they can be offered to withdraw only from the viral 
PCR swab component of the study.   
Should local laboratory workflows and capacity not enable results to be available within 8 days, 
disclosure to Occupational health will not be made as there will be no public health/ institutional 
implications. 
 
Signed informed consent (Appendix 3) will be obtained from all participants prior to inclusion. 
RedCap data collection instruments are in appendix 4. 
Inclusion criteria: 
- Age at least 18 years AND 
- Asymptomatic (meaning healthy enough to attend work according to Trust policy at the time) 
AND 
- Work in the designated clinical environments for at least 5 hours for at least one day during the 
study period. 
Participants will be free to withdraw from the study at any point, but collection of these data is 
considered to be in the public interest and will fall under the scope of a 'Public task' by the 
GDPR definition. Under these conditions rights to erasure and data portability do not apply, and 
archiving and further processing for scientific research purposes is compatible with the original 
purpose; no further participant data from medical records will be collected.  
The research team may withdraw a participant from the study in the following situations:  
-   No longer meets the inclusion/exclusion criteria if participants circumstance change  
b) Study period 

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The study period is 12 months, with baseline data collection and subsequent weekly sample 
and data collection for 16 weeks (until after the predicted peak of the pandemic in London). 
Data and samples will also be collected at 6 and 12 months (post-baseline) to monitor duration 
of protective immunity (i.e. decay in immunoprotection).  
c) Sample Size                                                                                   
We have designed a primary analysis around a baseline frequency of infection of less than 
0.2% average over recruitment period and a seroconversion rate of 30% of which 10% will be 
hospitalised and potentially enter ISARIC. However, this sample will link to other studies and the 
responses we are seeking are emergent and unknown. The incidence of SARS-CoV-2 among 
HCW (either symptomatic or asymptomatic) is not known and thus sample size calculations are 
challenging.  The basic reproduction number (R0) of this virus is assumed to be between 2 and 
3, but one cannot estimate the number of patients admitted and the effectiveness of staff 
protection measures. The original sample size of n=400 was chosen for pragmatic reasons. The 
lead site (Barts) recruited 400 participants in just over 7 working days. In order to be powered to 
identify genetic determinants of SARS CoV-2 infection disease severity a larger cohort is 
required; a sample size of n=1000 is considered to have sufficient power for assessing for 
genetic influences and feasible given the rapid recruitment rates at the Barts site.  
We anticipate using multiple sites to secure staff participation to 1000, subject to local site 
approval. Should it be possible with sufficient interest, staff and consumables, this number will 
be expanded. Furthermore, if there is sufficient interest in study participation, recruitment will be 
stratified by sampling by sex, age and ethnicity. Currently age categories proposed are between 
25-40,>40-55,>55. 
d) Study design  
A baseline questionnaire and sample collection will be performed, followed by weekly 
resampling (Figure 1) for 16 weeks, and two additional visits at 6 and 12 months time. 
  
 
1 Baseline questionnaire 
Consented study participants will complete a brief baseline questionnaire which collects 
standard variables related to demographics (including household size and details), 
anthropometry, past medical history including drug and vaccination history and SARS-CoV-2 
symptoms, exposure and prior testing, and contact history including details of work-based 
exposure and personal protective equipment used. See Appendix 4 (RedCap eCRF) for details. 
 
2 Baseline sample collection 
 
We aim to capture pre-infection levels of several markers (and how they evolve), including but 
not restricted to immune cell population (e.g., pre-infection antibody levels against other 
coronaviruses might influence host response to SARS-CoV-2), genomic and transcriptomic 
profiles. Sample collection will include: 
 

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a. Nose swabs: Nose swabs will be performed at baseline and weekly for the duration of the 
study. Participates will self-swab to minimise the risk of potential contamination or 
aerosolisation. Swab samples will be collected from a designated collection point by the 
research staff and submitted to the designated laboratory at each site within 48 hours of 
collection. Only staff who are asymptomatic and not currently self-isolating at home will be 
recruited for baseline sample collection. 
 
b. Blood samples (summarized in Table 1):  
-      Blood samples collected at baseline will consist of 1 x blue PAXgene RNA (2.5ml), 2 x 
yellow biochemistry gel tube (6ml), 2 purple EDTA plasma (5ml) and 1 purple EDTA DNA 
(5ml) totalling 29.5mL. Research staff will arrange blood sample collection in the hospital 
at a conveniently accessible location and at a suitable time for the participant. Blood 
samples will be stored at -20, 40 or 80°For the first week until delivery to secure -80C. 
Processing, aliquoting and analysis will be handled outside this fieldwork application.  
-      In the case of blood sample failure (vacuum partially gone, iv access only partial success, 
processing failure) we will ask the participant for a second sample (re-bleed request) if this 
is practically possible (e.g. immediately or at next scheduled follow-up; total <30mL).    
 
c. Saliva sample (summarized in Table 1):  
- 
We will ask participants to pool 2-3mL of saliva into commercially used saliva collection 
tube (see diagram on the right). This system is designed to prevent leak/ spillage and 
consists of the tube with an attached funnel and flip-top lid. 
- 
Saliva contains most of the same antibodies, proteins and nucleic acid markers that can be 
found in blood. We will use an ultrasensitive measurement technology, with single molecule 
sensitivity which enables even very low levels of molecular marker to be quantified. Only 
small quantities of saliva are needed for each test; the aims is to validate this test on 
COVID-19 and deliver High Throughput assay technology that can be used for the 
detection of IgM, IgG and IgA in saliva against SARS-CoV-2 with high reliability and 
precision. 
3 Interval questionnaire and sampling 
Following recruitment all participants will undertake weekly swabs, blood sampling and health 
questionnaire assessments. Additional questions that may be asked at this point include 
questions related to new symptoms, coronavirus test results (where relevant), new exposures, 
sense of smell (detailed validated smell questionnaire in collaboration with Mr Matt Lechner, 
Associate Professor ENT Surgery and Head and Neck Cancer Research, UCL) and other 
potential influences on disease severity (exercise, hormone status, micronutrients).  
Depending on the participant’s status progression (see Figure 1) such follow-up will take place 
in either of 3 places: at the workplace i.e. Barts (if well and attending work), in the 
ward/intensive care unit (if SARS-CoV-2 positive and admitted to hospital) or at home (if SARS-
CoV-2 positive and self-isolating at home).  
 
Four types of status progression are predicted for enrolled participants: 

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3.1) Asymptomatic course without exposure to SARS-CoV-2 positive cases necessitating 
isolation– samples will continue to be collected while at work in-hospital, by research staff. 
Participants will be serially screened for any symptoms consistent with SARS-CoV-2 , e.g. fever, 
continuous cough, shortness of breath. If COVID-19 prevalence in the community and among 
HCW is low, the study team may reduce the sampling frequency to alternate weeks. Participants 
will be informed about this change in the weekly appointment message (email / text / whatsapp 
depending on preference).    
 
3.1a) Nasal Swab: A nasal swab will be taken on each weekly follow-up.  
 
3.1b) Follow-up blood sampling: Blood samples collected at weekly intervals (8.5mL - 1 x 
blue PAXgene RNA [2.5ml] + 1 x yellow biochemistry gel tube [6ml]). 
 
-      Week 4,8,12,16: We will take an additional 1x EDTA for PBMCs at month 1,2,3,4 (+5mls). 
 
- 
At 6 months and 12 months follow-up, 50mL of blood will be taken: Serum (6mL), 
plasma (6mL), RNA pax (2.5mL), peripheral blood mononuclear cells (PBMC) for T cell 
response and neutralisation (35mL).   
3.1c) A saliva sample will also be taken at the first possible time point after ethics approval for 
baseline (baseline or week 4-6). In participants that are PCR or antibody positive (after 
disclosure), we would like to invite participants to increase frequency of saliva sampling to 
weekly to understand test performance over time. Consumables and a research nurse to cover 
this additional work are already in place. Saliva samples will also be collected at 6 months and 
12 months.  
 
 

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Table 1: List of laboratory samples to be taken during the study: Baseline and Follow-up 
 
Volume 
(in mL) Baseline Week 
2+3 
Week 
4 
Week 
5-7 
Week 
8 
Week 
9-11 
Week 
12 
Week 
13-15 
Week 
16 
Month 
6 
Month 
12 
*Convalecence 
(replacing 
scheduled 
collection) 
Optional 
Home 
Visit 
Nasal Swab 
 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
Saliva 
 
 
 
1 
0 
0 
0 
0 
0 
0 
1 
1 
1 
1 
Purple DNA 
5 
1 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
Purple 
PBMC/Plasma 
5 
2 
0 
1 
0 
1 
0 
1 
0 
1 
7 
7 
1 
0 
Blue Pax RNA 
2.5 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
0 
Yellow Serum 
6 
2 
1 
1 
1 
1 
1 
1 
1 
1 
2 
2 
2 
0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Volumes/visit 
 
29.5 
8.5 
13.5 
8.5 
13.5 
8.5 
13.5 
8.5 
13.5 
49.5 
49.5 
19.5 
0 
Total over 6 
months 
287 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Convalence 
visit = first visit 
after self-
isolation with 
symptoms  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 2. List of key samples to be collected and planned laboratory procedures.  
Biosample type 
[Time points] 
Processing 
[Volume] 
Key analyte 
[Analysis laboratory] 
Nasal swab 
[Baseline & F/U] 
Freeze -80°C 
Molecular testing for SARS-CoV-
2 ± other pathogens 
[UCLH virology lab] 
Saliva sample 
[Week 4, convalescent, 2x at months 6 
and 12] 
Freeze -80°C 
Molecular testing for SARS-CoV-
2 ± other pathogens 
Serum tube  
[Baseline, all follow ups, convalescent] 
Analyse 
  
SARS-CoV-2 antibody testing i.e. 
IgG, IgM 
 

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PAX RNA gene tube 
[Baseline, all follow ups, convalescent] 
Freeze -80°C 
  
Transcriptomics 
  
PAX DNA gene tube 
[Baseline only] 
Freeze -80°C 
  
Genetics  
  
F/U = follow-up. Other abbreviations see main text. 
 
3.2) Symptomatic course or suspected (not-confirmed) SARS-CoV-2 infection 
necessitating self-isolation at home– we will record the number of days participants 
remain away from work, any treatment received, and whether they receive a formal SARS-
CoV-2 diagnosis as the result of routine clinical testing. During their illness, they will be 
advised to follow Public Health England national guidance and will be assessed and treated 
by routine clinical services, as required. We will offer the participants to opt-in to have a 
swab and saliva collection tube sent to their home address for self-sampling.  
 
On the first return after a symptomatic course of suspected (not-confirmed) SARS-CoV-2 
infection necessitating self-isolation at home, they rejoin the sampling scheme as detailed 
in 3.1. On this visit we will take an additional 11mL blood (1 x biochemistry; 1 x EDTA for 
PBMCs = total 19.5mL) and a saliva sample. 
 
3.3)  SARS-CoV-2 positive participants admitted to hospital– participants with a confirmed 
SARS-CoV-2 positivity diagnosis (on the basis of research or clinically mediated testing) will 
be asked to report this to the study team. At the point of hospital admission, such 
participants automatically enter the ISARIC trial for subsequent sample collection and 
analysis.  
 
3.4) Target blood donation in selected participants: A specific objective of the bioresource 
is to provide the opportunity to undertake further in depth analysis of immune responses to 
SARS-CoV-2 in selected participants on the basis of demographic, clinical and laboratory 
characteristics during the follow up period. We will invite individuals to attend an additional 
study visit to give one extra blood sample of up to 120 mL. This volume of blood is equivalent 
to one quarter of the volume donated to routine blood bank service in the UK. This volume is 
necessary to undertake in depth analysis of specific subsets of circulating immune cells that 
contribute to the immune response to the virus. Requests for participant recall by investigators 
will be made in writing to the bioresource steering group, who will be responsible for ensuring 
that the request is within the scope of the aims of the bioresource, and responsible for inviting 
the participants for the additional sample. Participants will be free to decline this additional 
sample without giving a reason and without affecting their participation in the remainder of the 
study. 
 

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3.5) Cardiovascular Substudy:  
As the vast majority of infected participants have been pauci- or asymptomatic, this data will 
be important to contrast the cardiovascular effects of COVID-19 in hospitalised patients 
requiring simple oxygen or critical care treatment. This data will be compiled as part of the 
European CARTESIAN Consortium (Covid-19 effects on ARTErial StIffness and vascular 
AgeiNg Study). These adverse vascular effects of COVID-19 are likely to result in lasting 
damage to the vasculature and accelerated vascular aging. These vascular effects can be 
assessed using simple non-invasive tests. Identifying the presence, the causes and 
progression of early vascular ageing in COVID-19 patients will improve cardiovascular risk 
assessment and patient management.  If participants agree to take part, they will undergo 
non-invasive measurement of pulse wave velocity, central and peripheral blood pressure (15 
minutes) at the three or six and twelve months visits: 
● Resting clinic brachial BP and pulse readings will be taken using a Sphygmocor device. 
Central blood pressure will be estimated by pulse wave analysis (PWA).  
● Vascular stiffness will be assessed by carotid-femoral Pulse Wave Velocity (PWV) 
measurement using a Vicorder device.  
 
Safety measures related to staff, research team members, recruited participants are detailed in 
section 6 (“Duty of care”).  
 
4 Sample and data collection 
 
After sample collection all vials/tubes will be consolidated in a transport bag. Only the EDTA 
tube for PBMCs (peripheral blood mononuclear cells) will be spun (by Professor Aine Mcknight, 
QMUL) to reduce the risk to staff processing samples. All other tubes and nasal swabs will be 
frozen in the same gel separator tube used for sample collection immediately at -80 degrees on 
site. Table 2 details the sampling strategy.  
 
Data collection instruments are in RedCap and based on those of ISARIC. Specific questions 
related to immune status and home/work exposure are included in the eCRF. (appendix 4). 
5 Biosample procedures (as per Trust policy and PPE guidance) 
Obtaining baseline nasal swab samples 
-   Wear designated aprons, surgical masks and visors. 
-   Apply alcohol gel to hands and then apply fresh gloves. 
-   Explain procedure clearly to HCW. 
-   Label the sample tube with the appropriate participant number. 
-   Ask participants to open their mouths and say “ahhh”. 
-   Swab nostril and/or posterior pharynx (for the latter avoid saliva and tongue, rotating 
swab covering left and right faucial pillars). 
-   Place COPAN swab immediately into a sterile tube containing 2-3 ml of viral transport 
media. 
-   Follow the instructions in section below for transport of samples.  
 

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Obtaining baseline blood samples 
-   No sharp should be exposed/unsheathed without the necessary sharps container 
available in which to discard it. 
-   Label the blood tube with the appropriate participant number. 
-   Identify the vein and clean the overlying skin with a chlorhexidine skin swab. Discard in 
a clinical waste bag. 
-   Using the BD vacutainer push button blood collection set with pre-attached holder, 
insert needle into identified vein. Then attach to the vacutainer system: 
o   5ml yellow topped serum blood collection tube x 2  
o   5ml purple topped EDTA blood collection tube x 2  
o   2.5ml PAXgeneRNA blood collection tube 
    -   Once the blood tubes are full, remove the tube from the collection system, place in 2     
        leak proof bags with absorbent material (Safety gel granules) and seal. 
-   Press the push button on the blood collection system and the needle will retract from 
the vein into the plastic receptacle, ensuring a completely sharp safe system. 
-   Discard the used blood collection system into the sharps container. 
-   Discard any gauze used to stop bleeding into the clinical waste bag. 
-   Follow the instructions in section below for containment of samples for transport. 
 
 
Post-sampling 
All samples at the point of sampling should have been placed in a leak proof bag with absorbent 
material (safety gel granules) and sealed. Following this: 
-   Ensure the specimen bag is tightly sealed and wipes the outside of the bag with a 
Medical high level disinfectant wipe. They then discard the wipe in a clinical waste bag. 
-   Once sample collection is complete and samples are contained within their respective 
transport packs, personal protective equipment can be removed. 
-   Ensure a heavy duty clinical waste bag is available for disposal of waste. 
-   Clean gloves with alcohol gel. 
-   Tear apron ties and remove apron by folding in on itself, discard in waste bag 
-   Remove mask and visor by snapping ties and pulling forwards, then discard in a clinical 
waste bag. 
-   Remove gloves inside out without skin touching the outer aspect of the glove. Discard 
in the waste bag. 
-   Clean hands with alcohol gel. 
All waste to be disposed of at recruiting hospitals according to PHE recommendations.  
 
6 Follow-up: Subjects will be assessed weekly until 16 weeks, with a further visit at 6 months 
and 12 months from baseline visit.  Follow-up sampling will consist of one nasal swab, blood 
and saliva sample collection as per Table 1.  
In the event of participants being unable to attend for a follow-up visit (reasons might include 
being re-deployed to work at a different site, shifts preventing visits, self-isolation due to 
household symptoms, self-isolation due to infection), that visit will be omitted and the participant 
will attend the next scheduled visit.  

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If home-self isolation occurs due to symptoms, and subjects have consented to opt-in to self-
collection of nasal swabs and saliva, participants will be couriered the appropriate means to 
collect these samples. These samples will be collected by the study team and returned to the 
study laboratory using appropriate infection control procedures. 
When participants return to work following self-isolation due to symptoms, sample collection will 
include additional samples to capture convalescent serology including sputum collection. 
 
6. Duty of Care  
 
Usually for a study like this, all participants will receive clinical advice on managing any 
symptoms through the Chief Investigator as well as any clinically actionable results from FBC, 
U&E, CRP. Here however, with a rapidly evolving situation, recruited staff will use the same 
advice channels as all other staff in line with NHS/ Public Health England recommendations. 
                               
e) Safety: Potential Harm and Risks 
Study participants:This is a study recruiting HCW who are well and attending work. They are 
therefore self-declaring as asymptomatic, and are attending a “dirty” healthcare environment.  
Swabs are the standard COPAN nasal flu swabs and are not considered a coughing risk with 
training. Blood sample collection may cause slight bruising at the venepuncture site, but weekly 
sampling is not an unusual sampling periodicity. The total blood volume at baseline is estimated 
at ~30mL. As with all staff recruitment projects, there is concern about coercion to enrol. To 
mitigate against this we are following the Barts “Guidance on obtaining and using human blood 
and tissue from healthy volunteers for research purposes”. 
Research staff:  At enrolment study participants will consist of well and asymptomatic HCWs 
attending work, but during subsequent follow-up HCWs may well develop symptoms or a formal 
SARS-CoV-2 diagnosis. No participants should be attending if symptomatic as they should not 
be working. Protection of research staff collecting samples will consist of surgical masks, visor, 
gloves and apron implying minimal consumption of PPE as the visor and surgical mask can be 
reused by one nurse for multiple encounters whilst gloves will be changed each time. This will 
be as per Trust policy. Staff will train participants to obtain their own nasal swabs to minimise 
the risk of staff exposure and maximise yield. Saliva collection is via commercially-available kits 
to minimise potential for spillage. 
Sampling strategy: This has been designed to be as safe as possible for maximum scientific 
yield, and to minimise burden on stretched infrastructure. This means: no sampling of 
symptomatic subjects or of HCWs once they begin self-isolation or after confirmation of SARS-
CoV-2 positivity. No complex sample processing (no opening of tubes – no aliquoting, no 
lymphocyte isolation, no use of staff needed by PHE or NHS labs). Spinning is routine for 
multiple epidemiological studies and done in a sample preparation room, not category 2 lab. All 
samples can be batch spun (e.g. morning and evening). We note also that for coronavirus, 
blood is substantially virus free. Appropriate practice will be implemented in case of blood spills.  
Hospital infrastructure: Staffing will be stretched. For this project we anticipate around 10 staff 
being used.  At Barts, this will be 6 staff.  This compares to an employee base of 15,500 (ie 

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assuming one third at work clinically, this study consumes 0.1% of staff time. The attendance for 
bloods is estimated at 15 minutes. The space needed is 2 rooms for blood tests and 1 sample 
prep room per site for 50 subjects/day. At BHC for example, this would be the ante rooms of the 
MRI scanners (2 of which will be mothballed so the space is not otherwise used and has sinks 
and reclining chairs for blood sampling). We identify a clean route for travel to the site. We have 
multiple sites with centrifuges and local -40 or -80 freezers for interim sample storage. 
Contingency: Staff from UCL Lifelong health and aging are available to help recruitment/ 
follow-up should other staff not be available. Funding redundancy has been requested. 
f) Dissemination of results 
At completion of the study, findings will be disseminated to all participants, to the hospital 
management and relevant groups (for example, infection control), and to all hospital staff at 
arranged open meetings. It is anticipated that the samples will be analysed at the end of the 
project, so it will not be possible for individual staff members to be identified as having tested 
positive (or negative) for SARS-CoV-2 or immune response during this project. Individual staff 
members who are interested in their personal results will be able to access these via the study 
nurse or PI at the end of the study. 
g) Ethics: Ethical approval for the study is in place from the NHS Health Research 
Authority Research Ethics Committee and University College London Ethics board. 
h) Sample access: Samples will be coordinated by Professor Madhad Noursadeghi 
locally. We expect to make these nationally available subject to a process that 
maximises yield for society. 
i) Review process: Approvals are documented in appendix 7: Local review has 
been at Barts (Peer review group Riyaz Patel, Andrew Wragg), UCL (Professor Pier 
Lambiase and Alun Hughes), and JRMO (Professor Steffen Petersen) 
There has been additional review and approval by the Barts COVID-19 Research 
Committee (chair Professor Rupert Pearse) in conjunction with Barts JRMO - contact 
Mays Jaward, Governance operations manager JRMO M.jawad@qmul.ac.uk 
References 
1. ISARIC documentation, downloaded here  
https://www.dropbox.com/sh/2risg0y9tlmakit/AAAxXJ21kAjDMwLCpAD_kmvUa/branches/Englan
d/v8.2?dl=0&subfolder_nav_tracking=1 
2. Barts and QMUL Guidance on obtaining and using human blood and tissue from healthy 
volunteers for research purposes v1.0. Created 14/1/2020, author Amy Shou, available from the 
authors. 
 

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Appendix 1. Recruitment Poster                                              Version 1.4 21/09/2020 
 
 
 
 

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ADD PIS AND CONSENT AS APPENDIX 3 & 4 
 
 
 
Appendix 4. RedCap data Collection 
See document with highlighted changes attached  
Appendix 5. Biosample procedures 
1. Obtaining nasal swab samples 
-       Apply alcohol gel to hands and then apply fresh gloves. 
-       Explain procedure clearly to participants and explain that they will be collecting their own 
swabs and need to swab each nostril for 15 seconds etc. 
-       Label the sample tube with the appropriate participant number. 
-      Ask the participants to collect their own samples 
-       Place COPAN swabs immediately into sterile tubes containing 2-3 ml of viral transport 
media.  
-       Then follow the instructions in the section below for transport of samples. 
  
 2. Obtaining blood samples 
-       NO sharp should be exposed/unsheathed without the necessary sharps container 
available in which to discard it. 
-       Label the blood tube with the appropriate participant number. 
-       Identify the vein and clean the overlying skin with a chlorhexidine skin swab. Discard in a 
clinical waste bag. 
-       Using the BD vacutainer push button blood collection set with pre-attached holder, insert 
needle into identified vein. Then attach to the vacutainer system and collect the blood 
bottles outlined in Table 1 
-       Once the blood tubes are full, remove the tube from the collection system, place in 2 leak 
proof bags with absorbent material (Safety gel granules) and seal. 
-       Press the push button on the blood collection system and the needle will retract from the 
vein into the plastic receptacle, ensuring a completely sharp safe system.  
-       Discard the used blood collection system into the sharps container. 
-       Discard any gauze used to stop bleeding into the clinical waste bag. 
-       Follow the instructions in the section below for containment of samples for transport. 
 
3. Obtain saliva sample: collection kit including OmniGene 505 collection tube; a biohazard bag. 
Donation should typically take less than 5 minutes: 
I. 
Do NOT remove the plastic film from the funnel lid. 
II. 
Allow saliva to pool under the tongue.  

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III. 
With the head tilted forwards, gently guide saliva from the mouth into the collection tube. 
This way, a clear, non-foaming liquid is produced. 
IV. 
Spit into funnel until the amount of liquid (not bubbles) reaches the fill line shown in the 
picture below.  
V. 
Do not close the funnel lid. Hold the tube upright. Unscrew the funnel from the tube. 
VI. 
Use the small cap to close the tube tightly. Discard the funnel. 
VII. 
Place the tube into the biohazard bag and seal it closed. Place the biohazard bag into 
the fridge until collection. 
4. Post-sampling 
-       All samples at the point of sampling should have been placed in a leak proof bag and sealed. 
Following this: 
-       Once sample collection is complete and samples are contained within their respective 
transport packs, personal protective equipment can be removed. 
-       Ensure a heavy duty clinical waste bag is available for disposal of waste. 
-       Clean gloves with alcohol gel. 
-       Tear apron ties and remove apron by folding in on itself, discard in waste bag 
-       Clean gloves with alcohol gel. 
-       Remove mask and visor by snapping ties and pulling forwards, then discard in a clinical 
waste bag. 
-       Remove gloves inside out without skin touching the outer aspect of the glove. Discard in 
the waste bag. 
-       Clean hands with alcohol gel. 
  
  
Sample storage at source 
-      After all home visits have been conducted, samples may be consolidated in the transport 
bag. 
-      Samples of direct clinical relevance will be sent to UCLH NHS laboratory and actioned 
clinically within 48 hours. 
-      COPAN oropharyngeal swabs in symptomatic patients (c/o Dr Eleni Nastouli, Consultant 
Virologist, UCLH) for SARS-CoV-2 and other routine respiratory virus testing. 
-      Full blood count (FBC), urea and electrolytes (U&E), C reactive protein (CRP) (serum 
tube no. 1, EDTA tube no. 1.) 
-      Research samples will be transferred to Imperial College Infectious Diseases research 
laboratory (c/o Professor Michael Levin, Imperial College). 
-       Samples will be delivered at the end of each working day. 
  
Hospitalisation 
In the event a participant is hospitalised, we ask that the team is informed, and that they tell the 
admitting hospital highlight that they are in this project, and request that they be recruited to the 
main ISARIC protocol where appropriate. Local ISARIC teams and this project will liaise re 
collection of convalescent samples. 

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Data management and sharing 
All data will continue to be collected using existing RedCap infrastructure used at UCL and 
QMUL (AIMES hosted). All data is pseudoanonymised with no personal identifiable information 
available, with a participant identification number assigned to each participant for identification 
purposes on REDCAP. The key linking participant identification number with participant 
identifiable data will be stored on the research drive on the relevant NHS Trust Server. 
  
  
 
  
 
 
 
 
 
 
 
 
 
 
 

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Appendix 6. Flow Chart for SAE reporting 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix 7: Endorsements and approvals 
 
From: Hugh Davies <hughtdavies@gmail.com> 
Sent: 22 May 2020 19:32 
To: MOON, James (BARTS HEALTH NHS TRUST) 
Subject: Re: Fw: COVID19- Healthcare worker Bioresource: Immune Protection and Pathogenesis in 
SARS-CoV-2 Study 
  
Dear James 
 
Thank you for your email. 
 
You ask  
"Please may I be permitted to inform participants and their employers of the historic results?" 
 
As chair of the Oxford A REC, acting urgently, I would agree that the participants should be asked if they 
wish to be told their historic results now they are available and also asked if they wish occupational health 
to be informed.  They should also be told that if they wish to seek advice on these results then they 
should contact the Employee Well being service (number provided). 
 
This I think is a proportionate approach. 
 
I hope this helps and that this important study can continue. 
 
With best wishes 
 
Hugh Davies 
Chair Oxford A REC 
 
 

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Professor Alun Hughes 
 
  
Hughes, Alun vialiveuclac.onmicrosoft.com  
Sorry forgot to say that the MRC unit for 
Lifelong Health and Aging will be happy to 
assist through re-deployment of their clinic staff 
if required.  
I've discussed it with Nish  
BW Professor Alun Hughes 
Professor Pier Lambiase 
12:39 PM (28 minutes 
ago) 
  
 
 

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