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: Notice of Substantial 
Amendment Number 4. 
 

Page 2 
South Central / Oxford A Research Ethics Committee 
Bristol Research Ethics Committee Centre 
Whitefriars Level 3 Block B Lewins Mead Bristol BS1 2NT                                                                                
21st Sept 2020 
Dear Research Ethics Committee, Dear Dr Davies 
  
RE: IRAS 281844 “COVID-19 consortium (COVIDsortium): Healthcare worker Bioresource and 
preliminary analysis: Immune Protection and Pathogenesis in SARS-CoV-2 (COVID-HCW Study)” 
Chief Investigator: Professor James Moon; Principal Investigator (Barts Health): Dr Thomas Treibel, 
Principal Investigator (Royal Free Hospital): Dr Marianna Fontana. 
 
Notice of Substantial Amendment - Number 4 
 
We would like to start by thanking the Committee for their continued support in enabling us to 
both expedite and continue the COVID-HCW Study (NCT04318314) under the extraordinary 
circumstance of the COVID-19 pandemic. With permissions in place, we were able to recruit the 
entire initial cohort of 400 participants within 7 working days - completed on the 1st of April 
2020. Since then we have expanded the study to a total of 731 participants across St. 
Bartholomew Hospital, NHS Nightingale and the Royal Free Hospital. These participants 
returned on a weekly basis at a high follow-up rate for 16 weeks until early August. We also 
performed a “repeat bleed” of participants with symptoms and serology of interest (Amendment 
3). Samples have been analysed by Public Health England (PHE) and internationally leading 
immunology and virology labs at UCL (Maine/Noursadeghi), Imperial (Boyton/Altman) and 
QMUL (McKnight). Since the arrival of the 1st wave of SARS-CoV-2, our understanding of this 
new disease has exponentially increased. In order to adapt to the rapidly changing research and 
clinical environments as well as the accumulating scientific body, we would like to amend our 
protocol to adapt to the changing landscape and impending second 2nd wave of SARS-CoV-2: 
 
1 
Increase in blood sampling volume at 6 and 12 months 
2 
Simplification of the cardiovascular substudy 
 
 
Main changes: We would be grateful if you considered the following amendments of our study: 
 
1) Increase in blood sampling volume at 6 and 12 months: The host response to SARS-
CoV-2 is both mediated by neutralising antibodies and the T cell response. Whereas 
serological analysis can be performed on relatively small blood volumes, work on neutralising 
antibodies and the T cell response require larger volumes. We investigated this in a sub-
cohort of 120 participants in a targeted rebleed in early August (amendment 3). Findings of 
this analysis are currently prepared for publication and are highly significant. In order to 
understand the significance of neutralisation and T cell response across the whole cohort, we 
would like the permission to increase the blood sampling at the 6 and 12 months follow-up to 
increase up to a total of 50mL: Serum (6mL), plasma (6mL), RNA pax (2.5mL), peripheral 
blood mononuclear cells (PBMC) for T cell response and neutralisation (35mL). The 
additional blood volume requested will not inconvenience participants as provisions and 
request for phlebotomy at 6 months has been requested previously as per “Notice of 
substantial amendment - number 3”.  
 

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2) Simplification of the cardiovascular substudy: We have simplified this study and removed 
the 24h blood pressure monitoring as this will be too burdensome for the participants.    
 
 
Thank you for considering our application for further amendment. If you have questions/queries 
about any aspects of the study, please contact us immediately.  
 
Prof James Moon, Chief Investigator,  
Dr Thomas Treibel, Principal Investigator Barts Health,  
Dr Charlotte Manisty, Principal Investigator Barts Health,  
Dr Marianna Fontana, Principal Investigator Royal Free Hospital. 

Section 2: Summary of change(s)
Was the study a clinicial trial of an investigational medicinal product (CTIMP) 
OR does the amendment make it one?:
Did the study involve adults lacking capacity OR does the amendment 
introduce this?:
Did the study involve the use of research exposures to ionising radiation (not 
involving the administration of radioactive substances) OR does the 
amendment introduce this?:
Did the study involve non-NHS/HSC organisations OR does the amendment 
introduce them?:
Northern Ireland
Change 1
Scotland
Did the study involve NHS/HSC organisations prior to this amendment?:
Which nations had participating NHS/HSC organisations prior to this 
amendment?
Which nations will have participating NHS/HSC organisations after this 
amendment?
Area of change (select)*:
Specific change (select - only available when area of 
change is selected first)*:
Further information (free text):
Participant Procedures 
Amendment following urgent safety measure(s) taken to protect participants
p
g
(
;
08/06/2020), we will request:
a) 50mls of blood total at each sampling interval of 6 and 12months. 
b) 50mls of blood to be made up of: Serum (6mL), plasma (6mL), RNA pax (2.5mL), peripheral 
blood mononuclear cells (PBMC) for T cell response and neutralisation (35mL).
Northern Ireland
England
Wales
Scotland
Is all or part of this amendment being resubmitted to the Research Ethics 
Committee (REC) as a modified amendment?
England
Wales
Please note: Each change being made as part of the amendment must be entered separately. For example, if an amendment to a clinical trial of an 
investigational medicinal product (CTIMP) involves an update to the Investigator's Brochure (IB), affecting the Reference Safety Information (RSI) and so the 
information documents to be given to participants, these should be entered into the amendment tool as three separate changes. A list of all possible changes is 
available on the "Glossary of Changes" tab. To add another change, tick the "Add another change" box.
1. Increase in blood sampling volume at 6 and 12 months
2. Simplification of the cardiovascular substudy
What type of UKECA-recognised Research Ethics Committee (REC) review 
is applicable?:
Has the study been reviewed by a UKECA-recognised Research Ethics 
Committee (REC) prior to this amendment?:
For office use
QC: No
Section 1: Project information
Short project title*:
IRAS project ID* (or REC reference if no IRAS project ID is 
available):
Sponsor amendment reference number*:
Did the study involve prisoners OR does the amendment introduce this?:
Did the study involve access to confidential patient information without 
consent OR does the amendment introduce this?:
Sponsor amendment date* (enter as DD/MM/YY):
Summary of amendment including justification*:
 COVID-19: Healthcare worker Bioresource: Immune and Pathogenesis
Where is the NHS/HSC Research Ethics Committee (REC) that reviewed the 
study based?:
281844
Non Substantial Amendment 4
17 September 2020
Was the study a clinical investigation or other study of a medical device OR 
does the amendment make it one?:
Project type:
Did the study involve the administration of radioactive substances, therefore 
requiring ARSAC review, OR does the amendment introduce this?:
Lead nation for the study:
Amendment Tool
v1.1 22 May 2020
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
No
No
Yes
No
Yes
No
Specific study
Research tissue bank
Research database
NHS/HSC REC
Ministry of Defence (MoDREC)
Yes
No
Yes
No
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Y
Y
Y
N
Y
Y
Y
Y
Y
N
N
N
Review bodies
Name [first name and surname]*:
Email address*:
Section 4: Review bodies for the amendment
Please note: This section is for information only. Details in this section will complete automatically based on the options selected in Sections 1 and 2.
Lock for submission
Please note: This button will only become available when all mandatory (*) fields have been completed. When the button is available, clicking it
will generate a PDF copy of the completed amendment tool that can be included in the amendment submission. Please ensure that the amendment tool is 
completed correctly before locking it for submission.
Lock for submission
Declaration by the Sponsor or authorised delegate
 •  I confirm that the Sponsor takes responsibility for the completed amendment tool
 •  I confirm that I have been formally authorised by the Sponsor to complete the amendment tool on their behalf
Section 3: Declaration(s) and lock for submission
Pushpsen Joshi
pushpsen.joshi1@nhs.net 
A
Overall Category:
Change 2:
National coordinating function
CAG
HMPPS
Scotland:
ARSAC
England and Wales:
National coordinating function
HSC REC
HSC Data Guardians
Prisons
REC (MCA)
PBPP
SPS (RAEC)
UK wide:
Full review:
Overall reviews for the amendment:
Substantial for review
Overall amendment type:
A
Change 1:
A
REC
Competent Authority
MHRA - Medicines
Competent Authority
MHRA - Devices
HRA and HCRW Approval
Category:
Notification only:
Radiation Assurance
UKSW Governance
Northern Ireland:
REC (AWIA)
Study Design 
Data collection, transfer or processing of identifiable participant information - Changes in 
arrangements or organisations involved (other than the addition of new participating 
organisations)
Area of change (select)*:
Add another change:
Simplification of the cardiovascular substudy: We have simplified this study and removed the 
24h blood pressure monitoring as this will be too burdensome for the participants.   
Northern Ireland
England
Wales
Scotland
Applicability:
Specific change (select - only available when area of 
change is selected first)*:
Further information (free text):
Change 2
Where are the participating NHS/HSC organisations located that will be affected by 
this change?*:
Will all participating NHS/HSC organisations be affected by this change, or only 
some?:
Scotland
Northern Ireland
Applicability:
Add another change:
Where are the participating NHS/HSC organisations located that will be affected by 
this change?*:
England
Wales
Will all participating NHS/HSC organisations be affected by this change, or only 
some?:
All
All
Some
Some
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