Condition category
Infections and Infestations
Date applied
25/07/2019
Date assigned
01/06/2020
Last edited
03/08/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
The aim of this study is to help understand the story of infectious diseases in England. One of the ways bodies develop protection against infectious diseases is by developing antibodies, either after an infection or following vaccination. Researchers can measure the antibodies to see how well-protected people are from those infectious diseases. To start with they are looking at COVID-19, group C meningococcus (MenC) and diphtheria. By looking for antibodies against infectious diseases such as COVID-19 they can tell what proportion of the population has come into contact with the disease.

Who can participate?
Group 1: Male or female, aged 0 - 24 inclusive
Group 2: Male or female, aged 0 - 19 inclusive

What does the study involve?
The researchers are working with Public Health England to collect blood and saliva samples from a selection of 0-24-year-olds from across England. Basic demographic characteristics will be collected by questionnaire and/or case report form and will include: date of birth, gender, GP details, ethnic group, association with communities of special interest, household income and vaccination history.

What are the possible benefits and risks of participating?
This information collected will help Public Health England and the Scientific Advisory Group for Emergencies (SAGE) make decisions on how they manage the COVID-19 pandemic response now and in the future.

Where is the study run from?
University of Oxford (UK)

When is the study starting and how long is it expected to run for?
July 2019 to June 2021

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Dr Helen Ratcliffe
whatsthestory@ovg.ox.ac.uk

Trial website

http://whatsthestory.org.uk

Contact information

Type

Scientific

Primary contact

Dr Helen Ratcliffe

ORCID ID

Contact details

Oxford Vaccine Group Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
+44 (0)1865 611400
whatsthestory@ovg.ox.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

NCT04061382

Protocol/serial number

CPMS 42523, IRAS 263097

Study information

Scientific title

Sero-epidemiological survey of England in 2019/2020

Acronym

What's the STORY

Study hypothesis

Public Health England has an ongoing seroprevalence programme to assess how well the population is protected from vaccine-preventable diseases. The current way to check this is by testing leftover blood samples from participating healthcare laboratories around the country. However, these samples may not be representative of the general population, particularly in younger age groups who are often most at risk from vaccine-preventable diseases. In the Netherlands, they use a different system to assess how well the population is protected from vaccine-preventable diseases, actively collecting blood samples from a representative cross-section of society. This type of approach would address the limitations of using residual serum samples and allows the collection of additional relevant history e.g. number of family members and previous vaccines received. The investigators are therefore proposing a pilot study to assess the feasibility of establishing a national seroepidemiological survey in England in individuals aged 0 - 24 years. The investigators will be focusing initially on diphtheria and Group C invasive meningococcal disease, both of which are vaccine-preventable. This will involve enrolling 2300 participants in the study from different geographical and socioeconomic backgrounds across our test sites and taking a blood sample. This blood will be analysed to look at the level of immunity to vaccine-preventable diseases.

The original protocol has been amended to include the testing of antibodies against other infectious diseases, specifically COVID-19. A second group has been added to recruit an additional 500 to 1200 participants between the ages of 0-19 years. The additional funding has been used to open two more sites to recruit to group two across regions on England that are currently not represented by this study. Having a large number of blood samples from a range of age groups is useful when gathering information about an emerging disease such as the current novel coronavirus (COVID-19). These samples can help provide answers regarding the true number of infections with SARS-CoV-2 (the virus which causes COVID-19 disease) in this population.

In addition to increasing the sample size and the number of regions in the UK that are being sampled a longitudinal sampling cohort has been introduced. Approximately 20% of participants equally distributed over the age bands will be enrolled into the longitudinal aspect of the study where repeat blood and saliva samples are taken to look for antibodies against SARS-CoV-2. A questionnaire to ascertain whether the participant or any household contacts have had any symptoms of or been tested positive for COVID-19 will also be collected.

Added 29/07/2020:
A proportion of participants from this group from selected sites will also provide up to a maximum of three blood samples for separation of peripheral blood mononuclear cells (PBMCs) to evaluate T cell responses. These participants can be either seronegative or seropositive at their Visit 1.

Ethics approval

Approved 20/06/2019, London - Surrey Research Ethics Committee (Whitefriars, Level 3, Block B, Lewins Mead, Bristol, BS1 2NT, UK; +44 (0)207 1048310; surrey.rec@hra.nhs.uk), REC ref: 19/LO/1040

Study design

Prospective cross-sectional seroprevalence study

Primary study design

Observational

Secondary study design

Cross sectional study

Trial setting

Community

Trial type

Screening

Patient information sheet

Participant information sheets are available on the website http://whatsthestory.org.uk under each study site location

Condition

Diphtheria, group C meningococcus infection, COVID-19 (SARS-CoV-2 infection)

Intervention

This is a pilot study to assess the feasibility of establishing a national seroepidemiological survey in England in individuals aged 0-24 years, focusing initially on diphtheria and group C invasive meningococcal disease. The researchers are aiming to recruit 2300 individuals and are aiming to ensure that sample is broadly representative of the region according to IMD (Index of Multiple Deprivation scores). The PHE generated a list of all postcodes in recruiting regions and determining the quintiles of IMD within that region. Participants interested in taking part in the study will contact sites to arrange a visit. Basic demographic characteristics will be collected by questionnaire and/ or case report form (CRF) and will include: DOB, gender, GP details, ethnic group, association with communities of special interest, household income and vaccination history.

Randomised selection of population - Group 1
Group 1 will be focusing on COVID-19, diphtheria and group C invasive meningococcal disease. The investigators are aiming to recruit around 2300 individuals and the investigators are aiming to ensure that sample is broadly representative of the region according to IMD (Index of Multiple Deprivation scores). PHE has generated a list of all postcodes in recruiting regions and determining the quintiles of IMD within that region. Participants interested in taking part in the study will contact sites to arrange a visit. Basic demographic characteristics will be collected by questionnaire and/ or case report form (CRF) and will include: DOB, gender, GP details, ethnic group, association with communities of special interest, household income and vaccination history.

Group 2
Group 2 will focus on 0-19-year-olds only. They will not be restricted to postcode sampling. Instead, this will include standard recruitment methods such as social media advertisements within the normal recruiting regions for each site.

Added 29/07/2020:
A proportion of participants from this group from selected sites will also provide up to a maximum of three blood samples for separation of peripheral blood mononuclear cells (PBMCs) to evaluate T cell responses. These participants can be either seronegative or seropositive at their Visit 1.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Feasibility of a population-based seroepidemiological programme measured by response rate and participation in the study as proved by questionnaire completion, sample collection and database records at baseline
2. Added public health benefit measured by comparison with serological markers of immunity for vaccine-preventable diseases as measured in an age-matched cohort in the current residual sera programme which will occur at the end of the study

Secondary outcome measures

1. Effectiveness of recruitment methods measured by the number and rate of successfully enrolled participants at Visit 1
2. Antibody concentrations against infections and vaccine-preventable diseases starting with diphtheria, menC and SARS-CoV-2; measures include Anti-Diphtheria Toxoid concentrations, serum bactericidal activity (SBA) titres and serum IgG to SARS-CoV-2 antigens. SARS COV-2 samples will be tested as samples are being collected whereas serum for diphtheria and menC will be tested at the end of the study
3. Prevalence, kinetics of antibodies, of SARS-CoV-2 infections in 0–19-year-olds, and variation in prevalence in time, age and geography, measured by ELISA and/or neutralising assay at baseline and 3 subsequent visits every 2-3 months
4. Serum and salivary antibodies against SARS-CoV-2 measured by ELISA in 3 visits every 2-3 months following baseline

Exploratory outcome measures:
1. Presence of SARS-CoV-2 virus in saliva measured by saliva swab in 3 visits every 2-3 months following baseline
2. Recruitment strategies in Group 1 and Group 2 measured with demographic data collected by the questionnaire and regional census data at baseline

Added 29/07/2020:
3. T cell responses to SARS-CoV-2 antigens including, but not limited to S, M and N proteins, as measured by techniques including, but not limited to ELISpot ICS Proliferation assay at the 3 subsequent visits every 2-4 months
4. Antigen-specific IgG and T cells against non-SARS-CoV-2 coronaviruses (e.g. NL62 and 229E) at the 3 subsequent visits every 2-4 months

Overall trial start date

04/07/2019

Overall trial end date

30/06/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Parents/legal guardians or adult participant* is willing and able to give informed consent for participation in the study.
2. Male or female, aged 0 - 24 years inclusive (Group 1)
3. Male or female, aged 0 - 19 years inclusive (Group 2)
4. Parents/legal guardians or adult participants are willing to allow their General Practitioner or relevant NHS databases to be contacted for a full immunisation history

Participant type

Healthy volunteer

Age group

Mixed

Gender

Both

Target number of participants

Up to 3500

Participant exclusion criteria

If participants do not live in the postcode districts selected by PHE (Group 1 only)
1. Medically diagnosed bleeding disorder
2. Medically diagnosed platelet disorder
3. Anticoagulation medication
4. Pregnancy
5. If another member of their household is participating who is within 5 years of age of the potential participant's age

Temporary exclusion criteria:
The participant may not enter the study if they or any member of their household is under temporary isolation measures for suspected SARS-CoV-2 infection.

Recruitment start date

15/10/2019

Recruitment end date

31/12/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Oxford
Oxford Vaccine Group Churchill Hospital Old Road Headington
Oxford
OX3 7LE
United Kingdom

Trial participating centre

Bradford Teaching Hospitals NHS Foundation Trust
NIHR Clinical Research Network: Yorkshire and Humber Neonatal Research Office, Transitional care, M2
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

University Hospitals Bristol NHS Foundation Trust
Level 6, UH Bristol Education and Research Centre Upper Maudlin Street
Bristol
BS2 8AE
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
Great George Street
Leeds
LS1 3EX
United Kingdom

Trial participating centre

Royal Manchester Children’s Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Sheffield Children's Hospital
Research and Innovation D Floor Stephenson Wing Sheffield Children's Hospital Western Bank
Sheffield
S10 2TH
United Kingdom

Trial participating centre

University Hospital Southampton NHS Foundation Trust
SGH – Level E, Laboratory & Pathology Block, LE123 – MP 138
Southampton
SO16 6YD
United Kingdom

Trial participating centre

St George's University Hospitals NHS Foundation Trust
Paediatric Infectious Diseases Research Group St. Georges University of London Jenner Wing, Level 2, Room 2.216F, Mail Point J2C
London
SW17 0RE
United Kingdom

Trial participating centre

University of Nottingham Health Service
Cripps Health Centre University Park
Nottingham
NG7 2QW
United Kingdom

Trial participating centre

University Hospitals Plymouth NHS Trust
Derriford Road Crownhill
Plymouth
PL6 8DH
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Joint Research Office
1st Floor
Boundary Brook House
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
+44 (0)1865 611400
info@ovg.ox.ac.uk

Sponsor type

University/education

Website

https://www.ovg.ox.ac.uk/

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The study protocol is available on http://whatsthestory.org.uk.

The investigators will coordinate the dissemination of data from this study. All publications (e.g. manuscripts, abstracts, oral/slide presentations, book chapters) based on this study will be reviewed by all investigators prior to submission. Participants will have access to a summary of our study results either by post or an emailed link to our website with an abstract.

IPD sharing statement
The data-sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/06/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

03/08/2020: Internal review. 29/07/2020: The study hypothesis, interventions and secondary outcome measures were updated. 19/05/2020: Trial's existence confirmed by the NIHR.