Guidance

SIREN study

Providing vital research into COVID-19 immunity and vaccine effectiveness nationally.

From:
UK Health Security Agency
Published
20 June 2022
Last updated
5 April 2024 — See all updates

The SARS-CoV-2 immunity and reinfection evaluation (SIREN) study is a unique, large-scale partnership with NHS healthcare workers providing an agile response to an evolving pandemic. It is one of the national core studies established in response to COVID-19 and a National Institute for Health Research (NIHR) urgent priority study, and continues to provide vital research into immunity and vaccine effectiveness.

The SIREN study was established early in the pandemic with participants undergoing regular testing for up to 2 years. Analysis of these testing samples helps the UK to evaluate the immune response to COVID-19, build understanding of the protection offered by vaccines and provide insight into COVID-19 reinfections.

Healthcare workers are enrolled in the UK-wide SIREN study through the hospital site they work at. A total of 135 sites have participated in the study involving almost 45,000 participants, making SIREN the largest study of its kind globally.

In winter 2022 to 2023, multiplex polymerase chain reaction (PCR) testing was introduced through the SIREN Winter Pressures sub-study, adding testing for influenza (flu) and respiratory syncytial virus (RSV) alongside COVID-19.

SIREN 2.0, the new phase of the SIREN study, began in September 2023 with active testing on a smaller sub-cohort from the original cohort of 45,000 throughout winter 2023 to 2024.

SIREN 2.0 will continue to play a central role in surveillance of COVID-19 across the UK, including the detection of emerging new variants and other respiratory viruses using regular multiplex testing for COVID-19, influenza and RSV.

The SIREN study is registered with ISRCTN 284460.

Main findings from SIREN

The SIREN study has provided valuable evidence on immunity following SARS-CoV-2 infection and COVID-19 vaccination and provided surveillance data on infection and emerging variants. This evidence has played a critical role in informing the national COVID-19 response.

We have assessed the durability of protection following SARS-CoV-2 infection, COVID-19 vaccination, and a combination of the 2 (‘hybrid protection’) throughout the pandemic and across variant waves.

Our vaccine effectiveness findings, released in February 2021, demonstrating high short-term protection following the first 2 doses of COVID-19 vaccine in UK healthcare workers, provided important evidence to inform the UK roadmap out of lockdown.

In 2021, we established the SIREN Consortium consisting of academic, clinical and public health partners. This has allowed us to gain a better understanding of serological correlates of protection, and the role of T-cell responses in SARS-CoV-2. We are expanding this work for winter 2023 to 2024 for influenza and RSV.

We have also established a motivated and dynamic participant involvement panel in collaboration with the British Society for Immunology. The group is made up of SIREN study participants, with a diverse mix of gender, ethnicity and professions. They have helped to make sure SIREN continues to deliver relevant, feasible and translatable research, and have contributed directly to SIREN study protocols and co-author peer-reviewed papers.

Finally, SIREN will continue to work with our partners at Birmingham City University and within the UK Health Security Agency (UKHSA) to try and identify lessons from the pandemic, including understanding the barriers and facilitators for vaccination among healthcare workers, as part of our future pandemic preparedness response.

Watch videos for more information.

Our story:

The SIREN Study: Our story - YouTube

Learn from SIREN study research teams:

The SIREN Study: Hear from our research teams - YouTube

Learn from SIREN study participants:

The SIREN Study: Hear from our participants - YouTube

Learn about recent study findings:

SIREN 3 years on: Showcase of study findings - YouTube

Learn from the SIREN study team:

The SIREN Study: Hear from the SIREN study team - YouTube

Learn about SIREN 2.0:

Hear about SIREN 2.0:The SIREN Study: SIREN 2.0 update – YouTube

SIREN: the story so far

This infographic lists key moments during the SIREN study and indicates that the project has moved on to SIREN 2.0.

Text version of timeline

2020
May – ethics approval
June – first participant recruited
September – first reinfections investigated
December – vaccines introduced, SIREN investigates vaccine effectiveness, PITCH sub-study established

2021
January – first vaccine effectiveness analysis
March – 45,000 participants recruited in first year
July – SIREN continues for a second year
August – Medical Research Council £1.5 million funding establishes the SIREN consortium
October – serological re-infection analysis
December – first SIREN participant involvement panel (PIP)

2022
February – VIBRANT sub-study recruitment begins
October – enhanced questionnaires for symptoms
November to December – multiplex testing introduced
March – qualitative sub-study

2023
March – qualitative sub-study
August to September – recruitment opens to SIREN 2.0
September – SIREN 2.0

Partners

UKHSA runs the SIREN study in partnership with NHS sites, the Public Health Agency Northern Ireland, Public Health Scotland and Public Health Wales.

The SIREN study works with a number of academic partners. The SIREN Consortium was established in August 2021 and was successfully awarded a £1.57 million research grant by UK Research and Innovation (UKRI).

SIREN Consortium members include:

  • Wellcome Sanger Institute
  • The Francis Crick Institute
  • Protective Immunity from T cells to COVID-19 in Health workers (PITCH):
    • University of Oxford
    • University of Liverpool
    • University of Sheffield
    • Newcastle University
    • University of Birmingham
  • Humoral Immune Correlates for COVID-19 (HICC)
  • Imperial College London
  • University of Glasgow
  • British Society for Immunology
  • GenOMICC

For SIREN 2.0, we have established new collaborations with scientific partners, World Influenza Centre and the Wellcome Sanger Institute.

The Wellcome Sanger Institute in Cambridge is a world leader in genomic sequencing and metagenomics. They will sequence samples from the SIREN study and use metagenomics to investigate other pathogens that cause respiratory infection such as parainfluenza.

With the increasing interest in Influenza, we have also set up a collaboration with the World Influenza Centre (WIC) in London. The WIC is one of 6 centres in the world responsible for analysing influenza viruses circulating in the human population, overseen by the World Health Organization (WHO). We plan to share influenza viruses detected as part of SIREN 2.0, which may be used to design influenza vaccines for future seasons

Contributors

Staff across the 135 sites have helped with the running of the study.

Download a study contributors list (ODS, 26.8 KB).

Funding

The SIREN study is funded by UKHSA, the Department of Health and Social Care and NIHR, with contributions from the Scottish, Welsh and Northern Irish governments and funding awarded through research grants.

The SIREN study: answering the big questions.

SIREN: One year on.

SIREN: Two years on.

SIREN: The triple burden of flu, RSV and COVID-19 - UKHSA

SIREN Winter Pressure Study - Health Data Research UK

SIREN 2.0 press release


Scientific papers

Please find below a list of scientific outputs.

Published papers

  1. Hall V J, Foulkes S, Charlett A and others. ‘SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN)’ Lancet 2021: volume 397, issue 10,283, pages 1,459 to 1,469
  2. Hall V J, Foulkes S, Saei A and others. ‘COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study’ Lancet 2021: volume 397, issue 10,286, pages 1,725 to 1,735
  3. Atti A, Ferrari M, Castillo-Olivares J and others. ‘Serological profile of first SARS-CoV-2 reinfection cases detected within the SIREN study’ Journal of Infection 2022: volume 84, issue 2, pages 248 to 288
  4. Hall V, Foulkes S, Insalata F and others. ‘Protection against SARS-CoV-2 after COVID-19 vaccination and previous infection’ New England Journal of Medicine 2022: volume 386, issue 13, pages 1,207 to 1,220
  5. Wallace S, Hall V, Charlett A and others. ‘Impact of prior SARS-CoV-2 infection and COVID-19 vaccination on the subsequent incidence of COVID-19: a multicentre prospective cohort study among UK healthcare workers - the SIREN (Sarscov2 Immunity and REinfection EvaluatioN) study protocol’ British Medical Journal Open 2022: volume 12, issue 6, page e054336
  6. Pople D, Monk E, Evans S and others. ‘Burden of SARS-CoV-2 infection in healthcare workers during second wave in England and impact of vaccines: prospective multicentre cohort study (SIREN) and mathematical model’ British Medical Journal (Clinical research edition) 2022: volume 378, page e070379
  7. Atti A, Insalata F, Carr E J and others. SIREN Study Group and the Crick COVID Immunity Pipeline Consortium. ‘Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study’ The Journal of Infection 2022: volume 85, issue 5, pages 545 to 556
  8. Foulkes S, Monk EJM, Sparkes D and others. ‘Early Warning Surveillance for SARS-CoV-2 Omicron Variants, United Kingdom, November 2021 to September 2022’ Emerging Infectious Diseases 2023: volume 29, issue 1, pages 184 to 188
  9. Atti A, Insalata F, Carr E J and others. ‘Antibody correlates of protection against Delta infection after vaccination: a nested case-control within the UK-based Siren Study’ Journal of Infection 2023
  10. Howells A, Aquino EN, Bose D and others. ‘Demonstrating the learning and impact of embedding participant involvement in a pandemic research study: the experience of the SARS-CoV-2 immunity and reinfection evaluation (SIREN) study UK, 2020-2023’ Research Involvement and Engagement 2023
  11. Hall VJ, Insalata F, Foulkes S, and others. ‘Effectiveness of BNT162b2 mRNA vaccine third doses and previous infection in protecting against SARS-CoV-2 infections during the Delta and Omicron variant waves; the UK SIREN cohort study September 2021 to February 2022’ Journal of Infection November 2023: volume S0163-4453, issue 23, pages 00553 to 00554
  12. Kirwan PD, Hall VJ, Foulkes S et al. ‘Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort’. The Lancet Regional Health - Europe January 2024: volume 36, 100809

Pre-prints

  1. Wallace S, Hall V, Charlett A and others. ‘SIREN protocol: Impact of detectable anti-SARS-CoV-2 on the subsequent incidence of COVID-19 in 100,000 healthcare workers: do antibody positive healthcare workers have less reinfection than antibody negative healthcare workers?’ medRxiv 2020: 2020.12.15.20247981
  2. Hall V, Foulkes S, Charlett A and others (2021). ‘Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020’ medRxiv, 2021.2001.2013.21249642
  3. Hall V, Foulkes S, Insalata F and others (2021). ‘Effectiveness and durability of protection against future SARS-CoV-2 infection conferred by COVID-19 vaccination and previous infection; findings from the UK SIREN prospective cohort study of healthcare workers March 2020 to September 2021’ medRxiv, 2021.2011.2029.21267006
  4. Otter AD, D’Arcangelo S, Whitaker H and others (2022). ‘Determinants of SARS-CoV-2 anti-spike antibody levels following BNT162b2 vaccination: cross-sectional analysis of 6,000 SIREN study participants’ medRxiv, 2022.2004.2021.22274025
  5. Atti A, Insalata F, Carr E and others. ‘Antibody correlates of protection against Delta infection after vaccination: a nested case-control within the UK-Based SIREN study’
  6. Victoria J Hall, Ferdinando Insalata, Sarah Foulkes, Peter Kirwan, Dominic Sparkes,   Ana Atti, Michelle Cole, Elen de Lacy, Lesley Price, Diane Corrigan, Colin S Brown, Jasmin Islam, The SIREN Study Group, Andre Charlett, Susan Hopkins (2023). ‘Effectiveness of BNT162b2 mRNA vaccine third doses and previous infection in protecting against SARS-CoV-2 infections during the Delta and Omicron variant waves; the UK SIREN cohort study September 2021 to February 2022’
  7. Kirwan P, Hall V, Foulkes S and others (2023). ‘Protection of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort’ medRxiv 2023.09.29.23296330

Site list

In the first year of the SIREN study, 135 sites across the UK contributed, with 87 sites contributing to the second year extension.

The following table lists different SIREN study sites within England, Northern Ireland, Scotland and Wales. According to the year of the study, ‘active’ indicates sites with active SIREN testing and ‘closed’ indicates sites where SIREN testing has stopped.

Please note, SIREN participants at sites who are no longer actively testing remain important contributors to the study. They will continue to receive communications and key study updates from the SIREN team and may be offered opportunities for further involvement.

SIREN study site Year 1 Year 2 SIREN 2.0
England      
St George’s University Hospitals NHS Foundation Trust Active Active Active
University Hospitals Of Leicester NHS Trust Active Active Active
University Hospitals Plymouth NHS Trust Active Active Closed
Leeds Teaching Hospitals NHS Trust Active Active Active
Mid Essex Hospital Services NHS Trust Active Active Closed
North Middlesex University Hospital NHS Trust Active Active Closed
Liverpool University Hospitals NHS Foundation Trust Active Active Active
West Suffolk NHS Foundation Trust Active Active Closed
Sheffield Teaching Hospitals NHS Foundation Trust Active Active Active
University Hospitals of Morecambe Bay NHS Foundation Trust Active Active Active
Southend University Hospital NHS Foundation Trust Active Active Closed
University Hospitals Bristol and Weston NHS Foundation Trust Active Active Active
King’s College Hospital NHS Foundation Trust Active Active Closed
The Dudley Group NHS Foundation Trust Active Active Closed
Royal Devon and Exeter NHS Foundation Trust Active Active Closed
North Cumbria Integrated Care NHS Foundation Trust Active Active Closed
St Helens and Knowsley Teaching Hospitals NHS Trust Active Active Closed
Lewisham and Greenwich NHS Trust Active Active Closed
The Newcastle Upon Tyne Hospitals NHS Foundation Trust Active Active Active
The Princess Alexandra Hospital NHS Trust Active Active Active
Imperial College Healthcare NHS Trust Active Active Closed
Blackpool Teaching Hospitals NHS Foundation Trust Active Active Closed
East Suffolk and North Essex NHS Foundation Trust Active Active Closed
Hampshire Hospitals NHS Foundation Trust Active Active Closed
James Paget University Hospitals NHS Foundation Trust Active Active Active
Buckinghamshire Healthcare NHS Trust Active Active Active
Sheffield Children’s NHS Foundation Trust Active Active Active
Basildon and Thurrock University Hospitals NHS Foundation Trust Active Active Closed
Frimley Health NHS Foundation Trust Active Active Closed
Calderdale and Huddersfield NHS Foundation Trust Active Active Closed
United Lincolnshire Hospitals NHS Trust Active Active Closed
Isle Of Wight NHS Trust Active Active Active
Warrington and Halton Teaching Hospitals NHS Foundation Trust Active Active Closed
Royal Free London NHS Foundation Trust Active Active Closed
Whittington Health NHS Trust Active Active Active
The Clatterbridge Cancer Centre NHS Foundation Trust Active Active Closed
University Hospitals Of North Midlands NHS Trust Active Active Closed
Royal Papworth Hospital NHS Foundation Trust Active Active Active
Shrewsbury and Telford Hospital NHS Trust Active Active Active
Devon Partnership NHS Trust Active Active Closed
The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust Active Active Active
London North West University Healthcare NHS Trust Active Active Closed
Croydon Health Services NHS Trust Active Active Closed
Nottingham University Hospitals NHS Trust Active Active Active
Mid Cheshire Hospitals NHS Foundation Trust Active Active Active
Dartford and Gravesham NHS Trust Active Active Closed
Lancashire Teaching Hospitals NHS Foundation Trust Active Active Active
Bedfordshire Hospitals NHS Foundation Trust Active Active Closed
Shropshire Community Health NHS Trust Active Active Closed
Royal National Orthopaedic Hospital NHS Trust Active Active Closed
Stockport NHS Foundation Trust Active Active Active
Hounslow and Richmond Community Healthcare NHS Trust Active Active Active
Salisbury NHS Foundation Trust Active Active Active
Derbyshire Healthcare NHS Foundation Trust Active Active Active
Birmingham and Solihull Mental Health NHS Foundation Trust Active Active Closed
Black Country Healthcare NHS Foundation Trust Active Active Active
Solent NHS Trust Active Active Closed
Southern Health NHS Foundation Trust Active Active Active
George Eliot Hospital NHS Trust Active Active Closed
Lincolnshire Partnership NHS Foundation Trust Active Active Closed
The Hillingdon Hospitals NHS Foundation Trust Active Active Closed
Central and North West London NHS Foundation Trust Active Active Active
Lancashire and South Cumbria NHS Foundation Trust Active Active Active
Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust Active Active Closed
Bolton NHS Foundation Trust Active Active Closed
Southport and Ormskirk Hospital NHS Trust Active Active Closed
Norfolk and Norwich University Hospitals NHS Foundation Trust Active Active Active
Mid Yorkshire Hospitals NHS Trust Active Active Active
Somerset NHS Foundation Trust Active Closed Closed
University Hospitals Of Derby and Burton NHS Foundation Trust Active Closed Active
Sherwood Forest Hospitals NHS Foundation Trust Active Closed Closed
Gloucestershire Hospitals NHS Foundation Trust Active Closed Closed
Hull University Teaching Hospitals NHS Trust Active Closed Closed
Yeovil District Hospital NHS Foundation Trust Active Closed Closed
Sandwell and West Birmingham Hospitals NHS Trust Active Closed Closed
Royal Cornwall Hospitals NHS Trust Active Closed Closed
Moorfields Eye Hospital NHS Foundation Trust Active Closed Closed
Torbay and South Devon NHS Foundation Trust Active Closed Active
Ashford and St Peter’s Hospitals NHS Foundation Trust Active Closed Active
York Teaching Hospital NHS Foundation Trust Active Closed Closed
Northern Devon Healthcare NHS Trust Active Closed Closed
Countess Of Chester Hospital NHS Foundation Trust Active Closed Closed
Portsmouth Hospitals NHS Trust Active Closed Closed
Walsall Healthcare NHS Trust Active Closed Closed
Royal Surrey County Hospital NHS Foundation Trust Active Closed Active
University Hospital Southampton NHS Foundation Trust Active Closed Closed
Manchester University NHS Foundation Trust Active Closed Active
North West Anglia NHS Foundation Trust Active Closed Closed
Royal United Hospitals Bath NHS Foundation Trust Active Closed Closed
Surrey and Sussex Healthcare NHS Trust Active Closed Closed
Great Western Hospitals NHS Foundation Trust Active Closed Closed
Epsom and St Helier University Hospitals NHS Trust Active Closed Closed
University Hospitals Coventry and Warwickshire NHS Trust Active Closed Closed
Western Sussex Hospitals NHS Foundation Trust Active Closed Closed
The Royal Wolverhampton NHS Trust Active Closed Closed
Chesterfield Royal Hospital NHS Foundation Trust Active Closed Closed
Brighton and Sussex University Hospitals NHS Trust Active Closed Closed
Wye Valley NHS Trust Active Closed Closed
Wirral University Teaching Hospital NHS Foundation Trust Active Closed Closed
East Sussex Healthcare NHS Trust Active Closed Closed
Maidstone and Tunbridge Wells NHS Trust Active Closed Closed
Queen Victoria Hospital NHS Foundation Trust Active Closed Closed
Cornwall Partnership NHS Foundation Trust Active Closed Closed
The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust Active Closed Closed
Poole Hospital NHS Foundation Trust Active Closed Closed
Northern Lincolnshire and Goole NHS Foundation Trust Active Closed Closed
Leicestershire Partnership NHS Trust Active Closed Closed
Birmingham Community Healthcare NHS Foundation Trust Active Closed Closed
Dorset County Hospital NHS Foundation Trust Active Closed Closed
Alder Hey Children’s NHS Foundation Trust Active Closed Closed
Royal Berkshire NHS Foundation Trust Active Closed Closed
Dorset Healthcare University NHS Foundation Trust Active Closed Closed
Derbyshire Community Health Services NHS Foundation Trust Active Closed Active
Northern Ireland      
Southern Health and Social Care Trust Active Active Active
South Eastern Health and Social Care Active Active Active
Belfast Health and Social Care Trust Active Active Active
Western Health and Social Care Trust Active Active Closed
Northern Heath and Social Care Trust Active Active Closed
Scotland      
NHS Lothian Active Active Active
NHS Greater Glasgow and Clyde Active Active Active
NHS Lanarkshire Active Active Active
NHS Grampian Active Active Closed
NHS Highland Active Active Active
NHS Fife Active Active Active
NHS Forth Valley Active Active Active
Golden Jubilee National Hospital Active Active Active
NHS Western Isles Active Active Active
NHS Borders Active Active Closed
Wales      
Aneurin Bevan University LHB Active Active Active
Swansea Bay University LHB Active Active Closed
Cwm Taf Morgannwg University LHB Active Active Active
Hywel Dda University LHB Active Active Closed
Velindre NHS Trust Active Closed Closed
Betsi Cadwaladr University LHB Active Closed Closed
Powys Teaching LHB Active Closed Closed

SIREN 2.0 map

This map is a visual representation of the SIREN NHS sites listed above.

Published 20 June 2022
Last updated 5 April 2024 + show all updates

  1. Added reference 12 under 'published papers'.

  2. Added timeline infographic and map.

  3. Updated site list.

  4. Updated details of the study, main findings and added scientific papers.

  5. Added link to SIREN study video on recent findings.

  6. Added link to SIREN study team video and new study publication.

  7. Added videos about the SIREN study.

  8. Added link to 'Burden of SARS-CoV-2 infection in healthcare workers during second wave in England and impact of vaccines'.

  9. Added site contributors list.

  10. Added Study site list and link to 'SIREN: Two years on'.

  11. First published.

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