SIREN study

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

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.

Related articles

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. (2021). ‘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, 397(10283), 1459-1469
2. Hall, V. J., Foulkes, S., Saei, A., and others. (2021). ‘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, 397(10286), 1725-1735
3. Atti, A., Ferrari, M., Castillo-Olivares, J., and others. (2022) ‘Serological profile of first SARS-CoV-2 reinfection cases detected within the SIREN study’ J Infect, 84(2), 248-288
4. Hall, V., Foulkes, S., Insalata, F., and others. (2022). ‘Protection against SARS-CoV-2 after COVID-19 Vaccination and Previous Infection’ N Engl J Med, 386(13), 1207-1220
5. Wallace, S., Hall, V., Charlett, A., and others. (2022) ‘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 & REinfection EvaluatioN) study protocol’ BMJ Open, 12(6), e054336
6. Pople, D., Monk, E., Evans, S., and others. (2022) ‘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’ BMJ (Clinical research ed.), 378, e070379
7. Atti, A., Insalata, F., Carr, E. J., and others. SIREN Study Group and the Crick COVID Immunity Pipeline Consortium (2022) ‘Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study’. The Journal of infection, 85(5), 545–556.
8. Foulkes S, Monk E.J.M., Sparkes D, and others. ‘Early Warning Surveillance for SARS-CoV-2 Omicron Variants, United Kingdom, November 2021–September 2022’ Emerg Infect Dis. 2023;29(1):184-188
9. Atti, A., Insalata, F., Carr, E. J., and others. (2023) ‘Antibody correlates of protection against Delta infection after vaccination: A nested case-control within the UK-based Siren Study’ Journal of Infection
10. Howells, A, Aquino, EN, Bose, D, and others. (2023) ‘Demonstrating the learning and impact of embedding participant involvement in a pandemic research study: the experience of the SARS-CoV-2 immunity & reinfection evaluation (SIREN) study UK, 2020-2023’ Research Involvement and Engagement
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 2023 Nov 3:S0163-4453(23)00553-4

Pre-prints

1. S. Wallace, V. Hall, A. Charlett, P.D., and others. (2020) ‘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 2020.12.15.20247981; doi
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, A. D., 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 and Insalata, F and Carr, E., and others. ‘Antibody Correlates of Protection Against Delta Infection after Vaccination: A Nested Case-Control within the UK-Based Siren Study’ Available at SSRN
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-yearsecond year extension.

The Seefollowing listtable oflists 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	C;psed
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