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,study, providingand 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 viathrough 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.

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FindingsMain 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.

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Partners

The UK Health Security Agency (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
• The Francis Crick Institute
• 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 – study.

downloadDownload a study contributors list here (ODS, 26.926.8 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.

FurtherRelated informationarticles

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-year extension. See list of SIREN study sites.