SIREN study
The SIREN study has been investigating SARS-CoV-2 infections and acute respiratory illness in healthcare workers since 2020, and providing vital research into the immune response to infection and vaccination.
The SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study is a prospective cohort study of hospital-based healthcare workers across the UK. It was established in 2020 as a pandemic response study, with 44,543 healthcare workers recruited from 135 NHS trusts or health boards. The study initially investigated SARS-CoV-2 reinfections and the durability of immunity following infection, and subsequently COVID-19 vaccination. It has expanded its scope to evaluate the impact of winter pressures on the healthcare workforce, and questions related to immunity more broadly. Since 2023, SIREN has been centrally run by the UK Health Security Agency (UKHSA).
SIREN+ has been running since 2024. This has involved data collection on symptoms and absence from work in 5,000 participants recruited from the original SIREN cohort. In addition to investigating winter pressures, SIREN+ provides an opportunity to address new research questions of public health importance that impact healthcare workers, including the emergence of multidrug-resistant organisms and risk factors for healthcare-associated infections.
The SIREN study is registered with .
Main findings from SIREN to date
Evaluating protection following infection and vaccination
Throughout the pandemic, the SIREN study has provided valuable evidence on immunity following SARS-CoV-2 infection and COVID-19 vaccination, which has directly informed pandemic policy including the road map out of lockdown.
Before vaccine roll-out in the UK, we found that .
We then assessed immediate in our cohort during Alpha variant circulation, which was over 85% for 2 vaccine doses.
Following this, we demonstrated that , supporting the decision to deploy vaccine booster campaigns in the UK.聽
Subsequently, we showed that , but were less effective against the then newly emerged Omicron variant compared to Delta variant.
We continued to analyse , finding these boosters provided modest and short-lived additional benefit against infection, in a context of increasingly complex hybrid immunity in the population.聽聽聽
Monitoring SARS-CoV-2 infections and assessing risk factors for infection in UK healthcare workers
With continuous testing since June 2020 until March 2024, we have monitored infections in healthcare workers across successive pandemic waves. Exploring , we identified occupational risks despite vaccination during England鈥檚 second wave.
However, when community and household exposures were the main drivers of infection.聽聽聽
Understanding SARS-CoV-2 immunity
With large-scale longitudinal serological testing, paired with regular PCR testing, the SIREN study is well-placed to address different aspects of serological response associated with SARS-CoV-2 infection and vaccination.聽We have amassed collections of longitudinal serum, pre and post event for reinfections and vaccine breakthroughs across different variants that are highly valuable for future immunological studies.
In the early stages of the pandemic, we demonstrated that titres of neutralising antibodies, a type of antibody that can prevent infection, , highlighting that neutralising antibodies could be used as a potential correlate of protection against SARS-CoV-2 infection.
We then compared reinfection cases pre-vaccination with matched controls (February 2021), .
This was (April to October 2021), in which we found that Delta neutralising antibody titres over 40 were associated with a substantial reduction in odds of infection (89%).聽聽
Quantifying the impact of winter pressures on the NHS workforce
In winter 2022/23, to include Influenza and RSV as well as SARS-CoV-2 using multiplex PCR, to improve our understanding of the burden of respiratory viruses in healthcare workers in the UK.
For 2022/2023 and 2023/2024, we have , with SARS-CoV-2 infections dominating, compounding service pressures through significant staff absence.
Videos
Our story
SIREN study research teams
SIREN study participants
Recent study findings
The SIREN study team
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, including:
- World Health Organisation (Europe Region)
- Francis Crick Institute
- Wellcome Sanger Institute
- University College London
- University of Cardiff
- University of Cambridge
- University of Oxford
- University of Liverpool
- University of Sheffield
- Newcastle University
- University of Birmingham
- Birmingham City University
- Imperial College London
- University of Glasgow
- Kings College London
- British Society of Immunology
There is a standardised application process for those interested in accessing SIREN Study samples and/or associated metadata. Applicants are expected to complete an electronic SIREN Study Sample and Data Form (). This captures the key information required for the SIREN Study Collaboration Oversight Group to review.
If you, before submitting your form, you want to have an informal discussion about the SIREN study samples and available data, please contact Victoria Hall at: Victoria.Hall@UKHSA.gov.uk
Research grants
- (2024) MRC: Targeting Coronaviruses through Fc-dependent Antibody Activities
- (2023) UKRI HDR-UK: SIREN Winter Pressures WP0034
- (2022) Medical Research Council: Protective Immunity through T Cells in Healthcare workers 2 (PITCH 2) MR/X009297/1
- (2021) Medical Research Council: Investigation of proven vaccine breakthrough by SARS-CoV-2 variants in UK healthcare worker cohorts: SIREN consortium & PITCH Plus Pathway. MR/W02067X/1
SIREN public participant involvement and engagement聽
Within SIREN we recognised the value of actively involving a panel of participants in the study, particularly given its scale and the role SIREN has played in informing the national pandemic response.
Our Participant Involvement Panel (PIP) is an active partnership between study participants with researchers that influences and shapes research. The SIREN PIP was established in collaboration with the British Society for Immunology as part of the SIREN Consortium, with the aim of providing regular feedback as the study has evolved over time. By actively involving people who our research is for and about, including during the design, implementation and evaluation stages of research has ensured the research conducted has remained relevant to the study cohort.
The PIP consists of approximately 10 SIREN participants, from a range of professions, ethnicities, age and genders across the UK in order to reflect the cohort.
The PIP has been involved in the co-development of core participant and public engagement activities which are essential to the running of the study including newsletters, webinars, blog posts, and has co-authored a peer review article.
Contributors
Staff across the 135 sites have helped with the running of the study.
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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
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- Health Data Research UK
Scientific papers
Please find below a list of scientific outputs.
Published papers
- Hall V J, Foulkes S, Charlett A and others. 鈥樷�� Lancet 2021: volume 397, issue 10,283, pages 1,459 to 1,469
- Hall V J, Foulkes S, Saei A and others. 鈥樷�� Lancet 2021: volume 397, issue 10,286, pages 1,725 to 1,735
- Atti A, Ferrari M, Castillo-Olivares J and others. 鈥樷�� Journal of Infection 2022: volume 84, issue 2, pages 248 to 288
- Hall V, Foulkes S, Insalata F and others. 鈥樷�� New England Journal of Medicine 2022: volume 386, issue 13, pages 1,207 to 1,220
- Wallace S, Hall V, Charlett A and others. 鈥樷�� British Medical Journal Open 2022: volume 12, issue 6, article e054336
- Pople D, Monk E, Evans S and others. 鈥樷�� British Medical Journal (Clinical research edition) 2022: volume 378, article e070379
- Atti A, Insalata F, Carr E J and others. SIREN Study Group and the Crick COVID Immunity Pipeline Consortium. 鈥樷�� The Journal of Infection 2022: volume 85, issue 5, pages 545 to 556
- Foulkes S, Monk EJM, Sparkes D and others. 鈥樷�� Emerging Infectious Diseases 2023: volume 29, issue 1, pages 184 to 188
- Atti A, Insalata F, Carr E J and others. 鈥樷�� Journal of Infection 2023
- Howells A, Aquino EN, Bose D and others. 鈥樷�� Research Involvement and Engagement 2023
- Hall VJ, Insalata F, Foulkes S, and others. 鈥樷�� Journal of Infection November 2023: volume S0163-4453, issue 23, pages 00553 to 00554
- Kirwan PD, Hall VJ, Foulkes S and others.聽.聽The Lancet Regional Health - Europe January 2024: volume 36, 100809
- Broad J, Sparkes D, Platt N and others.聽鈥欌�樎燵version 2; peer review: 1 approved with reservations].聽NIHR Open Research 2024: volume 4, issue 1
- Foulkes S, Evans J, Neill C and others. 鈥樷�� Journal of Infection August 2024
- Kirwan PD, Foulkes S, Munro K and others. 鈥� Journal of Infection 2024: volume 89, issue 5, pages 106,293 to 106,293
- Evans JM, Sergenson N, Dembinsky M and others. 鈥� BMC Medical Research Methodology 2024: volume 24, issue 1
- Monk EJM, Foulkes S, Munro K and others. 鈥� Journal of Infection 2024: volume 90, issue 2, pages 106,393 to 106,393
- Howells A, Munro K, Foulkes S and others. 鈥� BMC Medical Research Methodology 2025: volume 25, issue 1
- Atti A, England A, Sung J and others. 鈥樷�櫬燰accine 2025: volume 51, page 126898
- Bustamante Q, Sparkes D, Findlater L and others. 鈥� Vaccine 2025: volume 56, pages 127,160 to 127,160
- Munro K, Bustamante Q, Findlater L and others. 鈥� Journal of Hospital Infection (published online 1 May 2025)
- Foulkes S, Munro K, Sparkes D and others. 鈥樷�� PLOS One 2025: volume 20, issue 5, article e0316131
- Kamal A, Haywood J, Sparkes D and others. 鈥樷�� Public Health 2025: volume 246, page 105,818
- Russell S, Munro K, Foulkes S, and others. 鈥樷�� PLOS One 2025: volume 20, issue 6, article e0310758
Pre-prints
- Wallace S, Hall V, Charlett A and others. 鈥樷�� medRxiv 2020: 2020.12.15.20247981
- Hall V, Foulkes S, Charlett A and others. 鈥樷�� medRxiv 2021.2001.2013.21249642
- Hall V, Foulkes S, Insalata F and others. 鈥樷�� medRxiv 2021.2011.2029.21267006
- Otter AD, D鈥橝rcangelo S, Whitaker H and others. 鈥樷�� medRxiv 2022.2004.2021.22274025
- Atti A, Insalata F, Carr E and others. 鈥樷��
- Hettiarachchi N, Blick D, Coleman T, and others. 颅颅鈥樷�� Research Square (Research Square) (published online 19 February 2025)
- Foulkes S, Munro K, Sparkes D, and others. 鈥� MedRxiv (published online 10 March 2025)
- Insalata F, Atti A, Carr EJ, and others. 鈥樷�� medRxiv (Cold Spring Harbor Laboratory) (published online 2 June 2025)
- McGeoch LJ, Foulkes S, Whitaker H, and others. 鈥樷�� MedRxiv (published online 8 June 2025)
To contact the SIREN study team, please email siren@ukhsa.gov.uk
Updates to this page
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Added reference 13 to the list of published papers.
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Added reference 12 under 'published papers'.
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Updated details of the study, main findings and added scientific papers.
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Added link to SIREN study video on recent findings.
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Added link to SIREN study team video and new study publication.
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Added videos about the SIREN study.
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Added link to 'Burden of SARS-CoV-2 infection in healthcare workers during second wave in England and impact of vaccines'.
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Added site contributors list.
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Added Study site list and link to 'SIREN: Two years on'.
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First published.