SIREN study

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 ISRCTN 284460.

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 previous SARS-CoV-2 infection reduced the risk of a new infection by 84% for up to 7 months following infection.

We then assessed immediate protection provided by BNT162b2 vaccines in our cohort during Alpha variant circulation, which was over 85% for 2 vaccine doses.

Following this, we demonstrated that protection from 2 COVID-19 vaccine doses waned after 6 months, supporting the decision to deploy vaccine booster campaigns in the UK. 

Subsequently, we showed that vaccine boosters increased protection, but were less effective against the then newly emerged Omicron variant compared to Delta variant.

We continued to analyse protection after subsequent vaccine boosters deployed 2022/23 and 2023/24, finding these boosters provided modest and short-lived additional benefit against infection, in a context of increasingly complex hybrid immunity in the population.   

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 risk factors for healthcare worker infections, we identified occupational risks despite vaccination during England’s second wave.

However, this risk was not observed in subsequent waves when community and household exposures were the main drivers of infection.   

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. 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, were low or absent before reinfection, 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), demonstrating that detectable neutralising antibody titres (over 40) were associated with a significant reduction in odds of reinfection (over 90%).

This was supported by findings post-vaccination (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%).  

Quantifying the impact of winter pressures on the NHS workforce

In winter 2022/23, SIREN expanded its testing 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 demonstrated that COVID-19, influenza and RSV are experienced simultaneously in healthcare workers, with SARS-CoV-2 infections dominating, compounding service pressures through significant staff absence.

Videos

Our story

The SIREN Study: Our story - YouTube

SIREN study research teams

The SIREN Study: Hear from our research teams - YouTube

SIREN study participants

The SIREN Study: Hear from our participants - YouTube

Recent study findings

SIREN 3 years on: Showcase of study findings - YouTube

The SIREN study team

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

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, 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 (SIREN Study Sample and/or Data Request 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 

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.

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: 2 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, article 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, article 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 and others. ‘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
13. Broad J, Sparkes D, Platt N and others. ’Adapting COVID-19 research infrastructure to capture influenza and respiratory syncytial virus alongside SARS-CoV-2 in UK healthcare workers winter 2022 to 2023 and beyond: protocol for a pragmatic sub-study‘ [version 2; peer review: 1 approved with reservations]. NIHR Open Research 2024: volume 4, issue 1
14. Foulkes S, Evans J, Neill C and others. ‘Prevalence and impact of persistent symptoms following SARS-CoV-2 infection among healthcare workers: a cross-sectional survey in the SIREN cohort’ Journal of Infection August 2024
15. Kirwan PD, Foulkes S, Munro K and others. ‘Protection of vaccine boosters and prior infection against mild/asymptomatic and moderate COVID-19 infection in the UK SIREN healthcare worker cohort: October 2023 to March 2024’ Journal of Infection 2024: volume 89, issue 5, pages 106,293 to 106,293
16. Evans JM, Sergenson N, Dembinsky M and others. ‘Recruiting and retaining healthcare workers in Scotland to a longitudinal COVID-19 study: a descriptive analysis’ BMC Medical Research Methodology 2024: volume 24, issue 1
17. Monk EJM, Foulkes S, Munro K and others. ‘Characterisation of the SARS-CoV-2 pandemic in healthcare workers within the United Kingdom: risk factors for infection during four successive waves’ Journal of Infection 2024: volume 90, issue 2, pages 106,393 to 106,393
18. Howells A, Munro K, Foulkes S and others. ‘Cohort retention in a pandemic response study: lessons from the SARS-CoV2 Immunity and Reinfection Evaluation (SIREN) study’ BMC Medical Research Methodology 2025: volume 25, issue 1
19. Atti A, England A, Sung J and others. ‘Estimating neutralising antibody responses against emerging SARS-CoV-2 variants utilising convalescent sera before the roll-out of XBB-lineage vaccines’ Vaccine 2025: volume 51, page 126898
20. Bustamante Q, Sparkes D, Findlater L and others. ‘Understanding occupational and attitudinal factors influencing UK healthcare worker decisions for COVID-19 and influenza vaccination: A cross-sectional survey within SIREN’ Vaccine 2025: volume 56, pages 127,160 to 127,160
21. Munro K, Bustamante Q, Findlater L and others. ‘Healthcare worker attitudes to lateral flow device testing and sick leave for influenza-like illness in the UK: A hypothetical scenario-based study’ Journal of Hospital Infection (published online 1 May 2025)
22. Foulkes S, Munro K, Sparkes D and others. ‘Adapting COVID-19 research infrastructure to capture influenza and respiratory syncytial virus alongside SARS-CoV-2 in UK healthcare workers winter 2022/23: Results of a pilot study in the SIREN cohort’ PLOS One 2025: volume 20, issue 5, article e0316131
23. Kamal A, Haywood J, Sparkes D and others. ‘A qualitative study exploring the barriers and facilitators of conducting the SARS-CoV2 Immunity and Reinfection Evaluation (SIREN) study during the COVID-19 pandemic: Implications for developing resilient NHS research structures’ Public Health 2025: volume 246, page 105,818
24. Russell S, Munro K, Foulkes S, and others. ‘Adapting COVID-19 research infrastructure to capture influenza and RSV alongside SARS-CoV-2 in UK healthcare workers winter 2022/23: evaluation of the SIREN Winter Pressures pilot study’ PLOS One 2025: volume 20, issue 6, article e0310758
25. Hettiarachchi N, Blick D, Coleman T, and others. ‘Evaluating blood sampling strategies within the SIREN study: the experience from a large cohort of healthcare workers in the UK.’ BMC Medical Research Methodology 2025: volume 25 issue 1 article 165

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. ‘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. ‘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. ‘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. Hettiarachchi N, Blick D, Coleman T, and others. ­­‘Evaluating blood sampling strategies within the SIREN study: the experience from a large cohort of healthcare workers in the UK’ Research Square (Research Square) (published online 19 February 2025)
7. Foulkes S, Munro K, Sparkes D, and others. ‘Prevalence and impact of SARS-CoV-2, influenza, respiratory syncytial virus (RSV) infection and respiratory illness on UK healthcare workers during winter 2023/24 (September 2023 to March 2024): SIREN cohort study’ MedRxiv (published online 10 March 2025)
8. Insalata F, Atti A, Carr EJ, and others. ‘Impact of first SARS-CoV-2 infection variant on serological responses against Omicron: findings from the SIREN study’ medRxiv (Cold Spring Harbor Laboratory) (published online 2 June 2025)
9. McGeoch LJ, Foulkes S, Whitaker H, and others. ‘Effectiveness of influenza vaccination against infection in UK healthcare workers during winter 2023 to 2024: the SIREN cohort study’ MedRxiv (published online 8 June 2025)

To contact the SIREN study team, please email siren@ukhsa.gov.uk