SIREN study
Providing vital research into COVID-19 immunity and vaccine effectiveness nationally.
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.
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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
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
Scientific papers
Please find below a list of scientific outputs.
Published papers
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Foulkes S, Evans J, 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
Pre-prints
- 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
- 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
- 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
- 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
- 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’
- 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’
- 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.
Updates to this page
Published 20 June 2022Last updated 13 September 2024 + show all updates
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Added published paper 14.
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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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Added timeline infographic and map.
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Updated site list.
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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.