The SARS-CoV-2 Immunityimmunity and Reinfectionreinfection Evaluationevaluation (SIREN) study is a prospectiveunique, cohortlarge-scale studypartnership ofwith hospital-basedNHS healthcare workers acrossproviding thean UK.agile Itresponse wasto establishedan inevolving 2020pandemic. asIt ais pandemicone responseof study,the withnational 44,543core healthcarestudies workersestablished recruitedin fromresponse 135to NHSCOVID-19 trustsand ora healthNational boards.Institute Thefor studyHealth initiallyResearch investigated(NIHR) SARS-CoV-2urgent reinfectionspriority study, and thecontinues durabilityto ofprovide immunityvital followingresearch infection,into immunity and subsequentlyvaccine COVID-19effectiveness.

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SIREN pandemic2.0, policy including the roadnew mapphase out of lockdown.

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We SARS-CoV-2have infectionsassessed andthe assessingdurability riskof factorsprotection forfollowing infectionSARS-CoV-2 ininfection, UKCOVID-19 healthcarevaccination, workers

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Our Exploringvaccine riskeffectiveness factorsfindings, forreleased healthcarein workerFebruary infections,2021, wedemonstrating identifiedhigh occupationalshort-term risksprotection despitefollowing vaccinationthe duringfirst England’s2 seconddoses wave.

However,of thisCOVID-19 riskvaccine was not observed in subsequentUK waveshealthcare whenworkers, communityprovided andimportant householdevidence exposuresto wereinform the mainUK driversroadmap out of infection.   lockdown.

Understanding SARS-CoV-2 immunity

WithIn large-scale2021, longitudinalwe serologicalestablished testing, paired with regular PCR testing, the SIREN studyConsortium isconsisting well-placedof toacademic, addressclinical differentand aspectspublic ofhealth serologicalpartners. responseThis associatedhas withallowed SARS-CoV-2us infectionto andgain vaccination. Wea havebetter amassedunderstanding collections of longitudinalserological serum,correlates preof andprotection, post event for reinfections and vaccine breakthroughs across different variants that are highly valuable for future immunological studies.

In the earlyrole stages of theT-cell pandemic,responses wein demonstratedSARS-CoV-2. thatWe titresare ofexpanding neutralisingthis antibodies,work afor typewinter of2023 antibodyto that2024 canfor preventinfluenza infection,and wereRSV.

We lowhave oralso absentestablished before reinfection, highlighting that neutralising antibodies could be used as a potentialmotivated correlateand ofdynamic protectionparticipant againstinvolvement SARS-CoV-2panel infection.

Wein thencollaboration compared reinfection cases pre-vaccination with matchedthe controlsBritish (FebruarySociety 2021),for demonstratingImmunology. thatThe detectablegroup neutralisingis antibodymade titresup (overof 40)SIREN werestudy associatedparticipants, with a significantdiverse reductionmix in odds of reinfectiongender, (overethnicity 90%).

Thisand wasprofessions. supportedThey byhave findingshelped post-vaccination (April to Octobermake 2021),sure inSIREN whichcontinues weto founddeliver thatrelevant, Deltafeasible neutralisingand antibodytranslatable titresresearch, overand 40have werecontributed associateddirectly withto aSIREN substantialstudy reductionprotocols inand oddsco-author ofpeer-reviewed infection (89%).  papers.

Quantifying the impact of winter pressures on the NHS workforce

InFinally, winter 2022/23, SIREN expandedwill itscontinue testing to includework Influenzawith andour RSVpartners asat wellBirmingham asCity SARS-CoV-2University usingand multiplexwithin PCR,the toUK improveHealth ourSecurity understandingAgency of(UKHSA) theto burdentry ofand respiratoryidentify viruseslessons infrom healthcare workers in the UK.

Forpandemic, 2022/2023including andunderstanding 2023/2024,the webarriers have demonstrated that COVID-19, influenza and RSVfacilitators arefor experiencedvaccination simultaneouslyamong in healthcare workers,workers, withas SARS-CoV-2part infectionsof dominating,our compoundingfuture servicepandemic pressurespreparedness throughresponse.

Watch significantvideos stafffor absence.more information.

Videos

Our story

story:

The SIREN Study: Our story - YouTube

Learn from SIREN study research teams

teams:

The SIREN Study: Hear from our research teams - YouTube

Learn from SIREN study participants

participants:

The SIREN Study: Hear from our participants - YouTube

Recent

Learn about recent study findings

findings:

SIREN 3 years on: Showcase of study findings - YouTube

The

Learn from the SIREN study team

team:

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

Learn about SIREN 2.0

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 Publicstory Healthso Agencyfar

This Northerninfographic Ireland,lists Publickey Healthmoments Scotlandduring andthe Public Health Wales.

The SIREN study worksand withindicates athat numberthe ofproject academichas partners,moved including:

• Worldon Healthto OrganisationSIREN (Europe2.0.

  

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• Francisversion Crick Institute
• Wellcome Sanger Institute
• University College London
• University of Cardiff
• Universitytimeline

  2020
  May of– Cambridge

• Universityethics ofapproval
  June Oxford
• University– offirst Liverpool
• Universityparticipant ofrecruited
  September Sheffield
• Newcastle– University
• Universityfirst ofreinfections Birmingham
• Birminghaminvestigated
  December City– University
• Imperialvaccines Collegeintroduced, London
• UniversitySIREN ofinvestigates Glasgow
• Kingsvaccine Collegeeffectiveness, London
• BritishPITCH Societysub-study of Immunology

established

There2021
January is– afirst standardisedvaccine applicationeffectiveness processanalysis
March for– those45,000 interestedparticipants recruited in accessingfirst year
July – SIREN Studycontinues samplesfor and/ora associatedsecond metadata.year
August Applicants– areMedical expectedResearch toCouncil complete£1.5 anmillion electronicfunding establishes the SIREN Studyconsortium
October Sample– andserological Datare-infection Formanalysis
December (– first SIREN Studyparticipant Sampleinvolvement and/orpanel Data(PIP)

2022
February Request– Form).VIBRANT Thissub-study capturesrecruitment thebegins
October key– informationenhanced requiredquestionnaires for thesymptoms
November SIRENto StudyDecember Collaboration– Oversightmultiplex Grouptesting tointroduced
March review.– qualitative sub-study

If2023
March you,– beforequalitative submittingsub-study
August your form, you want to haveSeptember an– informalrecruitment discussionopens aboutto the SIREN study2.0
September samples– and available data, please contact Victoria Hall at: Victoria.Hall@UKHSASIREN.gov.uk 2.0

Research grantsPartners

• (2024)

  UKHSA MRC:runs Targetingthe Coronaviruses through Fc-dependent Antibody Activities

• (2023) UKRI HDR-UK: SIREN Winterstudy Pressures WP0034
• (2022) Medical Research Council: Protective Immunity through T Cells in Healthcarepartnership workerswith 2NHS (PITCHsites, 2)the MR/X009297/1
• (2021)Public MedicalHealth ResearchAgency Council:Northern InvestigationIreland, ofPublic provenHealth vaccineScotland breakthroughand byPublic SARS-CoV-2Health variantsWales.

  The in UK healthcare worker cohorts: SIREN consortiumstudy &works PITCHwith Plusa Pathway.number MR/W02067X/1

SIRENof publicacademic participantpartners. involvementThe and engagement 

Within SIREN weConsortium recognisedwas theestablished valuein ofAugust actively2021 involvingand awas panelsuccessfully ofawarded participantsa in£1.57 themillion study,research particularlygrant givenby itsUK scaleResearch and theInnovation role (UKRI).

SIREN hasConsortium playedmembers ininclude:

• Wellcome informingSanger theInstitute
• The nationalFrancis pandemicCrick response.

  OurInstitute

• Protective ParticipantImmunity Involvementfrom PanelT (PIP)cells isto anCOVID-19 activein partnershipHealth betweenworkers study(PITCH):
  • University participantsof withOxford
  • University researchersof thatLiverpool
  • University influencesof andSheffield
  • Newcastle shapesUniversity
  • University research.of TheBirmingham
• Humoral SIRENImmune PIPCorrelates wasfor establishedCOVID-19 in(HICC)
• Imperial collaborationCollege withLondon
• University theof Glasgow
• British Society for Immunology
• GenOMICC

For asSIREN part2.0, ofwe thehave SIRENestablished Consortium,new collaborations with thescientific aimpartners, ofWorld providingInfluenza regularCentre feedbackand as the studyWellcome hasSanger evolvedInstitute.

The overWellcome time.Sanger ByInstitute activelyin involvingCambridge peopleis whoa ourworld researchleader isin forgenomic sequencing and about,metagenomics. includingThey duringwill thesequence design,samples implementationfrom andthe evaluationSIREN stagesstudy ofand researchuse hasmetagenomics ensuredto theinvestigate researchother conductedpathogens hasthat remainedcause relevantrespiratory toinfection thesuch studyas cohort.parainfluenza.

TheWith PIPthe consistsincreasing ofinterest approximatelyin 10Influenza, SIRENwe participants,have fromalso set up a rangecollaboration ofwith professions,the ethnicities,World ageInfluenza andCentre genders(WIC) acrossin theLondon. UKThe inWIC orderis toone reflectof 6 centres in the cohort.

Theworld PIPresponsible hasfor beenanalysing involvedinfluenza viruses circulating in the co-developmenthuman ofpopulation, coreoverseen participantby andthe publicWorld engagementHealth activitiesOrganization which(WHO). areWe essentialplan to theshare runninginfluenza ofviruses thedetected studyas includingpart newsletters,of webinars,SIREN blog2.0, posts,which andmay hasbe co-authoredused ato peerdesign reviewinfluenza article.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: 2Two 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 ReinfectionREinfection Evaluation)EvaluatioN) study protocol’ British Medical Journal Open 2022: volume 12, issue 6, articlepage 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, articlepage 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

Pre-prints

1. KirwanWallace PD, Foulkes S, MunroHall KV, Charlett A and others. ‘ProtectionSIREN ofprotocol: vaccineImpact boostersof anddetectable prioranti-SARS-CoV-2 infectionon againstthe mild/asymptomaticsubsequent andincidence moderateof COVID-19 infection in the100,000 UK SIREN healthcare workerworkers: cohort:do Octoberantibody 2023positive tohealthcare Marchworkers 2024’have Journalless ofreinfection Infectionthan 2024:antibody volumenegative 89,healthcare issueworkers?’ 5,medRxiv pages2020: 106,293 to 106,2932020.12.15.20247981
2. EvansHall JM,V, SergensonFoulkes N,S, DembinskyCharlett MA and others.others (2021). ‘RecruitingDo andantibody retainingpositive healthcare workers inhave Scotlandlower toSARS-CoV-2 ainfection longitudinalrates COVID-19than study:antibody anegative descriptivehealthcare analysis’workers? BMCLarge Medicalmulti-centre Researchprospective Methodologycohort 2024:study volume(the 24,SIREN issuestudy), 1England: June to November 2020’ medRxiv, 2021.2001.2013.21249642
3. MonkHall EJM,V, Foulkes S, MunroInsalata KF and others.others (2021). ‘CharacterisationEffectiveness and durability of theprotection against future SARS-CoV-2 pandemicinfection inconferred healthcareby workersCOVID-19 withinvaccination and previous infection; findings from the UnitedUK Kingdom:SIREN riskprospective factorscohort forstudy infectionof duringhealthcare fourworkers successiveMarch waves’2020 to September 2021’ JournalmedRxiv, 2021.2011.2029.21267006
4. Otter AD, D’Arcangelo S, Whitaker H and others (2022). ‘Determinants of InfectionSARS-CoV-2 2024:anti-spike volumeantibody 90,levels issuefollowing 2,BNT162b2 pagesvaccination: 106,393cross-sectional toanalysis 106,393of 6,000 SIREN study participants’ medRxiv, 2022.2004.2021.22274025
5. HowellsAtti A, MunroInsalata K,F, FoulkesCarr SE and others. ‘CohortAntibody retentioncorrelates inof aprotection pandemicagainst responseDelta study:infection lessonsafter fromvaccination: thea SARS-CoV2nested Immunitycase-control andwithin Reinfectionthe EvaluationUK-Based (SIREN) study’study’
6. Victoria BMCJ MedicalHall, ResearchFerdinando MethodologyInsalata, Sarah 2025:Foulkes, volumePeter 25,Kirwan, issueDominic 1
7. AttiSparkes,   A,Ana EnglandAtti, A,Michelle SungCole, JElen andde others.Lacy, Lesley Price, Diane Corrigan, Colin S Brown, Jasmin Islam, The SIREN Study Group, Andre Charlett, Susan Hopkins (2023). ‘EstimatingEffectiveness neutralisingof antibodyBNT162b2 responsesmRNA againstvaccine emergingthird doses and previous infection in protecting against SARS-CoV-2 variantsinfections utilisingduring convalescentthe seraDelta beforeand Omicron variant waves; the roll-outUK ofSIREN XBB-lineagecohort vaccines’ Vaccinestudy 2025:September volume2021 51,to pageFebruary 1268982022’
8. BustamanteKirwan Q,P, SparkesHall D,V, FindlaterFoulkes LS and others.others (2023). ‘UnderstandingProtection occupationalof second booster vaccinations and attitudinalprior factorsinfection influencingagainst SARS-CoV-2 in the UK SIREN healthcare worker decisionscohort’ formedRxiv COVID-192023.09.29.23296330

Site andlist

In influenzathe vaccination:first Ayear cross-sectionalof surveythe within SIREN’ Vaccinestudy, 2025:135 volumesites 56,across pagesthe 127,160UK contributed, with 87 sites contributing to 127,160

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Please Sparkesnote, DSIREN andparticipants others.at ‘Adaptingsites COVID-19who researchare infrastructureno longer actively testing remain important contributors to capturethe influenzastudy. They will continue to receive communications and respiratorykey syncytialstudy virusupdates alongsidefrom SARS-CoV-2the inSIREN UKteam healthcareand workersmay winterbe 2022/23:offered Resultsopportunities offor afurther pilotinvolvement.

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St PLOSGeorge’s OneUniversity 2025:Hospitals volumeNHS 20,Foundation issueTrust	Active	Active	Active
University 5,Hospitals articleOf e0316131 KamalLeicester A,NHS HaywoodTrust	Active	Active	Active
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Leeds others.Teaching ‘AHospitals qualitativeNHS studyTrust	Active	Active	Active
Mid exploringEssex theHospital barriersServices andNHS facilitatorsTrust	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 conductingMorecambe theBay SARS-CoV2NHS ImmunityFoundation Trust	Active	Active	Active
Southend University Hospital NHS Foundation Trust	Active	Active	Closed
University Hospitals Bristol and ReinfectionWeston EvaluationNHS (SIREN)Foundation studyTrust	Active	Active	Active
King’s duringCollege theHospital COVID-19NHS pandemic:Foundation ImplicationsTrust	Active	Active	Closed
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North PublicCumbria HealthIntegrated 2025:Care volumeNHS 246,Foundation pageTrust	Active	Active	Closed
St 105,818 RussellHelens S,and MunroKnowsley K,Teaching FoulkesHospitals S,NHS Trust	Active	Active	Closed
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The Princess Alexandra Hospital NHS Trust	Active	Active	Active
Imperial College Healthcare NHS Trust	Active	Active	Closed
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Dartford and others.Gravesham ‘EffectivenessNHS 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
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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 others.Sussex ‘PrevalenceHealthcare NHS Trust	Active	Closed	Closed
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Cornwall Partnership NHS Foundation Trust	Active	Closed	Closed
The Royal Bournemouth and others.Christchurch ‘ImpactHospitals ofNHS Foundation firstTrust	Active	Closed	Closed
Poole SARS-CoV-2Hospital infectionNHS variantFoundation onTrust	Active	Closed	Closed
Northern serologicalLincolnshire responsesand againstGoole Omicron:NHS findingsFoundation fromTrust	Active	Closed	Closed
Leicestershire thePartnership SIRENNHS study’Trust	Active	Closed	Closed
Birmingham medRxivCommunity (ColdHealthcare SpringNHS HarborFoundation Laboratory)Trust	Active	Closed	Closed
Dorset (publishedCounty onlineHospital 2NHS JuneFoundation 2025) McGeochTrust	Active	Closed	Closed
Alder LJ,Hey FoulkesChildren’s S,NHS WhitakerFoundation H,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 others.Social ‘EffectivenessCare ofTrust	Active	Active	Active
South influenzaEastern vaccinationHealth againstand infectionSocial inCare	Active	Active	Active
Belfast UKHealth healthcareand workersSocial duringCare winterTrust	Active	Active	Active
Western 2023Health toand 2024:Social theCare SIRENTrust	Active	Active	Closed
Northern cohortHeath study’and MedRxivSocial (publishedCare onlineTrust	Active	Active	Closed
Scotland
NHS 8Lothian	Active	Active	Active
NHS JuneGreater 2025)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

ToThis contactmap is a visual representation of the SIREN studyNHS team,sites pleaselisted email siren@ukhsa.gov.ukabove.