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An increase from the currently relatively low prevalence of CPE across much of England would have significant clinical and financial implications.  CPE are resistant to carbapenems which are normally used as last-line antibiotics to treat life-threatening conditions in hospital, so with limited therapeutic options for CPE-infected patients, clinical outcomes are poor, and outbreaks are both difficult and expensive to control for healthcare providers. Early identification of CPE-carriers via admission screening could be an important tool to reduce transmission and inform therapy, but existing evidence was limited for settings with lower CPE prevalence (as is the case in many English NHS Trusts)  

We performed model-based simulations of hospitals, with CPE prevalence covering the range of levels observed in England and used these models to evaluate the existing (2016) national CPE admission screening guidelines and alternatives to them.  Two beneficial protocol changes were identified 

1) broadening screening selection criteria to include all admissions who had been hospital inpatients anywhere in the last year, rather than just those who had been an inpatient in a ‘problem area;  

2) shortening the screening test pathway to a single swab sample, rather than three consecutive swabs, 48 hours apart.   

Our work showed the former could double the CPE-carriers identified for screening in low-prevalence hospitals, and the latter would reduce the burden on test facilities and pre-emptive infection prevention and control (IPC) measures during the screening process, as well as enabling a quicker determination of a screened patient’s CPE status.

The research findings informed new national guidelines“Framework of actions to contain carbapenemase-producing Enterobacterales (2020), with both changes identified above – screening recent inpatients and using a single swab sample – incorporated. These guidelines state that patients should be considered for screening on admission if “in the last 12 months, they have been an inpatient in any hospital, in the UK or abroad” and “A single rectal screening swab is sufficient to determine CPE colonisation status on admission unless patients have been previously identified as CPE positive”. 

Our research evaluated these changes as both clinically and operationally desirablemore previously unidentified CPE-carriers entering hospital would be selected for testing, and the shorter optimised testing pathway means result would be known more rapidly, importantly increasing the chance this would be prior to hospital discharge, without unduly compromising overall sensitivity/specificity.  

The modifications also have the advantages of simplifying a previously complicated selection criterion which could be a barrier to staff adherence - staff had previously been required to know which UK hospitals were “known to have problems with spread of CPE” - and reducing the numbers of rectal swabs which may not be clinically necessary nor easily obtained, itself improving both efficiency and patient experience. These advantages are aspects which may help facilitate the uptake of these new guidelines by hospitals.  

A survey published in 2023 [Bennet et alindicated that 69% of responding hospitals had “all patients who have been in any hospital (UK or abroad) in the last 12 months” in their CPE admission screening selection criteria, and that using one admission screen was the most common (47%) practice. 

We performed model-based simulations of multiple hospitals with a range of CPE prevalence, corresponding to observations for all England regions, hence the research produced evidence which was relevant to acute hospitals nationwide.  The research-informed national guideline changes, now being used by many hospitals, benefit: 

  • Hospital providers adopting the revised guidelines 

The changes offer efficient use of limited laboratory and IPC facilities as well as improved patient safetyPrompt identification of possible transmission sources could reduce the risk of in-hospital outbreaks of CPE (incurring significant financial and operational costs to control)Providers also benefit from an improved tool to control the rise of CPE, as seen in other countries, which would necessitate changes to operations and treatments, 

  • Hospital staff  

IPC staff can set evidence-based local protocols benefiting from evidence relevant to their settingCPE prevalence.  Ward and laboratory staff personally benefit from the efficiencies above. 

  • Hospital patients  

A higher proportion of patients with CPE are tested on admission and so receive a timely carbapenem-sensitivity determination. Hence these patients can receive appropriate treatment for an infection more rapidly or appropriate surgical prophylaxis. Enhanced IPC measures can be put in place to protect other patients from transmission from identified CPE-carriers. Some patients find the sample-taking process unpleasant; single-swab screening reduces the potential for their distress. 

  • Other health and social care settings 

A quicker CPE status determination via the single-swab pathway means results are available at discharge for more patients with CPE, which can be shared with their post-discharge destination (so these settings can plan appropriately for the benefit of that patient and their contacts) or with primary care (hence available for any future referrals) 


Our findings informed revised national guidelines which is the main route to communicate the research outcomes to healthcare staff in hospitals across England.  

Within this document, the screening protocol guidelines (informed by the research outcomes) are communicated in both written form and via a flowchart diagram.  A simple memorable acronym was introduced to help frontline staff assess admissions for screening selection. The final document incorporated feedback from hospital staff to an initial draft.   

The revised guidelines were published October 2020 to coincide with the introduction of mandatory reporting of CPE, when settings would be necessarily addressing their CPE procedures.  This timing was determined by legislative requirements and was unfortunately co-incident with the second wave of the Covid-19 pandemic, hence further communications happened in 2022, when settings would have been less overshadowed by pandemic-related work.     

The findings were presented at the UKHSA AMR programme forum March 2023 whose attendees include regional Health Protection Team AMR leads who are well-placed to offer local support to trusts on the adoption of the new guidelines.   


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. 

In January 2021 the SIREN study published its first analysis of protection following SARS-CoV-2 infection. Crucially the analysis showed that reinfection was possible and could occur, but that there was an over 80% reduction in infection among people who had previously contracted COVID-19 compared to those who had not.   

In Spring 2021 when the Alpha variant was dominant in the UK the SIREN study published its first analysis on the effectiveness of COVID-19 vaccines, focusing primarily on the Pfizer vaccine. The analysis showed that short-term vaccine effectiveness against infection 21 days after the first dose was 70% in the study population of healthcare workers and rose to 85% seven days after the second dose was received. 

In February 2022 a later publication by the SIREN study looked at protection against SARS-CoV-2 infection following both previous infection and vaccination. It found that in previously uninfected individuals, two doses of the Pfizer vaccine were associated with high short-term protection against SARS-CoV-2 infection but that this protection reduced considerably after six months.  Among those with a previous infection vaccination appeared to boost their immunity, providing strong and longer lasting protection.  This provided important insights for COVID-19 vaccination programmes. 

Additional active workstreams within SIREN include investigating correlates of protection and longitudinal antibody response, which is undertaken in collaboration with academic partners in the SIREN Consortium.

Throughout the evolving COVID-19 pandemic, the SIREN study has contributed timely evidence to inform key decisions in the COVID response.  SIREN surveillance reports are produced weekly and shared with key decision makers, research outputs, especially initial findings, are shared frequently, and bespoke analyses are prepared in response to requests.   

SIREN was one of three studies, providing rapid evidence on early vaccine effectiveness, cited by the Prime Minister in February 2021 when he announced the route out of lockdown.  SIREN data on waning effectiveness following two doses informed decision to introduce vaccine boosters to healthcare workers, and the rapid vaccine effectiveness analysis early in the Omicron-variant wave informed the decision to widen access to boosters. 

In addition to these impacts on the COVID-19 response, it is important to highlight the value of regular asymptomatic PCR testing for participants and sites at scale across the NHS.  By early detection of new infections in healthcare workers, enabling them to self-isolate, onward transmission in the healthcare setting is reduced. 

The insights from SIREN have informed national COVID-19 policy and therefore impacted the entire UK-population.  SIREN has also been a valuable source of authoritative evidence, given the study design and scale, for policymakers internationally. 

From our PPI panel members and feedback from our participant webinars we are also aware that participants generally have valued their experience in SIREN.  Our cohort retention has been very high, with 85% completing their 12-month follow-up, and of those who withdrew, the median length of follow-up was 7 months.  An important element has been valuing the reassurance provided by regular testing, particularly given anxieties about workplace exposures.  There has also been feedback about valuing ‘making a difference’ and being able to support the COVID-19 response, especially when confronted with the uncertainty of the pandemic. We are currently planning more formal qualitative research around the participant experience. 


  • Regular surveillance and update reports provided to senior policy makers and expert committees, including the Joint Committee on Vaccines and Immunisations, (JCVI), DHSC Data Debrief Group, and Variant Technical Group. 

  • Regular participant webinars which often have 500-1000 participants attending the live session (with recordings then circulated).  Key developments and latest research are presented, and half the session is used for Q&As to ensure we have a forum to directly engage and respond to participant enquiries.  We also produce regular participant newsletters and communications provided as part of our dynamic cohort retention programme 

  • Site webinars, newsletters, and briefings, are used regularly to ensure sites are engaged with the research, appropriately implementing the study protocol and any recent changes  

  • Videos providing accessible summaries of the study and current study priorities.  These are primarily aimed at promoting cohort retention by communicating the value of the study and thanking participants, and are timed around key events such as the anniversary celebrations 

  • We are currently focusing on developing accessible content about SIREN, including lay language summaries of our research papers, via the UKHSA website 

  • We use media to communicate our publications, preparing press releases, news stories on our website, presenting at Science Media Centre Briefings and social media (twitter messages and threads)  

  • In addition to scientific conferences, we present at a variety of external expert groups and clinical and professional networks (within NHS and UKHSA)


GPAS is the culmination of 20 years’ work, bringing genomic insights into medical microbiology, to improve the tools available for public health and patient care. Before the SARS-CoV-2 pandemic, we demonstrated that outbreaks of hospital bugs like C. difficile could be understood, treated, and stopped by looking at the genetic material of the pathogen. We could tell how individual patients’ bugs were related (which tells us whether they picked up the infection from the same source), and notice whether any dangerous new strains were emerging. We also developed tools to tell which antibiotics would not work on a specific patient’s tuberculosis, allowing physicians to make better prescriptions: this directly helps the patient get the right drugs, saves the health service money on potentially ineffective prescriptions, and helps reduce the spread of “superbugs” which are resistant to antimicrobial treatment.  

When COVID-19 struck, we repurposed these tools to look at SARS-CoV-2. 

We have developed an automated system to: 

  • determine which variant of COVID-19 is present in a sample; 

  • note all of the individual mutations in the sample (allowing us to watch for potentially dangerous new mutations); 

  • show how various samples are related; 

  • provide data quality metrics, so labs can have appropriate confidence in their data; 

  • provide the data in an easy-to-use web portal with visual analytics and multi-language support; 

  • make it possible to share data with other organisations, while at all times respecting the data sovereignty of the organisations using GPAS: this allows users to track spread and prevalence of different COVID variants across the world. 

Labs around the world usually have to wait days (or weeks) for these results to come back, and they need an in-house expert to do it. With GPAS they can have the answer in less than an hour, without expert staff. This allows public health agencies to have real-time data to drive their decisions. This is directly happening in the UK: we have worked extremely closely with the John Radcliffe Hospital microbiology laboratory, and have now integrated GPAS into their routine SARS-CoV-2 processing as a UK COVID Network Laboratory. 

Unlocking genomic insight requires expertise and access to high-performance computing, and sharing data across borders needs a highly secure digital environment (and patience, and trust). The necessary infrastructure and operational support are not evenly distributed – and are not always where they are needed. Sequencing information is often unattainable, slow to process or is stored in isolated pockets, leaving scientists and governments working in silos. 

GPAS was specifically designed to reduce the need for in-house bioinformatics expertise. Even in the UK, there is a severe bioinformatics skills shortage; the shortage is worse in low-resource settings. Labs without a bioinformatician can rely on GPAS for assembly and key analysis, and labs with in-house expertise can now focus their bioinformatics staff on deeper interrogation of the data rather than the routine grind of assembling and annotating sequences. 

GPAS has been processing samples under contract since January 2022: as of 15 June 2022, the “production” system had processed a total of 11,522 samples, for: 

 Institute of Public Health of Chile 

 National Institutes of Health Pakistan 

 Oxford University Hospitals NHS Foundation Trust (UK COVID Network Lab) 

 UK Health Security Agency 

 University of Virginia (USA) 

GPAS also works with test users from the Institute of Clinical Pathology and Medical Research (New South Wales, Australia), Muhimbili University of Health and Allied Sciences (Tanzania), National Institute for Communicable Diseases (South Africa), University of the Witwatersrand (South Africa), University of Montreal Health Centre (Canada), Oxford University Clinical Research Unit (Vietnam), and Oxford Nanopore Technologies. 

Since December 2021, we have worked closely with the John Radcliffe Hospital microbiology laboratory, to integrate GPAS into their routine SARS-CoV-2 processing as a UK COVID Network Laboratory. We developed a robust data workflow to process thousands of samples, contributing directly to the UK’s national COVID statistics. GPAS developers worked directly with the lab technicians, adjusting the interface and reports to support their requirements. 

They report that using GPAS has cut processing times from days to minutes, and allowed lab staff to be directly involved in analysis. Staff say: “Before GPAS, we used to do a run, put data into a spreadsheet, and send it off to a local bioinformatician. It took days to get our results (heaven help us if he had time off). If a run failed, we wouldn’t know for days, and would have to delay reporting to COG for up to a week while we went back to re-run the plate. Now, we can troubleshoot straight away: we can check our control samples, and the amplicon plots let you see primer issues immediatelyIt’s really nice to be able to see the full circle of your lab work: usually, we do all the sequencing, but never get to see the results. 

“This is even more useful for us, since we work in a hospital. If the hospital calls in for urgent results, we can look up the answer by ourselves, in a few minutes. Before, we’d have to email a bioinformatician, and hope they could reply by the end of the day. Communication between the wet lab and bioinformatics staff can be difficult, because our worlds are so different. Now we can both point at the same sample on the screen. Better still, if you understand the question, you can go look at GPAS and answer it yourself.”


GPAS is mentioned on the Modernising Medical Microbiology group website ( and the HPRU website ( 

GPAS has its own public-facing website ( and Twitter account (@_gpas_ / A demonstration of GPAS will be built into the Oxford BRC Showcase at the Oxford Town Hall on 5 July 2022. We anticipate this will actually be a live demonstration, with samples going through a sequencing machine, and being uploaded and analysed by GPAS, in real time in front of the public. Members of the public will be able to directly explore the GPAS interface, and look at historical COVID sequence data from samples contributed to public repositories. 


From the research supported by the NIHR HPRU, provide a plain English summary of the main findings that you would have reported to the research community. If you include health economic information, please specify the value of the QALY used. Please note that negative, definitive findings that could inform disinvestment are of equal validity (indicative 500 word maximum - insert below). 

This study was the first in the world to directly measure the infectiousness of infected individuals by following their immediate contacts both in and outside the household. 

 The research was in two parts. The first part directly measured the infectiousness of individuals infected with COVID-19. The PCR data from about 1 million individuals who tested positive by attending the Testing Centres from September 2020 to February 2021 (pillar 2) was used to determine their viral load. These infected individuals also routinely name their contacts and, from the Test and Trace database, the infection status of contacts could be determined. Overall about 9% of the 2.5 million contacts were shown to be infected. A large number of patient factors together with the timing and type of contact were also available for analysis.  

 We found that the index patient viral load was a major factor in determining whether or not an infected individual was likely to transmit COVID-19 to their contacts.  

 The second part of the research was to determine the ability of lateral flow devices (LFD) to detect individuals that are infectious rather than simply infected with the virus. Because the study looked at successive individuals attending the test centre the relative distribution of viral loads could be measured. From this, and from the known ability of LFD to detecting virus, the study showed that LFDs were able to detect individuals responsible for 83-90% of transmission events. This means that if LFDs are used to identify and isolate infectious individuals, the risk of passing on COVID-19 could be reduced by 83-90%. These results allowed the UK Government and PHE to make rational recommendations on how best to use LFDs in the wider population  

The study also gave precise details of the chances of individuals at different age groups spreading COVID-19 in separate settings. For example it showed that there was only a low chance of school children spreading COVID-19 to their fellow pupils at school and transmission rates were higher amongst household contacts. This has encouraged schools to re-open. It also showed that the ‘Kent’ strain (B.1.1.7) increased transmission by about 50% confirming the need to maintain social distancing and face mask usage. 

The outcomes of this work have directly led to the following projects being undertaken: 

  • MHRA approval of the Innova Lateral Flow Device (LFD) (December 2020) 

  • The Liverpool pilot study (Nov2020- ) 

  • A cluster randomized controlled study of Daily Contact Testing in schools to avoid quarantine (April 2021-  

  • A randomized study of daily contact testing using LFD to avoid quarantine in the general population (April 2021- ) 

  • A number of DHSC funded pilots on the role of LFD in reduce transmission in work places, care homes and places of work. (Feb 2021- ) 

As a direct result of our study, Innova LFD was given MHRA approval in Dec 2020. The UK Government provided Lateral Flow Devices widely throughout the country. The result of the findings that LFD are effective in detecting infectious individuals has encouraged their widespread use. They have been provided to all NHS workers and millions are being used every day. To date over 70,000 asymptomatic but infectious individuals have been identified, who otherwise would not have been, and their subsequent self-isolation has reduced the overall risk of infection to the public. There use is now being extended to allowing to ‘test to enable’ to screen individuals before attending large public gatherings (e.g. football matches), to attend work safely and to undertake daily testing of contacts to allow avoidance of quarantine. 

Lateral Flow Devices (LFD) are mainly used to detect asymptomatic individuals and therefore are used to reduce disease transmission. They therefore do not have direct effects on COVID-infected patients, although by reducing onwards transmission they prevent people getting COVID-19 in the first place. However, LFDs are also used in hospital settings for rapid identification and isolation of infectious parents to reduce the risk of within hospital transmission, and enabling self-isolation of healthcare workers who otherwise would not realise they were infected also prevents transmission within hospitals.