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.

Third doses of COVID-19 vaccines were widely deployed following the primary vaccine course waning and the emergence of the Omicron-variant. We investigated protection from third-dose vaccines and previous infection against SARS-CoV-2 infection during Delta-variant and Omicron-variant (BA.1 & BA.2) waves in our frequently PCR-tested cohort of healthcare-workers. Relative effectiveness of BNT162b2 third doses and infection-acquired immunity was assessed by comparing the time to PCR-confirmed infection in boosted participants with those with waned dose-2 protection (≥254 days after dose-2), by primary series vaccination type. Follow-up time was divided by dominant circulating variant: Delta 07 September 2021 to 30 November 2021, Omicron 13 December 2021t o 28 February 2022. We used a Cox regression model with adjustment/stratification for demographic characteristics and staff-type. We explored protection associated with vaccination, infection and both. We included 19,614 participants, 29% previously infected. There were 278 primary infections (4 per 10,000 person-days of follow-up) and 85 reinfections (0.8/10,000 person-days) during the Delta period and 2467 primary infections (43/10,000 person-days) and 881 reinfections (33/10,000) during the Omicron period. Relative Vaccine Effectiveness (VE) 0-2 months post-3rd dose (3rd dose) (3-doses BNT162b2) in the previously uninfected cohort against Delta infections was 63% (95% Confidence Interval (CI) 40%-77%) and was lower (35%) against Omicron infection (95% CI 21%-47%). The relative VE of 3rd dose (heterologous BNT162b2) was greater for primary course ChAdOX1 recipients, with VE 0-2 months post-3rd dose over ≥68% higher for both variants. Third-dose protection waned rapidly against Omicron, with no significant difference between two and three BNT162b2 doses observed after 4-months. Previous infection continued to provide additional protection against Omicron (67% (CI 56%-75%) 3-6 months post-infection), but this waned to about 25% after 9-months, approximately three times lower than against Delta. Infection rates surged with Omicron emergence. Third doses of BNT162b2 vaccine provided short-term protection, with rapid waning against Omicron infections. Protection associated with infections incurred before Omicron was markedly diminished against the Omicron wave. Our findings demonstrate the complexity of an evolving pandemic with the potential emergence of immune-escape variants and the importance of continued monitoring.

Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort.

Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI -11.4 to 27.8) and 1.7% (95% CI -17.0 to 17.4) at 2-4 and 4-6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0-6, and 6-12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.

Why local antibiotic resistance data matters - Informing empiric prescribing through local data collation, app design and engagement in Zambia.

BACKGROUND: Control of antimicrobial resistance (AMR) relies on local knowledge and local intervention implementation. Effective antibiotic stewardship requires locally-suitable prescribing guidelines. We aimed to use a novel digital tool (the ZARIApp) and a participatory approach to help develop locally-relevant empiric antibiotic prescribing guidelines for two hospitals in Lusaka, Zambia. METHODS: We produced an AMR report using samples collected locally and routinely from adults within the prior two years (April 2020 - April 2022). We developed the ZARIApp, which provides prescribing recommendations based on local resistance data and antibiotic prescribing practices. We used qualitative evaluation of focus group discussions among healthcare professionals to assess the feasibility and acceptability of using the ZARIApp and identify the barriers to and enablers of this stewardship approach. RESULTS: Resistance prevalence was high for many key pathogens: for example, 73% of 41 Escherichia coli isolates were resistant to ceftriaxone. We identified that high resistance rates were likely due to low levels of requesting and processing of microbiology samples from patients leading to insufficient and unrepresentative microbiology data. This emerged as the major barrier to generating locally-relevant guidelines. Through active stakeholder engagement, we modified the ZARIApp to better support users to generate empirical antibiotic guidelines within this context of unrepresentative microbiology data. Qualitative evaluation of focus group discussions suggested that the resulting ZARIApp was useful and easy to use. New antibiotic guidelines for key syndromes are now in place in the two study hospitals, but these have substantial residual uncertainty. CONCLUSIONS: Tools such as the free online ZARIApp can empower local settings to better understand and optimise how sampling and prescribing can help to improve patient care and reduce future AMR. However, the usability of the ZARIApp is severely limited by unrepresentative microbiology data; improved routine microbiology surveillance is vitally needed.

Aging attenuates the memory advantage for unexpected objects in real-world scenes.

Across the adult lifespan memory processes are subject to pronounced changes. Prior knowledge and expectations might critically shape functional differences; however, corresponding findings have remained ambiguous so far. Here, we chose a tailored approach to scrutinize how schema (in-)congruencies affect older and younger adults' memory for objects embedded in real-world scenes, a scenario close to everyday life memory demands. A sample of 23 older (52-81 years) and 23 younger adults (18-38 years) freely viewed 60 photographs of scenes in which target objects were included that were either congruent or incongruent with the given context information. After a delay, recognition performance for those objects was determined. In addition, recognized objects had to be matched to the scene context in which they were previously presented. While we found schema violations beneficial for object recognition across age groups, the advantage was significantly less pronounced in older adults. We moreover observed an age-related congruency bias for matching objects to their original scene context. Our findings support a critical role of predictive processes for age-related memory differences and indicate enhanced weighting of predictions with age. We suggest that recent predictive processing theories provide a particularly useful framework to elaborate on age-related functional vulnerabilities as well as stability.

Demonstrating the learning and impact of embedding participant involvement in a pandemic research study: the experience of the SARS-CoV-2 immunity & reinfection evaluation (SIREN) study UK, 2020-2023.

BACKGROUND: Participant involvement in research studies is not a new concept, yet barriers to implementation remain and application varies. This is particularly true for pandemic response research studies, where timeframes are condensed, pressure is high and the value and inclusion of participant involvement can be overlooked. The SIREN Participant Involvement Panel (PIP) provides a case study for participant involvement in pandemic research, working in partnership with people who the research is for and about. METHODS: SIREN and the British Society for Immunology (BSI) recruited and ran two phases of the PIP, involving 15 members in total over a 16-month period. Phase 1 ran between January and August 2022 and Phase 2 between October 2022 and March 2023. Activity figures including recruitment interest and PIP meeting attendance were recorded. To evaluate how the PIP has influenced SIREN, feedback was collected from (a) researchers presenting at the PIP and (b) PIP members themselves. Evaluation at the end of Phase 1 informed our approach to Phase 2. Thematic grouping was planned to identify key lessons learned. RESULTS: Applications increased from n = 30 to n = 485 between Phase 1 and Phase 2 of the PIP, a more than 15-fold increase. The SIREN PIP positively impacted the design, implementation and evaluation phases of the study and sub-studies. Feedback from PIP members themselves was positive, with members highlighting that they found the role rewarding and felt valued. Learnings from the PIP have been condensed into five key themes for applying to future pandemic response research studies: the importance of dedicated resources; recruiting the right panel; understanding motivations for participant involvement; providing flexible options for involvement and enabling the early involvement of participants. CONCLUSIONS: The SIREN PIP has demonstrated the value of actively involving people who research is for and about. The PIP has provided an active feedback mechanism for research and demonstrated a positive influence on both SIREN study researchers and PIP members themselves. This paper makes the case for participant involvement in future pandemic research studies. Future work should include improved training for researchers and we would support the development of a national PIP forum as part of future pandemic research preparedness.

The SARS-Cov2 Immunity & Reinfection Evaluation (SIREN) study was set-up at speed during the early stages of the pandemic to help answer key questions about COVID-19 and inform the national pandemic response. It has provided valuable insight into COVID-19 infections, reinfections, and how well the vaccines work. SIREN helped to find these answers by regularly testing over 44,000 healthcare staff working at 135 NHS organisations. To support participant retention, SIREN established a Participant Involvement Panel (PIP) involving 15 SIREN participants to date. PIP members provide guidance and feedback to SIREN researchers on key research priorities, changes to the study and strategies for maximising participant engagement. This paper provides insight into how the PIP was set-up, run and the resources required from the perspective of the PIP and SIREN researchers. Lessons learned from establishing the PIP are summarised to help inform future pandemic response research studies. The paper adds to the evidence base, and makes the case for, the valuable role participant involvement can play in pandemic response research studies.

Early Warning Surveillance for SARS-CoV-2 Omicron Variants, United Kingdom, November 2021-September 2022.

Since June 2020, the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study has conducted routine PCR testing in UK healthcare workers and sequenced PCR-positive samples. SIREN detected increases in infections and reinfections and delected Omicron subvariant waves emergence contemporaneous with national surveillance. SIREN's sentinel surveillance methods can be used for variant surveillance.

Development and Implementation of an Antimicrobial Stewardship Checklist in Sub-Saharan Africa: A Co-Creation Consensus Approach.

Antimicrobial stewardship (AMS) initiatives promote the responsible use of antimicrobials in healthcare settings as a key measure to curb the global threat of antimicrobial resistance (AMR). Defining the core elements of AMS is essential for developing and evaluating comprehensive AMS programmes. This project used co-creation and Delphi consensus procedures to adapt and extend the existing published international AMS checklist. The overall objective was to arrive at a contextualised checklist of core AMS elements and key behaviours for use within healthcare settings in Sub-Saharan Africa, as well as to implement the checklist in health institutions in four African countries. The AMS checklist tool was developed using a modified Delphi approach to achieve local expert consensus on the items to be included on the checklist. Fourteen healthcare/public health professionals from Tanzania, Zambia, Uganda, Ghana and the UK were invited to review, score and comment on items from a published global AMS checklist. Following their feedback, 8 items were rephrased, and 25 new items were added to the checklist. The final AMS checklist tool was deployed across 19 healthcare sites and used to assess AMS programmes before and after an AMS intervention in 14 of the 19 sites. The final tool comprised 54 items. Across the 14 sites, the completed checklists consistently showed improvements for all the AMS components following the intervention. The greatest improvements observed were the presence of formal multidisciplinary AMS structures (79%) and the execution of a point-prevalence survey (72%). The elements with the least improvement were access to laboratory/imaging services (7%) and the presence of adequate financial support for AMS (14%). In addition to capturing the quantitative and qualitative changes associated with the AMS intervention, project evaluation suggested that administering the AMS checklist made unique contributions to ongoing AMS activities. Furthermore, 29 additional AMS activities were reported as a direct result of the prompting checklist questions. Contextualised, co-created AMS tools are necessary for managing antimicrobial use across healthcare settings and increasing local AMS ownership and commitment. This study led to the development of a new AMS checklist, which proved successful in capturing AMS improvements in Tanzania, Zambia, Uganda, and Ghana. The tool also made unique contributions to furthering local AMS efforts. This study extends the existing AMS materials for low- and middle-income countries and provides empirical evidence for successful use in practice.

Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study.

OBJECTIVES: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. METHODS: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. RESULTS: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40). CONCLUSIONS: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. TRIAL REGISTRATION NUMBER: ISRCTN11041050.

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.

OBJECTIVE: To describe the incidence of, risk factors for, and impact of vaccines on primary SARS-CoV-2 infection during the second wave of the covid-19 pandemic in susceptible hospital healthcare workers in England. DESIGN: Multicentre prospective cohort study. SETTING: National Health Service secondary care health organisations (trusts) in England between 1 September 2020 and 30 April 2021. PARTICIPANTS: Clinical, support, and administrative staff enrolled in the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study with no evidence of previous infection. Vaccination status was obtained from national covid-19 vaccination registries and self-reported. MAIN OUTCOME MEASURE: SARS-CoV-2 infection confirmed by polymerase chain reaction. Mixed effects logistic regression was conducted to determine demographic and occupational risk factors for infection, and an individual based mathematical model was used to predict how large the burden could have been if vaccines had not been available from 8 December 2020 . RESULTS: During England's second wave, 12.9% (2353/18 284) of susceptible SIREN participants became infected with SARS-CoV-2. Infections peaked in late December 2020 and decreased from January 2021, concurrent with the cohort's rapid vaccination coverage and a national lockdown. In multivariable analysis, factors increasing the likelihood of infection in the second wave were being under 25 years old (20.3% (132/651); adjusted odds ratio 1.35, 95% confidence interval 1.07 to 1.69), living in a large household (15.8% (282/1781); 1.54, 1.23 to 1.94, for participants from households of five or more people), having frequent exposure to patients with covid-19 (19.2% (723/3762); 1.79, 1.56 to 2.06, for participants with exposure every shift), working in an emergency department or inpatient ward setting (20.8% (386/1855); 1.76, 1.45 to 2.14), and being a healthcare assistant (18.1% (267/1479); 1.43, 1.16 to 1.77). Time to first vaccination emerged as being strongly associated with infection (P<0.001), with each additional day multiplying a participant's adjusted odds ratio by 1.02. Mathematical model simulations indicated that an additional 9.9% of all patient facing hospital healthcare workers would have been infected were it not for the rapid vaccination coverage. CONCLUSIONS: The rapid covid-19 vaccine rollout from December 2020 averted infection in a large proportion of hospital healthcare workers in England: without vaccines, second wave infections could have been 69% higher. With booster vaccinations being needed for adequate protection from the omicron variant, and perhaps the need for further boosters for future variants, ensuring equitable delivery to healthcare workers is essential. The findings also highlight occupational risk factors that persisted in healthcare workers despite vaccine rollout; a greater understanding of the transmission dynamics responsible for these is needed to help to optimise the infection prevention and control policies that protect healthcare workers from infection and therefore to support staffing levels and maintain healthcare provision. TRIAL REGISTRATION: ISRCTN registry ISRCTN11041050.

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 & REinfection EvaluatioN) study protocol.

INTRODUCTION: Understanding the effectiveness and durability of protection against SARS-CoV-2 infection conferred by previous infection and COVID-19 is essential to inform ongoing management of the pandemic. This study aims to determine whether prior SARS-CoV-2 infection or COVID-19 vaccination in healthcare workers protects against future infection. METHODS AND ANALYSIS: This is a prospective cohort study design in staff members working in hospitals in the UK. At enrolment, participants are allocated into cohorts, positive or naïve, dependent on their prior SARS-CoV-2 infection status, as measured by standardised SARS-CoV-2 antibody testing on all baseline serum samples and previous SARS-CoV-2 test results. Participants undergo monthly antibody testing and fortnightly viral RNA testing during follow-up and based on these results may move between cohorts. Any results from testing undertaken for other reasons (eg, symptoms, contact tracing) or prior to study entry will also be captured. Individuals complete enrolment and fortnightly questionnaires on exposures, symptoms and vaccination. Follow-up is 12 months from study entry, with an option to extend follow-up to 24 months.The primary outcome of interest is infection with SARS-CoV-2 after previous SARS-CoV-2 infection or COVID-19 vaccination during the study period. Secondary outcomes include incidence and prevalence (both RNA and antibody) of SARS-CoV-2, viral genomics, viral culture, symptom history and antibody/neutralising antibody titres. ETHICS AND DISSEMINATION: The study was approved by the Berkshire Research Ethics Committee, Health Research Authority (IRAS ID 284460, REC reference 20/SC/0230) on 22 May 2020; the vaccine amendment was approved on 12 January 2021. Participants gave informed consent before taking part in the study.Regular reports to national and international expert advisory groups and peer-reviewed publications ensure timely dissemination of findings to inform decision making. TRIAL REGISTRATION NUMBER: ISRCTN11041050.

Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection.

BACKGROUND: The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters. METHODS: We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2. RESULTS: Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 95% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously. CONCLUSIONS: Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.).

COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study.

BACKGROUND: BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. METHODS: The SIREN study is a prospective cohort study among staff (aged ≥18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed-effect logistic regression analysis to identify factors associated with vaccine coverage. We used a piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing. FINDINGS: 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46·1 years (IQR 36·0-54·1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infections 7 days after the second dose (incidence density four infections per 10 000 person-days). In the unvaccinated cohort, 543 (56%) participants had typical COVID-19 symptoms and 140 (14%) were asymptomatic on or 14 days before their PCR positive test date, compared with 29 (36%) with typical COVID-19 symptoms and 15 (19%) asymptomatic in the vaccinated cohort. A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. INTERPRETATION: Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort was vaccinated when the dominant variant in circulation was B1.1.7 and shows effectiveness against this variant. FUNDING: Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.

The TACTIC experience: establishing an international, interdisciplinary network to tackle antimicrobial resistance.

Antimicrobial resistance (AMR) is a major global health threat that requires an interdisciplinary international approach to address. In response to calls from policymakers and funders alike, a growing number of research networks on AMR have been created with this approach in mind. However, there are many challenges facing researchers in establishing such networks and research projects. In this article, we share our experience of establishing the network 'TACTIC: Tackling AMR Challenges through Translational Interdisciplinary Collaborations'. Although presented with many challenges both scientific and logistical, the network has underpinned productive interaction between biomedical and social scientists from several countries and fostered true collaboration in an educative, stimulating and sustainable way that forms a platform for important research on AMR.

AMR Surveillance in low and middle-income settings - A roadmap for participation in the Global Antimicrobial Surveillance System (GLASS).

Drug-resistant infections caused by bacteria with increasing antimicrobial resistance (AMR) threaten our ability to treat life-threatening conditions. Tackling AMR requires international collaboration and partnership. An early and leading priority to do this is to strengthen AMR surveillance, particularly in low-income countries where the burden of infectious diseases is highest and where data are most limited. The World Health Organization (WHO) has developed the Global AMR Surveillance System (GLASS) as one of a number of measures designed to tackle the problem of AMR, and WHO member states have been encouraged to produce National Action Plans for AMR by 2017. However, low-income countries are unlikely to have the resources or capacity to implement all the components in the GLASS manual. To facilitate their efforts, we developed a guideline that is aligned to the GLASS procedures, but written specifically for implementation in low-income countries. The guideline allows for flexibility across different systems, but has sufficient standardisation of core protocols to ensure that, if followed, data will be valid and comparable. This will ensure that the surveillance programme can provide health intelligence data to inform evidence-based interventions at local, national and international levels.

Probiotics for the prevention and treatment of Clostridium difficile in older patients.

Clostridium difficile infection (CDI) is the leading cause of nosocomial diarrhoea in older people, causing substantial morbidity and mortality. The fact that CDI is almost exclusively a disease of older people and the debilitated indicates that patient susceptibility is a major determinant of who gets CDI. It would help efforts to combat this disease if we better understood and could reduce patient susceptibility. In this regard, several strategies are currently under investigation. The use of probiotics for CDI has received particular attention in the medical and lay media. Patients and their carers often ask doctors about them. In this review article, we describe the pathogenesis of CDI before looking at the ageing host in more detail. We discuss how probiotics may work and review the current evidence for their use in CDI.