Community interventions for pandemic preparedness: A scoping review of pandemic preparedness lessons from HIV, COVID-19, and other public health emergencies of international concern.

Community action is broadly recognised as central to comprehensive and effective system responses to pandemics. However, there is uncertainty about how and where communities can be best supported to bolster long-term resilience and preparedness. We applied a typology of community interventions (Community Informing, Consulting, Involving, Collaborating or Empowering-or CICICE) to cover the diverse range of interventions identified across the literature and used this to structure a scoping review addressing three linked topics: (i) how CICICE interventions have been understood and applied in the literature on epidemic and pandemic preparedness; (ii) the spectrum of interventions that have been implemented to strengthen CICICE and (iii) what evidence is available on their effectiveness in influencing preparedness for current and future emergencies. We drew on peer-reviewed and grey literature from the HIV (from 2000) and COVID-19 pandemics and recent public health emergencies of international concern (from 2008), identified through systematic searches in MEDLINE, Scopus, the Cochrane Collaboration database, supplemented by keyword-structured searches in GoogleScholar and websites of relevant global health organisations. Following screening and extraction, key themes were identified using a combined inductive/deductive approach. 130 papers met the criteria for inclusion. Interventions for preparedness were identified across the spectrum of CICICE. Most work on COVID-19 focused on informing and consulting rather than capacity building and empowerment. The literature on HIV was more likely to report interventions emphasising human rights perspectives and empowerment. There was little robust evidence on the role of CICICE interventions in building preparedness. Evidence of effect was most robust for multi-component interventions for HIV prevention and control. Much of the reporting focused on intermediate outcomes, including measures of health service utilisation. We put forward a series of recommendations to help address evidence shortfalls, including clarifying definitions, organising and stratifying interventions by several parameters and strengthening evaluation methods for CICICE.

Resilience in childhood vaccination: analysing delivery system responses to shocks in Lebanon.

INTRODUCTION: Despite rapidly growing academic and policy interest in health system resilience, the empirical literature on this topic remains small and focused on macrolevel effects arising from single shocks. To better understand health system responses to multiple shocks, we conducted an in-depth case study using qualitative system dynamics. We focused on routine childhood vaccination delivery in Lebanon in the context of at least three shocks overlapping to varying degrees in space and time: large-scale refugee arrivals from neighbouring Syria; COVID-19; and an economic crisis. METHODS: Semistructured interviews were performed with 38 stakeholders working at different levels in the system. Interview transcripts were analysed using purposive text analysis to generate individual stakeholder causal loop diagrams (CLDs) mapping out relationships between system variables contributing to changes in coverage for routine antigens over time. These were then combined using a stepwise process to produce an aggregated CLD. The aggregated CLD was validated using a reserve set of interview transcripts. RESULTS: Various system responses to shocks were identified, including demand promotion measures such as scaling-up community engagement activities and policy changes to reduce the cost of vaccination to service users, and supply side responses including donor funding mobilisation, diversification of service delivery models and cold chain strengthening. Some systemic changes were introduced-particularly in response to refugee arrivals-including task-shifting to nurse-led vaccine administration. Potentially transformative change was seen in the integration of private sector clinics to support vaccination delivery and depended on both demand side and supply side changes. Some resilience-promoting measures introduced following earlier shocks paradoxically increased vulnerability to later ones. CONCLUSION: Flexibility in financing and human resource allocation appear key for system resilience regardless of the shock. System dynamics offers a promising method for ex ante modelling of ostensibly resilience-strengthening interventions under different shock scenarios, to identify-and safeguard against-unintended consequences.

Oestrogen therapy for treating pelvic organ prolapse in postmenopausal women.

BACKGROUND: Pelvic organ prolapse (POP) is the descent of a woman's uterus, bladder, or rectum into the vagina. It affects 50% of women over 50 years old who have given birth to at least one child, and recognised risk factors are older age, higher number of births, and higher body mass index. This review assesses the effects of oestrogen therapy, alone or in combination with other treatments, on POP in postmenopausal women. OBJECTIVES: To assess the benefits and harms of local and systemic oestrogen therapy in the management of pelvic organ prolapse symptoms in postmenopausal women, and to summarise the principal findings of relevant economic evaluations. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register (up to 20 June 2022), which includes CENTRAL, MEDLINE, two trials registers, and handsearching of journals and conference proceedings. We also checked the reference lists of relevant articles for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs, multi-arm RCTs, and cross-over RCTs that evaluated the effects of oestrogen therapy (alone or in combination with other treatments) versus placebo, no treatment, or other interventions in postmenopausal women with any grade of POP. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials using prespecified outcome measures and a piloted extraction form. The same review authors independently assessed the risk of bias of eligible trials using Cochrane's risk of bias tool. Had data allowed, we would have created summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified 14 studies including a total of 1002 women. In general, studies were at high risk of bias in terms of blinding of participants and personnel, and there were also some concerns about selective reporting. Owing to insufficient data for the outcomes of interest, we were unable to perform our planned subgroup analyses (systemic versus topical oestrogen, parous versus nulliparous women, women with versus without a uterus). No studies assessed the effects of oestrogen therapy alone versus no treatment, placebo, pelvic floor muscle training, devices such as vaginal pessaries, or surgery. However, we did identify three studies that assessed oestrogen therapy in conjunction with vaginal pessaries versus vaginal pessaries alone and 11 studies that assessed oestrogen therapy in conjunction with surgery versus surgery alone. AUTHORS' CONCLUSIONS: There was insufficient evidence from RCTs to draw any solid conclusions on the benefits or harms of oestrogen therapy for managing POP symptoms in postmenopausal women. Topical oestrogen in conjunction with pessaries was associated with fewer adverse vaginal events compared with pessaries alone, and topical oestrogen in conjunction with surgery was associated with reduced postoperative urinary tract infections compared with surgery alone; however, these findings should be interpreted with caution, as the studies that contributed data varied substantially in their design. There is a need for larger studies on the effectiveness and cost-effectiveness of oestrogen therapy, used alone or in conjunction with pelvic floor muscle training, vaginal pessaries, or surgery, for the management of POP. These studies should measure outcomes in the medium and long term.

Adapting SARS-CoV-2 vaccination delivery in England to population needs: a thematic analysis of providers and commissioner's perceptions.

BACKGROUND: A national SARS-CoV-2 vaccination programme was implemented in England from 8th December 2020, adopting a series of local level service delivery models to maximise rollout. The evidence base informing service design programme at inception was limited. We examined the real-world implementation of the programme through an assessment of sub-national providers' and commissioners' perspectives on the service delivery models used, to strengthen evidence on the acceptability, effectiveness and efficiency of the service delivery approaches used for SARS-CoV-2 vaccination in England or elsewhere. METHODS: Qualitative, cross-sectional analysis based on semi-structured interviews conducted with 87 stakeholders working in SARS-CoV-2 vaccination delivery across four regions in England. Localities were selected according to geography and population socio-economic status. Participants were purposively sampled from health service providers, commissioners and other relevant bodies. Interviews were conducted between February and October 2021, and transcripts were thematically analysed using inductive and deductive approaches. RESULTS: Various service delivery models were implemented over the course of the programme, beginning with hospital hubs and mass vaccination sites, before expanding to incorporate primary care-led services, mobile and other outreach services. Each had advantages and drawbacks but primary care-led models, and to some extent pharmacies, were perceived to offer a better combination of efficiency and community reach for equitable delivery. Common factors for success included availability of a motivated workforce, predictability in vaccine supply chains and strong community engagement. However, interviewees noted a lack of coordination between service providers in the vaccination programme, linked to differing financial incentives and fragmentated information systems, among other factors. CONCLUSION: A range of delivery models are needed to enable vaccine rollout at pace and scale, and to mitigate effects on routine care provision. However, primary care-led services offer a tried-and-trusted framework for vaccine delivery at scale and pace and should be central to planning for future pandemic responses. Mass vaccination sites can offer delivery at scale but may exacerbate inequalities in vaccination coverage and are unlikely to offer value for money. Policymakers in England should prioritise measures to improve collaboration between service providers, including better alignment of IT systems.

Strengthening vaccination delivery system resilience in the context of protracted humanitarian crisis: a realist-informed systematic review.

BACKGROUND: Childhood vaccination is among the most effective public health interventions available for the prevention of communicable disease, but coverage in many humanitarian settings is sub-optimal. This systematic review critically evaluated peer-review and grey literature evidence on the effectiveness of system-level interventions for improving vaccination coverage in protracted crises, focusing on how they work, and for whom, to better inform preparedness and response for future crises. METHODS: Realist-informed systematic review of peer-reviewed and grey literature. Keyword-structured searches were performed in MEDLINE, EMBASE and Global Health, CINAHL, the Cochrane Collaboration and WHOLIS, and grey literature searches performed through the websites of UNICEF, the Global Polio Eradication Initiative (GPEI) and Technical Network for Strengthening Immunization Services. Results were independently double-screened for inclusion on title and abstract, and full text. Data were extracted using a pre-developed template, capturing information on the operating contexts in which interventions were implemented, intervention mechanisms, and vaccination-related outcomes. Study quality was assessed using the MMAT tool. Findings were narratively synthesised. RESULTS: 50 studies were included, most describing interventions applied in conflict or near-post conflict settings in sub-Saharan Africa, and complex humanitarian emergencies. Vaccination campaigns were the most commonly addressed adaptive mechanism (n = 17). Almost all campaigns operated using multi-modal approaches combining service delivery through multiple pathways (fixed and roving), health worker recruitment and training and community engagement to address both vaccination supply and demand. Creation of collaterals through service integration showed generally positive evidence of impact on routine vaccination uptake by bringing services closer to target populations and leveraging trust that had already been built with communities. Robust community engagement emerged as a key unifying mechanism for outcome improvement across almost all of the intervention classes, in building awareness and trust among crisis-affected populations. Some potentially transformative mechanisms for strengthening resilience in vaccination delivery were identified, but evidence for these remains limited. CONCLUSION: A number of interventions to support adaptations to routine immunisation delivery in the face of protracted crisis are identifiable, as are key unifying mechanisms (multi-level community engagement) apparently irrespective of context, but evidence remains piecemeal. Adapting these approaches for local system resilience-building remains a key challenge.

A cross-sectional national investigation of COVID-19 outbreaks in nurseries during rapid spread of the Alpha (B.1.1.7) variant of SARS-CoV-2 in England.

BACKGROUND: In England, the emergence the more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) led to a third national lockdown from December 2020, including restricted attendance at schools. Nurseries, however, remained fully open. COVID-19 outbreaks (≥ 2 laboratory-confirmed cases within 14 days) in nurseries were investigated to assess the risk of SARS-CoV-2 infection and cumulative incidence in staff and children over a three-month period when community SARS-CoV-2 infections rates were high and the Alpha variant was spreading rapidly across England. METHODS: This was a cross-sectional national investigation of COVID-19 outbreaks in nurseries across England. Nurseries reporting a COVID-19 outbreak to PHE between November 2020 and January 2021 were requested to complete a questionnaire about their outbreak. RESULTS: Three hundred and twenty-four nurseries, comprising 1% (324/32,852) of nurseries in England, reported a COVID-19 outbreak. Of the 315 (97%) nurseries contacted, 173 (55%) reported 1,657 SARS-CoV-2 cases, including 510 (31%) children and 1,147 (69%) staff. A child was the index case in 45 outbreaks (26%) and staff in 125 (72%) outbreaks. Overall, children had an incidence rate of 3.50% (95%CI, 3.21-3.81%) and was similar irrespective of whether the index case was a child (3.55%; 95%CI, 3.01-4.19%) or staff (3.44%; 95%CI, 3.10-3.82%). Among staff, cumulative incidence was lower if the index case was a child (26.28%; 95%CI, 23.54-29.21%%) compared to a staff member (32.98%; 95%CI, 31.19-34.82%), with the highest cumulative incidence when the index case was also a staff member (37.52%; 95%CI, 35.39-39.70%). Compared to November 2020, outbreak sizes and cumulative incidence was higher in January 2021, when the Alpha variant predominated. Nationally, SARS-CoV-2 infection rates in < 5 year-olds remained low and followed trends in older age-groups, increasing during December 2020 and declining thereafter. CONCLUSIONS: In this cross-sectional study of COVID-19 outbreaks in nurseries, one in three staff were affected compared to one in thirty children. There was some evidence of increased transmissibility and higher cumulative incidence associated with the Alpha variant, highlighting the importance of maintaining a low level of community infections.

COVID-19 vaccination beliefs, attitudes, and behaviours among health and social care workers in the UK: A mixed-methods study.

BACKGROUND: The UK began delivering its COVID-19 vaccination programme on 8 December 2020, with health and social care workers (H&SCWs) given high priority for vaccination. Despite well-documented occupational exposure risks, however, there is evidence of lower uptake among some H&SCW groups. METHODS: We used a mixed-methods approach-involving an online cross-sectional survey and semi-structured interviews-to gain insight into COVID-19 vaccination beliefs, attitudes, and behaviours amongst H&SCWs in the UK by socio-demographic and employment variables. 1917 people were surveyed- 1656 healthcare workers (HCWs) and 261 social care workers (SCWs). Twenty participants were interviewed. FINDINGS: Workplace factors contributed to vaccination access and uptake. SCWs were more likely to not be offered COVID-19 vaccination than HCWs (OR:1.453, 95%CI: 1.244-1.696). SCWs specifically reported uncertainties around how to access COVID-19 vaccination. Participants who indicated stronger agreement with the statement 'I would recommend my organisation as a place to work' were more likely to have been offered COVID-19 vaccination (OR:1.285, 95%CI: 1.056-1.563). Those who agreed more strongly with the statement 'I feel/felt under pressure from my employer to get a COVID-19 vaccine' were more likely to have declined vaccination (OR:1.751, 95%CI: 1.271-2.413). Interviewees that experienced employer pressure to get vaccinated felt this exacerbated their vaccine concerns and increased distrust. In comparison to White British and White Irish participants, Black African and Mixed Black African participants were more likely to not be offered (OR:2.011, 95%CI: 1.026-3.943) and more likely to have declined COVID-19 vaccination (OR:5.550, 95%CI: 2.294-13.428). Reasons for declining vaccination among Black African participants included distrust in COVID-19 vaccination, healthcare providers, and policymakers. CONCLUSION: H&SCW employers are in a pivotal position to facilitate COVID-19 vaccination access, by ensuring staff are aware of how to get vaccinated and promoting a workplace environment in which vaccination decisions are informed and voluntary.

Viewing the global health system as a complex adaptive system - implications for research and practice.

The global health system (GHS) is ill-equipped to deal with the increasing number of transnational challenges. The GHS needs reform to enhance global resilience to future risks to health. In this article we argue that the starting point for any reform must be conceptualizing and studying the GHS as a complex adaptive system (CAS) with a large and escalating number of interconnected global health actors that learn and adapt their behaviours in response to each other and changes in their environment. The GHS can be viewed as a multi-scalar, nested health system comprising all national health systems together with the global health architecture, in which behaviours are influenced by cross-scale interactions. However, current methods cannot adequately capture the dynamism or complexity of the GHS or quantify the effects of challenges or potential reform options. We provide an overview of a selection of systems thinking and complexity science methods available to researchers and highlight the numerous policy insights their application could yield.   We also discuss the challenges for researchers of applying these methods and for policy makers of digesting and acting upon them. We encourage application of a CAS approach to GHS research and policy making to help bolster resilience to future risks that transcend national boundaries and system scales.

Conceptualising and assessing health system resilience to shocks: a cross-disciplinary view.

Health systems worldwide face major challenges in anticipating, planning for and responding to shocks from infectious disease epidemics, armed conflict, climatic and other crises. Although the literature on health system resilience has grown substantially in recent years, major uncertainties remain concerning approaches to resilience conceptualisation and measurement. This narrative review revisits literatures from a range of fields outside health to identify lessons relevant to health systems. Four key insights emerge. Firstly, shocks can only be understood by clarifying how, where and over what timescale they interact with a system of interest, and the dynamic effects they produce within it. Shock effects are contingent on historical path-dependencies, and on the presence of factors or system pathways (e.g. financing models, health workforce capabilities or supply chain designs) that may amplify or dampen impact in unexpected ways. Secondly, shocks often produce cascading effects across multiple scales, whereas the focus of much of the health resilience literature has been on macro-level, national systems. In reality, health systems bring together interconnected sub-systems across sectors and geographies, with different components, behaviours and sometimes even objectives - all influencing how a system responds to a shock. Thirdly, transformability is an integral feature of resilient social systems: cross-scale interactions help explain how systems can show both resilience and transformational capability at the same time. We illustrate these first three findings by extending the socioecological concept of adaptive cycles in social systems to health, using the example of maternal and child health service delivery. Finally, we argue that dynamic modelling approaches, under-utilised in research on health system resilience to date, have significant promise for identification of shock-moderating or shock-amplifying pathways, for understanding effects at multiple levels and ultimately for building resilience.

COVID-19 outbreaks following full reopening of primary and secondary schools in England: Cross-sectional national surveillance, November 2020.

BACKGROUND: The full reopening of schools in September 2020 was associated with an increase in COVID-19 cases and outbreaks in educational settings across England. METHODS: Primary and secondary schools reporting an outbreak (≥2 laboratory-confirmed cases within 14 days) to Public Health England (PHE) between 31 August and 18 October 2020 were contacted in November 2020 to complete an online questionnaire. INTERPRETATION: There were 969 school outbreaks reported to PHE, comprising 2% (n = 450) of primary schools and 10% (n = 519) of secondary schools in England. Of the 369 geographically-representative schools contacted, 179 completed the questionnaire (100 primary schools, 79 secondary schools) and 2,314 cases were reported. Outbreaks were larger and across more year groups in secondary schools than in primary schools. Teaching staff were more likely to be the index case in primary (48/100, 48%) than secondary (25/79, 32%) school outbreaks (P = 0.027). When an outbreak occurred, attack rates were higher in staff (881/17,362; 5.07; 95%CI, 4.75-5.41) than students, especially primary school teaching staff (378/3852; 9.81%; 95%CI, 8.90-10.82%) compared to secondary school teaching staff (284/7146; 3.97%; 95%CI, 3.79-5.69%). Secondary school students (1105/91,919; 1.20%; 95%CI, 1.13-1.28%) had higher attack rates than primary school students (328/39,027; 0.84%; 95%CI, 0.75-0.94%). CONCLUSIONS: A higher proportion of secondary schools than primary schools reported a COVID-19 outbreak and experienced larger outbreaks across multiple school year groups. The higher attack rate among teaching staff during an outbreak, especially in primary schools, suggests that additional protective measures may be needed. FUNDING: PHE.

Measuring quality of life in people living with and beyond cancer in the UK.

PURPOSE: The aim of this study was to identify the most appropriate measure of quality of life (QoL) for patients living with and beyond cancer. METHODS: One hundred eighty-two people attending cancer clinics in Central London at various stages post-treatment, completed a series of QoL measures: FACT-G, EORTC QLQ-C30 , IOCv2 (positive and negative subscales) and WEMWBS, a wellbeing measure. These measures were chosen as the commonest measures used in previous research. Correlation tests were used to assess the association between scales. Participants were also asked about pertinence and ease of completion. RESULTS: There was a significant positive correlation between the four domain scores of the two health-related QoL measures (.32 ≤ r ≤ .72, P < .001), and a significant large negative correlation between these and the negative IOCv2 subscale scores (- .39 ≤ r ≤ - .63, P < .001). There was a significant moderate positive correlation between positive IOCv2 subscale and WEMWBS scores (r = .35, P < .001). However, neither the FACT-G nor the EORTC showed any significant correlation with the positive IOCv2 subscale. Participants rated all measures similarly with regards to pertinence and ease of use. CONCLUSION: There was little to choose between FACT-G, EORTC, and the negative IOC scales, any of which may be used to measure QoL. However, the two IOCv2 subscales capture unique aspects of QoL compared to the other measures. The IOCv2 can be used to identify those cancer survivors who would benefit from interventions to improve their QoL and to target specific needs thereby providing more holistic and personalised care beyond cancer treatment.

SARS-CoV-2 infections in children following the full re-opening of schools and the impact of national lockdown: Prospective, national observational cohort surveillance, July-December 2020, England.

INTRODUCTION: The reopening of schools during the COVID-19 pandemic has raised concern for the safety of staff and students, their families and the wider community. We monitored SARS-CoV-2 infection rates in school-aged children and compared them with adult infection rates before and after schools reopened in England. METHODS: Public Health England receives daily electronic reports of all SARS-CoV-2 tests nationally. SARS-CoV-2 infection rates by school year from July to December 2020 were analysed, including the effect of a national month-long lockdown whilst keeping schools open in November 2020 RESULTS: SARS-CoV-2 infections rates were low during early summer but started increasing in mid-August, initially in young adults followed by secondary and then primary school-aged children prior to schools reopening in September 2020. Cases in school-aged children lagged behind and followed adult trends after schools reopened, with a strong age gradient in weekly infection rates. There was a strong (P<0.001) correlation in regional infection rates between adults and secondary (R2=0.96-0.98), primary (R2=0.93-0.94) and preschool-aged (R2=0.62-0.85) children. The November lockdown was associated with declines in adult infection rates, followed a week later, by declines in student cases. From 23 November 2020, cases in adults and children increased rapidly following the emergence of a more transmissible novel variant of concern (VOC-202,012/01; B.1.1.7). CONCLUSIONS: In school-aged children, SARS-CoV-2 infections followed the same trajectory as adult cases and only declined after national lockdown was implemented whilst keeping schools open. Maintaining low community infection rates is critical for keeping schools open during the pandemic.

T cell response to SARS-CoV-2 infection in humans: A systematic review.

BACKGROUND: Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and disease control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published from 01/01/2020-26/06/2020. METHODS: For this systematic review, keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS: 61 articles were included. 55 (90%) studies used observational designs, 50 (82%) involved hospitalised patients with higher acuity illness, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. CONCLUSION: A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies, as well as a striking lack of research in asymptomatic or pauci-symptomatic individuals. In contrast to antibody responses, population-level surveillance of the T cell response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised.

SARS-CoV-2 infection and transmission in educational settings: a prospective, cross-sectional analysis of infection clusters and outbreaks in England.

BACKGROUND: Understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission in educational settings is crucial for ensuring the safety of staff and children during the COVID-19 pandemic. We estimated the rate of SARS-CoV-2 infection and outbreaks among staff and students in educational settings during the summer half-term (June-July, 2020) in England. METHODS: In this prospective, cross-sectional analysis, Public Health England initiated enhanced national surveillance in educational settings in England that had reopened after the first national lockdown, from June 1 to July 17, 2020. Educational settings were categorised as early years settings (<5-year-olds), primary schools (5-11-year-olds; only years 1 and 6 allowed to return), secondary schools (11-18-year-olds; only years 10 and 12), or mixed-age settings (spanning a combination of the above). Further education colleges were excluded. Data were recorded in HPZone, an online national database for events that require public health management. RT-PCR-confirmed SARS-CoV-2 event rates and case rates were calculated for staff and students, and direction of transmission was inferred on the basis of symptom onset and testing dates. Events were classified as single cases, coprimary cases (at least two confirmed cases within 48 h, typically within the same household), and outbreaks (at least two epidemiologically linked cases, with sequential cases diagnosed within 14 days in the same educational setting). All events were followed up for 28 days after educational settings closed for the summer holidays. Negative binomial regression was used to correlate educational setting events with regional population, population density, and community incidence. FINDINGS: A median of 38 000 early years settings (IQR 35 500-41 500), 15 600 primary schools (13 450-17 300), and 4000 secondary schools (3700-4200) were open each day, with a median daily attendance of 928 000 students (630 000-1 230 000) overall. There were 113 single cases of SARS-CoV-2 infection, nine coprimary cases, and 55 outbreaks. The risk of an outbreak increased by 72% (95% CI 28-130) for every five cases per 100 000 population increase in community incidence (p<0·0001). Staff had higher incidence than students (27 cases [95% CI 23-32] per 100 000 per day among staff compared with 18 cases [14-24] in early years students, 6·0 cases [4·3-8·2] in primary schools students, and 6·8 cases [2·7-14] in secondary school students]), and most cases linked to outbreaks were in staff members (154 [73%] staff vs 56 [27%] children of 210 total cases). Probable direction of transmission was staff to staff in 26 outbreaks, staff to student in eight outbreaks, student to staff in 16 outbreaks, and student to student in five outbreaks. The median number of secondary cases in outbreaks was one (IQR 1-2) for student index cases and one (1-5) for staff index cases. INTERPRETATION: SARS-CoV-2 infections and outbreaks were uncommon in educational settings during the summer half-term in England. The strong association with regional COVID-19 incidence emphasises the importance of controlling community transmission to protect educational settings. Interventions should focus on reducing transmission in and among staff. FUNDING: Public Health England.

Horses for courses? Assessing the potential value of a surrogate, point-of-care test for SARS-CoV-2 epidemic control.

Point-of-care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID-19 by providing timely information to guide decision-making, but data on real-world performance are in short supply. Besides SARS-CoV-2-specific tests, there is growing interest in the role of surrogate (non-specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza-like illnesses. This short report assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS-CoV-2-specific POCTs. While FebriDx shows some potential in supporting triage for early-stage infection in acute care settings, this is dependent on SARS-CoV-2 being the most likely cause for influenza-like illnesses, with reduction in discriminatory power when COVID-19 case numbers are low, and when co-circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts, and further evaluation is needed. Reliable SARS CoV2-specific POCTs-when they become available-are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide.

Antibody response to SARS-CoV-2 infection in humans: A systematic review.

BACKGROUND: Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. METHODS: Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS: 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14-22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. CONCLUSIONS: Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

Considerations for planning COVID-19 treatment services in humanitarian responses.

The COVID-19 pandemic has the potential to cause high morbidity and mortality in crisis-affected populations. Delivering COVID-19 treatment services in crisis settings will likely entail complex trade-offs between offering services of clinical benefit and minimising risks of nosocomial infection, while allocating resources appropriately and safeguarding other essential services. This paper outlines considerations for humanitarian actors planning COVID-19 treatment services where vaccination is not yet widely available. We suggest key decision-making considerations: allocation of resources to COVID-19 treatment services and the design of clinical services should be based on community preferences, likely opportunity costs, and a clearly articulated package of care across different health system levels. Moreover, appropriate service planning requires information on the expected COVID-19 burden and the resilience of the health system. We explore COVID-19 treatment service options at the patient level (diagnosis, management, location and level of treatment) and measures to reduce nosocomial transmission (cohorting patients, protecting healthcare workers). Lastly, we propose key indicators for monitoring COVID-19 health services.

Capacity for health economics research and practice in Jordan, Lebanon, the occupied Palestinian territories and Turkey: needs assessment and options for development.

BACKGROUND: Capacity for health economics analysis and research is indispensable for evidence-informed allocations of scarce health resources; however, little is known about the experience and capacity strengthening preferences of academics and practitioners in the Eastern Mediterranean region. This study aimed to assess the needs for strengthening health economics capacity in Jordan, Lebanon, the occupied Palestinian territories and Turkey as part of the Research for Health in Conflict in the Middle East and North Africa (R4HC) project. METHODS: We combined a bibliometric analysis of health economics outputs based on a literature search conducted across seven databases with an online survey of academic researchers and non-academic practitioners. The records included in the bibliometric analysis were original studies and reviews with an explicit economic outcome related to health, disease or disability, had at least one author in Jordan, Lebanon, Palestine or Turkey, and were published between January 2014 and December 2018. Two types of analyses were conducted using VOSviewer software, namely keyword co-occurrence and co-publication networks across countries and organisations. The online survey asked academic researchers, analysts and decision-makers - identified through the bibliometric analysis and regional professional networks - about previous exposure to and priorities for capacity development in health economics. RESULTS: Of 15,185 records returned by the literature search, 566 were included in the bibliometric analysis. Organisations in Turkey contributed more than 80% of records and had the broadest and most diverse network of collaborators, nationally and internationally. Only 1% (n = 7) of studies were collaborations between researchers in two or more different jurisdictions. Cost analysis, cost-effectiveness analysis and health system economics were the main health economics topics across the included studies. Economic evaluations, measuring the economic burden of disease and health equity, were reported by survey respondents (n = 80) as the most important areas to develop in. Short courses, learn-by-doing and mentoring from an experienced professional were, in aggregate, the most preferred learning styles. CONCLUSIONS: Existing pockets of health economic expertise in the region can constitute the base of future capacity development efforts. Building confidence toward applying specific methods and trust toward stimulating cross-jurisdiction collaborations appear essential components for sustainably developing health economics capacity.

A Qualitative Research Study Which Explores Humanitarian Stakeholders' Views on Healthcare Access for Refugees in Greece.

Introduction: As of January 2020, 115,600 refugees remain in Greece; most are Afghani, Iraqi or Syrian nationals. This qualitative research study explores the views of key stakeholders providing healthcare for refugees in Greece between 2015 and 2018. The focus was on identifying key barriers and facilitators to healthcare access for refugees in Greece. Methods: 16 interviewees from humanitarian and international organisations operating in Greece were identified through purposive and snowball sampling. Semi-structured interviews were conducted between March and April 2018. Data were analysed using the Framework Method. Results: Key themes affecting healthcare access included the influence of socio-cultural factors (healthcare expectations, language, gender) and the ability of the Greek health system to respond to existing and evolving demands; these included Greece's ongoing economic crisis, human resource shortages, weak primary healthcare system, legal barriers and logistics. The evolution of the humanitarian response from emergency to sustained changes to EU funding, coordination and comprehensiveness of services affected healthcare access for refugees. Conclusion: The most noted barriers cited by humanitarian stakeholders to healthcare access for refugees in Greece were socio-cultural and language differences between refugees and healthcare providers and poor coordination among stakeholders. Policies and interventions which address these could improve healthcare access for refugees in Greece with coordination led by the EU.