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.

Background Inappropriate attendances may account for up to 40% of presentations at accident and emergency (A&E) departments. There is considerable interest from health practitioners and policymakers in interventions to reduce this burden. Aim To review the evidence on primary care service interventions to reduce inappropriate A&E attendances. Design and setting Systematic review of UK and international primary care interventions. Method Studies published in English between 1 January 1986 and 23 August 2011 were identified from PubMed, the NHS Economic Evaluation Database, the Cochrane Collaboration, and Health Technology Assessment databases. The outcome measures were A&E attendances, patient satisfaction, clinical outcome, and intervention cost. Two authors reviewed titles and abstracts of retrieved results, with adjudication of disagreements conducted by the third. Studies were quality assessed using the Scottish Intercollegiate Guidelines Network checklist system where applicable. Results In total, 9916 manuscripts were identified, of which 34 were reviewed. Telephone triage was the single best-evaluated intervention. This resulted in negligible impact on A&E attendance, but exhibited acceptable patient satisfaction and clinical safety; cost effectiveness was uncertain. The limited available evidence suggests that emergency nurse practitioners in community settings and community health centres may reduce A&E attendance. For all other interventions considered in this review (walk-in centres, minor injuries units, and out-of-hours general practice), the effects on A&E attendance, patient outcomes, and cost were inconclusive. Conclusion Studies showed a negligible effect on A&E attendance for all interventions; data on patient outcomes and cost-effectiveness are limited. There is an urgent need to examine all aspects of primary care service interventions that aim to reduce inappropriate A&E attendance.

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.

Background Although the literature on effects of armed conflict on population health is extensive, detailed assessments of effects on public health ‘systems’ are few. This article aims to help address this deficit through the medium of a case study on Yemen, describing health system and health outcome performance prior to the internationalisation of the conflict there in March 2015, before assessing the impact of war on health system functionality since that time. Method Review of peer- and non-peer reviewed literature from 2005 to 2016 from academic sources, multilateral organizations, donors and governmental and non-governmental organizations, augmented by secondary data analysis. Results Despite significant health system weaknesses and structural vulnerabilities pre-conflict, there were important improvements in selected health outcome measures in Yemen up to early 2015 (life expectancy, and infant and maternal mortality, e.g.), partly driven by a fragile health sector that was heavily reliant on out-of-pocket expenditure, and hampered by weak service penetration especially in rural areas. High intensity conflict has resulted in rising mortality and injury rates since March 2015, the first decline in life expectancy and increase in child and maternal mortality in Yemen for some years, and worsening levels of malnutrition. Service delivery has become increasingly challenging in the context of a funding crisis, destruction of health facilities, widespread shortages of essential medicines and equipment across the country, and governance fragmentation. Conclusion Conflict in Yemen has resulted in humanitarian disaster on a wide scale in a short period of time, and crippled an already weak health system. Important areas of uncertainty remain, however, including the scale of health worker flight, and the extent to which alternative providers have stepped in to fill widening service gaps as the conflict has unfolded. Planning for longer-term health system reconstruction should begin as soon as possible.

Background: The social determinants of health have been widely recognised yet there remains a lack of clarity regarding what constitute the macro-economic determinants of health and what can be done to address them. An umbrella review of systematic reviews was conducted to identify the evidence for the health and health inequalities impact of population level macroeconomic factors, strategies, policies and interventions. Methods: Nine databases were searched for systematic reviews meeting the Database of Abstracts of Reviews of Effects (DARE) criteria using a novel conceptual framework. Studies were assessed for quality using a standardised instrument and a narrative overview of the findings is presented. Results: The review found a large (n = 62) but low quality systematic review-level evidence base. The results indicated that action to promote employment and improve working conditions can help improve health and reduce gender-based health inequalities. Evidence suggests that market regulation of tobacco, alcohol and food is likely to be effective at improving health and reducing inequalities in health including strong taxation, or restriction of advertising and availability. Privatisation of utilities and alcohol sectors, income inequality, and economic crises are likely to increase health inequalities. Left of centre governments and welfare state generosity may have a positive health impact, but evidence on specific welfare interventions is mixed. Trade and trade policies were found to have a mixed effect. There were no systematic reviews of the health impact of monetary policy or of large economic institutions such as central banks and regulatory organisations. Conclusions: The results of this study provide a simple yet comprehensive framework to support policy-makers and practitioners in addressing the macroeconomic determinants of health. Further research is needed in low and middle income countries and further reviews are needed to summarise evidence in key gaps identified by this review. Trial registration: Protocol for umbrella review prospectively registered with PROSPERO CRD42017068357.

To describe trends in major communicable diseases in Syria during the ongoing conflict, and the challenges to communicable disease surveillance and control in the context of dynamic, large-scale population displacement, unplanned mass gatherings, and disruption to critical infrastructure. A rapid review of the peer-reviewed and non-peer-reviewed literature from 2005 to 2015 was performed, augmented by secondary analysis of monitoring data from two disease early warning systems currently operational in Syria, focusing mainly on three diseases: tuberculosis (TB), measles, and polio. Trend data show discrepancies in case report numbers between government and non-government controlled areas, especially for TB, but interpretation is hampered by uncertainties over sentinel surveillance coverage and base population numbers. Communicable disease control has been undermined by a combination of governance fragmentation, direct and indirect damage to facilities and systems, and health worker flight. Five years into the crisis, some progress has been made in disease surveillance, but governance and coordination problems, variable immunization coverage, and the dynamic and indiscriminate nature of the conflict continue to pose a serious threat to population health in Syria and surrounding countries. The risk of major cross-border communicable disease outbreaks is high, and challenges for health in a post-conflict Syria are formidable.