Summary SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2 1 , and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro , the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.

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Sexual behaviours determined incidence and reinfection, regardless of healthcare setting. Our results suggest annual screening of women aged 16-24 years who are chlamydia negative, or sooner if partner change occurs. Rescreening chlamydia-positive women within 6 months of baseline infection may be sensible, especially if partner change occurs or all partners are not treated.

BackgroundAdverse childhood experiences (ACEs) including maltreatment and exposure to household stressors can impact the health of children. Community factors that provide support, friendship and opportunities for development may build children’s resilience and protect them against some harmful impacts of ACEs. We examine if a history of ACEs is associated with poor childhood health and school attendance and the extent to which such outcomes are counteracted by community resilience assets.MethodsA national (Wales) cross-sectional retrospective survey (n = 2452) using a stratified random probability sampling methodology and including a boost sample (n = 471) of Welsh speakers. Data collection used face-to-face interviews at participants’ places of residence. Outcome measures were self-reported poor childhood health, specific conditions (asthma, allergies, headaches, digestive disorders) and school absenteeism.ResultsPrevalence of each common childhood condition, poor childhood health and school absenteeism increased with number of ACEs reported. Childhood community resilience assets (being treated fairly, supportive childhood friends, being given opportunities to use your abilities, access to a trusted adult and having someone to look up to) were independently linked to better outcomes. In those with ≥4 ACEs the presence of all significant resilience assets (vs none) reduced adjusted prevalence of poor childhood health from 59.8 to 21.3%.ConclusionsBetter prevention of ACEs through the combined actions of public services may reduce levels of common childhood conditions, improve school attendance and help alleviate pressures on public services. Whilst the eradication of ACEs remains unlikely, actions to strengthen community resilience assets may partially offset their immediate harms.Electronic supplementary materialThe online version of this article (10.1186/s12889-018-5699-8) contains supplementary material, which is available to authorized users.

ObjectivesThe lifelong health impacts of adverse childhood experiences are increasingly being identified, including earlier and more frequent development of non-communicable disease. Our aim was to examine whether adverse childhood experiences are related to increased use of primary, emergency and in-patient care and at what ages such impact is apparent.MethodsHousehold surveys were undertaken in 2015 with 7414 adults resident in Wales and England using random probability stratified sampling (age range 18–69 years). Nine adverse childhood experiences (covering childhood abuse and household stressors) and three types of health care use in the last 12 months were assessed: number of general practice (GP) visits, emergency department (ED) attendances and nights spent in hospital.ResultsLevels of use increased with increasing numbers of adverse childhood experiences experienced. Compared to those with no adverse childhood experiences, odds (±95% CIs) of frequent GP use (≥6 visits), any ED attendance or any overnight hospital stay were 2.34 (1.88–2.92), 2.32 (1.90–2.83) and 2.67 (2.06–3.47) in those with ≥ 4 adverse childhood experiences. Differences were independent of socio-economic measures of deprivation and other demographics. Higher health care use in those with ≥ 4 adverse childhood experiences (compared with no adverse childhood experiences) was evident at 18–29 years of age and continued through to 50–59 years. Demographically adjusted means for ED attendance rose from 12.2% of 18-29 year olds with no adverse childhood experiences to 28.8% of those with ≥ 4 adverse childhood experiences. At 60–69 years, only overnight hospital stay was significant (9.8% vs. 25.0%).ConclusionsAlong with the acute impacts of adverse childhood experiences on child health, a life course perspective provides a compelling case for investing in safe and nurturing childhoods. Disproportionate health expenditure in later life might be reduced through childhood interventions to prevent adverse childhood experiences.

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Background We assessed whether body mass index (BMI) affects social and socio-economic outcomes. Methods We used Mendelian randomization (MR), non-linear MR and non-genetic and MR within-sibling analyses, to estimate relationships of BMI with six socio-economic and four social outcomes in 378 244 people of European ancestry in UK Biobank. Results In MR of minimally related individuals, higher BMI was related to higher deprivation, lower income, fewer years of education, lower odds of degree-level education and skilled employment. Non-linear MR suggested both low (bottom decile, <22 kg/m2) and high (top seven deciles, >24.6 kg/m2) BMI, increased deprivation and reduced income. Non-genetic within-sibling analysis supported an effect of BMI on socio-economic position (SEP); precision in within-sibling MR was too low to draw inference about effects of BMI on SEP. There was some evidence of pleiotropy, with MR Egger suggesting limited effects of BMI on deprivation, although precision of these estimates is also low. Non-linear MR suggested that low BMI (bottom three deciles, <23.5 kg/m2) reduces the odds of cohabiting with a partner or spouse in men, whereas high BMI (top two deciles, >30.7 kg/m2) reduces the odds of cohabitation in women. Both non-genetic and MR within-sibling analyses supported this sex-specific effect of BMI on cohabitation. In men only, higher BMI was related to lower participation in leisure and social activities. There was little evidence that BMI affects visits from friends and family or having someone to confide in. Conclusions BMI may affect social and socio-economic outcomes, with both high and low BMI being detrimental for SEP, although larger within-family MR studies may help to test the robustness of MR results in unrelated individuals. Triangulation of evidence across MR and within-family analyses supports evidence of a sex-specific effect of BMI on cohabitation.