Background Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant. Methods In this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths. Findings Of 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72–1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76–1·38]). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 [SD 4·7] vs 32·0 [4·8]; p=0·0085) and genomic read depth (1280 [1004] vs 831 [682]; p=0·0011). Interpretation Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort. Funding University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council.

No abstract

Introduction: The HIV epidemics in the Caribbean, Central America and South America (CCASA), Eastern Europe (EE) and Asia and Pacific (AP) regions are diverse epidemics affecting different key populations in predominantly middle-income countries. This narrative review describes the populations of HIV-positive youth approaching adolescence and adulthood in CCASA, EE and AP, what is known of their outcomes in paediatric and adult care to date, ongoing research efforts and future research priorities.Methods: We searched PubMed and abstracts from recent conferences and workshops using keywords including HIV, transition and adolescents, to identify published data on transition outcomes in CCASA, EE and AP. We also searched within our regional clinical/research networks for work conducted in this area and presented at local or national meetings. To give insight into future research priorities, we describe published data on characteristics and health status of young people as they approach age of transition, as a key determinant of health in early adulthood, and information available on current transition processes.Results and discussion: The perinatally HIV-infected populations in these three regions face a range of challenges including parental death and loss of family support; HIV-related stigma and socio-economic disparities; exposure to maternal injecting drug use; and late disclosure of HIV status. Behaviourally HIV-infected youth often belong to marginalized sub-groups, with particular challenges accessing services and care. Differences between and within countries in characteristics of HIV-positive youth and models of care need to be considered in comparisons of outcomes in young adulthood. The very little data published to date on transition outcomes across these three regions highlight some emerging issues around adherence, virological failure and loss to follow-up, alongside examples of programmes which have successfully supported adolescents to remain engaged with services and virologically suppressed.Conclusions: Limited data available indicate uneven outcomes in paediatric services and some shared challenges for adolescent transition including retention in care and adherence. The impact of issues specific to low prevalence, concentrated epidemic settings are poorly understood to date. Outcome data are urgently needed to guide management strategies and advocate for service provision in these regions.

Our data support a link between the initiation of RTV-boosted/lopinavir-based ART preconception and PTD in subsequent pregnancies, with implications for treatment guidelines. Continued monitoring of PTD risk is needed as increasing numbers of pregnancies are conceived on new drugs.

Vaccination during pregnancy is a safe and effective intervention to protect women from potentially severe consequences of influenza and reduce risk of influenza and pertussis in their infants. However, coverage remains variable. In this mini-review we update findings from a 2015 systematic review to describe results from recent studies in high income countries on the uptake of influenza and pertussis vaccination in pregnancy, reasons for vaccine hesitancy and barriers to increasing uptake, from maternal and healthcare provider (HCP) perspectives. Studies reported highly variable uptake (from 0% to 78%). A main facilitator for uptake among pregnant women was receiving a recommendation from their HCP. However, studies showed that HCP awareness of guidelines did not consistently translate into them recommending vaccines to pregnant women. Safety concerns are a well-established barrier to uptake/coverage of maternal immunization; 7%-52% of unvaccinated women gave safety concerns as a reason but these were also present in vaccinated women. Knowledge/awareness gaps among pregnant women and lack of confidence among HCPs to discuss vaccination were both important barriers. Several studies indicated that midwives were more likely to express safety concerns than other HCPs, and less likely to recommend vaccination to pregnant women. Women who perceived the risk of infection to be low were less likely to accept vaccination in several studies, along with women with prior vaccine refusal. Findings highlight the importance of further research to explore context-specific barriers to vaccination in pregnancy, which may include lack of vaccine confidence among pregnant woman and HCPs, and policy and structural factors.

Background: This study aims to assess the cost-effectiveness of a routine

No abstract

Summary Background & Aims It is estimated that 3.26 million children and adolescents worldwide have chronic HCV infection. To date, the global response has focused on the adult population, but direct-acting antiviral (DAA) regimens are now approved for children aged ≥3 years. This global review describes the current status of policies on HCV testing and treatment in children, adolescents, and pregnant women in WHO Member States. Methods We identified national strategic plans and/or clinical practice guidelines (CPGs) for HCV infection from a World Health Organization (WHO) database of national policies from Member States as of August 2019. A standardised proforma was used to abstract data on polices or recommendations on testing and treatment in children, adolescents and pregnant women. Analysis was stratified according to the country–income status and results were validated through WHO regional focal points through August 2020. Results National HCV policies were available for 122 of the 194 WHO Member States. Of these, the majority (n = 71/122, 58%) contained no policy recommendations for either testing or treatment in children or adolescents. Of the 51 countries with policies, 24 had specific policies for both testing and treatment, and were mainly from the European region; 18 countries for HCV testing only (12 from high- or upper-middle income); and 9 countries for treatment only (7 high- or upper-middle income). Twenty-one countries provided specific treatment recommendations: 13 recommended DAA-based regimens for adolescents ≥12 years and 6 still recommended interferon/ribavirin-based regimens. Conclusions There are significant gaps in policies for HCV-infected children and adolescents. Updated guidance on testing and treatment with newly approved DAA regimens for younger age groups is needed, especially in most affected countries. Lay summary To date, the predominant focus of the global response towards elimination of hepatitis C has been on the testing and treatment of adults. Much less attention has been paid to testing and treatment among children and adolescents, although in 2018 an estimated 3.26 million were infected with HCV. Our review shows that many countries have no national guidance on HCV testing and treatment in children and adolescents. It highlights the urgent need for advocacy and updated policies and guidelines specific for children and adolescents.