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Background: data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. Methods: in this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18–55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (0·05 for all analyses). Interpretation: in this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Duration of protection from SARS-CoV-2 infection in people with HIV (PWH) following vaccination is unclear. In a sub-study of the phase 2/3 the COV002 trial (NCT04400838), 54 HIV positive male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells >350 cells/ul) received two doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and MesoScale Discovery (MSD)), neutralisation, ACE-2 inhibition, gamma interferon ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that 6 months after vaccination the majority of measurable immune responses were greater than pre-vaccination baseline, but with evidence of a decline in both humoral and cell mediated immunity. There was, however, no significant difference compared to a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although were lower than wild type. Pre-existing cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater post-vaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the on-going policy to vaccinate PWH against SARS-CoV-2, and underpin the need for long-term monitoring of responses after vaccination.

Coronavirus disease 2019 (COVID-19) is a public health emergency of international concern1. People living with HIV (PLWH) are at increased risk for adverse COVID-19 outcomes compared with HIV-negative individuals2-5, and are a high-risk group for COVID-19 prevention4. The ChAdOx1 nCoV-19 (AZD1222) vaccine has demonstrated safety and efficacy against COVID-19 in clinical trials6-8. To date, there are no reports on the safety and immunogenicity of this, or any COVID-19 vaccine, in PLWH, and reports on the immunogenicity of COVID-19 vaccines in Africa are limited9. Here, we show comparable safety and immunogenicity of two doses of ChAdOx1 nCoV-19 between PLWH and HIV-negative individuals in South Africa. Furthermore, in PLWH previously exposed to SARS-CoV-2, antibody responses increased substantially from baseline following a priming dose, with modest increases after a booster dose. Full-length spike and receptor-binding domain IgG geometric mean concentrations after a single dose of ChAdOx1 nCoV-19 in PLWH previously exposed to SARS-CoV-2 were 6.49–6.84-fold higher than after two doses in those who were SARS-CoV-2 naïve at enrollment. Neutralizing antibody responses were consistent with the antibody-binding responses. This is the first report of a COVID-19 vaccine specific to PLWH, and specific to Africa, and demonstrates favorable safety and immunogenicity of ChAdOx1 nCoV-19 in PLWH.

BackgroundAssessing safety and efficacy of Covid-19 vaccines in different populations is essential, as is investigation of efficacy against emerging SARS-CoV-2 variants of concern including the B.1.351 (501Y.V2) variant first identified in South Africa.MethodsWe conducted a randomized multicentre, double blinded controlled trial on safety and efficacy of ChAdOx1-nCoV19 in HIV-uninfected people in South Africa. Participants age 18 to 10viral particles or placebo (0.9%NaCl) 21-35 days apart. Post 2nd-dose serum samples (n=25) were tested by pseudotyped (PSVNA) and live virus (LVNA) neutralization assays against the D614G and B.1.351 variants. Primary endpoints were safety and vaccine efficacy (VE) >14 days following second dose against laboratory confirmed symptomatic Covid-19.Results2026 HIV-uninfected adults were enrolled between June 24thand Nov 9th, 2020; 1010 and 1011 received at least one dose of placebo or vaccine, respectively. Median age was 31 years. The B.1.351 variant showed increased resistance to vaccinee sera using the PSVNA and LVNA. In the primary endpoint analysis, 23/717 (3.2%) placebo and 19/750 (2.5%) vaccine recipients developed mild-moderate Covid-19; VE 21.9% (95%Confidence Interval: −49.9; 59.8). Of the primary endpoint cases, 39/42 (92.9%) were the B.1.351 variant; against which VE was 10.4% (95%CI: −76.8; 54.8) analyzed as a secondary objective. The incidence of serious adverse events was balanced between the vaccine and placebo groups.ConclusionsA two-dose regimen of ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, VE against severe Covid-19 is undetermined.(Funded by The Bill & Melinda Gates Foundation and South African Medical Research Council; ClinicalTrails.gov number,NCT04444674).

A set of twin brothers with Klinefelter’s syndrome were seen in community paediatric clinic following concern about severe learning disabilities requiring special educational needs school. As Klinefelter’s is not commonly associated with severe learning disabilities, they were enrolled in the 100,000 genome project. Whole exome sequencing revealed a mutation involving the SOX5 gene on chromosome 12p12, which is associated with Lamb-Shaffer syndrome. Lamb-Shaffer syndrome is a neurodevelopmental disorder characterised by global developmental delay, learning disability, poor expressive speech and mild dysmorphic facial features (Nesbitt et al 2015). Less than 100 cases have been reported since the condition was first described in 2012. This new genetic diagnosis has enabled the health care professionals and the parents to understand more about the clinical features, including what surveillance and investigations the patients may require based upon other reported cases with the same mutation. For parents and patients, having a named diagnosis allows them to connect via support groups with other families who have been diagnosed with the same condition. Historically the ‘diagnostic odyssey’ in a child with a rare disease could continue for many years, with serial testing of different genes, often with no answers found for patients or their parents. Learning disability is genetically heterogeneous and has previously presented challenges for molecular diagnoses using traditional genetic testing methods. Next generation sequencing has made it possible to sequence millions of fragments of DNA simultaneously, enabling the sequencing of whole patient exomes as part of the 100,000 genome project. These patients are two of many new genetic diagnoses that are a result of the genome project, which are highlighting the utility of exome sequencing in clinically and genetically heterogeneous conditions such as learning disability. In this unusual case these twins have two different genetic underlying conditions, which demonstrates the importance of investigating further possible causes when previous diagnoses do not explain the evolving clinical phenotype.

Background Interpersonal violence is the third leading cause of death within the European Region (as defined by World Health Organisation (WHO)) [1]. To address this concern the World Health Assembly passed a resolution (WHA 49.25) [2] declaring violence to be a public health priority. Furthermore the assembly passed resolution (WHA 56.24) [3] in 2003 urging continued development of a sciencebased public health approach to prevention of youth violence. The public health problem is also specifically present in England where in 2006/2007 National Health Service data shows that 5,720 people were admitted to hospital following “assault by sharp object”[4]. Of these 179 were aged under 16 and a further 752 were aged between 16 and 18. Analysing Home Office data Hall and Innes found that the most likely victims of violent crime are young men aged between 16 and 24. The risk of being a victim of violent crime in this cohort is 13.3%, over four times higher than the average risk (3%)[5]. Other features of high risk groups include; trauma recidivism, previous exposure to violence, fear of violence and social relationships with violent peers. Furthermore those young people who have previously been involved in delinquency and are known to the criminal system are significantly more likely to be participants in carrying and using a weapon[6].

The value of and need for paediatric outpatient review attendance as perceived by parents, children, consultants, and general practitioners (GPs) were assessed. One hundred and ninety one parents of 239 children over 7 years of age undergoing review were randomly selected for a semistructured interview. For each parent interviewed, an audit questionnaire was completed after case note review by another paediatrician. A random sample of the patients' GPs was surveyed by postal questionnaire. Twenty per cent of parents and 26% of GPs felt that the GP could care for the child as well as or better than the hospital, whereas only 6% of consultants felt this to be so. Regarding future attendance of the child at the hospital, 48% of parents and 32% of GPs felt the child could either be discharged or seen when parents were worried, whereas consultants felt 24% of patients should have been discharged.