Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Based on a Scottish study, this article presents findings from qualitative analysis of interview data, on views of people with enduring mental disorders (people) regarding services provided by community psychiatric nurses (CPNs) and what these people value in working with CPNs. Thirteen people took part in semi-structured interviews, and data were analysed using strategies including thematic analysis. The main finding was that people value their interpersonal relationship with CPNs. This relationship has a specific function in the individual's overall social network. The CPN-person relationship forms the context of 'purposeful talk', and is shaped and developed through the talk. It provides comfort and a greater sense of confidence with which people can cope with daily life. A valued feature of the personalized relationship with CPNs is continuity, associated with regularity of contact with CPNs, accessibility (both physical and emotional) and respect for and commitment to people as individuals. We interpret CPNs, as they appear in these accounts given by people with enduring mental disorders, as 'beings-in-between', bridging symbolically the worlds of hospital and community. They are figures between 'friends' and professionals, to whom people who have been ill can relate and show feelings which would, if otherwise expressed, compromise participation in community. CPNs help sustain people experiencing 'illness in the context of life' and enhance their potential for participation in the community. In doing so they contribute to public health. Viability of sustaining relationships and personal care, valued at the micro-level of interaction, depends on support at the meso-level by managers, and at the macro-level by policy makers and funders. Health service managers who play a key role in instigating and managing service changes should engage in regular dialogue with CPNs about the impact of change on the ability of CPNs to maintain sustaining relationships with people. The adaptability of CPNs to the situation and the person-in-the-situation needs to be facilitated, not compromised, by the requirements of record-keeping and accounting systems. Practice described in this study indicates the possibility of CPNs relating to the person in ways consistent with a 'community development approach'. Limitations of the study are noted. Our findings are highly contextualized and based on a small sample. Nonetheless, they are consistent with findings from other studies also based on listening to service users' accounts of problems of living with enduring mental disorder. Implications of the analysis of peoples' perceptions of the role of CPNs are considered, with attention to service providers, policy makers and future research.

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Background: Recent policy and organisational changes within UK primary care have emphasised graduated access to care, speed of access to the first available general practitioner (GP) and care being provided by a range of healthcare professionals. These trends have been strengthened by the current GP contract and Quality and Outcomes Framework (QOF). Concern has been expressed that the potential for personal care is being diminished as a result and that this will reduce quality standards. This paper presents data from a study that explored with patients and GPs what personal care means and whether it has continuing importance to them.

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