Hospital Mortality and Resource Implications of Hospitalisation with COVID-19 in London, UK: A Prospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) had a significant impact on the National Health Service in the United Kingdom (UK), with over 35 000 cases reported in London by July 30, 2020. Detailed hospital-level information on patient characteristics, outcomes, and capacity strain is currently scarce but would guide clinical decision-making and inform prioritisation and planning. METHODS: We aimed to determine factors associated with hospital mortality and describe hospital and ICU strain by conducting a prospective cohort study at a tertiary academic centre in London, UK. We included adult patients admitted to the hospital with laboratory-confirmed COVID-19 and followed them up until hospital discharge or 30 days. Baseline factors that are associated with hospital mortality were identified via semiparametric and parametric survival analyses. RESULTS: Our study included 429 patients: 18% of them were admitted to the ICU, 52% met criteria for ICU outreach team activation, and 61% had treatment limitations placed during their admission. Hospital mortality was 26% and ICU mortality was 34%. Hospital mortality was independently associated with increasing age, male sex, history of chronic kidney disease, increasing baseline C-reactive protein level, and dyspnoea at presentation. COVID-19 resulted in substantial ICU and hospital strain, with up to 9 daily ICU admissions and 41 daily hospital admissions, to a peak census of 80 infected patients admitted in the ICU and 250 in the hospital. Management of such a surge required extensive reorganisation of critical care services with expansion of ICU capacity from 69 to 129 beds, redeployment of staff from other hospital areas, and coordinated hospital-level effort. CONCLUSIONS: COVID-19 is associated with a high burden of mortality for patients treated on the ward and the ICU and required substantial reconfiguration of critical care services. This has significant implications for planning and resource utilisation.

N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome.

Mutations of the Wiskott-Aldrich syndrome gene (WAS) are responsible for Wiskott-Aldrich syndrome (WAS), a disease characterized by thrombocytopenia, eczema, immunodeficiency, and autoimmunity. Mice with conditional deficiency of Was in B lymphocytes (B/WcKO) have revealed a critical role for WAS protein (WASP) expression in B lymphocytes in the maintenance of immune homeostasis. Neural WASP (N-WASP) is a broadly expressed homolog of WASP, and regulates B-cell signaling by modulating B-cell receptor (BCR) clustering and internalization. We have generated a double conditional mouse lacking both WASP and N-WASP selectively in B lymphocytes (B/DcKO). Compared with B/WcKO mice, B/DcKO mice showed defective B-lymphocyte proliferation and impaired antibody responses to T-cell-dependent antigens, associated with decreased autoantibody production and lack of autoimmune kidney disease. These results demonstrate that N-WASP expression in B lymphocytes is required for the development of autoimmunity of WAS and may represent a novel therapeutic target in WAS.

Acceptability and practicality of a Spanish translation of paediatric Gait Arms Legs and Spine (pGALS) in Peruvian children.

BACKGROUND: The paediatric Gait, Arms, Legs and Spine (pGALS) musculoskeletal examination tool is validated for use in school-aged English Speaking children and shown to be practical and effective in acute paediatric practice in the UK and Malawi. Our aim was to assess the acceptability and practicality of a Spanish translation of pGALS in an acute paediatric setting in Peru. FINDINGS: Fifty-three school-aged children presenting to Hospital Regional de Loreto, Peru were recruited to undergo a pGALS examination using a Spanish translation of the instructions. The pGALS examination was completed in 92.5% (49/53), with the time taken (median 4.42 minutes) being acceptable to most parents (98.1%, 52/53). Most children (88.7%, 47/53), found the pGALS examination caused 'little' or 'no additional discomfort'. Using pGALS, significant findings were observed in 18/53 (34%) children; these related to fractures (4/18), hypermobility (4/18), infectious causes (5/18) and soft tissue trauma (5/18). CONCLUSION: Using this Spanish translation, pGALS assessment was practical, acceptable and effective in detecting musculoskeletal changes in many children.