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).

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In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.

Background Burn injury is one of the most devastating forms of trauma which can have physical, pyschological and sociological consquences (Blakeney et al , 2007). It requies a multi-disciplinary team approach for optimum outcome (Butler, 2013). An in-house training programme has been developed at Pinderfields Hospital in Wakefield to improve the knowledge, skills and competency of the team working within the Burn service and to deliver a high quality, evidence-based service. Methodology The training programme is still in it’s infancy and has been delivered utilising a variety of teaching methods such as didactic teaching, case-based discussion and a simulated burn scenario in mock clinical environment. Results Eight participants engaged in the simulated scenario which was about the admission of a patient with a significant burn. They felt that it re-enforced the importance of early intervention and need to calculate burn size, depth and appropriate resuscitation fluids which they were given the opportunity to do as individuals. Conclusion Simulation has been found to be a relaible tool in assessment and of both teamwork and communication skills (Okuda et al, 2009). Clinical medicine is increasingly focused on patient safety issues and quality- understandably patients are reluctant to have staff "practice" on them, so simulation allows us to bridge the educational gap and train the multi-disciplinary team in theory, practice and human factors in a realistic and safe clinical environment (Wilford and Doyle 2006). References Blakeney P, Rosenberg L, Rosenberg M, Faber A. Pyschosocial care of the person with severe burns. BURNS 2007b;34(4):433–440 Butler D. The 21st Century Burn Team. BURNS 2013;39:375–379 Okuda Y, Bryson EO, DeMaria S Jr, et al. The utility of simulation in medical education MOUNT SINAI. Journal of Medicine 2009;76(4):330–343 Wilford A, Doyle T. Integrating simulation into the Nursing Curriculum. British Journal of Nursing 2006;15(11)

In extensive thermal injuries with posterior involvement early necrectomy and split thickness skin gra9ing of the back is notoriously difficult due to exposure of skin gra9s to shear stress and pressure. An addi?onal tool in the management of burn wounds is the air fluidized bed. The aim of this retrospec?ve study was to evaluate the impact of air fluidized support on the outcome of pa?ents with thermal injuries of the posterior trunk. MethodsAll pa?ents with TBSA ≥15% admiIed to the Burn Intensive Care Unit of the Division of Plas?c and Reconstruc?ve Surgery, Vienna General Hospital, Austria, between January 2003 and December 2014 were included in this retrospec?ve study. Demographical data, ICU records and surgical records were collected and sta?s?cally evaluated in respect of different treatment regimens (air fluidized bed versus conven?onal pressure--reducing maIresses).