Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Desastres naturais: convivência com o risco

Estudos sobre riscos de desastres naturais têm-se aprimorado de uma abordagem fisicalista para uma perspectiva socioambiental. No entanto, planejamento e gestão ainda seguem o paradigma antropocêntrico da superioridade humana e do poder ilimitado da ciência e tecnologia. Evidencia-se uma incapacidade cognitiva, cultural e de ação por parte de especialistas, científicos e tomadores de decisão (claimmakers) para identificar e atuar sobre as causas sociais da produção de risco. Frente a uma ciência cartesiana e positivista na resolução de problemas, baseada na segurança e controle sobre o mundo natural, propõe-se uma ciência pós-normal que considera os riscos e incertezas do conhecimento científico e das problemáticas ambientais. Essa nova proposta também incide sobre a participação e o diálogo entre stakeholders como referência para ampliar a qualidade do saber científico e o entendimento da complexidade das questões ambientais. Este artigo discute a necessidade de se promover um salto epistemológico sobre a forma de pensar e produzir conhecimentos, bem como implementar a gestão dos riscos de desastres, tendo como objeto de estudo processos de comunicação e educação para prevenção de desastres.Studies on the risks of natural disasters have improved from a physicalist approach to a social and environmental perspective. However, planning and management still follow the anthropocentric paradigm of human superiority and the unlimited power of science and technology, evincing a cognitive, cultural and action inability on the part of experts, scientists and decision makers (or, rather, claim makers) to identify and act upon the social causes of risk production. In view of the Cartesian and Positivist science used to solve problems, based on security and on control over the natural world, a post-normal science has been proposed that considers the risks and uncertainties of scientific knowledge and environmental issues. This new approach encompasses participation and dialogue among stakeholders as a means to increase the quality of scientific knowledge and acknowledge the complexity of environmental issues. This article discusses the need for an epistemological leap on how we think and produce knowledge, as well as for implementing the management of disaster risk. Its objects of study are communication processes and education for disaster prevention

The Adult Repetitive Behaviours Questionnaire-2 (RBQ-2A): A Self-Report Measure of Restricted and Repetitive Behaviours

In two studies we developed and tested a new self-report measure of restricted and repetitive behaviours (RRB) suitable for adults. In Study 1, The Repetitive Behaviours Questionnaire-2 for adults (RBQ-2A) was completed by a sample of 163 neurotypical adults. Principal components analysis revealed two components: Repetitive Motor Behaviours and Insistence on Sameness. In Study 2, the mean RBQ-2A scores of a group of adults with autism spectrum disorder (ASD; N = 29) were compared to an adult neurotypical group (N = 37). The ASD sample had significantly higher total and subscale scores. These results indicate that the RBQ-2A has utility as a self-report questionnaire measure of RRBs suitable for adults, with potential clinical application

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

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