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

O direito à informação e a manifestação da autonomia de idosos hospitalizados The right to information and the autonomy of the hospitalized elderly

Partindo-se do pressuposto que a avaliação da qualidade para a organização e o funcionamento dos serviços de saúde não deva estar restrita a variáveis tecnicistas e financeiras, mas que contemple o respeito dos direitos do paciente, procurou-se conhecer e analisar a manifestação da autonomia de idosos hospitalizados, baseada nas informações que possuem sobre seu estado de saúde, através da pesquisa de suas expectativas, compreensão sobre o direito à informação e a utilização deste para a deliberação e o consentimento esclarecido às propostas diagnósticas e terapêuticas envolvidas na assistência à sua saúde. Os resultados evidenciaram carência da informação fornecida ao idoso, manifestação de insatisfação quanto ao padrão de informação revelada, o papel da família como intermediária da informação na relação do idoso com a equipe de saúde e o comprometimento do processo decisório autonômico do paciente bem como comprometimento da manifestação do consentimento esclarecido.<br>It was carried out a study with the aim to analyse the autonomy of hospitalised elderly, based on the comprehension about their rights of information and the informed consent on proposals of diagnosis and terapheutics. The results showed patient's lack of information, dissatisfaction on the degree of information. It was also verified that the patient's family frequently acts as information intermediary between the health team and the patient. Therefore, autonomy process of decision making was compromissed, as well as the informed consent of the elderly