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

Pets and people in residential care Towards a model of good practice; a project funded by the Joseph Rowntree Foundation

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Singly living people and their cats: a study of human mood and subsequent behavior.

We sought to examine how cat owners’ moods correlated with subsequent interactions with their cats. Such a relationship has not been previously documented. Data from 47 women and 49 men living alone with their cats were collected. Participants were visited at their homes for one two-hour session each. Approximately five minutes before and after the observation period, the owners filled out a standard questionnaire (EWL, list of adjectives) to indicate their current mood. The EWL allowed the authors to later assign owner moods to one or more of 14 sub-scales. In this study, results on correlates of moods at the beginning and during the subsequent first half hour of interactions are presented. Multiple regression analyses showed that related mood sub-scales, e.g. anxiety and depressiveness, can influence human behavior in different directions, and that bipolar mood sub-scales, e.g. introvertedness and extrovertedness, do not necessarily work in opposite directions. Four human behaviors were related to mood: intents to interact, starts of interactions, and approaches and vocalizations while interacting. While the start of an interaction was influenced by eight different mood sub-scales, the others mentioned were only related to four sub-scales at most. The only recorded behavior of the cat that was significantly correlated with the owner’s mood was approaches to the owner within an ongoing interaction