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

Beyond stages of change: multi-determinant continuum models of action readiness and menu-based interventions

The merits of modelling action readiness as a series of stages is discussed, focusing on the Health Action Process Approach (HAPA) which postulates a motivational stage (for non-intenders) and a volitional stage (for intenders). The HAPA helpfully clarifies that the relationship between self-efficacy and action may be different for inexperienced intenders and experienced actors. This model also usefully distinguishes between different types of planning undertaken by intenders and it is suggested that further specification of planning tasks could explain why some intenders act while others do not. Despite the advantages of the HAPA, it is argued that the distinction between intenders and non-intenders is fuzzy and unstable and that demarcation of the stage boundary is arbitrary. A multi-determinant, multi-goal continuum approach is recommended. Such modelling recognises graded discontinuities throughout the development of action readiness from attitude formation to behaviour change maintenance. It is argued that menu-based interventions designed to deliver different messages and materials to people with different action-readiness deficits may be more cost effective than stage-tailored interventions. © 2007 International Association for Applied Psychology

The mind's eye on personal profiles: how to inform initial trustworthiness assessments in virtual project teams

Personal information is an important precursor for the trust formation process in virtual project teams. However, till today it has remained unclear what specific personal information most trustors prefer. Insight in their preferences as well as in their foundation could support the development of templates that provide communication support to virtual teams. In this paper, we describe and empirically test an approach that links trustors’ common information preferences and a TrustWorthiness’ ANtecedents (TWAN) framework. Thus, we provide ‘the mind’s eye’ on interpreting and valuing information elements