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

Supply chain and logistics competencies in humanitarian aid

The continuing incidence of disasters and their associated challenges has increased the demand for humanitarian logisticians. However, there is a dearth of research on their essential competencies. This paper proposes, therefore, a humanitarian logistics competency framework (HlCF) to assist with the professional development of humanitarian logisticians. In creating the HlCF, nine competency domains containing 29 specific competencies across four levels (entry to senior management) were identified. This study makes two key contributions to the literature: (i) it extends the discussion of competency frameworks in humanitarian logistics; and (ii) it presents a framework designed to support the human resource plans and practices of aid agencies. The HlCF allows not only individual humanitarian logisticians to develop the competencies necessary for career success, but also humanitarian organisations to map their own competency frameworks to a common standard. This will, in turn, facilitate workforce mobility and support the overall concept of a certified humanitarian logistics professional.peerReviewe