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

Introduction to the cyanobacteria

Summary: Features of cyanobacteria are introduced for non-specialists by highlighting topics in the various chapters. Aspects where much more is known now than a decade ago are pointed out, such as the importance of cyanobacterial nitrogen fixation in the oceans. This is followed by an account of the recent molecular studies most relevant for ecologists, especially topics not mentioned elsewhere in the book. Several ecological subjects of current interest are discussed, including research which seems important, but has sometimes been overlooked. Topics mentioned include sensing the environment and other organisms and signalling between cyanobacterial cells and between cyanobacteria and other organisms, and methods for studying N and P. The authors air their views on past and present matters concerning cyanobacterial taxonomy and nomenclature. Finally, comments are made on practical topics such as the use of cyanobacteria for inoculating soils, barley straw to control blooms and the likely contribution of cyanobacteria to developments in algal biotechnology during the coming decade.Scopu