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

Studies on caret wings at super orbital speeds

This paper reports an experimental study on the effect of high enthalpy flows on the aerodynamics of caret wings. The experiments were conducted in the super orbital expansion tunnel X3 at an equivalent flight of 9,25 Km/s. Mach number of 11.5. Reynolds number of 80000 and enthalpy of 43 MJ/Kg. An external three component stress wave balance was used for measuring the forces and moments on a caret wing which had a design Mach number of 8 which was production of a configuration used at lower enthalpy (Kipke). Due to the low Reynolds no. of the flow, a detached shock is observed instead of the attached shock with subsequent inboard shocks. Because of this, there is a considerable loss in the high pressure on the wind ward side and this results in a lower magnitude of lift pitching moment, L/D and higher drag. In contrast to this, Kipke had an attached shock and hence more lift, L/D, pitching moment and less drag for the same configuration at Mach no. of 10.9 and Re. No of 0 56 million. The data will be very useful for assessing waveriders at real conditions and for evaluation of CFD models