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

Spallation strength of single crystal and polycrystalline copper

The spallation strength of single crystal copper foils 100 micrometers thick of the and orientations and of polycrystalline copper foils has been determined. Laser driving was used to launch miniature plates. Also, the spallation strength of polycrystalline copper was measured using conventional gas gun techniques and plates for comparison. Experimental measurements include VISAR records of the free surface particle velocity and micrographs of recovered flyers. A 1D hydrocode was used to simulate the VISAR records to determine the dynamic pressure history of the spallation process. Judging by the calculated pressures, it was found that the foils were somewhat stronger than the foils, which were about twice as strong as the polycrystalline foils. These were, in turn, substantially stronger than the larger sample plates (1.5 mm thick) of the gas gun. In the polycrystalline foils, small voids are found in recovered samples impacted at flyer plate velocities almost producing spallation in the gas gun, indicating that this sparse damage in the foils is able to grow substantially more in the much larger gas gun plates and under much slower gas gun loading