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

Integrated halide perovskite photoelectrochemical cells with solar driven water splitting efficiency of 20.8

Achieving high solar to hydrogen STH efficiency concomitant with long term durability using low cost, scalable photo absorbers is a long standing challenge. Here we report the design and fabrication of a conductive adhesive barrier CAB that translates gt;99 of photoelectric power to chemical reactions. The CAB enables halide perovskite based photoelectrochemical cells with two different architectures that exhibit record STH efficiencies. The first, a co planar photocathode photoanode architecture, achieved an STH efficiency of 13.4 and 16.3 amp; 8201;h to t60, solely limited by the hygroscopic hole transport layer in the n i p device. The second was formed using a monolithic stacked silicon perovskite tandem, with a peak STH efficiency of 20.8 and 102 amp; 8201;h of continuous operation before t60 under AM 1.5G illumination. These advances will lead to efficient, durable, and low cost solar driven water splitting technology with multifunctional barrier