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

Mechanical and thermomechanical properties of clay-Bambara nut shell polyester bio-composite

Ecological impact of improper disposal of growing agricultural waste is huge. These low cost, renewable, and biodegradable materials can be utilized in production of eco-friendly polymer composite. However, further property enhancement can be achieved by hybridization. This work evaluated the feasibility of enhancing the properties of Bambara nut shell particulate (BNSp) reinforced polyester composite by incorporation of clay. Ultimate tensile strength (UTS) of 23.98 MPa was recorded for the hybrid composite of 3 wt% clay + 12 wt% BNSp compared to 19.86 MPa for 12wt% BNSp polymer composite. DMA analysis showed a damping factor of 0.586 at 89.51 °C for 3 wt% clay + 12 wt% BNSp composite. Clay addition modifies and improves the properties of agro-waste reinforced polymer composites with clay/BNSp/polyester composite exhibiting higher mechanical properties compared to the BNSp reinforced polyester composite due to the ability of the clay to insert themselves between the layers of the polyester matrix. This work also showed that Bambara nut is a potential low-cost filler material for polymer composites and can be used in areas requiring medium strength but lightweight materials