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

Exopolymeric substances (EPS) from Salmonella enterica: polymers, proteins and their interactions with plants and abiotic surfaces

When Salmonella enterica is not in a planktonic state, it persists in organised communities encased in extracellular polymeric substances (EPS), defined as biofilms. Environmental conditions ultimately dictate the key properties of the biofilms such as porosity, density, water content, charge, sorption and ion exchange properties, hydrophobicity and mechanical stability. S. enterica has been extensively studied due to its ability to infect the gastrointestinal environment. However, only during the last decades studies on its persistence and replication in soil, plant and abiotic surfaces have been proposed. S. enterica is an environmental bacterium able to effectively persist outside the human host. It does so by using EPS as tools to cope with environmental fluctuations. We therefore address this mini-review to classify those EPS that are produced by Salmonella with focus on the environment (plant, soil, and abiotic surfaces) by using a classification of EPS proposed by Flemming and collaborators in 2007. The EPS are therefore classified as structural, sorptive, surface-active, active, and informative