Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

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

Bioavailability of sedimentary contaminants subject to deposit-feeder digestion

cited By 173International audienceContaminants in sediments are less available than their concentrations might imply, but measures of this availability have been generally lacking. Sediments ingested by benthic animals can be expected to undergo a unique chemical environment controlled by the digestive chemistry of the organism. We measured solubilization of sedimentary contaminants-Cu, Pb, and polycyclic aromatic hydrocarbons (PAH)-by digestive fluids extracted from marine invertebrates. Bioavailability of these contaminants, thus measured, is a small fraction of total contaminant loading-typically 1-10%. The amounts of metals solubilized by digestive fluids were orders of magnitude greater than would be predicted from water-solid partitioning with clean seawater, although they correlated well with solubilization by seawater. Digestive fluids from two different animal species solubilized different amounts of metals, indicating that bioavailability varies among species even under constant mode of uptake. High concentrations of solubilizing agents, such as amino acids for metals and surfactants for PAH, in the digestive fluids can explain the enhanced solubilization. This biomimetic approach to contaminant measurement provides the basis for more accurate mechanistic and routine assessments of environmental impact