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

Análise comparativa entre a fecundidade de Dilocarcinus pagei Stimpson e Sylviocarcinus australis Magalhães & Turkay (Crustacea, Decapoda, Trichodactylidae) no Pantanal do Rio Paraguai, Porto Murtinho, Mato Grosso do Sul Comparative analysis of fecundity between Dilocarcinus pagei Stimpson and Sylviocarcinus australis Magalhães & Turkay (Crustacea, Decapoda, Trichodactylidae) in the Pantanal region of Paraguay River, Porto Murtinho, Mato Grosso do Sul

<abstract language="eng">The aim of this study was to estimate the fecundity of Dilocarcinus pagei Stimpson, 1861 and Sylviocarcinus australis Magalhães & Turkay, 1996, collected in the Paraguay River, Porto Murtinho County, State of Mato Grosso do Sul, Brazil, between coordinates 21º42,000'S 57º33,649'W and 21º41,449'S 57º33,770'W, in the period of April 1999 to March 2000. After general collection procedures, the specimens were measured and processed in laboratory conditions. The river water crab species hatch like juveniles and, frequently, female specimens were observed carrying eggs in different stages of development, besides juveniles and eggs at the same time. It was apparent in the frequency distributions that D. pagei has a carapace width average greater than S. australis. The number of eggs and juveniles transported varied amongst species and amongst size class. A size superposition was observed between young and adult females for both species. According to the calculated fecundity index, D. pagei presented slightly more elevated values (7.41) than S. australis (6.65). Eggs are spherical and are not adhering to pleopods. Egg size did not varied during development, continuing with 2mm diameters