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

The contemporary distribution of Trypanosoma cruzi infection in humans, alternative hosts and vectors

Chagas is a potentially fatal chronic disease affecting large numbers of people across the Americas and exported throughout the world through human population movement. It is caused by the Trypanosoma cruzi parasite, which is transmitted by triatomine vectors to humans and a wide range of alternative host species. The database described here was compiled to allow the risk of vectorial transmission to humans to be mapped using geospatial models. The database collates all available records, published since 2003, for prevalence and occurrence of infection in humans, vectors and alternative hosts, and links each record to a defined time and location. A total of 16,802 records of infection have been extracted from the published literature and unpublished sources. The resulting database can be used to improve our understanding of the geographic variation in vector infection prevalence and to estimate the risk of vectorial transmission of T. cruzi to human