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

Similarity in flight behaviour between the honeybee Apis mellifera (Hymenoptera: apidae) and its presumed mimic, the dronefly Eristalis tenax (Diptera: syrphidae)

It is generally accepted that the dronefly Eristalis tenax is a Batesian mimic of the honeybee Apis mellifera. Previous work has established that the foraging behaviour of droneflies is more similar to that of its model than to that of other more closely related flies, suggesting that behaviour may be important in the mimicry. Locomotor mimicry has been demonstrated in mimetic Heliconius butterflies but not in hoverflies. This study therefore investigated aspects of the flight behaviour of Eristalis tenax, Apis mellifera and two other flies, Syrphus ribesii and a Musca sp. Insects were filmed foraging on Helichrysum bracteum flowers, and flight sequences were analysed to determine flight velocities, flight trajectories and the percentage of time spent hovering. It was found that the flight behaviour of droneflies was more similar to that of honeybees than to that of the other flies. This suggests that the flight behaviour of Eristalis tenax may be mimetic.</jats:p