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

Competitive interactions among three ectomycorrhizal fungi and their relation to host plant performance

1. Competition strongly influences many species assemblages, but its role in mycorrhizal fungal interactions is not well understood. We examined interactions among three ectomycorrhizal (ECM) species to determine if the structure of competition could be characterized by either competitive networks (where no clear hierarchy exists in the outcome of competition between various species pairs) or competitive hierarchies (where one species out competes all other species). 2. Using a bioassay experiment, we inoculated Pinus muricata seedlings with three Rhizopogon species (R. occidentalis, R. salebrosus, and R. vulgaris) in single-, two-, and three-species treatments. After 7 months, we assessed the relative abundance of each species in each treatment using real-time PCR of internal transcribed spacer rDNA. 3. We found that R. occidentalis was strongly inhibited by R. vulgaris and R. salebrosus in all competition treatments. In contrast, R. vulgaris and R. salebrosus had similar ECM biomasses in the two-species treatment, but R. vulgaris had significantly higher biomass than R. salebrosus in the three-species treatment. 4. In the single-species treatments, seedlings colonized by the competitive dominants had higher shoot biomass and total leaf nitrogen, but also higher percentage ECM biomass. In the multi-species treatments, seedlings had either equivalent or somewhat lower shoot biomass and total leaf nitrogen than their respective single-species treatments. 5. Synthesis. Our results indicate that ECM competition does not appear to be characterized by strict networks or hierarchies. Instead, the outcome is dependent on the conditions of the local environment in which it occurs. There also does not seem to be a clear relationship between ECM competitive ability and plant performance, but competition does appear to negatively affect the ability of ECM fungi to provide benefits to their hosts