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

A multiparty multi-session logic

Recent work on the enhancement of multiparty sessions types with logical annotations enables not only the validation of structural properties of the conversations and on the sorts of the messages, but also the validation of properties on the actual values exchanged. However, the specification and verification of the mutual effects of multiple cross-session interactions is still an open problem. We introduce a multiparty logical proof system with virtual states that enables the tractable specification and validation of fine-grained inter-session correctness properties of processes participating in several interleaved sessions. We present a sound and relatively complete static verification method

Intertidal colonization rates. A matched latitude, north v. south, remote v. near shore island experiment

Colonization of artificial substrata was monitored on sheltered rocky shores at Husvik, South Georgia (54° 11′S; 36° 40′W) and Cumbrae, Scotland (55° 46′N; 4° 55′W) from mid summer to early autumn. South Georgia is a remote island (1,330 km from other land); Cumbrae is only 2 km from nearby coasts. Both islands were heavily glaciated for a period up to about 10,000 ybp, so the intertidal fauna is of geologically recent origin. The South Georgian fauna is depauperate and consists mainly of direct developers; that of Cumbrae is rich and largely larviparous. Colonization rates at Cumbrae were one to four orders of magnitude greater than at Husvik. It is suggested that the fauna of South Georgian shores stems from colonization by rafting from remote sources, while Cumbrae has been supplied predominantly by short-range pelagic larval dispersal. The measured differences in colonization rates reflect the substantial local advantage of larval dispersal over direct development in established communitie