Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

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

Escalators, elevators and travelators: the occupational mobility of migrants to South-East England

In a meritocratic society it is assumed that the chance of achieving occupational mobility (OM) is not strongly influenced by one's starting position in terms of class or ethnicity. This paper seeks to explain the drivers of the high levels of OM achieved by one ethnically defined group: the Scots. Educational attainment is shown to be particularly important. A second level of interest is the changing role of internal migrants to a global city in the face of increased international skilled immigration. We investigate whether there is any evidence that the OM of internal migrants is being hindered as a result. The evidence points instead to immobile local labour being more disadvantaged occupationally than mobile labour from peripheral regions of the state

Alcohol actions on GABA(A) receptors: from protein structure to mouse behavior.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were R. Adron Harris and Susumu Ueno. The presentations were (1) Protein kinase Cepsilon-regulated sensitivity of gamma-aminobutyric acid type A (GABAA) receptors to allosteric agonists, by Robert O. Messing, A. M. Sanchez-Perez, C. W. Hodge, T. McMahon, D. Wang, K. K. Mehmert, S. P. Kelley, A. Haywood, and M. F. Olive; (2) Genetic and functional analysis of a GABAA receptor gamma2 subunit variant: A candidate for quantitative trait loci involved in alcohol sensitivity and withdrawal, by Kari J. Buck and Heather M. Hood; (3) Tryptophan-scanning mutagenesis in GABAA receptor subunits: Channel gating and alcohol actions, by Susumu Ueno; and (4) Can a single binding site account for actions of alcohols on GABAA and glycine receptors

Characteristics and dying trajectories of adult hospital patients from acute care wards who die following review by the rapid response team.

A third of patients reviewed by rapid response teams (RRT) require end-of-life care. However, little is known about the characteristics and management of these patients following RRT review. This paper presents results of a retrospective, descriptive audit that explored the dying trajectory of adult ward inpatients who died outside of intensive care following RRT review. The study setting was a 430-bed tertiary New Zealand hospital during 2013. RRT, inpatient databases and hospital notes were used to identify 100 consecutive adult inpatients who died subsequent to RRT review. Outcome measures included time from RRT review to death, place of death, pre-existing co-morbidities and frequency of medical review. Results demonstrated that patients were old (median 77 years, IQR 63-85years), emergency admissions (n=100) and admitted under a medical specialty (n=71). All but one of the cohort had pre-existing co-morbidities (mean 3.2, SD 1.7), almost a third (n=31) had cancer and 51% had 1-4 previous inpatient admissions within the previous 12 months. The mean length of stay prior to RRT review was 4.9 days (SD 5.5) during which patients were frequently reviewed by senior medical staff (mean 6.8 times, SD 6.9, range 0-44). Twenty per cent of patients died after their first RRT review with a further 40% receiving treatment limitation/palliation. Fifty-two per cent of patients had a pre-existing DNAR. Eighty per cent of patients died in hospital. Whilst the RRT fulfils an unmet need in decision-making at end of life, there is a need to understand what RRT, instead of ward-based or palliative care teams, offers dying patients