Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Women’s Political Empowerment: A New Global Index, 1900-2012

The V-Dem index on women’s political empowerment provides information about women’s civil liberties, civil society participation, and political participation globally. Spanning from 1900 to 2012, three dimensions of empowerment, and over 170 countries, it is among the most comprehensive measures of women’s empowerment available. This paper presents a conceptualization of women’s political empowerment and provides an overview of the construction of the index and operationalization of its three sub-dimensions: Women’s civil liberties, civil society participation, and political participation. Compared to other indices measuring women’s empowerment, such as the GDI, the GEM, the GII and the CIRI data on human rights, the V-Dem index allows more precise measurement and is superior in temporal scope and coverage of countries of the Global South. The paper demonstrates the benefits of this new index and its sub-dimensions through several empirical illustrations

V-Dem: A New Way to Measure Democracy

In the last few decades, Western governments have spent huge sums of money to promote democracy abroad. We do not know which, if any, of these programs actually work. If we cannot measure democracy in sufficient detail and with the necessary nuance, we cannot mark its progress and setbacks or affect its future course. While distinguishing the most democratic countries from the least democratic ones is fairly easy, it has proven to be much harder to make finer distinctions. Here we present a new effort aimed at measuring democracy, the Varieties of Democracy Project (V-Dem)