SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Aplicações do fluxo de Ricci à teoria da relatividade geral: estudo dos buracos negros

The flow of Ricci is an analytical tool, and a similar equation for heat geometry, a diffusive process which acts on a variety of metrics Riemannian and thus can be used in mathematics to understand the topology of varieties and also in the study geometric theories. Thus, the Ricci curvature plays an important role in the General Theory of Relativity, characterized as a geometric theory, which is the dominant term in the Einstein field equations. The present work has as main objectives to develop and apply Ricci flow techniques to general relativity, in this case, a three-dimensional asymptotically flat Riemannian metric as a set of initial data for Einstein equations and establish relations and comparisons between them.O fluxo de Ricci é uma ferramenta analítica e, um análogo da equação do calor para a geometria, um processo difusivo que atua sobre as métricas de uma variedade Riemanniana e assim, pode ser utilizado na matemática para entender a topologia de variedades e também no estudo das teorias geométricas. Sendo assim, a curvatura de Ricci desempenha um papel importante na Teoria da Relatividade Geral, uma teoria geométrica, em que é o termo dominante nas equações de campo de Einstein. O presente trabalho tem como principais objetivos desenvolver e aplicar técnicas de fluxo de Ricci à Relatividade Geral, no caso, uma métrica Riemanniana tridimensional assintoticamente plana como um conjunto de dados iniciais para equações de Einstein e estabelecer relações e comparações entre os mesmo

Conceitos de Vigotski no Brasil: produção divulgada nos Cadernos de Pesquisa Vygotsky's concepts in Brazil: the production published in Cadernos de Pesquisa

O objetivo desse artigo é identificar como os conceitos de Vigotski foram apropriados por autores vinculados à área da Psicologia da Educação que divulgaram seus trabalhos no Brasil, bem como suas metas e o momento em que tais idéias foram aqui utilizadas. Serviram de base para a pesquisa os artigos publicados nos Cadernos de Pesquisa - revista da Fundação Carlos Chagas -, que citavam, nas referências bibliográficas, alguma obra de Vigotski. Foram encontrados 37 artigos, entre 1971 e 2000. A produção foi organizada por década e analisada por meio de categorias construídas a posteriori. Os resultados mostram que os trabalhos que fizeram uso dos conceitos de Vigotski não avançaram suficientemente do ponto de vista teórico, ficando restritos aos processos de desenvolvimento e aprendizagem, bem como à relação entre pensamento e linguagem.<br>The purpose of this article is to identify how Vygotsky's concepts were appropriated by authors related to Education Psychology in Brazil, as well as their aims and the moment in which such ideas were here employed. The basis for this research was the whole of articles published in Cadernos de Pesquisa, journal of Fundação Carlos Chagas, which mentioned, in their bibliographical references, any work of Vygotsky. Since 1971 up to 2000, 37 articles were found. The production was organized by decade and analysed through categories built a posteriori. The results have shown that works based on Vygotsky concepts not only did not advance sufficiently from the theoretical point of view, but were also restricted to development and learning processes and to the relationship between thought and language

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)

COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19

The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p