#Sepsis-associated #ARDS in individuals of #European #ancestry: a #genome-wide association study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Sepsis-associated acute respiratory distress syndrome in individuals of European ancestry: a genome-wide association study

Beatriz Guillen-Guio, MSc, Jose M Lorenzo-Salazar, MSc, Shwu-Fan Ma, PhD, Pei-Chi Hou, PhD, Tamara Hernandez-Beeftink, MSc, Almudena Corrales, LT, M Isabel García-Laorden, PhD, Jonathan Jou, MD, Elena Espinosa, MD, Arturo Muriel, MD, David Domínguez, MD, Leonardo Lorente, MD, María M Martín, MD, Carlos Rodríguez-Gallego, MD, Jordi Solé-Violán, MD, Alfonso Ambrós, MD, Demetrio Carriedo, MD, Jesús Blanco, MD, José M Añón, MD, John P Reilly, MD, Tiffanie K Jones, MD, Caroline AG Ittner, PhD, Rui Feng, PhD, Franziska Schöneweck, MSc, Michael Kiehntopf, MD, Imre Noth, MD, Markus Scholz, PhD, Frank M Brunkhorst, MD, André Scherag, PhD, Nuala J Meyer, MD, Jesús Villar, MD, Carlos Flores, PhD

Published: January 23, 2020 / DOI: https://doi.org/10.1016/S2213-2600(19)30368-6

 

Summary

Background

Acute respiratory distress syndrome (ARDS) is a lung inflammatory process caused mainly by sepsis. Most previous studies that identified genetic risks for ARDS focused on candidates with biological relevance. We aimed to identify novel genetic variants associated with ARDS susceptibility and to provide complementary functional evidence of their effect in gene regulation.

Methods

We did a case-control genome-wide association study (GWAS) of 1935 European individuals, using patients with sepsis-associated ARDS as cases and patients with sepsis without ARDS as controls. The discovery stage included 672 patients admitted into a network of Spanish intensive care units between January, 2002, and January, 2017. The replication stage comprised 1345 individuals from two independent datasets from the MESSI cohort study (Sep 22, 2008–Nov 30, 2017; USA) and the VISEP (April 1, 2003–June 30, 2005) and MAXSEP (Oct 1, 2007–March 31, 2010) trials of the SepNet study (Germany). Results from discovery and replication stages were meta-analysed to identify association signals. We then used RNA sequencing data from lung biopsies, in-silico analyses, and luciferase reporter assays to assess the functionallity of associated variants.

Findings

We identified a novel genome-wide significant association with sepsis-associated ARDS susceptibility (rs9508032, odds ratio [OR] 0·61, 95% CI 0·41–0·91, p=5·18 × 10 −8) located within the Fms-related tyrosine kinase 1 ( FLT1) gene, which encodes vascular endothelial growth factor receptor 1 (VEGFR-1). The region containing the sentinel variant and its best proxies acted as a silencer for the FLT1 promoter, and alleles with protective effects in ARDS further reduced promoter activity (p=0·0047). A literature mining of all previously described ARDS genes validated the association of vascular endothelial growth factor A ( VEGFA; OR 0·55, 95% CI 0·41–0·73; p=4·69 × 10 −5).

Interpretation

A common variant within the FLT1 gene is associated with sepsis-associated ARDS. Our findings support a role for the vascular endothelial growth factor signalling pathway in ARDS pathogenesis and identify VEGFR-1 as a potential therapeutic target.

Funding

Instituto de Salud Carlos III, European Regional Development Funds, Instituto Tecnológico y de Energías Renovables.

Keywords: ARDS; Sepsis; Genetics.

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Real-time tentative #assessment of the #epidemiological characteristics of novel #coronavirus infections in #Wuhan, #China, as at 22 January 2020 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020

Peng Wu1, Xinxin Hao1, Eric H Y Lau1, Jessica Y Wong1, Kathy S M Leung1, Joseph T Wu1, Benjamin J Cowling1,2, Gabriel M Leung1,2

Affiliations: 1 World Health Organization (WHO) Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; 2 These authors are joint senior authors with equal contribution

Correspondence:  Benjamin J Cowling

Citation style for this article: Wu Peng, Hao Xinxin, Lau Eric H Y, Wong Jessica Y, Leung Kathy S M, Wu Joseph T, Cowling Benjamin J, Leung Gabriel M. Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020. Euro Surveill. 2020;25(3):pii=2000044. https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000044

Received: 21 Jan 2020;   Accepted: 23 Jan 2020

 

Abstract

A novel coronavirus (2019-nCoV) causing severe acute respiratory disease emerged recently in Wuhan, China. Information on reported cases strongly indicates human-to-human spread, and the most recent information is increasingly indicative of sustained human-to-human transmission. While the overall severity profile among cases may change as more mild cases are identified, we estimate a risk of fatality among hospitalised cases at 14% (95% confidence interval: 3.9–32%).

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: 2019-nCoV; China.

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The Amazement of the Gods, Hans von Aachen (1590)

Annotazione 2020-01-23 191843

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The Amazement of the Gods
Hans von Aachen
Date: 1590
Style: Mannerism (Late Renaissance)
Genre: mythological painting
Location: National Gallery, London, UK

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Permissions: Public Domain.

Source: WikiArt, full page: https://www.wikiart.org/en/hans-von-aachen/the-amazement-of-the-gods-1590

 

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Homologous #Recombination Within the #Spike Glycoprotein of the Newly Identified #Coronavirus May Boost Cross-Species #Transmission From Snake to Human (J Med Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Med Virol  /  2020 Jan 22 [Online ahead of print]

Homologous Recombination Within the Spike Glycoprotein of the Newly Identified Coronavirus May Boost Cross-Species Transmission From Snake to Human

Wei Ji 1, Wei Wang 2, Xiaofang Zhao 3, Junjie Zai 4, Xingguang Li 5

Affiliations: 1 Department of Microbiology, Peking University Health Science Center School of Basic Medical Sciences, Beijing, China. 2 Department of Spleen and Stomach Diseases, The First affiliated Hospital of Guangxi university of Chinese Medicine, Nanning, 530023, China. 3 Department of Science and Technology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530011, China. 4 Immunology innovation team, School of Medicine, Ningbo University, Ningbo, 315211, China. 5 Hubei Engineering Research Center of Viral Vector, Wuhan University of Bioengineering, Wuhan, 430415, China.

PMID: 31967321 DOI: 10.1002/jmv.25682

 

Abstract

The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many patients were potentially exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To determine the possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on existing sequences of the newly identified coronavirus 2019-nCoV. Results obtained from our analyses suggest that the 2019-nCoV appears to be a recombinant virus between the bat coronavirus and an origin-unknown coronavirus. The recombination occurred within the viral spike glycoprotein, which recognizes cell surface receptor. Additionally, our findings suggest that snake is the most probable wildlife animal reservoir for the 2019-nCoV based on its RSCU bias resembling snake compared to other animals. Taken together, our results suggest that homologous recombination within the spike glycoprotein may contribute to cross-species transmission from snake to humans.

Keywords: 2019-nCoV; RSCU; cross-species transmission; phylogenetic analysis; recombination.

This article is protected by copyright. All rights reserved.

Keywords: Coronavirus; Bats; 2019-nCoV.

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#Coronaviruses: #Genome Structure, #Replication, and #Pathogenesis (J Med. Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Coronaviruses: Genome Structure, Replication, and Pathogenesis

Yu Chen 1, Qianyun Liu 1, Deyin Guo 2

Affiliations: 1 State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, P. R. China. 2 Center for Infection & Immunity Study, School of Medicine, Sun Yat-sen University, Guangzhou, P. R. China.

PMID: 31967327 DOI: 10.1002/jmv.25681

 

Abstract

The recent emergence of a novel coronavirus (2019-nCoV), which caused an outbreak of unusual viral pneumonia in tens of people in Wuhan, a central city of China, restated the risk of coronaviruses posed to public health. In this mini-review, we give a brief introduction of the general features of coronaviruses and describe various diseases caused by different coronaviruses in humans and animals. This review will help understand the biology and potential risk of coronaviruses that exist in richness in wildlife such as bats.

Keywords: Coronavirus; Epidemiology; Pathogenesis; Respiratory tract; Virus classification; Zoonoses.

This article is protected by copyright. All rights reserved.

Keywords: Coronavirus; Wildlife; 2019-nCoV.

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Seascape Study with Rain Cloud, John Constable (c.1827)

Annotazione 2020-01-21 190429

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Seascape Study with Rain Cloud
John Constable
Date: c.1827
Style: Romanticism
Genre: marina
Tag: seas-and-oceans
Location: Royal Academy of Arts (RA), London, UK
Dimensions: 22.2 x 31.1 cm

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Permissions: Public Domain.

Source: WikiArt, full page: https://www.wikiart.org/en/john-constable/seascape-study-with-rain-cloud-1

 

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