scholarly journals Comparative infectivity and pathogenesis of emerging SARS-CoV-2 variants in Syrian hamsters

Author(s):  
Rana Abdelnabi ◽  
Robbert Boudewijns ◽  
Caroline S. Foo ◽  
Laura Seldeslachts ◽  
Lorena Sanchez-Felipe ◽  
...  

AbstractWithin one year after its emergence, more than 108 million people contracted SARS-CoV-2 and almost 2.4 million succumbed to COVID-19. New SARS-CoV-2 variants of concern (VoC) are emerging all over the world, with the threat of being more readily transmitted, being more virulent, or escaping naturally acquired and vaccine-induced immunity. At least three major prototypic VoC have been identified, i.e. the UK (B.1.1.7), South African (B.1.351) and Brazilian (B.1.1.28.1), variants. These are replacing formerly dominant strains and sparking new COVID-19 epidemics and new spikes in excess mortality. We studied the effect of infection with prototypic VoC from both B.1.1.7 and B.1.351 lineages in Syrian golden hamsters to assess their relative infectivity and pathogenicity in direct comparison to two basal SARS-CoV-2 strains isolated in early 2020. A very efficient infection of the lower respiratory tract of hamsters by these VoC is observed. In line with clinical evidence from patients infected with these VoC, no major differences in disease outcome were observed as compared to the original strains as was quantified by (i) histological scoring, (ii) micro-computed tomography, and (iii) analysis of the expression profiles of selected antiviral and pro-inflammatory cytokine genes. Noteworthy however, in hamsters infected with VoC B.1.1.7, a particularly strong elevation of proinflammatory cytokines was detected. Overall, we established relevant preclinical infection models that will be pivotal to assess the efficacy of current and future vaccine(s) (candidates) as well as therapeutics (small molecules and antibodies) against two important SARS-CoV-2 VoC.

Author(s):  
Julian W. Tang ◽  
Oliver T.R. Toovey ◽  
Kirsty N. Harvey ◽  
David D.S. Hui
Keyword(s):  

2021 ◽  
Vol 22 (4) ◽  
pp. 1695
Author(s):  
Bruno O. Villoutreix ◽  
Vincent Calvez ◽  
Anne-Geneviève Marcelin ◽  
Abdel-Majid Khatib

SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually in part due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor, several in silico methods and numerous experimental data reported recently to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both the UK and South African strains) should be favorable for the interaction with ACE2, while the K417N and E484K substitutions (South African strain) would seem neutral or even unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the K417N and E484K Spike replacements with regard to ACE2 binding. Our finding suggests that the UK strain should have higher affinity toward ACE2 and therefore likely increased transmissibility and possibly pathogenicity. If indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions located outside the direct Spike–ACE2 interface but not so much to the K417N and E484K replacements. Yet, it should be noted that amino acid changes at Spike position 484 can lead to viral escape from neutralizing antibodies. Further, these amino acid substitutions do not seem to induce major structural changes in this region of the Spike protein. This structure–function study allows us to rationalize some observations made for the UK strain but raises questions for the South African strain.


2010 ◽  
Vol 51 (12) ◽  
pp. 1362-1369 ◽  
Author(s):  
Cheryl Cohen ◽  
Lone Simonsen ◽  
Jong‐Won Kang ◽  
Mark Miller ◽  
Jo McAnerney ◽  
...  

2018 ◽  
Vol 21 (18) ◽  
pp. 3431-3439
Author(s):  
Paraskevi Seferidi ◽  
Anthony A Laverty ◽  
Jonathan Pearson-Stuttard ◽  
Maria Guzman-Castillo ◽  
Brendan Collins ◽  
...  

AbstractObjectiveAn industry levy on sugar-sweetened beverages (SSB) was implemented in the UK in 2018. One year later, Brexit is likely to change the UK trade regime with potential implications for sugar price. We modelled the effect of potential changes in sugar price due to Brexit on SSB levy impacts upon CHD mortality and inequalities.DesignWe modelled a baseline SSB levy scenario; an SSB levy under ‘soft’ Brexit, where the UK establishes a free trading agreement with the EU; and an SSB levy under ‘hard’ Brexit, in which World Trade Organization tariffs are applied. We used the previously validated IMPACT Food Policy model and probabilistic sensitivity analysis to estimate the effect of each scenario on CHD deaths prevented or postponed and life-years gained, stratified by age, sex and socio-economic circumstance, in 2021.SettingEngland.SubjectsAdults aged 25 years or older.ResultsThe SSB levy was associated with approximately 370 (95 % uncertainty interval 220, 560) fewer CHD deaths and 4490 (2690, 6710) life-years gained in 2021. Associated reductions in CHD mortality were 4 and 8 % greater under ‘soft’ and ‘hard’ Brexit scenarios, respectively. The SSB levy was associated with approximately 110 (50, 190) fewer CHD deaths in the most deprived quintile compared with 60 (20, 100) in the most affluent, under ‘hard’ Brexit.ConclusionsOur study found the SSB levy resilient to potential effects of Brexit upon sugar price. Even under ‘hard’ Brexit, the SSB levy would yield benefits for CHD mortality and inequalities. Brexit negotiations should deliver a fiscal and regulatory environment which promotes population health.


2021 ◽  
Vol 12 ◽  
Author(s):  
Don M. Matshazi ◽  
Cecil J. Weale ◽  
Rajiv T. Erasmus ◽  
Andre P. Kengne ◽  
Saarah F. G. Davids ◽  
...  

MicroRNAs are non-coding, post-transcriptional regulators of gene expression and their dysregulation has been associated with development of various diseases, including hypertension. Consequently, understanding their role in the pathogenesis and progression of disease is essential. Prior research focusing on microRNAs in disease has provided a basis for understanding disease prognosis and offered possible channels for therapeutic interventions. Herein, we aimed to investigate possible differences in the expression profiles of five microRNAs in the blood of participants grouped on the basis of their hypertension status. This was done to elucidate the possible roles played by these microRNAs in the development of hypertension. Using quantitative reverse transcription polymerase chain reaction, we evaluated the expression levels of miR-126-3p, 30a-5p, 182-5p, 30e-3p, and 1299 in the whole blood of 1456 participants, normotensive (n = 573), screen-detected hypertensive (n = 304) and known hypertensive (n = 579). The expression of miR-126-3p and 182-5p was significantly higher in known hypertensives relative to both screen-detected hypertensives and normotensives, and also in screen-detected hypertensives vs normotensives. A significant association between the expression of miR-126-3p, 182-5p, and 30a-5p and known hypertension was also evident. This study demonstrated dysregulated miR-126-3p, 182-5p, and 30a-5p expression in hypertension, highlighting the possible efficacy of these microRNAs as targets for the diagnosis of hypertension as well as the development of microRNA-based therapies.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Dan G. O’Neill ◽  
Rowena M.A. Packer ◽  
Peter Francis ◽  
David B. Church ◽  
Dave C. Brodbelt ◽  
...  

Abstract Background The French Bulldog is a highly popular dog breed but is linked with many serious health issues. A holistic view of breed health in French Bulldogs would assist efforts to appreciate the overall health strengths and weaknesses in the French Bulldog and to take appropriate steps to mitigate these. Based on random sampling of French Bulldogs and non-French Bulldogs under primary veterinary care during 2016 within the VetCompass Programme, a cohort study design was used to estimate the one-year (2016) period prevalence of the most commonly diagnosed disorders in each group. Risk factor analysis used multivariable logistic regression modelling methods. Results The analysis included 2,781 French Bulldogs and 21,850 non-French Bulldogs. French Bulldogs were younger (1.51 years, IQR 0.86 – 2.77 vs. 4.48 years, IQR 1.94 – 8.14) (p < 0.001) and lighter (12.45 kg, IQR 11.00 – 14.03 versus 13.80 kg, IQR 8.10 – 25.12) (p < 0.001) than non-French Bulldogs. Of 43 common specific-level disorders across both groups, French Bulldogs had significantly increased adjusted odds of 20/43 (46.5 %) disorders and significantly reduced adjusted odds of 11/43 (25.6 %) disorders compared to non-French Bulldogs. Highly predisposed disorders in French Bulldogs included stenotic nares (OR 42.14; 95 % CI 18.50 to 95.99; p < 0.001), Brachycephalic Obstructive Airway Syndrome (OR 30.89; 95 % CI 20.91 to 45.64; p < 0.001), aural discharge (OR 14.40; 95 % CI 9.08 to 22.86; p < 0.001), skin fold dermatitis (OR 11.18; 95 % CI 7.19 to 17.40; p < 0.001) and dystocia (OR 9.13; 95 % CI 5.17 to 16.13; p < 0.001). At a grouped-level of diagnostic precision, French Bulldogs had increased adjusted odds of 12/32 (37.5 %) disorders and reduced adjusted odds of 6/32 (18.8 %) disorders compared to non-French Bulldogs. Conclusions These results identified ultra-predispositions with worryingly higher odds in French Bulldogs for several disorders, suggesting that the health of French Bulldogs has diverged substantially from, and may be lower than, the health of the wider non-French Bulldog population. Many of these predispositions are closely associated with the conformational extremes that define the French Bulldog breed. Shifting the typical conformation of the French Bulldog population towards a more moderate phenotype is proposed as a logical opportunity to reduce the serious health issues endemic in the French Bulldog breed.


Itinerario ◽  
2014 ◽  
Vol 38 (3) ◽  
pp. 45-58
Author(s):  
John Connor

On the outbreak of war, men from the Dominions were scattered across the British Empire. As each Dominion began recruiting their expeditionary forces at home, the issue arose whether these expatriates, especially those resident in the United Kingdom, should join the British Army or be able to enlist in their Dominion's force. Canada and New Zealand allowed recruiting for the CEF and NZEF in the UK. Many Anglophone White South Africans joined a “colonial” battalion of the Royal Fusiliers. The Australian Government refused to allow Australians in the UK to join the AIF, despite the repeated requests of the Australian expatriate community. This paper examines the questions of British and sub-Imperial Dominion identities as well as the practical policy considerations raised by this issue. It argues that there is some evidence of nascent Dominion nationalism—the Canadian High Commission in London issued what became known as “a Certificate of Canadian Citizenship” to expatriates— but that Dominion Governments generally based their decisions on this issue based on cost and domestic political considerations.


Author(s):  
Julie Hennessy

Stella Artois, an AB InBev brand, is the world's best-selling Belgian beer. In early 2017, Ricardo Tadeu, AB InBev Zone President for Africa, is planning the brand's entry into its next export market: South Africa. The case explores Stella's introduction strategies into three of its export markets—the UK (1976), the US (2000), and Mexico (2016)—examining the drivers of the brand's success as well as its failures. Students will analyze the brand's previous launches to determine what made it successful in some markets and not in others. They will apply these learnings to develop a strategy for the brand's introduction to the South African market. Beyond the central discussion of growth through international expansion, the case addresses issues of brand positioning for premium products, changing consumer perceptions, the use of cause marketing, category development and maturity, and competitive strategy.


2014 ◽  
pp. 1400-1418
Author(s):  
Irina Turner

The colonization of discourses (Chilton & Schäffner, 2002) is a wide-spread phenomenon of globalization and naturally affects politics. The power of business-speak over politics and the media seems to be steadily increasing. Most vulnerable to that development, which the author calls businification, seem to be countries in transition that have to assert themselves rhetorically on a global scale while keeping traditional voters content at home. In an application of critical discourse analysis, the chapter seeks to trace this businification by comparing three presidential state-of-the-nation-addresses (SoNA) of three South African presidents after one year in office (1995, 2000, and 2010). Through contextualizing these texts with their media reception from a corpus of 15 newspaper articles reporting on the speeches, the outer influences on the core text become transparent. The findings suggest a parallelism between a growing professionalism in politics and the businification of political rhetoric whose development cannot be viewed as exclusively negative.


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