asiairan4
asiairan4
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The SARS-CoV-2 virus infects cells of the airway and lungs in humans causing the disease COVID-19. This disease is characterized by cough, shortness of breath, and in severe cases causes pneumonia and acute respiratory distress syndrome (ARDS) which can be fatal. Bronchial alveolar lavage fluid (BALF) and plasma from mild and severe cases of COVID-19 have been profiled using protein measurements and bulk and single cell RNA sequencing. Onset of pneumonia and ARDS can be rapid in COVID-19, suggesting a potential neuronal involvement in pathology and mortality. We sought to quantify how immune cells might interact with sensory innervation of the lung in COVID-19 using published data from patients, existing RNA sequencing datasets from human dorsal root ganglion neurons and other sources, and a genome-wide ligand-receptor pair database curated for pharmacological interactions relevant for neuro-immune interactions. Our findings reveal a landscape of ligand-receptor interactions in the lung caused by SARS-CoV-2 viral infection and point to potential interventions to reduce the burden of neurogenic inflammation in COVID-19 disease. In particular, our work highlights opportunities for clinical trials with existing or under-development rheumatoid arthritis and other (e.g. CCL2, CCR5 or EGFR inhibitors) drugs to treat high risk or severe COVID-19 cases.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19) has rapidly spread from an initial outbreak in Wuhan, China in December 2019 to the rest of the world within a few months. On March 11th 2020, the rapidly evolving COVID-19 situation was characterized as a pandemic by the WHO. Much attention has been drawn to the origin of SARS-CoV-2, a virus which is related to the lineage B betacoronavirus SARS-CoV and SARS-related coronaviruses found in bat species. The closest known relative to SARS-CoV-2 is a bat coronavirus named RaTG13 (BatCoV-RaTG13). Early characterizations of the SARS-CoV-2 genome revealed the existence of a distinct 4 amino acid insert (underlined, SPRRAR↓S), found within the spike (S) protein, at a position termed the S1/S2 site located at the interface between the S1 receptor binding subunit and the S2 fusion subunit. Notably, this S1/S2 insert appears to be distinguishing feature among SARS-related sequences and introduces a potential cleavage site for the protease furin. Here, we investigate the potential role of this novel S1/S2 cleavage site and present direct biochemical evidence for proteolytic processing by a variety of proteases, including furin, trypsin-like proteases and cathepsins. We discuss these findings in the broader context of the origin of SARS-CoV-2, viral stability and transmission. Funding Work in the author's laboratory is supported by the National Institutes of Health (research grant R01AI35270).Here we propose a vaccination strategy for SARS-CoV-2 based on identification of both highly conserved regions of the virus and newly acquired adaptations that are presented by MHC class I and II across the vast majority of the population, are highly dissimilar from the human proteome, and are predicted B cell epitopes. We present 65 peptide sequences that we expect to result in a safe and effective vaccine which can be rapidly tested in DNA, mRNA, or synthetic peptide constructs. These include epitopes that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor, and within a novel furin cleavage site thought to increase membrane fusion. This vaccination strategy specifically targets unique vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the human population. Funding This work was supported by a St. Baldrick's-Stand Up To Cancer Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT2727) and the Beau Biden Cancer Moonshot Pediatric Immunotherapy Discovery and Development Networ (NCI Grant U54 CA232568). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. This work was also supported by NIH R35 CA220500 and the Giulio D'Angio Endowed Chair and the Quod Erat Demonstrandum (QED) program at the Science Center in Philadelphia.In the absence of vaccines or therapeutics, and with cases of COVID-19 continuing to grow each day, most countries are relying on non-pharmaceutical interventions (NPIs) to reduce the spread of SARS-CoV-2. The goal of NPIs - decreasing mobility in order to decrease contact - comes with competing socioeconomic costs and incentives that are not well-understood. Using Google's Community Mobility data, we visualized changes in mobility and explored the effect of economic, social, and governmental factors on mobility via regression. We found decreases in mobility for all movement categories except in residential areas; these changes corresponded strongly with country-specific outbreak trajectory. Mobility increased with GDP per capita, though this relationship varied among movement categories. Finally, countries with more authoritarian governments were more responsive with respect to mobility changes as local case counts increased; however, these countries were also less likely to report mobility data to Google. These preliminary findings suggest that country-specific outbreak trajectory, GDP per capita, and democracy index may be important indicators in assessing a given population's adherence to NPIs. The novel coronavirus disease 2019 (COVID-19) pandemic has generated many questions on its screening, diagnosis and management. One important question emerging from this discussion of regional differences pertains to the healthcare workforce not just in absolute numbers but also in terms of skill-mix. As nurses comprise over half the skilled healthcare workforce worldwide, it is important to consider them as part of a health systems strengthening approach to quality improvement. We sought to investigate the influence of the registered nurse (RN) concentration and the impact on COVID-19 mortality between countries worldwide. We conducted an observational cohort study to examine the association between COVID-19 mortality rates and concentrations of registered nurses. Data on nursing concentrations by country provided from the World Health Organization were merged with March 2020 COVID-19 mortality rates. DHA inhibitor ic50 Descriptive statistics, geographical information systems (GIS) mapping and multilevel linear regression with mixed effects were applied to examine this association with regional clustering of countries.

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