Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 14
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    SARS-CoV-2 infection MESHD, neuropathogenesis and transmission TRANS among deer mice: Implications for reverse zoonosis MESHD to New World rodents

    Authors: Anna Fagre; Juliette Lewis; Miles Eckley; Shijun Zhan; Savannah M Rocha; Nicole R Sexton; Bradly Burke; Brian J Geiss; Olve Peersen; Rebekah Kading; Joel Rovnak; Gregory D Ebel; Ronald B Tjalkens; Tawfik Aboellail; Tony Schountz

    doi:10.1101/2020.08.07.241810 Date: 2020-08-07 Source: bioRxiv

    Coronavirus disease MESHD-19 (COVID-19) emerged in November, 2019 in China and rapidly became pandemic. As with other coronaviruses, a preponderance of evidence suggests the virus originated in horseshoe bats (Rhinolophus spp.) and likely underwent a recombination event in an intermediate host prior to entry into human populations. A significant concern is that SARS-CoV-2 could become established in secondary reservoir hosts outside of Asia. To assess this potential, we challenged deer mice (Peromyscus maniculatus) with SARS-CoV-2 and found robust virus replication in the upper respiratory tract, lungs and intestines, with detectable viral RNA for up to 21 days in oral swabs and 14 days in lungs. Virus entry into the brain also occurred, likely via gustatory-olfactory-trigeminal pathway with eventual compromise to the blood SERO brain barrier. Despite this, no conspicuous signs of disease MESHD were observed and no deer mice succumbed to infection MESHD. Expression of several innate immune response genes were elevated in the lungs, notably IFN, Cxcl10, Oas2, Tbk1 and Pycard. Elevated CD4 and CD8{beta} expression in the lungs was concomitant with Tbx21, IFN{gamma} and IL-21 expression, suggesting a type I inflammatory immune response. Contact transmission TRANS occurred from infected to naive deer mice through two passages, showing sustained natural transmission TRANS. In the second deer mouse passage, an insertion of 4 amino acids occurred to fixation in the N-terminal domain of the spike protein that is predicted to form a solvent-accessible loop. Subsequent examination of the source virus from BEI Resources indicated the mutation was present at very low levels, demonstrating potent purifying selection for the insert during in vivo passage. Collectively, this work has determined that deer mice are a suitable animal model for the study of SARS-CoV-2 pathogenesis, and that they have the potential to serve as secondary reservoir hosts that could lead to periodic outbreaks of COVID-19 in North America.

    Whence the next pandemic? The intersecting global geography of the animal-human interface, poor health systems and air transit centrality reveals conduits for high-impact spillover

    Authors: Michael G Walsh; Shailendra Sawleshwarkar; Shah Hossain; Siobhan Mor

    doi:10.1101/2020.07.27.20163196 Date: 2020-07-29 Source: medRxiv

    The health and economic impacts of infectious disease MESHD pandemics are catastrophic as most recently manifested by coronavirus disease MESHD 2019 (COVID-19). The emerging infections MESHD that lead to substantive epidemics or pandemics are typically zoonoses MESHD that cross species boundaries at vulnerable points of animal-human interface. The sharing of space between wildlife and humans, and their domesticated animals, has dramatically increased in recent decades and is a key driver of pathogen spillover. Increasing animal-human interface has also occurred in concert with both increasing globalisation and failing health systems, resulting in a trifecta with dire implications for human and animal health. Nevertheless, to date we lack a geographical description of this trifecta that can be applied strategically to pandemic prevention. This investigation provides the first geographical quantification of the intersection of animal-human interfaces, poor human health system performance SERO and global connectivity via the network of air travel TRANS. In so doing, this work provides a systematic, data-driven approach to classifying spillover hazard based on the distribution of animal-human interfaces while simultaneously identifying globally connected cities that are adjacent to these interfaces and which may facilitate global pathogen dissemination. We present this geography of high-impact spillover as a tool for developing targeted surveillance systems and improved health infrastructure in vulnerable areas that may present conduits for future pandemics.

    North American deer mice are susceptible to SARS-CoV-2

    Authors: Bryan D Griffin; Mable Chan; Nikesh Tailor; Emelissa J Mendoza; Anders Leung; Bryce M Warner; Ana T Duggan; Estella Moffat; Shihua He; Lauren Garnett; Kaylie N Tran; Logan Banadyga; Alixandra Albietz; Kevin Tierney; Jonathan Audet; Alexander Bello; Robert Vendramelli; Amrit S Boese; Lisa Fernando; L Robbin Lindsay; Claire M Jardine; Heidi Wood; Guillaume Poliquin; James E Strong; Michael Drebot; David Safronetz; Carissa Embury-Hyatt; Darwyn Kobasa

    doi:10.1101/2020.07.25.221291 Date: 2020-07-26 Source: bioRxiv

    The zoonotic spillover of the pandemic SARS-coronavirus 2 (SARS-CoV-2) from an animal reservoir, currently presumed to be the Chinese horseshoe bat, into a naive human population has rapidly resulted in a significant global public health emergency MESHD. Worldwide circulation of SARS-CoV-2 in humans raises the theoretical risk of reverse zoonosis MESHD events with wildlife, reintroductions of SARS-CoV-2 into permissive non-domesticated animals, potentially seeding new host reservoir species and geographic regions in which bat SARS-like coronaviruses have not historically been endemic. Here we report that North American deer mice (Peromyscus maniculatus) and some closely related members of the Cricetidae family of rodents possess key amino acid residues within the angiotensin-converting enzyme 2 (ACE2) receptor known to confer SARS-CoV-2 spike protein binding. Peromyscus rodent species are widely distributed across North America and are the primary host reservoirs of several emerging pathogens that repeatedly spill over into humans including Borrelia burgdorferi, the causative agent of Lyme disease MESHD, deer tick virus, and Sin Nombre orthohantavirus, the causative agent of hantavirus pulmonary syndrome MESHD (HPS). We demonstrate that adult TRANS deer mice are susceptible to SARS-CoV-2 infection MESHD following intranasal exposure to a human isolate, resulting in viral replication in the upper and lower respiratory tract with little or no signs of disease MESHD. Further, shed infectious virus is detectable in nasal washes, oropharyngeal and rectal swabs, and viral RNA is detectable in feces and occasionally urine. We further show that deer mice are capable of transmitting SARS-CoV-2 to naive deer mice through direct contact. The extent to which these observations may translate to wild deer mouse populations remains unclear, and the risk of reverse zoonosis MESHD and/or the potential for the establishment of Peromyscus rodents as a North American reservoir for SARS-CoV-2 is unknown. Nevertheless, efforts to monitor wild, peri-domestic Peromyscus rodent populations are likely warranted as the SARS-CoV-2 pandemic progresses.

    Integrate Structural Analysis, Isoform Diversity, and Interferon-Inductive Propensity of ACE2 to Refine SARS-CoV2 Susceptibility Prediction in Vertebrates

    Authors: Eric R. Sang; Yun Tian; Yuanying Gong; Laura C Miller; Yongming Sang

    doi:10.1101/2020.06.27.174961 Date: 2020-06-28 Source: bioRxiv

    The current new coronavirus disease MESHD (COVID-19) has caused globally near 0.4/6 million confirmed deaths MESHD/infected cases across more than 200 countries. As the etiological coronavirus (a.k.a. SARS-CoV2) may putatively have a bat origin, our understanding about its intermediate reservoir between bats and humans, especially its tropism in wild and domestic animals, are mostly unknown. This constitutes major concerns in public health for the current pandemics and potential zoonosis MESHD. Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad SARS-CoV2 susceptibility in wild and particularly domestic animals. Through integration of key immunogenetic factors, including the existence of S-binding-void ACE2 isoforms and the disparity of ACE2 expression upon early innate immune response, we further refine the SARS-CoV2 susceptibility prediction to fit recent experimental validation. In addition to showing a broad susceptibility potential across mammalian species based on structural analysis, our results also reveal that domestic animals including dogs, pigs, cattle and goats may evolve ACE2-related immunogenetic diversity to restrict SARS-CoV2 infections MESHD. Thus, we propose that domestic animals may be unlikely to play a role as amplifying hosts unless the virus has further species-specific adaptation. These findings may relieve relevant public concerns regarding COVID-19-like risk in domestic animals, highlight virus-host coevolution, and evoke disease MESHD intervention through targeting ACE2 molecular diversity and interferon optimization.

    No evidence of coronaviruses or other potentially zoonotic viruses in Sunda pangolins (Manis javanica) entering the wildlife trade via Malaysia.

    Authors: Jimmy Lee; Tom Hughes; Mei-Ho Lee; Hume Field; Jeffrine Japning Rovie-Ryan; Frankie Thomas Sitam; Symphorosa Sipangkui; Senthilvel K.S.S. Nathan; Diana Ramirez; Subbiah Vijay Kumar; Helen Lasimbang; Jonathan H. Epstein; Peter Daszak

    doi:10.1101/2020.06.19.158717 Date: 2020-06-19 Source: bioRxiv

    The legal and illegal trade in wildlife for food, medicine and other products is a globally significant threat to biodiversity that is also responsible for the emergence of pathogens that threaten human and livestock health and our global economy. Trade in wildlife likely played a role in the origin of COVID-19, and viruses closely related to SARS-CoV-2 have been identified in bats and pangolins, both traded widely. To investigate the possible role of pangolins as a source of potential zoonoses MESHD, we collected throat and rectal swabs from 334 Sunda pangolins (Manis javanica) confiscated in Peninsular Malaysia and Sabah between August 2009 and March 2019. Total nucleic acid was extracted for viral molecular screening using conventional PCR protocols used to routinely identify known and novel viruses in extensive prior sampling (>50,000 mammals). No sample yielded a positive PCR result for any of the targeted viral families - Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. In light of recent reports of coronaviruses including a SARS-CoV-2 related virus in Sunda pangolins in China, the lack of any coronavirus detection in our upstream market chain samples suggests that these detections in downstream animals more plausibly reflect exposure to infected humans, wildlife or other animals within the wildlife trade network. While confirmatory serologic studies are needed, it is likely that Sunda pangolins are incidental hosts of coronaviruses. Our findings further support the importance of ending the trade in wildlife globally.

    Analysis the Dynamics of SIHR Model: Covid-19 Case in Djibouti

    Authors: Yahyeh Souleiman; Abdoulrazack Mohamed; Liban Ismail

    id:10.20944/preprints202006.0210.v1 Date: 2020-06-17 Source:

    The COVID-19 epidemic is an emerging infectious disease MESHD of the viral zoonosis MESHD type caused by the corona-virus strain SARS-CoV-2, is classified as a human-to-human communicable disease MESHD and is currently a pandemic worldwide. In this paper, we propose conceptual mathematical models the epidemic dynamics of four compartments. We have collected data from the Djibouti health ministry. We define the positivity, boundedness of solutions and basic reproduction number TRANS. Then, we study local and global stability and bifurcation analysis of equilibrium to examine its epidemiological relevance. Finally, we analyze the fit of the data in comparison with the result of our mathematical results, to validate the model and estimating the important model parameters and prediction about the disease MESHD, we consider the real cases of Djibouti from 23th March to 10th June, 2020.

    A Machine Learning Explanation of Incidence Inequalities of SARS-CoV-2 Across 88 Days in 157 Countries

    Authors: Eric Luellen

    doi:10.1101/2020.06.06.20124529 Date: 2020-06-08 Source: medRxiv

    Because the SARS-CoV-2 (COVID-19) pandemic viral outbreaks will likely continue until effective vaccines are widely administered, (1) new capabilities to accurately predict incidence rates by location and time to know in advance the disease MESHD burden and specific needs for any given population are valuable to minimize morbidity and mortality. In this study, a random forest of 9,250 regression trees was applied to 6,941 observations of 13 statistically significant predictor variables targeting SARS-CoV-2 incidence rates per 100,000 across 88 days in 157 countries. One key finding is an algorithm that can predict the incidence rate per day of a SARS-CoV-2 epidemic cycle with a pseudo-R2 accuracy of 98.5% and explain 97.4% of the variances. Another key finding is the relative importance of 13 demographic, economic, environmental, and public health modulators to the SARS-CoV-2 incidence rate. Four factors proposed in earlier research as potential modulators have no statistically significant relationship with incidence rates (2)(3). These findings give leaders new capabilities for improved capacity planning and targeting stay-at-home interventions and prioritizing programming by knowing the atypical social determinants that are the root causes of SARS-CoV-2 incidence variance. This work also proves that machine learning can accurately and quickly explain disease MESHD dynamics for zoonoses MESHD with pandemic potential.

    We Need to Address the Underlying Ecological Determinants of COVID-19

    Authors: Chris Kenyon

    id:10.20944/preprints202006.0040.v1 Date: 2020-06-04 Source:

    The probability of zoonoses MESHD, such as the novel coronavirus (COVID-19), emerging is strongly related to remediable factors such as habitat encroachment and trade in wild animals. Tackling these underlying determinants is important to prevent future pandemics from the approximately 700,000 viruses with the potential to cause zoonoses MESHD. Reversing habitat destruction is also vital to halt the accelerating rate of extinction of a wide array of life forms - with all the adverse consequences these extinctions will have for human health. These insights depend on viewing health and disease MESHD from within an ecological theoretical framework. We therefore argue that preventing future zoonotic outbreaks as well as dealing with a range of contemporary health issues would be facilitated by grounding our health sciences in more a more explicitly ecological conceptual framework.

    Pathogenesis, transmission TRANS and response to re-exposure of SARS-CoV-2 in domestic cats

    Authors: Angela Bosco-Lauth; Airn E. Hartwig; Stephanie Porter; Paul Gordy; Mary Nehring; Alex Byas; Sue VandeWoude; Izabela Ragan; Rachel Maison; Richard Bowen

    doi:10.1101/2020.05.28.120998 Date: 2020-06-01 Source: bioRxiv

    The pandemic caused by SARS-CoV-2 has reached nearly every country in the world with extraordinary person-to-person transmission TRANS. The most likely original source of the virus was spillover from an animal reservoir and subsequent adaptation to humans sometime during the winter of 2019 in Wuhan Province, China. Because of its genetic similarity to SARS-CoV-1, it is likely that this novel virus has a similar host range and receptor specificity. Due to concern for human-pet transmission TRANS, we investigated the susceptibility of domestic cats and dogs to infection MESHD and potential for infected cats to transmit to naive cats. We report that cats are highly susceptible to subclinical infection MESHD, with a prolonged period of oral and nasal viral shedding that is not accompanied by clinical signs, and are capable of direct contact transmission TRANS to other cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection MESHD, but are unlikely to develop clinical disease MESHD. Further, we document that cats develop a robust neutralizing antibody SERO response that prevented re- infection MESHD to a second viral challenge. Conversely, we found that dogs do not shed virus following infection MESHD, but do mount an anti-viral neutralizing antibody SERO response. There is currently no evidence that cats or dogs play a significant role in human exposure; however, reverse zoonosis MESHD is possible if infected owners expose their domestic pets during acute infection MESHD. Resistance to re-exposure holds promise that a vaccine strategy may protect cats, and by extension humans, to disease susceptibility MESHD.

    The coronavirus proofreading exoribonuclease mediates extensive viral recombination

    Authors: Jennifer Gribble; Andrea J Pruijssers; Maria L Agostini; Jordan Anderson-Daniels; James D Chappell; Xiaotao Lu; Laura J Stevens; Andrew Laurence Routh; Mark R Denison

    doi:10.1101/2020.04.23.057786 Date: 2020-04-25 Source: bioRxiv

    Coronaviruses (CoVs) emerge as zoonoses MESHD and cause severe disease MESHD in humans, demonstrated by the SARS-CoV-2 (COVID-19) pandemic. RNA recombination is required during normal CoV replication for subgenomic mRNA (sgmRNA) synthesis and generates defective viral genomes (DVGs) of unknown function. However, the determinants and patterns of CoV recombination are unknown. Here, we show that divergent {beta}-CoVs SARS-CoV-2, MERS-CoV, and murine hepatitis MESHD hepatitis MESHD hepatitis HP virus (MHV) perform extensive RNA recombination in culture, generating similar patterns of recombination junctions and diverse populations of DVGs and sgmRNAs. We demonstrate that the CoV proofreading nonstructural protein (nsp14) 3-to-5 exoribonuclease (nsp14-ExoN) is required for normal CoV recombination and that its genetic inactivation causes significantly decreased frequency and altered patterns of recombination in both infected cells and released virions. Thus, nsp14-ExoN is a key determinant of both high fidelity CoV replication and recombination, and thereby represents a highly-conserved and vulnerable target for virus inhibition and attenuation.

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MeSH Disease
Human Phenotype

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