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MeSH Disease


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    Substantial Decreases in NO2 Pollution Measured by Ground-Based Monitors in US Cities During COVID-19 MESHD Shutdowns from Reduced Transportation Volumes

    Authors: Asrah Heintzelman; Vijay Lulla; Gabriel Filippelli

    id:10.20944/preprints202011.0695.v1 Date: 2020-11-27 Source:

    The air pollutant NO2 is derived largely from transportation sources and is known to cause respiratory disease MESHD. A substantial reduction in transport and industrial processes around the globe from the novel SARS-CoV-2 coronavirus MESHD and subsequent pandemic resulted in sharp declines MESHD in emissions, including for NO2. Additionally, the COVID-19 MESHD disease that results from the coronavirus may present in its most severe form in those who have been exposed to high levels of air pollution. To explore these links, we compared ground-based NO2 sensor data from 11 US cities from a two-month window (March-April) over the previous five years versus the same window during 2020 shutdowns. NO2 declined roughly 12-41% in the 11 cities. This decreased coincided with a sharp drop in vehicular traffic from shutdown-related travel TRANS restrictions. To explore this link more closely, we gathered more detailed traffic count data in one city, Indianapolis, Indiana, and found a strong correlation between traffic counts/classification and vehicle miles travelled TRANS, and a moderate correlation between NO2 and traffic related data. This finding indicates that we can use such analysis in targeting reduction in pollutants like NO2 by examining and manipulating traffic patterns, thus potentially leading to more population-level health resilience in the future.

    A Nasal Spray Solution of Grapefruit Seed Extract plus Xylitol Displays Virucidal Activity Against SARS-Cov-2 In Vitro

    Authors: Gustavo A Ferrer; Arian Betancour; Camille C Go; Hector Vazquez; Jonna B Westover; Valeria Cagno; Caroline Tapparel; Marcos A Sanchez-Gonzalez

    doi:10.1101/2020.11.23.394114 Date: 2020-11-25 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), responsible for the ongoing pandemic coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) has triggered worldwide concerted efforts in an attempt to identify effective therapies. In the present study, we have identified two candidate agents with potential activity against SARS-CoV-2 which can be administered intranasally, namely, xylitol and grape seed fruit extract (GSE). A commercially available nasal spray (Xlear) combining xylitol and GSE has been available for years, but the antiviral effects of this solution have not been documented. This in vitro study examined the virucidal effect of Xlear against SARS-CoV-2. To this end, two independent sets of experiments were carried out to test the hypothesis that Xlear is an effective (Experiment I) and replicable (Experiment II) means to deactivate SARS-CoV-2. When tested against SARS-CoV-2, the test compound GSE 0.2% was the only compound effective at reducing >3 log10 CCID50 infectious virus from, 3.67 log10 CCID50/0.1 mL to an undetectable amount of infectious virus. The present results validated by two independent sets of experiments, performed by different labs, on different viral strains, provide early evidence to encourage further pilot and clinical studies aimed at investigating the use of Xlear as a potential treatment for COVID-19 MESHD

    SARS-CoV-2 utilizes a multipronged strategy to suppress host protein synthesis MESHD

    Authors: Yaara Finkel; Avi Gluck; Roni Winkler; Aharon Nachshon; Orel Mizrahi; Yoav Lubelsky; Binyamin Zuckerman; Boris Slobodin; Yfat Yahalom-Ronen; Hadas Tamir; Igor Ulitsky; Tomer Israely; Nir Paran; Michal Schwartz; Noam Stern-Ginossar; Qing Ye; Tian-Shu Cao; Nan Wang; Lei Wang; Lei Cao; Huiyu Wang; Desheng Kong; Juan Ma; Chunxia Luo; Yanjing Zhang; Jianhui Nie; Yao Sun; Zhe Lv; Neil Shaw; Qianqian Li; Xiao-Feng Li; Junjie Hu

    doi:10.1101/2020.11.25.398578 Date: 2020-11-25 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease MESHD 19 ( COVID-19 MESHD) pandemic. Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis and its ability to antagonize innate immune responses. Here, we use RNA-sequencing and ribosome profiling along SARS-CoV-2 infection MESHD and comprehensively define the mechanisms that are utilized by SARS-CoV-2 to shutoff cellular protein synthesis. We show SARS-CoV-2 infection MESHD leads to a global reduction in translation but that viral transcripts are not preferentially translated. Instead, we reveal that infection leads to accelerated degradation of cytosolic cellular mRNAs which facilitates viral takeover of the mRNA pool in infected cells. Moreover, we show that the translation of transcripts whose expression is induced in response to infection, including innate immune genes, is impaired, implying infection MESHD prevents newly transcribed cellular mRNAs from accessing the ribosomes. Overall, our results uncover the multipronged strategy employed by SARS-CoV-2 to commandeer the translation machinery and to suppress host defenses.

    3D8, a nucleic acid-hydrolyzing scFv, confers antiviral activity against SARS-CoV-2 and multiple coronaviruses in vitro

    Authors: Gunsup Lee; Shailesh Budhathoki; Hyeok Soon Choi; Kwang-ji Oh; Geum-Young Lee; Yeon Kyoung Ham; Young Jun Kim; Ye Rin Lim; Phuong Thi Hoang; Yongjun Lee; Seok-Won Lim; Jun-Mo Kim; Seungchan Cho; Jin-Won Song; Sukchan Lee; Won-Keun Kim; Tian-Shu Cao; Nan Wang; Lei Wang; Lei Cao; Huiyu Wang; Desheng Kong; Juan Ma; Chunxia Luo; Yanjing Zhang; Jianhui Nie; Yao Sun; Zhe Lv; Neil Shaw; Qianqian Li; Xiao-Feng Li; Junjie Hu

    doi:10.1101/2020.11.25.398909 Date: 2020-11-25 Source: bioRxiv

    The current pandemic severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) pose a critical public health threat worldwide. Coronaviruses (subfamily Orthocoronavirinae, family Coronaviridae, order Nidovirales) are a group of enveloped positive-sense single-stranded RNA viruses. Six pathogenic human coronaviruses, likely zoonotic viruses, cause the common cold in humans. A new emerging coronavirus, SARS-CoV-2, become a crucial etiology for the Coronavirus-induced disease 19 ( COVID-19 MESHD). However, effective therapeutics and vaccines against multiple coronaviruses remain unavailable. This study aimed to investigate an antiviral molecule, single chain variable fragment (scFv), against SARS-CoV-2 and other coronaviruses. 3D8, a recombinant scFv, exhibits broad-spectrum antiviral activity against DNA and RNA viruses owing to its nucleic acid-hydrolyzing property. Here, we report that 3D8 scFv inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43), and porcine epidemic diarrhea virus MESHD diarrhea HP virus (PEDV). Our results revealed the prophylactic and therapeutic effects of 3D8 scFv against SARS-CoV-2 in Vero E6 cells. Immunoblot and plaque assays showed the absence of coronavirus nucleoproteins and infectious particles in 3D8 scFv-treated cells, respectively. In addition, we observed the antiviral effects of 3D8 against HCoV-OC43 and PEDV. In conclusion, this study provides insights into the broad-spectrum antiviral agent of 3D8 scFv; thus, it could be considered a potential antiviral countermeasure against SARS-CoV-2 and zoonotic coronaviruses.

    Loneliness among older adults TRANS in the community during COVID-19 MESHD

    Authors: Rachel D Savage; Wei Wu; Joyce Li; Andrea Lawson; Susan E Bronskill; Stephanie A. Chamberlain; Jim Grieve; Andrea Gruneir; Christina Reppas-Rindlisbacher; Nathan M. Stall; Paula A Rochon; Fanlong Bu; Sarah Klingenberg; Christian Gluud; Janus Christian Jakobsen; Willem Hanekom; Bernadett I Gosnell; COMMIT-KZN Team; Emily Wong; Tulio de Oliveira; Mahomed-Yunus S Moosa; Alasdair Leslie; Henrik Kloverpris; Alex Sigal

    doi:10.1101/2020.11.23.20237289 Date: 2020-11-24 Source: medRxiv

    Objective: Physical distancing and stay-at-home measures implemented to slow transmission TRANS of novel coronavirus disease MESHD ( COVID-19 MESHD) may intensify feelings of loneliness in older adults TRANS, especially those living alone. Our aim was to characterize the extent of loneliness in a sample of older adults TRANS living in the community and assess characteristics associated with loneliness. Design: Online cross-sectional survey between May 6 and May 19, 2020 Setting: Ontario, Canada Participants: Convenience sample of the members of a national retired educators' organization. Primary outcome measures: Self-reported loneliness, including differences between women and men. Results: 4879 respondents (71.0% women; 67.4% 65-79 years) reported that in the preceding week, 43.1% felt lonely at least some of the time, including 8.3% that felt lonely always or often. Women had increased odds of loneliness compared to men, whether living alone (adjusted Odds Ratio (aOR) 1.52 [95% Confidence Interval (CI) 1.13-2.04]) or with others (2.44 [95% CI 2.04-2.92]). Increasing age group TRANS decreased the odds of loneliness (aOR 0.69 [95% CI 0.59-0.81] 65-79 years and 0.50 [95% CI 0.39-0.65] 80+ years compared to <65 years). Living alone was associated with loneliness, with a greater association in men (aOR 4.26 [95% CI 3.15-5.76]) than women (aOR 2.65 [95% CI 2.26-3.11]). Other factors associated with loneliness included: fair or poor health (aOR 1.93 [95% CI 1.54-2.41]), being a caregiver (aOR 1.18 [95% CI 1.02-1.37]), receiving care (aOR 1.47 [95% CI 1.19-1.81]), high concern for the pandemic (aOR 1.55 [95% CI 1.31-1.84]), not experiencing positive effects of pandemic distancing measures (aOR 1.94 [95% CI 1.62-2.32]), and changes to daily routine (aOR 2.81 [95% CI 1.96-4.03]). Conclusions: While many older adults TRANS reported feeling lonely during COVID-19 MESHD, several characteristics - such as being female TRANS and living alone - increased the odds of loneliness. These characteristics may help identify priorities for targeting interventions to reduce loneliness.

    How closely is COVID-19 MESHD related to HCoV, SARS, and MERS? : Clinical comparison of coronavirus infections MESHD and identification of risk factors influencing the COVID-19 MESHD severity using common data model (CDM)

    Authors: Yeon Hee Kim; YeHee Ko; Soo Young Kim; Kwangsoo Kim

    doi:10.1101/2020.11.23.20237487 Date: 2020-11-24 Source: medRxiv

    South Korea was one of the epicenters for both the 2015 MERS and 2019 COVID-19 MESHD outbreaks. However, there has been a lack of published literature, especially using the EMR records, that provides a comparative summary of the prognostic factors present in the coronavirus-derived diseases patients. Therefore, in this study, we aimed to compare and evaluate the distinct clinical traits between the patients of different coronaviruses, including the lesser pathogenic HCoV strains, SARS-CoV MESHD, MERS-CoV, and SARS-CoV-2. We also conducted observed the risk factors by the COVID severity to investigate the extent of resemblance in clinical features between the disease groups and to identify unique factor that may influence the prognosis of the COVID-19 MESHD patients. Here, we utilize the common data model (CDM), which is the database that houses the EMR records transformed into the common format to be used by the multiple institutions. For the comparative analyses between the disease groups, we used independent t-test, Scheffe post-hoc test, and Games-howell post-hoc test and for the continuous variables, chi-square test and Fisher exact test. Based on the analyses, we selected the variables with p-values less than 0.05 to predict COVID-19 MESHD severity by nominal logistic regression with adjustments to age TRANS and gender TRANS. From the study, we observed diabetes MESHD, cardio and cerebrovascular diseases MESHD, cancer MESHD, pulmonary disease MESHD, gastrointestinal disease MESHD, and renal disease MESHD in all patient groups. Of all, the proportions of cancer MESHD patients were highest in all groups with no statistical significance. Most interestingly, we observed a high degree of clinical similarity between the COVID-19 MESHD and SARS patients with more than 50% of measured clinical variables to show statistical similarities between two groups. Our research reflects the great significance within the bioinformatics field that we were able to effectively utilize the integrated CDM to reflect real-world challenges in the context of coronavirus. We expect the results from our study to provide clinical insights that can serve as predicator of risk factors from the future coronavirus outbreak as well as the prospective guidelines for the clinical treatments.

    Sensitive quantitative detection of SARS-CoV-2 in clinical samples using digital warm-start CRISPR assay

    Authors: Xiong Ding; Kun Yin; Ziyue Li; Maroun M. Sfeir; Changchun Liu; Samarth Swarup; Madhav Marathe; Maryam Azimzadeh Irani; Martin Kuper; Orlando Quintero; Kent Feng; Catherine Ley; Dean Winslow; Jennifer Newberry; Karlie Edwards; Colin Hislop; Ingrid Choong; Yvonne Maldonado; Jeffrey Glenn; Ami Bhatt; Catherine Blish; Taia Wang; Chaitan Khosla; Benjamin Pinsky; Manisha Desai; Julie Parsonnet; Upinder Singh

    doi:10.1101/2020.11.21.20236109 Date: 2020-11-23 Source: medRxiv

    Quantifying severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) in clinical samples is crucial for assessing the infectivity of coronavirus disease MESHD coronavirus disease 2019 MESHD and the efficacy of antiviral drugs. Here, we describe a digital warm-start CRISPR (WS-CRISPR) assay for sensitive quantitative detection of SARS-CoV-2 in clinical samples. The WS-CRISPR assay combines low-temperature reverse transcription dual-priming mediated isothermal amplification (RT-DAMP) and CRISPR-Cas12a-based detection in one-pot, attributed to the mediation role by pyrophosphatase and phosphorothioated primers. The WS-CRISPR assay is initiated at above 50 {degrees}C and overcomes undesired premature target amplification at room temperature, enabling accurate digital nucleic acid quantification. By targeting SARS-CoV-2's nucleoprotein gene, digital WS-CRISPR assay is able to detect down to 5 copies/l SARS-CoV-2 RNA in the chip within 90 minutes. It is clinically validated by quantitatively determining 32 clinical swab samples and three clinical saliva samples, showing 100% agreement with RT-PCR results. Moreover, the digital WS-CRISPR assay has been demonstrated to directly detect SARS-CoV-2 in heat-treated saliva samples without RNA extraction, showing high tolerance to inhibitors. Thus, the digital WS-CRISPR method, as a sensitive and reliable CRISPR assay, facilitates accurate SARS-CoV-2 detection toward digitized quantification.

    Duration of SARS-CoV-2 viral shedding in faeces as a parameter for wastewater-based epidemiology: Re-analysis of patient data using a shedding dynamics model

    Authors: Fuminari Miura; Masaaki Kitajima; Ryosuke Omori; Monjuri Kataki; Dina Raja; Divyashree Medhi; Ridip Dutta; Achu Chena; Divya Daimary; Aakangkhita Choudhurydo; Lahari Saikia; Annabelle Mai; Caroline Colijn; Judith Breuer; Matthew Buckland; Kimberly Gilmour; David Goldblatt; - The Co-Stars Study Team; Huong T Kratochvil; - QCRG Structural Biology Consortium; Anthony Aimon; James M Bennett; Jose Brandao Neto; Aina E Cohen; Alexandre Dias; Alice Douangamath; Louise Dunnett; Oleg Fedorov; Matteo P Ferla; Martin Fuchs; Tyler J Gorrie-Stone; James M Holton; Michael G Johnson; Tobias Krojer; George Meigs; Ailsa J Powell; Johannes Gregor Matthias Rack; Victor L Rangel; Silvia Russi; Rachael E Skyner; Clyde A Smith; Alexei S Soares; Jennifer L Wierman; Kang Zhu; Natalia Jura; Alan Ashworth; John Irwin; Michael C Thompson; Jason E Gestwicki; Frank von Delft; Brian K Shoichet; James S Fraser; Ivan Ahel

    doi:10.1101/2020.11.22.20236323 Date: 2020-11-23 Source: medRxiv

    Background: Wastewater-based epidemiology (WBE) is one of the most promising approaches to effectively monitor the spread of the novel coronavirus disease 2019 MESHD ( COVID-19 MESHD). The virus concentration in faeces and its temporal variations are essential information for WBE. While some clinical studies have reported severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) concentrations in faeces, the value varies amongst patients and changes over time. Aim: The present study aimed to examine how the temporal variations in the concentration of virus in faeces affect the monitoring of disease incidence. We re-analysed the experimental findings of clinical studies to estimate the duration of virus shedding and the faecal virus concentration. Method: Available experimental data as of 23 October, 2020 were collected and patient data reported in Germany were included for further analysis. The viral shedding kinetics was modelled, and the dynamic model was fitted to the collected experimental data by a Bayesian framework. Using samples of posterior distributions, the duration of viral shedding and the concentration of virus copies in faeces over time were computed. Results: We estimated the median concentration of SARS-CoV-2 in faeces as 2.6 (95% Credible Interval (CrI): 0.22-4.8) log copies per gram (g) of faeces over the shedding period, and our model implied that the duration of viral shedding was 23.2 days (95% CrI: 19.5-31.5), given the current standard quantification limit (Ct = 40). With simulated incidences, our results also indicated that a one-week delay between symptom onset TRANS and wastewater sampling increased the estimation of incidence by 13.5%. Conclusions: Our results demonstrated that the temporal variation in virus concentration in faeces affects microbial monitoring systems such as WBE. The present study also implied the need for adjusting the estimates of virus concentration in faeces by incorporating the kinetics of unobserved concentrations. The method used in this study is easily implemented in further simulations; therefore, the results of this study might contribute to enhancing disease surveillance and risk assessments that require quantities of virus to be excreted into the environment.

    Persisting antibody SERO response to SARS-CoV-2 in a local Austrian population

    Authors: Dennis Ladage; Delia Roesgen; Clemens Schreiner; Dorothee Ladage; Christoph Adler; Oliver Harzer; Ralf Braun; Savita Kamble; Christiaan de Vries; Orlando Quintero; Kent Feng; Catherine Ley; Dean Winslow; Jennifer Newberry; Karlie Edwards; Colin Hislop; Ingrid Choong; Yvonne Maldonado; Jeffrey Glenn; Ami Bhatt; Catherine Blish; Taia Wang; Chaitan Khosla; Benjamin Pinsky; Manisha Desai; Julie Parsonnet; Upinder Singh

    doi:10.1101/2020.11.20.20232140 Date: 2020-11-23 Source: medRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has caused a global pandemic. The prevalence SERO and persistence of antibodies SERO following a peak SARS-CoV-2 infection MESHD provides insights into the potential for some level of population immunity. In June 2020 we succeeded in testing almost half of the population of an Austrian township with a higher incidence for COVID-19 MESHD infections. Now we performed a follow-up study to reassess the prevalence SERO of SARS-CoV-2-specific IgA and IgG antibodies SERO. In 121 people, including 68 participants of the previous study we found the prevalence SERO of IgG and IgA antibodies SERO remaining remarkably stable with 84% of our cohort prevailing SARS-CoV-2-specific antibodies SERO, which is only a slight decrease from 93% four months before. Most patients with confirmed COVID-19 MESHD seroconvert, potentially providing immunity to reinfection. Our results suggest a stable antibody SERO response that we observed for at least six months post infection with implications for developing strategies for testing and protecting the population.

    BCG vaccine derived peptides induce SARS-CoV-2 T cell cross-reactivity

    Authors: Peter J Eggenhuizen; Boaz H Ng; Janet Chang; Ashleigh L Fell; Wey Y Wong; Poh-yi Gan; Stephen R Holdsworth; Joshua D Ooi; Martin Kuper; Orlando Quintero; Kent Feng; Catherine Ley; Dean Winslow; Jennifer Newberry; Karlie Edwards; Colin Hislop; Ingrid Choong; Yvonne Maldonado; Jeffrey Glenn; Ami Bhatt; Catherine Blish; Taia Wang; Chaitan Khosla; Benjamin Pinsky; Manisha Desai; Julie Parsonnet; Upinder Singh

    doi:10.1101/2020.11.21.20236018 Date: 2020-11-23 Source: medRxiv

    Epidemiological studies suggest that the Bacillus Calmette-Guerin (BCG) vaccine may have protective effects against coronavirus disease 2019 MESHD ( COVID-19 MESHD); and, there are now more than 15 ongoing clinical trials seeking to determine if BCG vaccination can prevent or reduce the severity of COVID-19 MESHD (1). However, the mechanism by which BCG vaccination can induce a severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) specific T cell response is unknown. Here, in silico, we identify 8 BCG derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 MESHD or NSP13 derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG derived peptide developed enhanced reactivity to its corresponding SARS-CoV-2 derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2 derived peptides. These findings provide a mechanistic basis for the epidemiologic observation that BCG vaccination confers protection from COVID-19 MESHD; and supports the use of BCG vaccination to induce cross-reactive SARS-CoV-2 specific T cell responses.

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MeSH Disease

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