Corpus overview


MeSH Disease

Human Phenotype

Pneumonia (1049)

Fever (651)

Cough (525)

Hypertension (362)

Anxiety (286)


age categories (2647)

Transmission (2432)

gender (1227)

fomite (1108)

contact tracing (876)

    displaying 51 - 60 records in total 12932
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    Computational Hot-Spot Analysis of the SARS-CoV-2 Receptor Binding Domain / ACE2 Complex

    Authors: Pedro A. Rosario; Brian R McNaughton

    doi:10.1101/2020.08.06.240333 Date: 2020-08-06 Source: bioRxiv

    Infection MESHD and replication of SARS CoV-2 (the virus that causes COVID-19) requires entry to the interior of host cells. In humans, a Protein-Protein Interaction (PPI) between the SARS CoV-2 Receptor-Binding Domain (RBD) and the extracellular peptidase domain of ACE2, on the surface of cells in the lower respiratory tract, is an initial step in the entry pathway. Inhibition of the SARS CoV-2 RBD / ACE2 PPI is currently being evaluated as a target for therapeutic and/or prophylactic intervention. However, relatively little is known about the molecular underpinnings of this complex. Employing multiple computational platforms, we predicted hot-spot residues in a positive control PPI (PMI / MDM2) and the CoV-2 RBD/ACE2 complex. Computational alanine scanning mutagenesis was performed to predict changes in Gibbs free energy that are associated with mutating residues at the positive control (PMI/MDM2) or SARS RBD/ACE2 binding interface to alanine. Additionally, we used the Adaptive Poisson-Boltzmann Solver to calculate macromolecular electrostatic surfaces at the interface of the positive control PPI and SARS CoV-2 / ACE2 PPI. Collectively, this study illuminates predicted hot-spot residues, and clusters, at the SARS CoV-2 RBD / ACE2 binding interface, potentially guiding the development of reagents capable of disrupting this complex and halting COVID-19.

    The Trend of Neutralizing Antibody SERO Response Against SARS-CoV-2 and the Cytokine/Chemokine Release in Patients with Differing Severities of COVID-19: All Individuals Infected with SARS-CoV-2 Obtained Neutralizing Antibody SERO

    Authors: Lidya Handayani Tjan; Tatsuya Nagano; Koichi Furukawa; Mitsuhiro Nishimura; Jun Arii; Sayo Fujinaka; Sachiyo Iwata; Yoshihiro Nishimura; Yasuko Mori

    doi:10.1101/2020.08.05.20168682 Date: 2020-08-06 Source: medRxiv

    Background: COVID-19 patients show a wide clinical spectrum ranging from mild respiratory symptoms to severe and fatal disease MESHD, and older individuals are known to be affected more severely. Neutralizing antibody SERO for viruses is critical for their elimination, and increased cytokine/chemokine levels are thought to be related to COVID-19 severity. However, the trend of the neutralizing antibody SERO production and cytokine/chemokine levels during the clinical course of COVID-19 patients with differing levels of severity has not been established. Methods: We serially collected 45 blood SERO samples from 12 patients with different levels of COVID-19 severity, and investigated the trend of neutralizing antibody SERO production using authentic SARS-CoV-2 and cytokine/chemokine release in the patients' clinical courses. Results: All 12 individuals infected with SARS-CoV-2 had the neutralizing antibody SERO against it, and the antibodies SERO were induced at approx. 4-10 days after the patients' onsets. The antibodies SERO in the critical and severe cases showed high neutralizing activity in all clinical courses. Most cytokine/chemokine levels were clearly high in the critical patients compared to those with milder symptoms. Conclusion: Neutralizing antibodies SERO against SARS-CoV-2 were induced at a high level in the severe COVID-19 patients, indicating that abundant virus replication occurred. Cytokines/chemokines were expressed more in the critical patients, indicating that high productions of cytokines/chemokines have roles in the disease MESHD severity. These results may indicate that plasma SERO or neutralizing antibody SERO therapy could be a first-line treatment for older patients to eliminate the virus, and corticosteroid therapy could be effective to suppress the cytokine storm after the viral genome's disappearance.

    Rapid, reliable, and cheap point-of-care bulk testing for SARS-CoV-2 by combining hybridization capture with improved colorimetric LAMP (Cap-iLAMP)

    Authors: Lukas Bokelmann; Olaf Nickel; Tomislav Maricic; Svante Paabo; Matthias Meyer; Stephan Borte; Stephan Riesenberg

    doi:10.1101/2020.08.04.20168617 Date: 2020-08-06 Source: medRxiv

    Efforts to contain the spread of SARS-CoV-2 have spurred the need for reliable, rapid, and cost-effective diagnostic methods which can easily be applied to large numbers of people. However, current standard protocols for the detection of viral nucleic acids while sensitive, require a high level of automation, sophisticated laboratory equipment and trained personnel to achieve throughputs that allow whole communities to be tested on a regular basis. Here we present Cap-iLAMP (capture and improved loop-mediated isothermal amplification). This method combines a hybridization capture-based RNA extraction of non-invasive gargle lavage samples to concentrate samples and remove inhibitors with an improved colorimetric RT-LAMP assay and smartphone-based color scoring. Cap-iLAMP is compatible with point-of-care testing and enables the detection of SARS-CoV-2 positive samples in less than one hour. In contrast to direct addition of the sample to improved LAMP (iLAMP), Cap-iLAMP does not result in false positives and single infected samples can be detected in a pool among 25 uninfected samples, thus reducing the technical cost per test to ~1 Euro per individual.

    Prediction of Single Point Mutations in Ganglioside-Binding Domain of SARS-CoV-2 S and Their Effects on Binding of 9-O-Acetylated Sialic Acid and Hidroxychloroquine

    Authors: Petar M. Mitrasinovic

    doi:10.26434/chemrxiv.12765953.v1 Date: 2020-08-06 Source: ChemRxiv

    The infectious disease MESHD CoViD-19 is caused by a new severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), also referred to as hCoV-19. A possible infection MESHD mechanism includes dual host receptor recognitions by the SARS-CoV-2 transmembrane spike (S) glycoproteins. SARS-CoV-2 S contains two different domains, the receptor-binding domain (RBD) and the N-terminal domain (NTD), which interact with the angiotensin-converting enzyme 2 (ACE2) and the ganglioside-rich domain of the plasma SERO membrane at the surface of respiratory cell, respectively. The NTD amino acid residues (111-162) form a functional ganglioside-binding domain (GBD) that is conserved in all clinical isolates. Herein, the single point mutations (SPMs) of the GBD residues to which the virus is prone during genetic adaptation are predicted using an in silico protein engineering approach. Consequently, their effects on the attachment of SARS-CoV-2 S to the ganglioside-linked 9-O-acetylated sialic acid (9-O-Ac-Sia) are explored using molecular docking simulations. Val120Tyr and Asn122Trp are found to be the most likely SPMs in the GBD of SARS-CoV-2 S being involved in very specific recognition with 9-O-Ac-Sia through electrostatic interactions. Val120Tyr and Asn122Trp are also found to be the most likely SPMs in the GBD of SARS-CoV-2 S that is involved in conspicuously hydrophobic recognition with hidroxychloroquine (Hcq), thereby indicating the ability of Hcq to competitively inhibit GBD interactions with lipid rafts. However, the considerably non-specific binding of Hcq and the micromolar range of the dissociation constants of the SARS-CoV-2 S/Hcq complexes do not support the proposal of treating Hcq as a drug candidate. Maintaining a clear resemblance of the structure of a potential drug candidate to a natural substrate, accompanied by essential functional group modifications, may be a usable guideline for the structure-based design of anti-CoViD-19 drugs.

    Transient dynamics of SARS-CoV-2 as England exited national lockdown

    Authors: Steven Riley; Kylie E. C. Ainslie; Oliver Eales; Caroline E Walters; Haowei Wang; Christina J Atchison; Peter Diggle; Deborah Ashby; Christl A. Donnelly; Graham Cooke; Wendy Barclay; Helen Ward; Ara Darzi; Paul Elliott

    doi:10.1101/2020.08.05.20169078 Date: 2020-08-06 Source: medRxiv

    Control of the COVID-19 pandemic requires a detailed understanding of prevalence SERO of SARS-CoV-2 virus in the population. Case-based surveillance is necessarily biased towards symptomatic individuals and sensitive to varying patterns of reporting in space and time. The real-time assessment of community transmission TRANS antigen study (REACT-1) is designed to overcome these limitations by obtaining prevalence SERO data based on a nose and throat swab RT-PCR test among a representative community-based sample in England, including asymptomatic TRANS individuals. Here, we describe results comparing rounds 1 and 2 carried out during May and mid June / early July 2020 respectively across 315 lower tier local authority areas. In round 1 we found 159 positive samples from 120,620 tested swabs while round 2 there were 123 positive samples from 159,199 tested swabs, indicating a downwards trend in prevalence SERO from 0.13% (95% CI, 0.11%, 0.15%) to 0.077% (0.065%, 0.092%), a halving time of 38 (28, 58) days, and an R of 0.89 (0.86, 0.93). The proportion of swab-positive participants who were asymptomatic TRANS at the time of sampling increased from 69% (61%, 76%) in round 1 to 81% (73%, 87%) in round 2. Although health care and care home workers were infected far more frequently than other workers in round 1, the odds were markedly reduced in round 2. Age TRANS patterns of infection MESHD changed between rounds, with a reduction by a factor of five in prevalence SERO in 18 to 24 year olds. Our data were suggestive of increased risk of infection TRANS risk of infection TRANS infection MESHD in Black and Asian (mainly South Asian) ethnicities. Using regional and detailed case location data, we detected increased infection MESHD intensity in and near London. Under multiple sensitivity SERO analyses, our results were robust to the possibility of false positives. At the end of the initial lockdown in England, we found continued decline in prevalence SERO and a shift in the pattern of infection MESHD by age TRANS and occupation. Community-based sampling, including asymptomatic TRANS individuals, is necessary to fully understand the nature of ongoing transmission TRANS.

    COVID-19: Beliefs in misinformation in the Australian community

    Authors: Kristen Pickles; Erin Cvejic; Brooke Nickel; Tessa Copp; Carissa Bonner; Julie Leask; Julie Ayre; Carys Batcup; Samuel Cornell; Thomas Dakin; Rachael Dodd; Jennifer MJ Isautier; Kirsten J McCaffery

    doi:10.1101/2020.08.04.20168583 Date: 2020-08-06 Source: medRxiv

    Objectives: To investigate prevalence SERO of beliefs in COVID-19 misinformation and examine whether demographic, psychosocial and cognitive factors are associated with these beliefs, and how they change over time. Study design: Prospective national longitudinal community online survey. Setting: Australian general public. Participants: Adults TRANS aged TRANS over 18 years (n=4362 baseline/Wave 1; n=1882 Wave 2; n=1369 Wave 3). Main outcome measure: COVID-19 misinformation beliefs. Results: Stronger agreement with misinformation beliefs was significantly associated with younger age TRANS, male TRANS gender TRANS, lower education, and primarily speaking a language other than English at home (all p<0.01). After controlling for these variables, misinformation beliefs were significantly associated (p<0.001) with lower digital health literacy, lower perceived threat of COVID-19, lower confidence in government, and lower trust in scientific institutions. The belief that the threat of COVID-19 is greatly exaggerated increased between Wave 1-2 (p=0.002), while belief that herd immunity benefits were being covered up decreased (p<0.001). Greatest support from a list of Australian Government identified myths was for those regarding hot temperatures killing the virus (22%) and Ibuprofen exacerbates COVID-19 (13%). Lower institutional trust and greater rejection of official government accounts were associated with greater support for COVID-19 myths after controlling for sociodemographic variables. Conclusion: These findings highlight important gaps in communication effectiveness. Stronger endorsement of misinformation was associated with male TRANS gender TRANS, younger age TRANS, lower education and language other than English spoken at home. Misinformation can undermine public health efforts. Public health authorities must urgently target groups identified in this study when countering misinformation and seek ways to enhance public trust of experts, governments, and institutions.

    Paediatric Attendances and Acuity in the Emergency MESHD Department during the COVID-19 Pandemic

    Authors: Katy Rose; Kerry Van-Zyl; Rachel Cotton; Susan Wallace; Francesca Cleugh

    doi:10.1101/2020.08.05.20168666 Date: 2020-08-06 Source: medRxiv

    Aim: To investigate the difference in both numbers and acuity of presentations to the Paediatric Emergency MESHD Department (PED) during the peak time period of the current global SARS-CoV-2 pandemic. Design: This single centre retrospective observational study used routinely collected electronic health data to compare patient presentation characteristics between 21st March and 26th April 2020 compared to the equivalent time period in 2019. Results: There was a 90% decrease in attendances to PED, with a 10.23% reduction re-attendance rate. Children TRANS presenting were younger during the pandemic, with a median age TRANS difference of 2 years. They were more likely to present in an ambulance (9.63%), be admitted to hospital (5.75%) and be assigned the highest two Manchester triage categories (6.26%). There was a non-significant trend towards longer lengths of stay. The top 10 presenting complaints remained constant (although the order changed) between time periods. There was no difference in mortality or admission to PICU. Implications: Our data demonstrates that there has been a significant decrease in numbers of children TRANS seeking emergency MESHD department care. It suggests that presenting patients were proportionally sicker during the pandemic; however, we would argue that this is more in keeping with appropriate acuity for PED presentations, as there were no differences in PICU admission rate or mortality. We explore some of the possible reasons behind the decrease in presentations and the implications for service planning ahead of the winter months.

    Inflammasome activation in COVID-19 patients

    Authors: Tamara S Rodrigues; Keyla SG Sa; Adriene Y Ishimoto; Amanda Becerra; Samuel Oliveira; Leticia Almeida; Augusto V Goncalves; Debora B Perucello; Warrison A Andrade; Ricardo Castro; Flavio P Veras; Juliana E Toller-Kawahisa; Daniele C Nascimento; Mikhael HF de Lima; Camila MS Silva; Diego B Caetite; Ronaldo B Martins; Italo A Castro; Marjorie C Pontelli; Fabio C de Barros; Natalia B do Amaral; Marcela C Giannini; Leticia P Bonjorno; Maria Isabel F Lopes; Maira N Benatti; Rodrigo C Santana; Fernando C Vilar; Maria Auxiliadora-Martins; Rodrigo Luppino-Assad; Sergio CL de Almeida; Fabiola R de Oliveira; Sabrina S Batah; Li Siyuan; Maira N Benatti; Thiago M Cunha; Jose C Alves-Filho; Fernando Q Cunha; Larissa D Cunha; Fabiani G Frantz; Tiana Kohlsdorf; Alexandre T Fabro; Eurico Arruda; Rene DR de Oliveira; Paulo Louzada-Junior; Dario S Zamboni

    doi:10.1101/2020.08.05.20168872 Date: 2020-08-06 Source: medRxiv

    Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death MESHD. The NLRP3 inflammasome is a molecular platform that promotes inflammation MESHD via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1{beta} and IL-18. Although the participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease MESHD is unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection MESHD and it is active in COVID-19, influencing the clinical outcome of the disease MESHD. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of post-mortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease MESHD severity and poor clinical outcome. Our results suggest that the inflammasome is key in the pathophysiology of the disease MESHD, indicating this platform as a marker of disease MESHD severity and a potential therapeutic target for COVID-19.

    OpenStreetMap data use cases during the early months of the COVID-19 pandemic

    Authors: Peter Mooney; A. Yair Grinberger; Marco Minghini; Serena Coetzee; Levente Juhasz; Godwin Yeboah

    id:2008.02653v1 Date: 2020-08-06 Source: arXiv

    At the time of writing most governments around the whole world are prioritising the limiting of the spread of the Covid-19 epidemic through a series of lockdown measures affecting schools, sports, leisure, commercial and travel TRANS activities. The gradual reversal of these measures is being carried out individually by countries and regions based on the public health emergency MESHD advice and other epidemiological modelling outcomes. As is the case in any humanitarian crisis situation, there is a need for specific, accurate and up-to-date geospatial information to facilitate emergency MESHD response, management of the overall response and public information. OpenStreetMap (OSM) has played a pivotal and often leading role in national and international humanitarian and citizen-led responses to crises such as natural disasters over the last decade or so. OSM can take these leading roles for a number of potential reasons, including; geospatial data availability under an open access license, facilitating the development of open services such as mapping, routing, etc. This paper critically assesses and reflects upon this new context and challenge for OpenStreetMap and humanitarian mapping from a number of different positions which are outlined as follows: OpenStreetMap usage as a cartographic basemap in Covid-19 related applications; Applications or services using OpenStreetMap data; Initiatives or applications aimed at the collection of new OSM data immediately relevant to the Covid-19 pandemic response or management; Import of authoritative geospatial data into OpenStreetMap where there are gaps in the OpenStreetMap database for a particular country or region; and, Academic research about the role or usage of OpenStreetMap in the Covid-19 response.

    Genomic epidemiology reveals transmission TRANS patterns and dynamics of SARS-CoV-2 in Aotearoa New Zealand

    Authors: Jemma L Geoghegan; Xiaoyun Ren; Matthew Storey; James Hadfield; Lauren Jelley; Sarah Jefferies; Jill Sherwood; Shevaun Paine; Sue Huang; Jordan Douglas; Fabio K L Mendes; Andrew Sporle; Michael G Baker; David R Murdoch; Nigel French; Colin R Simpson; David Welch; Alexei J Drummond; Edward C Holmes; Sebastian Duchene; Joep de Ligt

    doi:10.1101/2020.08.05.20168930 Date: 2020-08-06 Source: medRxiv

    New Zealand, a geographically remote Pacific island with easily sealable borders, implemented a nation-wide lockdown of all non-essential services to curb the spread of COVID-19. New Zealand has now effectively eliminated the virus, with low numbers of new cases limited to new arrivals in managed quarantine facilities at the border. Here, we generated 649 SARS-CoV-2 genome sequences from infected patients in New Zealand with samples collected between 26 February and 22 May 2020, representing 56% of all confirmed cases TRANS in this time period. Despite its remoteness, the viruses imported into New Zealand represented nearly all of the genomic diversity sequenced from the global virus population. The proportion of D614G variants in the virus spike protein increased over time due to an increase in their importation frequency, rather than selection within New Zealand. These data also helped to quantify the effectiveness of public health interventions. For example, the effective reproductive number TRANS, Re, of New Zealand's largest cluster decreased from 7 to 0.2 within the first week of lockdown. Similarly, only 19% of virus introductions into New Zealand resulted in a transmission TRANS lineage of more than one additional case. Most of the cases that resulted in a transmission TRANS lineage originated from North America, rather than from Asia where the virus first emerged or from the nearest geographical neighbour, Australia. Genomic data also helped link more infections MESHD to a major transmission TRANS cluster than through epidemiological data alone, providing probable sources of infections MESHD for cases in which the source was unclear. Overall, these results demonstrate the utility of genomic pathogen surveillance to inform public health and disease MESHD mitigation.

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MeSH Disease
Human Phenotype

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