Corpus overview


MeSH Disease

Human Phenotype


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    Classification of COVID-19 in CT Scans using Multi-Source Transfer Learning

    Authors: Alejandro R. Martinez

    id:2009.10474v1 Date: 2020-09-22 Source: arXiv

    Since December of 2019, novel coronavirus disease MESHD COVID-19 has spread around the world infecting millions of people and upending the global economy. One of the driving reasons behind its high rate of infection MESHD is due to the unreliability and lack of RT-PCR testing. At times the turnaround results span as long as a couple of days, only to yield a roughly 70% sensitivity SERO rate. As an alternative, recent research has investigated the use of Computer Vision with Convolutional Neural Networks (CNNs) for the classification of COVID-19 from CT scans. Due to an inherent lack of available COVID-19 CT data, these research efforts have been forced to leverage the use of Transfer Learning. This commonly employed Deep Learning technique has shown to improve model performance SERO on tasks with relatively small amounts of data, as long as the Source feature space somewhat resembles the Target feature space. Unfortunately, a lack of similarity is often encountered in the classification of medical images as publicly available Source datasets usually lack the visual features found in medical images. In this study, we propose the use of Multi-Source Transfer Learning (MSTL) to improve upon traditional Transfer Learning for the classification of COVID-19 from CT scans. With our multi-source fine-tuning approach, our models outperformed baseline models fine-tuned with ImageNet. We additionally, propose an unsupervised label creation process, which enhances the performance SERO of our Deep Residual Networks. Our best performing model was able to achieve an accuracy of 0.893 and a Recall SERO score of 0.897, outperforming its baseline Recall SERO score by 9.3%.

    Evaluating the effects of cardiometabolic exposures on circulating proteins which may contribute to SARS-CoV-2 severity

    Authors: Tom G Richardson; Si Fang; Ruth E Mitchell; Michael V Holmes; George Davey Smith; Dominik Schulz; Ulrich Mayr; Jochen Schneider; Christoph Spinner; Fabian Geisler; Roland M. Schmid; Tobias Lahmer; Wolfgang Huber; Xiushan Yin; Arsen Arakelyan; Denise Haslwanter; Rohit Jangra; Alev Celikgil; Duncan Kimmel; James H Lee; Margarette Mariano; Antonio Nakouzi; Jose Quiroz; Johanna Rivera; Wendy A Szymczak; Karen Tong; Jason Barnhill; Mattias NE Forsell; Clas Ahlm; Daniel T. Stein; Liise-anne Pirofski; Doctor Y Goldstein; Scott J. Garforth; Steven C. Almo; Johanna P. Daily; Michael B. Prystowsky; James D. Faix; Amy S. Fox; Louis M. Weiss; Jonathan R. Lai; Kartik Chandran

    doi:10.1101/2020.09.10.20191932 Date: 2020-09-11 Source: medRxiv

    Background: Developing insight into the pathogenesis of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is of critical importance to overcome the global pandemic caused by coronavirus disease MESHD 2019 (covid-19). In this study, we have applied Mendelian randomization (MR) to systematically evaluate the effect of 10 cardiometabolic risk factors and genetic liability to lifetime smoking on 97 circulating host proteins postulated to either interact or contribute to the maladaptive host response of SARS-CoV-2. Methods: We applied the inverse variance weighted (IVW) approach and several robust MR methods in a two-sample setting to systemically estimate the genetically predicted effect of each risk factor in turn on levels of each circulating protein. Multivariable MR was conducted to simultaneously evaluate the effects of multiple risk factors on the same protein. We also applied MR using cis-regulatory variants at the genomic location responsible for encoding these proteins to estimate whether their circulating levels may influence SARS-CoV-2 severity. Findings: In total, we identified evidence supporting 105 effects between risk factors and circulating proteins which were robust to multiple testing corrections and sensitivity SERO analyses. For example, body mass index provided evidence of an effect on 23 circulating proteins with a variety of functions, such as inflammatory markers c-reactive protein (IVW Beta=0.34 per standard deviation change, 95% CI=0.26 to 0.41, P=2.19x10-16) and interleukin-1 receptor antagonist (IVW Beta=0.23, 95% CI=0.17 to 0.30, P=9.04x10-12). Further analyses using multivariable MR provided evidence that the effect of BMI on lowering immunoglobulin G, an antibody SERO class involved in protecting the body from infection MESHD, is substantially mediated by raised triglycerides levels (IVW Beta=-0.18, 95% CI=-0.25 to -0.12, P=2.32x10-08, proportion mediated=44.1%). The strongest evidence that any of the circulating proteins highlighted by our initial analysis influence SARS-CoV-2 severity was identified for soluble glycoprotein 130 (odds ratio=1.81, 95% CI=1.25 to 2.62, P=0.002), a signal transductor for interleukin-6 type cytokines which are involved in the bodys inflammatory response. However, based on current case samples for severe SARS-CoV-2 we were unable to replicate findings in independent samples. Interpretation: Our findings highlight several key proteins which are influenced by established exposures for disease. Future research to determine whether these circulating proteins mediate environmental effects onto risk of SARS-CoV-2 are warranted to help elucidate therapeutic strategies for covid-19 disease severity.

    Development, clinical translation, and utility of a COVID-19 antibody test SERO with qualitative and quantitative readouts

    Authors: Robert H. Bortz III; Catalina Florez; Ethan Laudermilch; Ariel S Wirchnianski; Gorka Lasso; Ryan J Malonis; George I Georgiev; Olivia Vergnolle; Natalia G Herrera; Nicholas C Morano; Sean T Campbell; Erika P. Orner; Amanda Mengotto; M Eugenia Dieterle; Jens Maximilian Fels; Denise Haslwanter; Rohit Jangra; Alev Celikgil; Duncan Kimmel; James H Lee; Margarette Mariano; Antonio Nakouzi; Jose Quiroz; Johanna Rivera; Wendy A Szymczak; Karen Tong; Jason Barnhill; Mattias NE Forsell; Clas Ahlm; Daniel T. Stein; Liise-anne Pirofski; Doctor Y Goldstein; Scott J. Garforth; Steven C. Almo; Johanna P. Daily; Michael B. Prystowsky; James D. Faix; Amy S. Fox; Louis M. Weiss; Jonathan R. Lai; Kartik Chandran

    doi:10.1101/2020.09.10.20192187 Date: 2020-09-11 Source: medRxiv

    The COVID-19 global pandemic caused by severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) continues to place an immense burden on societies and healthcare systems. A key component of COVID-19 control efforts is serologic testing SERO to determine the community prevalence SERO of SARS-CoV-2 exposure and quantify individual immune responses to prior infection MESHD or vaccination. Here, we describe a laboratory-developed antibody test SERO that uses readily available research-grade reagents to detect SARS-CoV-2 exposure in patient blood SERO samples with high sensitivity SERO and specificity. We further show that this test affords the estimation of viral spike-specific IgG titers from a single sample measurement, thereby providing a simple and scalable method to measure the strength of an individual's immune response. The accuracy, adaptability, and cost-effectiveness of this test makes it an excellent option for clinical deployment in the ongoing COVID-19 pandemic.

    Antibody SERO Responses to SARS-CoV-2 in Coronavirus Diseases MESHD 2019 Patients with Different Severity

    Authors: Ekasit Kowitdamrong; Thanyawee Puthanakit; Watsamon Jantarabenjakul; Eakachai Prompetchara; Pintip Suchartlikitwong; Opass Putcharoen; Nattiya Hirankarn; Ke Lan; Yu Chen; Huabin Zhao

    doi:10.1101/2020.09.06.20189480 Date: 2020-09-08 Source: medRxiv

    Background: More understanding of antibody SERO responses in the SARS-CoV-2 infected MESHD population is useful for vaccine development. Aim: To investigate SARS-CoV-2 IgA MESHD and IgG among COVID-19 Thai patients with different severity. Methods: We used plasma SERO from 118 adult TRANS patients who have confirmed SARS-CoV-2 infection MESHD and 49 patients under investigation without infection MESHD, 20 patients with other respiratory infections MESHD, and 102 healthy controls. Anti-SARS-CoV-2 IgA and IgG were performed by enzyme-linked immunosorbent assay SERO from Euroimmun. The optical density ratio cut off for positive test was 1.1 for IgA and 0.8 for IgG. The association of antibody SERO response with the severity of diseases and the day of symptoms was performed. Results: From Mar 10 to May 31, 2020, 289 participants were enrolled, and 384 samples were analyzed. Patients were categorized by clinical manifestations to mild (n=59), moderate (n=27) and severe (n=32). The overall sensitivity SERO of IgA and IgG from samples collected after day 7 is 87.9% (95% CI 79.8-93.6) and 84.8% (95% CI 76.2-91.3), respectively. The severe group had a significantly higher level of specific IgA and IgG to S1 antigen compared to the mild group. All moderate to severe patients have specific IgG while 20% of the mild group did not have any IgG detected after two weeks. Interestingly, SARS-CoV-2 IgG level was significantly higher in males TRANS compared to females TRANS among the severe group (p=0.003). Conclusion: The serologic test SERO for SARS-CoV-2 has high sensitivity SERO after the second week after onset of illness. Serological response differs among patients with different severity and different sex.

    Utility of Olfactory test as screening tool for COVID-19: A pilot study

    Authors: Pragyanshu Khare; Atul Munish Chander; Kanhaiya Agrawal; Satyam Singh Jayant; Soham Mukherjee; Kamalendra Yadav; Rahul Gupta; Shakun Chaudhary; Sumit Srivastava; Sanuj Muralidharan; Rijin Mohan; Shikha Chaudhary; Rimesh Pal; Sandeep Bansal; Kanthi Kiran Kondepudi; Govardhan Dutt Puri; MAHENDRA BISHNOI; Sanjay Kumar Bhadada

    doi:10.1101/2020.09.03.20187294 Date: 2020-09-05 Source: medRxiv

    Loss of smell function ( Anosmia HP Anosmia MESHD) is reported to be associated with novel coronavirus disease MESHD 2019 (COVID-19) infection MESHD. The present study was designed to evaluate the effectiveness of an indigenously developed prototype smell test to identify/diagnose asymptomatic TRANS COVID-19 positive individuals. A panel of five different odorants belonging to Indian household with unique and mutually exclusive odor were used to develop prototype kit to test the hypothesis. The developed prototype kit was tested at 2 centers (N=49 and 34) with slight modifications. Simultaneously, the kit was also tested on 55 (N=35 and 20) healthy controls. Our results indicate that otherwise asymptomatic TRANS COVID-19 positive individuals were having quantifiable deficit in smell sensation. Interestingly, the variable sensitivity SERO of different odorants was observed in different patients. None of the healthy controls reported difficulty in sensing any of the odorant, whereas, some of healthy controls did misidentify the odorants. Overall, the present study provides a preliminary data that loss in smell sensation for various odorants can be exploited as a quick and affordable screening test to identify infected cases among at risk individuals.

    Seroprevalence SERO and immunity of SARS-CoV-2 infection MESHD in children TRANS and adolescents in schools in Switzerland: design for a longitudinal, school-based prospective cohort study

    Authors: Agne Ulyte; Thomas Radtke; Irene Abela; Sarah H Haile; Julia Braun; Ruedi Jung; Christoph Berger; Alexandra Trkola; Jan Fehr; Milo A Puhan; Susi Kriemler; Anel Nurtay; Lucie Abeler-Dörner; David G Bonsall; Michael V McConnell; Shawn O'Banion; Christophe Fraser; Scott Roberts; Jose A. Gonzalez; Marciano Sablad; Rodrigo Yelin; Wendy Taylor; Kiyoshi Tachikawa; Suezanne Parker; Priya Karmali; Jared Davis; Sean M Sullivan; Steve G. Hughes; Pad Chivukula; Eng Eong Ooi

    doi:10.1101/2020.08.30.20184671 Date: 2020-09-02 Source: medRxiv

    Introduction Seroprevalence SERO and transmission TRANS routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD in children TRANS and adolescents, especially in school setting, are not clear. Resulting uncertainty is reflected in very different decisions on school closures and reopenings across countries. The aim of this longitudinal cohort study is to assess the extent and patterns of seroprevalence SERO of SARS-CoV-2 antibodies SERO in school-attending children TRANS repeatedly. It will examine risk factors for infection MESHD, relationship between seropositivity and symptoms, and temporal persistence of antibodies SERO. Additionally, it will include testing of school personnel and parents TRANS. Methods and analysis The study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children TRANS aged TRANS 5 to 16 years, attending classes in primary and secondary schools are invited. Venous blood MESHD blood SERO and saliva samples are collected for SARS-CoV-2 serological testing SERO after the first wave of infections (June/July 2020), in fall HP (October/November 2020), and after winter (March/April 2021). Venous blood MESHD blood SERO is also collected for serological testing SERO of parents TRANS and school personnel. Bi-monthly questionnaires to children TRANS, parents TRANS and school personnel cover SARS-CoV-2 symptoms MESHD and tests, health, preventive behavior, lifestyle and quality of life information. Total seroprevalence SERO and cumulative incidence will be calculated. Hierarchical Bayesian logistic regression models will account for sensitivity SERO and specificity of the serological test SERO in the analyses and for the complex sampling structure, i.e., clustering within classes and schools. Ethics and dissemination The study was approved by the Ethics Committee of the Canton of Zurich, Switzerland (2020-01336). The results of this study will be published in peer-reviewed journals and will be made available to study participants and participating schools, the Federal Office of Public Health, and the Educational Department of the canton of Zurich. Trial registration number NCT04448717.

    Real-time Prediction of COVID-19 related Mortality using Electronic Health Records

    Authors: Patrick Schwab; Arash Mehrjou; Sonali Parbhoo; Leo Anthony Celi; Jürgen Hetzel; Markus Hofer; Bernhard Schölkopf; Stefan Bauer

    id:2008.13412v1 Date: 2020-08-31 Source: arXiv

    Coronavirus Disease MESHD 2019 (COVID-19) is an emerging respiratory disease MESHD caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) with rapid human-to-human transmission TRANS and a high case fatality rate particularly in older patients. Due to the exponential growth of infections, many healthcare systems across the world are under pressure to care for increasing amounts of at-risk patients. Given the high number of infected MESHD patients, identifying patients with the highest mortality risk early is critical to enable effective intervention and optimal prioritisation of care. Here, we present the COVID-19 Early Warning System (CovEWS), a clinical risk scoring system for assessing COVID-19 related mortality risk. CovEWS provides continuous real-time risk scores for individual patients with clinically meaningful predictive performance SERO up to 192 hours (8 days) in advance, and is automatically derived from patients' electronic health records (EHRs) using machine learning. We trained and evaluated CovEWS using de-identified data from a cohort of 66430 COVID-19 positive patients seen at over 69 healthcare institutions in the United States (US), Australia, Malaysia and India amounting to an aggregated total of over 2863 years of patient observation time. On an external test cohort of 5005 patients, CovEWS predicts COVID-19 related mortality from $78.8\%$ ($95\%$ confidence interval [CI]: $76.0$, $84.7\%$) to $69.4\%$ ($95\%$ CI: $57.6, 75.2\%$) specificity at a sensitivity SERO greater than $95\%$ between respectively 1 and 192 hours prior to observed mortality events - significantly outperforming existing generic and COVID-19 specific clinical risk scores. CovEWS could enable clinicians to intervene at an earlier stage, and may therefore help in preventing or mitigating COVID-19 related mortality.

    Parameter Estimation of COVID-19 Pandemic Model with Self Protection Behavior Changes

    Authors: Kassahun Getnet Mekonen; Tatek Getachew Habtemicheal; Shiferaw Feyissa Balcha; Binita Goswami; Naina Makwane; Vikas Manchanda; Bidhan Chandra Koner; Christopher T. Rentsch; Ian J Douglas; Rohini Mathur; Angel Wong; Jennifer K Quint; Nick Andrews; Jamie Lopez Bernal; J Anthony Scott; Mary Ramsay; Liam Smeeth; Helen I McDonald

    doi:10.1101/2020.08.24.20180695 Date: 2020-08-26 Source: medRxiv

    A mathematical model for the transmission TRANS dynamics of Coronavirus diseases MESHD (COVID-19) is proposed by incorporating self-protection behavior changes in the population. The disease-free equilibrium point is computed and its stability analysis is studied. The basic reproduction number TRANS(R 0 ) of the model is computed and the disease-free equilibrium point is locally and globally stable for R 0<1 and unstable for R 0 >1. Based on the available data the unknown model parameters are estimated using a combination of least square and Bayesian estimation methods for different countries. Using forward sensitivity SERO index the model parameters are carried out to determine and identify the key factors for the spread of disease TRANS dynamics. From country to country the sensitive parameters for the spread of the virus varies. It is found out that the reproduction number TRANS depends mostly on the infection rates, the threshold value of the force of infection MESHD for a population, the recovery rates, and the virus decay rate in the environment. It is also demonstrated that control of the effective transmission TRANS rate (recommended human behavioral change towards self-protective measures) is essential to stop the spreading of the virus. Numerical simulations also show that the virus transmission TRANS dynamics depend mostly on those sensitive parameters.

    Multi-species ELISA SERO for the detection of antibodies SERO against SARS-CoV-2 in animals

    Authors: Kerstin Wernike; Andrea Aebischer; Anna Michelitsch; Donata Hoffmann; Conrad Freuling; Anne Balkema-Buschmann; Annika Graaf; Thomas Mueller; Nikolaus Osterrieder; Melanie Rissmann; Dennis Rubbenstroth; Jacob Schoen; Claudia Schulz; Jakob Trimpert; Lorenz Ulrich; Asisa Volz; Thomas Mettenleiter; Martin Beer; Thamar Loser; Susanne Mangold; Christel Herzog; Dieter Schiegg; Christian Reichen; Filip Radom; Andreas Bosshart; Andreas Lehmann; Micha A. Haeuptle; Alexander Zuercher; Toni Vagt; Gabriel Sigrist; Marcel Straumann; Karl Proba; Niina Veitonmaki; Keith M. Dawson; Christof Zitt; Jennifer Mayor; Sarah Ryter; Heyrhyoung Lyoo; Chunyan Wang; Wentao Li; Ieva Drulyte; H. Kaspar Binz; Leon de Waal; Koert J. Stittelaar; Seth Lewis; Daniel Steiner; Frank J.M. van Kuppeveld; Olivier Engler; Berend-Jan Bosch; Michael T. Stumpp; Patrick Amstutz

    doi:10.1101/2020.08.26.266825 Date: 2020-08-26 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has caused a pandemic with millions of infected humans and hundreds of thousands of fatalities. As the novel disease - referred to as COVID-19 - unfolded, occasional anthropozoonotic infections of animals by owners or caretakers were reported in dogs, felid species and farmed mink. Further species were shown to be susceptible under experimental conditions. The extent of natural infections of animals, however, is still largely unknown. Serological methods will be useful tools for tracing TRANS SARS-CoV-2 infections MESHD in animals once test systems are validated for use in different species. Here, we developed an indirect multi-species ELISA SERO based on the receptor-binding domain (RBD) of SARS-CoV-2. The newly established ELISA SERO was validated using 59 sera of infected MESHD or vaccinated animals including ferrets, raccoon dogs, hamsters, rabbits, chickens, cattle and a cat, and a total of 220 antibody SERO-negative sera of the same animal species. Overall, a diagnostic specificity of 100.0% and sensitivity SERO of 98.31% was achieved, and the functionality with every species included in this study could be demonstrated. Hence, a versatile and reliable ELISA SERO protocol was established that enables high-throughput antibody SERO detection in a broad range of animal species, which may be used for outbreak investigations, to assess the seroprevalence SERO in susceptible species or to screen for reservoir or intermediate hosts.

    Testing for coronavirus (SARS-CoV-2) infection MESHD in populations with low infection MESHD prevalence SERO: the largely ignored problem of false positives and the value of repeat testing

    Authors: Cathie Sudlow; Peter Diggle; Oliver Warlow; David Seymour; Ben Gordon; Rhos Walker; Charles Warlow

    doi:10.1101/2020.08.19.20178137 Date: 2020-08-22 Source: medRxiv

    Background: Calls are increasing for widespread SARS-CoV-2 infection MESHD testing of people from populations with a very low prevalence SERO of infection MESHD. We quantified the impact of less than perfect diagnostic test accuracy on populations, and on individuals, in low prevalence SERO settings, focusing on false positives and the role of confirmatory testing. Methods: We developed a simple, interactive tool to assess the impact of different combinations of test sensitivity SERO, specificity and infection MESHD prevalence SERO in a notional population of 100,000. We derived numbers of true positives, true negatives, false positives and false negatives, positive predictive value SERO (PPV, the percentage of test positives that are true positives) and overall test accuracy for three testing strategies: (1) single test for all; (2) add repeat testing in test positives; (3) add further repeat testing in those with discrepant results. We also assessed the impact on test results for individuals having one, two or three tests under these three strategies. Results: With sensitivity SERO of 80%, infection prevalence SERO of 1 in 2,000, and specificity 99.9% on all tests, PPV in the tested population of 100,000 will be only 29% with one test, increasing to >99.5% (100% when rounded to the nearest %) with repeat testing in strategies 2 or 3. More realistically, if specificity is 95% for the first and 99.9% for subsequent tests, single test PPV will be only 1%, increasing to 86% with repeat testing in strategy 2, or 79% with strategy 3 (albeit with 6 fewer false negatives than strategy 2). In the whole population, or in particular individuals, PPV increases as infection MESHD becomes more common in the population but falls HP to unacceptably low levels with lower test specificity. Conclusion: To avoid multiple unnecessary restrictions on whole populations, and in particular individuals, from widespread population testing for SARS-CoV-2, the crucial roles of extremely high test specificity and of confirmatory testing must be fully appreciated and incorporated into policy decisions.

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MeSH Disease
Human Phenotype

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