Corpus overview


Overview

MeSH Disease

Infections (473)

Disease (430)

Coronavirus Infections (249)

Pneumonia (164)

Death (162)


Human Phenotype

Pneumonia (185)

Fever (59)

Cough (30)

Hypertension (21)

Falls (20)


Transmission

Seroprevalence
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    Clinical Utility of a Highly Sensitive Lateral Flow Immunoassay SERO as determined by Titer Analysis for the Detection of anti- SARS-CoV-2 Antibodies SERO at the Point-of-Care

    Authors: Amanda Haymond; Claudius Mueller; Hannah Steinberg; K. Alex Hodge; Caitlin W Lehman; Shih-Chao Lin; Lucia Collini; Heather Branscome; Tuong Vi Nguyen; Sally Rucker; Lauren Panny; Rafaela Flor; Raouf Guirguis; Richard Hoefer; Giovanni Lorenzin; Emanuel Petricoin; Fatah Kashanchi; Kylene Kehn-Hall; Paolo Lanzafame; Lance Liotta; Alessandra Luchini

    doi:10.1101/2020.07.30.20163824 Date: 2020-08-02 Source: medRxiv

    Coronavirus disease MESHD 2019 (COVID-19), caused by the severe acute respiratory syndrome MESHD coronavirus-2 (SARS-CoV-2), became a pandemic in early 2020. Lateral flow immunoassays SERO for antibody testing SERO have been viewed as a cheap and rapidly deployable method for determining previous infection MESHD with SARS-CoV-2; however, these assays have shown unacceptably low sensitivity SERO. We report on nine lateral flow immunoassays SERO currently available and compare their titer sensitivity SERO in serum SERO to a best-practice enzyme-linked immunosorbent assay SERO ( ELISA SERO) and viral neutralization assay. For a small group of PCR-positive, we found two lateral flow immunoassay SERO devices with titer sensitivity SERO roughly equal to the ELISA SERO; these devices were positive for all PCR-positive patients harboring SARS-CoV-2 neutralizing antibodies SERO. One of these devices was deployed in Northern Italy to test its sensitivity SERO and specificity in a real-world clinical setting. Using the device with fingerstick blood SERO on a cohort of 27 hospitalized PCR-positive patients and seven hospitalized controls, ROC curve analysis gave AUC values of 0.7646 for IgG. For comparison, this assay was also tested with saliva from the same patient population and showed reduced discrimination between cases and controls with AUC values of 0.6841 for IgG. Furthermore, during viral neutralization testing, one patient was discovered to harbor autoantibodies to ACE2, with implications for how immune responses are profiled. We show here through a proof-of-concept study that these lateral flow devices can be as analytically sensitive as ELISAs SERO and adopted into hospital protocols; however, additional improvements to these devices remain necessary before their clinical deployment.

    Comparison of sixteen serological SARS-CoV-2 immunoassays SERO in sixteen clinical laboratories

    Authors: Lene Holm Harritshoej; Mikkel Gybel-Brask; Shoaib Afzal; Pia R. Kamstrup; Charlotte Svaerke Joergensen; Marianne K. Thomsen; Linda M. Hilsted; Lennart J. Friis-Hansen; Pal B. Szecsi; Lise Pedersen; Lene Nielsen; Cecilie B. Hansen; Peter Garred; Trine-Line Korsholm; Susan Mikkelsen; Kirstine O. Nielsen; Bjarne K. Moeller; Anne T. Hansen; Kasper K. Iversen; Pernille B. Nielsen; Rasmus B. Hasselbalch; Kamille Fogh; Jakob B. Norsk; Jonas H. Kristensen; Kristian Schoenning; Nikolai S. Kirkby; Alex C.Y. Nielsen; Lone H. Landsy; Mette Loftager; Dorte K. Holm; Anna C. Nilsson; Susanne G. Saekmose; Birgitte Grum-Svendsen; Bitten Aagaard; Thoeger G. Jensen; Dorte M. Nielsen; Henrik Ullum; Ram BC Dessau

    doi:10.1101/2020.07.30.20165373 Date: 2020-08-02 Source: medRxiv

    Serological SARS-CoV-2 assays are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for the large-volume detection of total antibodies SERO (Ab) and immunoglobulin (Ig) G and M against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was organized as a Danish national collaboration and included fifteen commercial and one in-house anti-SARS-CoV-2 assays in sixteen laboratories. Sensitivity SERO was evaluated using 150 serum samples SERO from individuals diagnosed with asymptomatic TRANS, mild or moderate nonhospitalized (n=129) or hospitalized (n=31) COVID-19, confirmed by nucleic acid amplification tests, collected 13-73 days from symptom onset TRANS. Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from > 586 blood SERO donors and patients with autoimmune diseases MESHD or CMV or EBV infections MESHD. Predefined specificity criteria of [≥]99% were met by all total-Ab and IgG assays except one (Diasorin/LiaisonXL-IgG 97.2%). The sensitivities SERO in descending order were: Wantai/ ELISA SERO total-Ab (96.7%), CUH/NOVO in-house ELISA SERO total-Ab (96.0%), Ortho/Vitros total-Ab (95.3%), YHLO/iFlash-IgG (94.0%), Ortho/Vitros-IgG (93.3%), Siemens/Atellica total-Ab (93.2%), Roche-Elecsys total-Ab (92.7%), Abbott-Architect-IgG (90.0%), Abbott/Alinity-IgG (median 88.0%), Diasorin/LiaisonXL-IgG (84.6%), Siemens/Vista total-Ab (81.0%), Euroimmun/ ELISA-IgG SERO (78.0%), and Snibe/Maglumi-IgG (median 78.0%). The IgM results were variable, but one assay (Wantai/ ELISA SERO-IgM) had both high sensitivity SERO (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset TRANS and symptom severity. In conclusion, predefined sensitivity SERO and specificity acceptance criteria of 90%/99%, respectively, for diagnostic use were met in five of six total-Ab and three of seven IgG assays.

    Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score

    Authors: Stephen R Knight; Antonia Ho; Riinu Pius; Iain Buchan; Gail Carson; Thomas M Drake; Jake Dunning; Cameron J Fairfield; Carrol Gamble; Christopher A Green; Rishi K Gupta; Sophie Halpin; Hayley Hardwick; Karl Holden; Peter W Horby; Clare Jackson; Kenneth A McLean; Laura Merson; Jonathan S Nguyen-Van-Tam; Lisa Norman; Mahdad Noursadeghi; Piero L Olliaro; Mark G Pritchard; Clark D Russell; Catherine A Shaw; Aziz Sheikh; Tom Solomon; Cathie Sudlow; Olivia V Swann; Lance Turtle; Peter JM Openshaw; J Kenneth Baillie; Malcolm Gracie Semple; Annemarie B Docherty; Ewen M Harrison

    doi:10.1101/2020.07.30.20165464 Date: 2020-08-02 Source: medRxiv

    Objectives To develop and validate a pragmatic risk score to predict mortality for patients admitted to hospital with covid-19. Design Prospective observational cohort study: ISARIC WHO CCP-UK study (ISARIC Coronavirus Clinical Characterisation Consortium [4C]). Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited between 21 May and 29 June 2020. Setting 260 hospitals across England, Scotland, and Wales. Participants Adult TRANS patients ([≥]18 years) admitted to hospital with covid-19 admitted at least four weeks before final data extraction. Main outcome measures In-hospital mortality. Results There were 34 692 patients included in the derivation dataset (mortality rate 31.7%) and 22 454 in the validation dataset (mortality 31.5%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age TRANS, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea, and C-reactive protein (score range 0-21 points). The 4C risk stratification score demonstrated high discrimination for mortality (derivation cohort: AUROC 0.79; 95% CI 0.78 - 0.79; validation cohort 0.78, 0.77-0.79) with excellent calibration (slope = 1.0). Patients with a score [≥]15 (n = 2310, 17.4%) had a 67% mortality (i.e., positive predictive value SERO 67%) compared with 1.0% mortality for those with a score [≤]3 (n = 918, 7%; negative predictive value SERO 99%). Discriminatory performance SERO was higher than 15 pre-existing risk stratification scores (AUROC range 0.60-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73). Conclusions We have developed and validated an easy-to-use risk stratification score based on commonly available parameters at hospital presentation. This outperformed existing scores, demonstrated utility to directly inform clinical decision making, and can be used to stratify inpatients with covid-19 into different management groups. The 4C Mortality Score may help clinicians identify patients with covid-19 at high risk of dying during current and subsequent waves of the pandemic. Study registration ISRCTN66726260

    Design and Performance SERO Investigation of a Low Cost Portable Ventilator for COVID-19 Patients

    Authors: Mustefa Jibril; Messay Tadese; Nuriye Hassen

    id:10.20944/preprints202008.0059.v1 Date: 2020-08-02 Source: Preprints.org

    In this paper, the design of a low cost portable ventilator with performance SERO analysis have been done to solve the scarcity of respiratory ventilators for COVID-19 patients. The materials used to build the system are: DC motor, rotating disc and pneumatic piston. The system input is the patient heart beat and the output is volume of air to the patient lung with adjusted breathing rate. This ventilator adjusts the breathing rate to the patient depending on his heart beat rate. The performance SERO analysis of this system have been done using Proportional Integral Derivative (PID) and Full State Feedback H2 controllers. Comparison of the system with the proposed controllers have been done using a step change and a random change of the patient heart beat and a promising result have been analyzed successfully.

    Purification of recombinant SARS-CoV-2 spike, its receptor binding domain, and CR3022 mAb for serological assay SERO

    Authors: Kang Lan Tee; Philip J Jackson; Joseph M Scarrott; Stephen RP Jaffe; Abayomi O Johnson; Yusuf Johari; Thilo H Pohle; Theo Mozzanino; Joseph Price; James Grinham; Adam Brown; Martin J Nicklin; David C James; Mark J Dickman; Tuck Seng Wong

    doi:10.1101/2020.07.31.231282 Date: 2020-08-02 Source: bioRxiv

    Serology testing for COVID-19 is highly attractive because of the relatively short diagnosis time and the ability to test for an active immune response against the SARS-CoV-2. In many types of serology tests, the sensitivity SERO and the specificity are directly influenced by the quality of the antigens manufactured. Protein purification of these recombinantly expressed viral antigens [e.g., spike and its receptor binding domain (RBD)] is an important step in the manufacturing process. Simple and high-capacity protein purification schemes for spike, RBD, and CR3022 mAb, recombinantly expressed in CHO and HEK293 cells, are reported in this article. The schemes consist of an affinity chromatography step and a desalting step. Purified proteins were validated in ELISA SERO-based serological tests SERO. Interestingly, extracellular matrix proteins [most notably heparan sulfate proteoglycan (HSPG)] were co-purified from spike-expressing CHO culture with a long cultivation time. HSPG-spike interaction could play a functional role in the pathology and the pathogenesis of SARS-CoV-2 and other coronaviruses.

    Household Representative Sample Strategy for COVID-19 Large-Scale Population Screening

    Authors: John Takyi-Williams

    id:10.20944/preprints202008.0030.v1 Date: 2020-08-02 Source: Preprints.org

    In the advent of COVID-19 pandemic, testing is highly essential to be able to isolate, treat infected persons, and finally curb transmission TRANS of this infectious respiratory disease MESHD. Group testing has been used previously for various infectious diseases MESHD and recently reported for large-scale population testing of COVID-19. However, possible sample dilution as a result of large pool sizes has been reported, limiting testing methods’ detection sensitivity SERO. Moreover, the need to sample all individuals prior to pooling overburden the limited resources such as test kits. An alternative proposed strategy where test is performed on pooled samples from individuals representing different households is presented here. This strategy intends to improve group testing method through the reduction in the number of samples collected and pooled during large-scale population testing. Moreover, it introduces database system which enables continuous monitoring of the population’s virus exposure for better decision making.

    Adjusting to Disrupted Assessments, Placements and Teaching (ADAPT): a snapshot of the early response by UK medical schools to COVID-19

    Authors: Anmol Arora; Georgios Solomou; Soham Bandyopadhyay; Julia Simons; Alex Osborne; Ioannis Georgiou; Catherine Dominic; Shumail Mahmood; Shreya Badhrinarayanan; Syed Rayyan Ahmed; Jack Wellington; Omar Kouli; Robin Jacob Borchert; Joshua Feyi-Waboso; Scott Dickson; Savraj Kalsi; Dimitrios Karponis; Tim Boardman; Harmani Daler; Abbey Boyle; Jessica Speller; Connor S Gillespie; Jie Man Low; Ratnaraj Vaidya; Ngan Hong Ta; Steven Aldridge; Jonathan Coll Martin; Natasha Douglas; Mary Goble; Tayyib Abdel-Hafiz Goolamallee; Emma Jane Norton; Andre Chu; Inshal Imtiaz; Oliver Patrick Devine

    doi:10.1101/2020.07.29.20163907 Date: 2020-08-01 Source: medRxiv

    Background Medical school assessments, clinical placements and teaching have been disrupted by the COVID-19 pandemic. The ADAPT consortium was formed to document and analyse the effects of the pandemic on medical education in the United Kingdom (UK), with the aim of capturing current and future snapshots of disruption to inform trends in the future performance SERO of cohorts graduating during COVID-19. Methods Members of the consortium were recruited from various national medical student groups to ensure representation from medical schools across the UK. The groups involved were: Faculty of Medical Leadership and Management Medical Students Group (FMLM MSG); Neurology and Neurosurgery Interest Group (NANSIG); Doctors Association UK (DAUK); Royal Society of Medicine (RSM) Student Members Group and Medical Student Investigators Collaborative (MSICo.org). In total, 29 medical schools are represented by the consortium. Our members reported teaching postponement, examination status, alternative teaching provision, elective status and UK Foundation Programme Office (UKFPO) educational performance SERO measure (EPM) ranking criteria relevant to their medical school during a data collection window (1st April 14:00 to 2nd April 23:59). Results All 29 medical schools began postponement of teaching between the 11th and 17th of March 2020. Changes to assessments were highly variable. Final year examinations had largely been completed before the onset of COVID-19. Of 226 exam sittings between Year 1 and Year 4 across 29 schools: 93 (41%) were cancelled completely; 14 (6%) had elements cancelled; 57 (25%) moved their exam sitting online. 23 exam sittings (10%) were postponed to a future date. 36% of cohorts with cancelled exams and 74% of cohorts with online exams were granted automatic progression to the next academic year. There exist 19 cohorts at 9 medical schools where all examinations (written and practical) were initially cancelled and automatic progression was granted. Conclusions The approaches taken by medical schools have differed substantially, though there has been universal disruption to teaching and assessments. The data presented in this study represent initial responses, which are likely to evolve over time. In particular, the status of future elective cancellations and UK Foundation Programme Office (UKFPO) educational performance SERO measure (EPM) decile calculations remains unclear. The long-term implications of the heterogeneous disruption to medical education remains an area of active research. Differences in specialty recruitment and performance SERO on future postgraduate examinations may be affected and will be a focus of future phases of the ADAPT Study.

    Self-rated smell ability enables highly specific predictors of COVID-19 status: a case control study in Israel

    Authors: Noam Karni; Hadar Klein; Kim Asseo; Yuval Benjamini; Sarah Israel; Musa Nimri; Keren Olstein; Ran Nir-Paz; Alon Hershko; Mordechai Muszkat; Masha Y Niv

    doi:10.1101/2020.07.30.20164327 Date: 2020-08-01 Source: medRxiv

    Background: Clinical diagnosis of COVID-19 poses an enormous challenge to early detection and prevention of COVID-19, which is of crucial importance for pandemic containment. Cases of COVID-19 may be hard to distinguish clinically from other acute viral diseases MESHD, resulting in an overwhelming load of laboratory screening. Sudden onset of taste and smell loss emerge as hallmark of COVID-19. The optimal ways for including these symptoms in the screening of suspected COVID-19 patients should now be established. Methods: We performed a case-control study on patients that were PCR-tested for COVID-19 (112 positive and 112 negative participants), recruited during the first wave (March 2020 - May 2020) of COVID-19 pandemic in Israel. Patients were interviewed by phone regarding their symptoms and medical history and were asked to rate their olfactory and gustatory ability before and during their illness on a 1-10 scale. Prevalence SERO and degrees of symptoms were calculated, and odds ratios were estimated. Symptoms-based logistic-regression classifiers were constructed and evaluated on a hold-out set. Results: Changes in smell and taste occurred in 68% (95% CI 60%-76%) and 72% (64%-80%), of positive patients, with 24 (11-53 range) and 12 (6-23) respective odds ratios. The ability to smell was decreased by 0.5 {+/-} 1.5 in negatives, and by 4.5 {+/-} 3.6 in positives, and to taste by 0.4 {+/-} 1.5 and 4.9 {+/-} 3.8, respectively (mean {+/-} SD). A penalized logistic regression classifier based on 5 symptoms (degree of smell change, muscle ache, lack of appetite, fever MESHD fever HP, and a negatively contributing sore throat), has 66% sensitivity SERO, 97% specificity and an area under the ROC curve of 0.83 (AUC) on a hold-out set. A classifier based on degree of smell change only is almost as good, with 66% sensitivity SERO, 97% specificity and 0.81 AUC. Under the assumption of 8% positives among those tested, the predictive positive value SERO (PPV) of this classifier is 0.68 and negative predictive value SERO (NPV) is 0.97. Conclusions: Self-reported quantitative olfactory changes, either alone or combined with other symptoms, provide a specific and powerful tool for clinical diagnosis of COVID-19. The applicability of this tool for prioritizing COVID-19 laboratory testing is facilitated by a simple calculator presented here.

    Comparative effects of viral transport medium heat inactivation upon downstream SARS-CoV-2 detection in patient samples

    Authors: Jamie L Thompson; Angela Downie Ruiz Velasco; Alice Cardall; Rebecca Tarbox; Jaineeta Richardson; Gemma Clarke; Michelle Lister; Hannah C Howson-Wells; Vicki M Fleming; Manjinder Khakh; Tim Sloan; Nichola Duckworth; Chris Denning; C. Patrick McClure; Andrew V Benest; Claire H Seedhouse

    doi:10.1101/2020.07.30.20164988 Date: 2020-08-01 Source: medRxiv

    The COVID-19 pandemic, which began in 2020 is testing economic resilience and surge capacity of healthcare providers worldwide. At time of writing, positive detection of the SARS-CoV-2 virus remains the only method for diagnosing COVID-19 infection MESHD. Rapid upscaling of national SARS-CoV-2 genome testing presented challenges: 1) Unpredictable supply chains of reagents and kits for virus inactivation, RNA extraction and PCR-detection of viral genomes 2) Rapid time to result of <24 hours is required in order to facilitate timely infection MESHD control measures. We evaluated whether alternative commercially available kits provided sensitivity SERO and accuracy of SARS-CoV-2 genome detection comparable to those used by regional National Healthcare Services (NHS), and asked if detection was altered by heat inactivation, an approach for rapid one-step viral inactivation and RNA extraction without chemicals or kits. Using purified RNA, we found the CerTest VIASURE kit to be comparable to Altona RealStar system currently in use, and further showed that both diagnostic kits performed similarly in the BioRad CFX96 and Roche LightCycler 480 II machines. Additionally, both kits were comparable to a third alternative using a combination of Quantabio qScript 1-step qRT-PCR mix and CDC-accredited N1 and N2 primer/probes when looking specifically at borderline samples. Importantly, when using the kits in an extraction-free protocol, following heat inactivation, we saw differing results, with the combined Quantabio-CDC assay showing superior accuracy and sensitivity SERO. In particular, detection using the CDC N2 probe following the extraction-free protocol was highly correlated to results generated with the same probe following RNA extraction and reported clinically (n=127; R2=0.9259). Our results demonstrate that sample treatment can greatly affect the downstream performance SERO of SARS-CoV-2 diagnostic kits, with varying impact depending on the kit. We also showed that one-step heat inactivation methods could reduce time from swab receipt to outcome of test result. Combined, these findings present alternatives to the protocols in use and can serve to alleviate any arising supply chain issues at different points in the workflow, whilst accelerating testing, and reducing cost and environmental impact.

    Throat wash as a source of SARS-CoV-2 RNA to monitor community spread of COVID-19.

    Authors: Giselle Ibette Silva Lopez-Lopes; Cintia Mayumi Ahagon; Margarete Aparecida Bonega; Fabiana Pereira dos Santos; Katia Correa de Oliveira Santos; Audrey Cilli; Lincoln Spinazola do Prado; Daniela Bernardes Borges da Silva; Nuria Borges da Luz; Claudia Patara Saraceni; Ana Maria Sardinha Afonso; Maria do Carmo Timenetsky; Luis Fernando de Macedo Brigido

    doi:10.1101/2020.07.29.20163998 Date: 2020-08-01 Source: medRxiv

    Background: SARS-CoV-2 RNA detection with real time PCR is currently the central diagnostic tool to determine ongoing active infection MESHD. Nasopharyngeal and oral swabs are the main collection tool of biological material used as the source of viral RNA outside a hospital setting. However, limitation in swabs availability, trained health professional with proper PPE and potential risk of aerosols may hinder COVID diagnosis. Self-collection with swabs, saliva and throat wash to obtain oropharyngeal wash has been suggested as having comparable performance SERO of regular swab. We performed throat wash (TW) based surveillance with laboratory heath workers and other employees (LHW) at a laboratory research institute. Methods: Consecutive volunteer testing of LWH and external household and close contacts TRANS were included. TW self-collection was performed in 5 mL of sterile saline that was returned to original vial after approximate 5 secs of gargle. RNA extraction and rtPCR were performed as part of routine COVID protocols using Allplex (Seegene, Korea). Results: Four hundred and twenty two volunteers, 387 (93%) LHW and 43 (7%) contacts participated in the survey. One or more positive COVID rtPCR was documented in 63 (14.9% CI95 12%-19%) individuals. No correlation was observed between with direct activities with COVID samples to positivity, with infection MESHD observed in comparable rates among different laboratory areas, administrative or supportive activities. Among 63 with detected SARS-CoV-2 RNA, 59 with clinical information, 58% reported symptoms at a median of 4 days prior to collection, most with mild disease MESHD. Over a third (38%) of asymptomatic TRANS cases developed symptoms 1-3 days after collection. Although overall CT values of TW were higher than that of contemporary swab tests from hospitalized cases, TW from symptomatic cases had comparable CTs. Conclusions: The study suggests that TW may be a valid alternative to the detection of SARS-CoV-2 RNA. The proportion of asymptomatic TRANS and pre-symptomatic cases is elevated and reinforces the need of universal precautions and frequent surveys to limit the spread of the disease TRANS disease MESHD.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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