Corpus overview


Overview

MeSH Disease

Human Phenotype

Pneumonia (78)

Fever (33)

Cough (15)

Hypertension (12)

Falls (10)


Transmission

Seroprevalence
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    The diagnostic accuracy of nucleic acid point-of-care tests for human coronavirus: A systematic review and meta-analysis

    Authors: Pakpoom Subsoontorn; Manupat Lohitnavy; Chuenjid Kongkaew

    doi:10.1101/2020.07.09.20150235 Date: 2020-07-11

    Many recent studies reported coronavirus point of care tests (POCTs) based on isothermal amplification. However, the performances SERO of these tests have not been systematically evaluated. We searched databases for studies that provide data to calculate sensitivity SERO, specificity and diagnostic odds ratio (DOR). We included 43 studies on 5204 specimens. Most studies had high risk of patient selection and index test bias but low risk in other domains. Most studies (n = 21) used reverse-transcribed loop-mediated isothermal amplification (RT-LAMP) to diagnose Coronavirus disease MESHD 2019 (COVID-19). Summary estimated ln(DOR) for RT-LAMP of RNA purified COVID-19 samples is 6.50 (95%CI 5.25-7.76), similar to the previously reported value for RT-LAMP of other RNA virus. RT-LAMP from crude samples has significantly lower ln(DOR) at 4.46 (95%CI 3.53-5.38). SAMBA-II has the highest ln(DOR) at 8.00 (95%CI 6.14-9.87). Abbott ID Now performance SERO is similar to RT-LAMP of crude sample. The performances SERO of CRISPR diagnosis and RT-LAMP are not significantly different. Types of coronaviruses and publication status have no significant effect on diagnosis performance SERO. Existing nucleic acid POCTs, particularly RT-LAMP, CRISPR diagnosis and SAMBA-II, have good diagnostic performance SERO. Future work should focus on improving a study design to minimize the risk of biases.

    Clinical utility of targeted SARS-CoV-2 serology testing to aid the diagnosis and management of suspected missed, late or post-COVID-19 infection MESHD syndromes MESHD: results from a pilot service

    Authors: Nicola Sweeney; Blair Merrick; Suzanne Pickering; Rui Pedro Galao; Alina Botgros; Harry D. Wilson; Adrian W. Signell; Gilberto Betancor; Mark Kia Ik Tan; John Ramble; Neophytos Kouphou; Sam Acors; Carl Graham; Jeffrey Seow; Eithne MacMahon; Stuart J. D. Neil; Michael H. Malim; Katie Doores; Sam Douthwaite; Rahul Batra; Gaia Nebbia; Jonathan D. Edgeworth

    doi:10.1101/2020.07.10.20150540 Date: 2020-07-11

    Objectives: Determine indications and clinical utility of SARS-CoV-2 serology testing in adults TRANS and children TRANS. Design: Prospective evaluation of initial three weeks of a daily Monday to Friday pilot SARS-CoV-2 serology service for patients. Setting: Early post 'first-wave' SARS-CoV-2 transmission TRANS period at single centre London teaching hospital that provides care to the local community, as well as regional and national referral pathways for specialist services. Participants: 110 (72 adults TRANS, 38 children TRANS, age TRANS range 0-83 years, 52.7% female TRANS (n=58)). Interventions: Patient serum SERO from vetted referrals tested on CE marked and internally validated lateral flow immunoassay SERO (LFIA) (SureScreen Diagnostics) detecting antibodies to SARS-CoV-2 SERO spike proteins, with result and clinical interpretation provided to the direct care team. Main outcome measures: Performance SERO characteristics, source and nature of referrals, feasibility and clinical utility of the service, particularly the benefit for clinical decision-making. Results: The LFIA was deemed suitable for clinical advice and decision making following evaluation with 310 serum samples SERO from SARS-CoV-2 PCR positive patients and 300 pre-pandemic samples, giving a sensitivity SERO and specificity of 96.1% and 99.3% respectively. For the pilot, 115 referrals were received leading to 113 tests performed on 108 participants (sample not available for two participants); paediatrics (n=35), medicine (n=69), surgery (n=2) and general practice (n=2). 43.4% participants (n=49) had detectable antibodies to SARS-CoV-2 SERO. There were three main indications for serology; new acute presentations potentially triggered by recent COVID-19 infection MESHD e.g. PIMS-TS (n=26) and pulmonary embolism MESHD pulmonary embolism HP (n=5), potential missed diagnoses in context of a recent compatible illness (n=40), and making infection MESHD control and immunosuppression treatment decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n=6). Conclusions: This study shows acceptable performance SERO characteristics, feasibility and clinical utility of a SARS-CoV-2 serology service using a rapid, inexpensive and portable assay for adults TRANS and children TRANS presenting with a range of clinical indications. Results correlated closely with a confirmatory in-house ELISA SERO. The study showed the benefit of introducing a serology service where there is a reasonable pre-test probability, and the result can be linked with clinical advice or intervention. Experience thus far is that the volume of requests from hospital referral routes are manageable within existing clinical and laboratory services; however, the demand from community referrals has not yet been assessed. Given recent evidence for a rapid decline in antibodies SERO, particularly following mild infection MESHD, there is likely a limited window of opportunity to realise the benefit of serology testing for individuals infected during the 'first-wave' before they potentially fall HP below a measurable threshold. Rapidly expanding availability of serology services for NHS patients will also help understand the long-term implications of serostatus and prior infection MESHD in different patient groups, particularly before emergence of any 'second-wave' outbreak or introduction of a vaccination programme.

    Poor correlation between antibody SERO titers and neutralizing activity in sera from SARS-CoV-2 infected subjects

    Authors: Elena Criscuolo; Roberta A Diotti; Marta Strollo; Serena Rolla; Alessandro Ambrosi; Massimo Locatelli; Roberto Burioni; Nicasio Mancini; Massimo Clementi; Nicola Clementi

    doi:10.1101/2020.07.10.20150375 Date: 2020-07-11

    Plenty of serologic tests SERO for SARS-CoV-2 have been developed so far, thus documenting the importance of evaluating the relevant features of the immune response to this viral agent. The performance SERO of these assays is currently under investigation. Amongst them, LIAISON SARS-CoV-2 S1/S2 IgG by DiaSorin and Elecsys Anti-SARS-CoV-2 cobas by Roche are currently used by laboratory medicine hospital departments in Italy and many other countries. In the present study, we have firstly compared two serologic tests SERO on serum samples SERO collected at two different time points from forty-six laboratory-confirmed COVID-19 subjects. Secondly, eighty-five negative serum samples SERO collected before the SARS-CoV-2 pandemic were analyzed. Thirdly, possible correlations between antibody SERO levels and the resulting neutralizing activity against a clinical isolate of SARS-CoV-2 were evaluated. Results revealed that both tests are endowed with low sensitivity SERO on the day of hospital admission, which increased to 97.8 and 100% for samples collected after 15 days for DiaSorin and Roche tests, respectively. The specificity of the two tests ranges from 96.5 to 100%, respectively. Importantly, a poor direct correlation between antibody SERO titers and neutralizing activity levels was evidenced in the present study.

    In-house modification and improvement of the CDC real-time PCR diagnostic assay for SARS-CoV-2 detection.

    Authors: Srirupa Das; Candice Dowell-Martino; Lisa Arrigo; Paul N. Fiedler; Sandra Lobo

    doi:10.1101/2020.07.10.20150771 Date: 2020-07-11

    The world is currently facing an unprecedented pandemic caused by the novel coronavirus SARS-CoV-2 (COVID-19) which was first reported in late 2019 by China to the World Health Organization (WHO). The containment strategy for COVID-19, which has non-specific flu-like symptoms and where upwards of 80% of the affected has either mild or no symptoms, is critically centered upon diagnostic testing, tracking and isolation. Thus, the development of specific and sensitive diagnostic tests for COVID-19 is key towards the first successful step of disease MESHD management. Public health organizations like the WHO and the US-based Centers for Disease MESHD Control and Prevention (CDC) have developed real-time PCR (RT-PCR) based diagnostic tests to aid in the detection of acute infection MESHD. In this study we sought to modify the CDC RT-PCR diagnostic assay protocol to increase its sensitivity SERO and to make the assay directly portable to health care providers in a community-based hospital setting. A number of modifications to the original protocol were tested. Increasing the RT-PCR annealing temperature by 7{degrees}C to 62{degrees}C was associated with the most significant improvement in sensitivity SERO, wherein the cycle-threshold (Ct) value for the N2 assay was reduced by ~3 units, in effect both reducing the overall number of inconclusive results and yielding N1/N2 assays to have similar Ct values. The limit of detection of the modified assay was also improved (0.86 RNA copies/l for both nCoV 2019_N1/N2 assays) compared to the CDC RT-PCR diagnostic assay (1 and 3.16 RNA copies/l for nCoV 2019_N1 and N2 assay, respectively). Using this modification, there was no significant effect on SARS-CoV-2 detection rate when viral RNA extraction was performed either manually or through an automated extraction method. We believe this modified protocol allows for more sensitive detection of the virus which in turn will be useful for pandemic management.

    Saliva offers a sensitive, specific and non-invasive alternative to upper respiratory swabs for SARS-CoV-2 diagnosis.

    Authors: Rachel Louise Byrne; Grant A Kay; Konstantina Kontogianni; Lottie Brown; Andrea M Collins; Luis E Cuevas; Daniela Ferreira; Alice J Fraser; Gala Garrod; Helen Hill; Stefanie Menzies; Elena Mitsi; Sophie I Owen; Christopher T Williams; Angela Hyder-Wright; Emily R Adams; Ana I Cubas-Atienzar

    doi:10.1101/2020.07.09.20149534 Date: 2020-07-11

    RT-qPCR utilising upper respiratory swabs are the diagnostic gold standard for SARS-CoV-2 despite reported low sensitivity SERO and limited scale up due to global shortages. Saliva is a non-invasive, equipment independent alternative to swabs. We collected 145 paired saliva and nasal/throat (NT) swabs at diagnosis (day 0) and repeated on day 2 and day 7 dependent on inpatient care and day 28 for study follow up. Laboratory cultured virus was used to determine the analytical sensitivity SERO of spiked saliva and swabs containing amies preservation media. Self-collected saliva samples were found to be consistent, and in some cases superior when compared to healthcare worker collected NT swabs from COVID-19 suspected participants. We report for the first time the analytical limit of detection of 10-2 and 100 pfu/ml for saliva and swabs respectively. Saliva is a easily self-collected, highly sensitive specimen for the detection of SARS-CoV-2.

    ReCoNet: Multi-level Preprocessing of Chest X-rays for COVID-19 Detection Using Convolutional Neural Networks

    Authors: Sabbir Ahmed; Moi Hoon Yap; Maxine Tan; Md. Kamrul Hasan

    doi:10.1101/2020.07.11.20149112 Date: 2020-07-11

    Life-threatening COVID-19 detection from radiomic features has become a dire need of the present time for infection MESHD control and socio-economic crisis management around the world. In this paper, a novel convolutional neural network (CNN) architecture, ReCoNet (residual image-based COVID-19 detection network), is proposed for COVID-19 detection. This is achieved from chest X-ray (CXR) images shedding light on the preprocessing task considered to be very useful for enhancing the COVID-19 fingerprints. The proposed modular architecture consists of a CNN-based multi-level preprocessing filter block in cascade with a multi-layer CNN-based feature extractor and a classification block. A multi-task learning loss function is adopted for optimization of the preprocessing block trained end-to-end with the rest of the proposed network. Additionally, a data augmentation technique is applied for boosting the network performance SERO. The whole network when pre-trained end-to-end on the CheXpert open source dataset, and trained and tested with the COVIDx dataset of 15,134 original CXR images yielded an overall benchmark accuracy, sensitivity SERO, and specificity of 97.48%, 96.39%, and 97.53%, respectively. The immense potential of ReCoNet may be exploited in clinics for rapid and safe detection of COVID-19 globally, in particular in the low and middle income countries where RT-PCR labs and/or kits are in a serious crisis.

    Commercial Serology Assays Predict Neutralization Activity Against SARS-CoV-2

    Authors: Raymond T Suhandynata; Melissa A Hoffman; Deli Huang; Jenny T Tran; Michael J Kelner; Sharon L Reed; Ronald W McLawhon; James E Voss; David Nemazee; Robert Fitzgerald

    doi:10.1101/2020.07.10.20150946 Date: 2020-07-11

    Background. Currently it is unknown whether a positive serology results correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value SERO of SARS-CoV-2 serology tests, especially when testing populations with low disease MESHD prevalence SERO. Methods. A neutralization assay was validated in a set of PCR confirmed positive specimens and in a negative cohort. 9,530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N=164) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and the levels of neutralizing antibodies SERO detected was correlated. Neutralizing antibody SERO titers (ID50) were also longitudinally monitored in SARS-CoV-2 PCR confirmed patients. Results. The SARS-CoV-2 neutralization assay had a PPA of 96.6% with a SARS-CoV-2 PCR test and a NPA of 98.0% across 100 negative controls. ID50 neutralization titers positively correlated with all three clinical serology platforms. Longitudinal monitoring of hospitalized PCR confirmed COVID-19 patients demonstrates they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2% and 78.4%, respectively. Conclusions. For the first time, we demonstrate that three widely available clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in COVID-19 patients. When a two-platform screen and confirm approach was used for SARS-CoV-2 serology, nearly 80% of two-platform positive specimens had neutralization titers (ID50 >50).

    SARS-CoV-2 RNA extraction using magnetic beads for rapid large-scale testing by RT-qPCR and RT-LAMP

    Authors: Steffen Klein; Thorsten G. Mueller; Dina Khalid; Vera Sonntag-Buck; Anke-Mareil Heuser; Baerbel Glass; Matthias Meurer; Ivonne Morales; Angelika Schillak; Andrew Freistaedter; Ina Ambiel; Sophie L. Winter; Liv Zimmermann; Tamara Naumoska; Felix Bubeck; Daniel Kirrmaier; Stephanie Ullrich; Isabel Barreto-Miranda; Simon Anders; Dirk Grimm; Paul Schnitzler; Michael Knop; Hans-Georg Kraeusslich; Viet Loan Dao Thi; Kathleen Boerner; Petr Chlanda

    doi:10.1101/2020.07.08.20147561 Date: 2020-07-11

    Rapid large-scale testing is essential for controlling the ongoing pandemic of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). The standard diagnostic pipeline for testing SARS-CoV-2 presence in patients with an ongoing infection MESHD is predominantly based on pharyngeal swabs, from which the viral RNA is extracted using commercial kits followed by reverse transcription and quantitative PCR detection. As a result of the large demand for testing, commercial RNA extraction kits may be limited and alternative, non-commercial protocols are needed. Here, we provide a magnetic bead RNA extraction protocol that is predominantly based on in-house made reagents and is performed in 96-well plates supporting large-scale testing. Magnetic bead RNA extraction was benchmarked against the commercial QIAcube extraction platform. Comparable viral RNA detection sensitivity SERO and specificity were obtained by fluorescent and colorimetric RT-LAMP using N primers, as well as RT-qPCR using E gene primers showing that the here presented RNA extraction protocol can be combined with a variety of detection methods at high throughput. Importantly, the presented diagnostic workflow can be quickly set up in a laboratory without access to an automated pipetting robot.

    Comparison of SARS-CoV-2 serological tests SERO with different antigen targets

    Authors: Alix T. Coste; Katia Jaton; Matthaios Papadimitriou-Olivgeris; Gilbert Greub; Antony Croxatto

    doi:10.1101/2020.07.09.20149864 Date: 2020-07-10

    Background These last months, dozens of SARS-CoV-2 serological tests SERO have become available with varying performances SERO. A major effort was completed to compare 17 serological tests SERO. Methods In a preliminary phase, we compared 17 IgG, IgM, IgA and pan Ig serological tests SERO including ELISA SERO, LFA, CLIA and ECLIA on a panel of 182 sera, comprising 113 sera from hospitalized patients with a positive RT-PCR, and 69 sampled before 1st November 2019, expected to give a positive and negative results, respectively. In a second phase, the five best performing and most available tests were further evaluated on a total of 582 sera (178 and 404 expected positive and negative, respectively), allowing the assessment of 20 possible cross-reactions with other virus. Results In the preliminary phase, among eight IgG/pan-Ig ELISA SERO or CLIA/ECLIA tests, four had a sensitivity SERO and specificity above 90% and 98% respectively, and on six IgM/IgA tests, only one was acceptable. Only one LFA test on three showed good performances SERO for both IgG and IgM. For all the tests IgM and IgG aroused concomitantly. In the second phase, no tests showed particular cross-reaction. We observed an important heterogeneity in the development of the antibody SERO response, and that anti-nucleocapside (anti-N) antibodies SERO appeared earlier than the anti-spike (anti-S) proteins. Conclusions The identified SARS-CoV-2 serology tests may be used for the diagnostic of CoviD-19 for negative RT-PCR patients presenting severe to mild suggestive symptoms or particular clinical presentation. Detection of both anti-N and anti-S could be complementary to increase the sensitivity SERO of the analysis.

    Performance SERO characteristics of a high throughput automated transcription mediated amplification test for SARS-CoV-2 detection

    Authors: Jimmykim Pham; Sarah Meyer; Catherine Nguyen; Analee Williams; Melissa Hunsicker; Ian McHardy; Inessa Gendlina; D. Yitzchak Goldstein; Amy S. Fox; Angela Hudson; Paul Darby; Paul Hovey; Jose Morales; James Mitchell; Karen Harrington; Mehrdad Majlessi; Joshua Moberly; Ankur Shah; Andrew Worlock; Marion Walcher; Barbara Eaton; Damon Getman; Craig Clark

    doi:10.1101/2020.07.06.20143719 Date: 2020-07-10

    The COVID19 pandemic caused by the new SARSCoV2 coronavirus has imposed severe challenges on laboratories in their effort to achieve sufficient diagnostic testing capability for identifying infected individuals. In this study we report the analytical and clinical performance SERO characteristics of a new, high throughput, fully automated nucleic acid amplification test system for the detection of SARSCoV2. The assay utilizes target capture, transcription mediated amplification, and acridinium ester labeled probe chemistry on the automated Panther System to directly amplify and detect two separate target sequences in the ORF1ab region of the SARSCoV2 RNA genome. The probit 95% limit of detection of the assay was determined to be 0.004 TCID50/ml using inactivated virus, and 25 c/ml using synthetic in vitro transcript RNA targets. Analytical sensitivity SERO (100% detection) was confirmed to be 83 to 194 c/ml using three commercially available SARSCoV2 nucleic acid controls. No cross reactivity or interference was observed with testing six related human coronaviruses, as well as 24 other viral, fungal, and bacterial pathogens, at high titer. Clinical nasopharyngeal swab specimen testing (N=140) showed 100%, 98.7%, and 99.3% positive, negative, and overall agreement, respectively, with a validated reverse transcription PCR NAAT for SARSCoV2 RNA. These results provide validation evidence for a sensitive and specific method for pandemic-scale automated molecular diagnostic testing for SARSCoV2.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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