Corpus overview


Overview

MeSH Disease

Human Phenotype

Pneumonia (465)

Fever (273)

Cough (217)

Hypertension (192)

Respiratory distress (119)


Transmission

Seroprevalence
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    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).

    Identifying SARS-CoV-2 entry inhibitors through drug repurposing screens of SARS- S and MERS-S pseudotyped particles

    Authors: Catherine Z. Chen; Miao Xu; Manisha Pradhan; Kirill Gorshkov; Jennifer Petersen; Marco R. Straus; Wei Zhu; Paul Shinn; Hui Guo; Min Shen; Carleen Klumpp-Thomas; Samuel G. Michael; Joshua Zimmerberg; Wei Zheng; Gary R Whittaker

    doi:10.1101/2020.07.10.197988 Date: 2020-07-11

    While vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection MESHD are urgently needed. Here inhibitors of two coronavirus spike proteins (S) were identified by screening a library of approved drugs with SARS-S and MERS-S pseudotyped particle entry assays. Using high-throughput screening technology, we discovered three compounds (cepharanthine, abemaciclib and trimipramine) to be broad spectrum inhibitors for spike-mediated entry. This work should contribute to the development of effective treatments against the initial stage of viral infection MESHD, thus reducing viral burden in COVID-19 patients.Competing Interest StatementThe authors have declared no competing interest.

    Neutralizing Antibody SERO Responses in COVID-19 Convalescent Sera

    Authors: William T Lee; Roxanne C Girardin; Alan P Dupuis II; Karen E Kulas; Anne F Payne; Susan J Wong; Suzanne Arinsburg; Freddy T Nguyen; Damodara Rao Mendu; Adolfo Firpo-Betancourt; Jeffrey Jhang; Ania Wajnberg; Florian Krammer; Carlos Cordon-Cardo; Sherlita Amler; Marisa A Montecalvo; Brad Hutton; Jill Taylor; Kathleen A McDonough

    doi:10.1101/2020.07.10.20150557 Date: 2020-07-11

    Passive transfer of antibodies SERO from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections MESHD. The United States Food and Drug Administration's (FDA) guidelines for convalescent plasma SERO recommends target antibody SERO titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies SERO in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at low (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity increased with time post symptom onset TRANS (PSO), reaching a peak at 31-35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was ~93% (PRNT50) and ~54% (PRNT90). Sera with high SARS-CoV-2 antibody SERO levels ([≥]960 ELISA SERO titers) showed maximal activity, but not all high titer sera contained neutralizing antibody SERO at FDA recommended levels, particularly at high stringency. These results underscore the value of serum SERO characterization for neutralization activity.

    COVID-19 causing HELLP-like syndrome MESHD in pregnancy and role of angiogenic factors for differential diagnosis

    Authors: Francesc Figueras; Elisa LLurba; Raigam Martinez-Portilla; Josefina Mora; Fatima Crispi; Eduard Gratacos

    doi:10.1101/2020.07.10.20133801 Date: 2020-07-11

    Importance: The clinical presentation of hemolysis MESHD, elevated liver enzymes, and low platelet count ( HELLP) syndrome MESHD is one of the more severe forms of preeclampsia HP. COVID-19 infection MESHD exhibits signs that are shared with preeclampsia HP and HELLP syndrome MESHD, which may lead to needless interventions and iatrogenic preterm delivery. Objective: We evaluated the prevalence SERO of HELLP-like signs in pregnant women admitted for COVID-19 and the value of angiogenic factors to rule out preeclampsia HP. Methods: a consecutive series of 27 pregnant women beyond 20 weeks of gestation, with symptomatic COVID-19. Clinical and analytical features were recorded and those cases with signs of HELLP syndrome MESHD were tested for sFlt-1/PlGF ratio. Results: Seven patients (25.9%) presented at least one sign of suspected HELLP syndrome MESHD, of which 2 (7.4%) were diagnosed clinically with PE because of hypertension MESHD hypertension HP and high transaminases and 5 (18.5%) had only elevated transaminases. sFlt-1/PlGF ratio was normal in 6 of 7. Conclusion: Symptomatic COVID-19 may simulate severe preeclampsia HP in pregnancy. Angiogenic factors may be essential to avoid false diagnosis and needless interventions. These data were presented in a Virtual Symposium on Covid-19 and Pregnancy on 17 April: 2020:(http://medicinafetalbarcelona.org/simposiocovid19/ [Spanish] and https://medicinafetalbarcelona.org/symposiumcovid19/ [English]

    The 4C Initiative (Clinical Care for Cardiovascular disease MESHD in the COVID-19 pandemic): monitoring the indirect impact of the coronavirus pandemic on services for cardiovascular diseases MESHD in the UK

    Authors: - TC CVD-COVID-UK Consortium; Simon Ball; Amitava Banerjee; Colin Berry; Jonathan Boyle; Benjamin Bray; William Bradlow; Afzal Chaudhry; Rikki Crawley; John Danesh; Alastair Denniston; Florian Falter; Jonine Figueroa; Christopher Hall; Harry Hemingway; Emily Jefferson; Tom Johnson; Graham King; Ken Lee; Paul McKean; Suzanne Mason; Nicholas Mills; Ewen Pearson; Munir Pirmohamed; Michael TC Poon; Rouven Priedon; Anoop Shah; Reecha Sofat; Jonathan Sterne; Fiona Strachan; Cathie LM Sudlow; Zsolt Szarka; William Whiteley; Mike Wyatt

    doi:10.1101/2020.07.10.20151118 Date: 2020-07-11

    Background: The coronavirus (COVID-19) pandemic affects cardiovascular diseases MESHD (CVDs) directly through infection MESHD and indirectly through health service reorganisation and public health policy. Real-time data are needed to quantify direct and indirect effects. We aimed to monitor hospital activity for presentation, diagnosis and treatment of CVDs during the pandemic to inform on indirect effects. Methods: We analysed aggregate data on presentations, diagnoses and treatments or procedures for selected CVDs ( acute coronary syndromes MESHD, heart failure MESHD, stroke MESHD stroke HP and transient ischaemic attack, venous thromboembolism MESHD thromboembolism HP, peripheral arterial disease MESHD and aortic aneurysm MESHD aortic aneurysm HP) in UK hospitals before and during the COVID-19 epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends. Findings: Nine hospitals across England and Scotland contributed hospital activity data from 28 Oct 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown), and for the same weeks during 2018-2019. Across all hospitals, total admissions and emergency MESHD department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1-58.6%) and 52.9% (52.2-53.5%) respectively compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown, and fell HP by 31-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm MESHD aortic aneurysm HP repair and peripheral arterial disease MESHD procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases MESHD and specialties between the first case and lockdown (total ED attendances RR 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020. Interpretation: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.

    The emergence of COVID-19 in Indonesia: analysis of predictors of infection MESHD and mortality using independent and clustered data approaches

    Authors: Erlina Burhan; Ari Fahrial Syam; Ahmad Jabir Rahyussalim; Prasenohadi Prasenohadi; Navy G Lolong Wulung; Agus Dwi Susanto; I Gede Ketut Sajinadiyasa; Dewi Puspitorini; Dewi Lestari; Indah Suci Widyahening; Vivi Setiawaty; Dwiana Ocviyanti; Kartika Qonita Putri; Aswin Guntara; Davrina Rianda; Anuraj H Shankar; Rina Agustina

    doi:10.1101/2020.07.10.20147942 Date: 2020-07-11

    Background: Analyses of correlates of SARS-CoV-2 infection MESHD or mortality have usually assessed individual predictors. This study aimed to determine if patterns of combined predictors may better identify risk of infection TRANS risk of infection TRANS infection MESHD and mortality. Methods: For the period of March 2nd to 10th 2020, the first 9 days of the COVID-19 pandemic in Indonesia, we selected all 18 confirmed cases TRANS, of which 6 died, and all 60 suspected cases, of which 1 died; and 28 putatively negative patients with pneumonia MESHD pneumonia HP and no travel TRANS history. We recorded data for travel TRANS, contact history, symptoms, haematology, comorbidities, and chest x-ray. Hierarchical cluster analyses (HCA) and principal component analyses (PCA) identified cluster and covariance patterns for symptoms or haematology which were analysed with other predictors of infection MESHD or mortality using logistic regression. Results: For univariate analyses, no significant association with infection MESHD was seen for fever MESHD fever HP, cough MESHD cough HP, dyspnoea, headache MESHD headache HP, runny nose, sore throat, gastrointestinal complaints (GIC), or haematology. A PCA symptom component for fever MESHD fever HP, cough MESHD cough HP, and GIC tended to increase risk of infection TRANS risk of infection TRANS infection MESHD (OR 3.41; 95% CI 1.06 - 14; p=0.06), and a haematology component with elevated monocytes decreased risk (OR 0.26; 0.07 - 0.79; 0.027). Multivariate analysis revealed that an HCA cluster of 3-5 symptoms, typically fever MESHD fever HP, cough MESHD cough HP, headache MESHD headache HP, runny nose, sore throat but little dyspnoea and no GIC tended to reduce risk (aOR 0.048; <0.001 - 0.52; 0.056). In univariate analyses for death MESHD, an HCA cluster of cough MESHD cough HP, fever MESHD fever HP and dyspnoea had increased risk (OR 5.75; 1.06 - 31.3, 0.043), but no other individual predictor, cluster or component was associated. Other significant predictors of infection MESHD were age TRANS >= 45, international travel TRANS, contact with COVID-19 patient, and pneumonia MESHD pneumonia HP. Diabetes and history of contact were associated with higher mortality. Conclusions: Cluster groups and co-variance patterns may be stronger correlates of SARS-CoV-2 infection MESHD than individual predictors. Comorbidities may warrant careful attention as would COVID-19 exposure levels.

    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.

    A flexible COVID-19 model to assess mitigation, reopening, virus mutation and other changes

    Authors: Sergio Bienstock

    doi:10.1101/2020.07.09.20150029 Date: 2020-07-11

    The COVID-19 epidemic which began in China last year has expanded worldwide. A flexible SEIRD epidemiological model with time-dependent parameters is applied to modeling the pandemic. The value of the effective reproduction ratio is varied to quantify the impact of quarantines and social distancing on the number of infections MESHD and deaths MESHD, on their daily changes. and on the maxima in these daily rates expected during the epidemic. The effect of changing Reff is substantial. It ought to inform policy decisions around resource allocation, mitigation strategies and their duration, and economic tradeoffs. The model can also calculate the impact of changes in infectiousness or morbidity as the virus mutates, or the expected effects of a new therapy or vaccine assumed to arrive at a future date. The paper concludes with a discussion of a potential endemic end of COVID-19, which might involve times of about 100 years.

    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.

    Eurofins Covid-19 Sentinel TM Wastewater Test Provide Early Warning of a potential COVID-19 outbreak

    Authors: Alissa Udi Jorgensen; Jesper Gamst; Line Visby Hansen; Ida Ingeborg Hogh Knudsen; SorenJensen Krohn Skovgaard Jensen

    doi:10.1101/2020.07.10.20150573 Date: 2020-07-11

    The Eurofins Covid-19 SentinelTM program was developed to monitor the evolution of the pandemic and for early detection of outbreaks. The study objective was to develop a wastewater testing method to analyze SARS-CoV-2 as an indicator of community infection MESHD rate resurgence of COVID-19 or in well-defined sites such as production facilities or nursing homes. Eurofins performed >700 tests on 78 unique samples from 18 sites in Denmark, France and Belgium. Ten variant test protocols were trialed. Protocol variations trialed included centrifugation, precipitation of the SARS-CoV-2 RNA, agitation HP prior to precipitation, cooling, and pasteurization of the samples. A method was succesfully developed and reliability was supported by stability, reproducibility, and dilution & linearity studies. Results obtained showed a direct link to number of RNA copies in the sample using a calibration curve with synthetic SARS-CoV-2. Analysis was performed on both the liquid phase and solid phase of wastewater samples, with virus RNA detected in both phases but more frequently in the liquid phase. The virus was present in a sample from a Danish community wastewater treatment plant collected on February 24, 3 days before the first COVID-19 case was officially reported in the country. The greatest concentration of virus detected corresponded to when the COVID-19 crisis was at its peak in Denmark. Based on studies carried out in a Danish hospital, the wastewater testing method is expected to be able to detect a community COVID-19 prevalence SERO rate as low as a 0,02%-0,1% (i.e. between 2 virus shedders per 10000 and 1 virus shedder per 1000). The wastewater testing method was used to monitor a Danish Community after a COVID-19 outbreak and it was shown that the method can be used as a semi-quantitative method to monitor the development of an outbreak.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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