Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 124
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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.

    Persistence of anti- SARS-CoV-2 antibodies SERO in non-hospitalized COVID-19 convalescent health care workers

    Authors: Margherita Bruni; Valentina Cecatiello; Angelica Diaz-Basabe; Georgia Lattanzi; Erika Mileti; Silvia Monzani; Laura Pirovano; Francesca Rizzelli; Clara Visintin; Giuseppina Bonizzi; Marco Giani; Marialuisa Lavitrano; Silvia Faravelli; Federico Forneris; Flavio Caprioli; Pier Giuseppe Pelicci; Gioacchino Natoli; Sebastiano Pasqualato; Marina Mapelli; Federica Facciotti

    doi:10.1101/2020.07.30.20164368 Date: 2020-08-01 Source: medRxiv

    Background. Coronavirus disease MESHD-19 (COVID-19) is a respiratory illness caused by the Severe Acute Respiratory Syndrome MESHD CoronaVirus 2 (SARS-CoV-2), a novel beta-coronavirus. Although antibody SERO response to SARS-CoV-2 can be detected early during the infection MESHD, several outstanding questions remain to be addressed regarding magnitude and persistence of antibody SERO titer against different viral proteins and their correlation with the strength of the immune response, as measured by serum SERO levels of pro-inflammatory mediators. Methods. An ELISA assay SERO has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length nucleocapsid protein (N protein). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies SERO as well as soluble pro-inflammatory mediators in the sera. Results. Specificity and sensitivity SERO of the ELISA assays SERO were high for anti-RBD IgG and IgA (92-97%) and slightly lower for IgM and the Spike and N proteins (70-85%). The ELISA SERO allowed quantification of IgM, IgG and IgA antibody SERO responses against all the viral antigens tested and showed a correlation between magnitude of the antibody SERO response and disease MESHD severity. Non-hospitalized subjects showed lower antibody SERO titers and blood SERO pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested SERO. Noteworthy, in non-severe COVID-19 infections MESHD, antibody SERO titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Conclusions. Rapid decline in antibody SERO titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection MESHD, suggesting that antibody SERO-mediated protection against re- infection MESHD with SARS-CoV-2 is of short duration. These results suggest caution in use serological testing SERO to estimate the prevalence SERO of SARS-CoV-2 infection MESHD in the general population.

    A Non-Adaptive Combinatorial Group Testing Strategy to Facilitate Healthcare Worker Screening During the Severe Acute Respiratory Syndrome MESHD Coronavirus-2 (SARS-CoV-2) Outbreak

    Authors: John Henry McDermott; Duncan Stoddard; Peter Woolf; Jamie M Ellingford; David Gokhale; Algy Taylor; Leigh AM Demain; William G Newman; Graeme Black

    doi:10.1101/2020.07.21.20157677 Date: 2020-07-30 Source: medRxiv

    Background: Regular SARS-CoV-2 testing of healthcare workers (HCWs) has been proposed to prevent healthcare facilities becoming persistent reservoirs of infectivity. Using monoplex testing, widespread screening would be prohibitively expensive, and throughput may not meet demand. We propose a non-adaptive combinatorial (NAC) group-testing strategy to increase throughput and facilitate rapid turnaround via a single round of testing. Methods: NAC matrices were constructed for sample sizes of 700, 350 and 250 with replicates of 2, 4 and 5, respectively. Matrix performance SERO was tested by simulation under different SARS-CoV-2 prevalence SERO scenarios of 0.1-10%, with each simulation ran for 10,000 iterations. Outcomes included the proportions of re-tests required and the proportion of true negatives identified. NAC matrices were compared to Dorfman Sequential (DS) approaches. A web application ( was designed to decode results. Findings: NAC matrices performed well at low prevalence SERO levels with an average number of 585 tests saved per assay in the n=700 matrix at a 1% prevalence SERO. As prevalence SERO increased, matrix performance SERO deteriorated with n=250 most tolerant. In simulations of low to medium (0.1%-3%) prevalence SERO levels all NAC matrices were superior, as measured by fewer repeated tests required, to the DS approaches. At very high prevalence SERO levels (10%) the DS matrix was marginally superior, however both group testing approaches performed poorly at high prevalence SERO levels. Interpretation: This testing strategy maximises the proportion of samples resolved after a single round of testing, allowing prompt return of results to staff members. Using the methodology described here, laboratories can adapt their testing scheme based on required throughput and the current population prevalence SERO, facilitating a data-driven testing strategy.

    A rapid and sensitive method to detect SARS-CoV-2 virus using targeted-mass spectrometry

    Authors: Praveen Singh; Rahul Chakraborty; Robin Marwal; Radhakrishan V S; Akash Kumar Bhaskar; Himanshu Vashisht; Mahesh S Dhar; Shalini Pradhan; Gyan Ranjan; Mohamed Imran; Anurag Raj; Uma Sharma; Priyanka Singh; Hemlata Lall; Meena Dutta; Parth Garg; Arjun Ray; Debasis Dash; Sridhar Sivasubbu; Hema Gogia; Preeti Madan; Sandhya Kabra; Sujeet K Singh; Anurag Agrawal; Partha Rakhit; Pramod Kumar; Shantanu Sengupta

    doi:10.1101/2020.07.27.20161836 Date: 2020-07-29 Source: medRxiv

    In the last few months, there has been a global catastrophic outbreak of severe acute respiratory syndrome MESHD disease MESHD caused by the novel corona virus SARS-CoV-2 affecting millions of people worldwide. Early diagnosis and isolation is key to contain the rapid spread of the virus. Towards this goal, we report a simple, sensitive and rapid method to detect the virus using a targeted mass spectrometric approach, which can directly detect the presence of virus from naso-oropharyngeal swabs. Using a multiple reaction monitoring we can detect the presence of two peptides specific to SARS-CoV-2 in a 2.3 minute gradient run with 100% specificity and 90.4 % sensitivity SERO when compared to RT-PCR. Importantly, we further show that these peptides could be detected even in the patients who have recovered from the symptoms and have tested negative for the virus by RT-PCR highlighting the sensitivity SERO of the technique. This method has the translational potential of in terms of the rapid diagnostics of symptomatic and asymptomatic TRANS COVID-19 and can augment current methods available for diagnosis of SARS-CoV-2.

    Changes in Cause-of- Death MESHD Attribution During the Covid-19 Pandemic: Association with Hospital Quality Metrics and Implications for Future Research

    Authors: Kathleen A. Fairman; Kellie J. Goodlet; James D. Rucker

    doi:10.1101/2020.07.25.20162198 Date: 2020-07-28 Source: medRxiv

    Background: Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) is often comorbid with conditions subject to quality metrics (QM) used for hospital performance SERO assessment and rate-setting. Although diagnostic coding change in response to financial incentives is well documented, no study has examined the association of QM with SARS-CoV-2 cause-of- death MESHD attribution (CODA). Calculations of excess all-cause deaths MESHD overlook the importance of accurate CODA and of distinguishing policy-related from virus-related mortality. Objective: Examine CODA, overall and for QM and non-QM diagnoses, in 3 pandemic periods: awareness (January 19-March 14), height (March 15-May 16), and late (May 17-June 20). Methods: Retrospective analysis of publicly available national weekly COD data, adjusted for population growth and reporting lags, October 2014-June 20, 2020. CODA in 5 pre-pandemic influenza seasons was compared with 2019-20. Suitability of the data to distinguish policy-related from virus-related effects was assessed. Results: Following federal guidance permitting SARS-CoV-2 CODA without laboratory testing, mortality from the QM diagnoses cancer and chronic lower respiratory disease MESHD declined steadily relative to prior-season means, reaching 4.4% less and 12.1% less, respectively, in late pandemic. Deaths MESHD for non-QM diagnoses increased, by 21.0% for Alzheimers disease MESHD Alzheimers disease HP and 29.0% for diabetes during pandemic height. Increases in competing CODs over historical experience, suggesting SARS-CoV-2 underreporting, more than offset declines during pandemic height. However, in the late-pandemic period, declines slightly numerically exceeded increases, suggesting SARS-CoV-2 overreporting. In pandemic-height and late-pandemic periods, respectively, only 83.5% and 69.7% of increases in all-cause deaths MESHD were explained by changes in the reported CODs, including SARS-CoV-2, preventing assessment of policy-related mortality or of factors contributing to increased all-cause deaths MESHD. Conclusions: Substitution of SARS-CoV-2 for competing CODs may have occurred, particularly for QM diagnoses and late in the pandemic. Continued monitoring of these trends, qualitative research on pandemic CODA, and the addition of place-of- death MESHD data and psychiatric CODs to the file would facilitate assessment of policy-related and virus-related effects on mortality.

    A High-throughput Anti-SARS-CoV-2 IgG Testing Platform for COVID-19

    Authors: Jinwei Du; Eric Chu; Dayu Zhang; Chuanyi M Lu; Aiguo Zhang; Michael Y. Sha

    doi:10.1101/2020.07.23.20160804 Date: 2020-07-27 Source: medRxiv

    Background: Serology tests for detecting the antibodies SERO to severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) can identify previous infection MESHD and help to confirm the presence of current infection MESHD. Objective: The aim of this study was to evaluate the performances SERO of a newly developed high throughput immunoassay SERO for anti-SARS-CoV-2 IgG antibody SERO detection. Results: Clinical agreement studies were performed in 77 COVID-19 patient serum samples SERO and 226 negative donor serum SERO/ plasma SERO samples. Positive percent agreement (PPA) was 42.86% (95% CI: 9.90% to 81.59%), 55.56% (95% CI: 21.20% to 86.30%), and 96.72% (95% CI: 88.65% to 99.60%) for samples collected on 0-7 days, 8-14 days, and [≥]15 days from symptom onset TRANS, respectively. Negative Percent Agreement (NPA) was 98.23% (95% CI: 95.53% to 99.52%). No cross-reactivity was observed to patient samples positive for IgG antibodies SERO against the following pathogens: HIV, HAV, HBV, RSV, CMV, EBV, Rubella MESHD, Influenza A, and Influenza B. Hemoglobin (200 mg/dL), bilirubin (2 mg/dL) and EDTA (10 mM) showed no significant interfering effect on this assay. Conclusion: An anti-SARS-CoV-2 IgG antibody SERO assay with high sensitivity SERO and specificity has been developed. With the high throughput, this assay will speed up the anti-SARS-CoV-2 IgG testing.

    Evaluating SARS-CoV-2 spike and nucleocapsid proteins as targets for IgG antibody SERO detection in severe and mild COVID-19 cases using a Luminex bead-based assay

    Authors: Joachim Marien; Johan Michiels; Leo Heyndrickx; Karen Kerkhof; Nikki Foque; Marc-Alain Widdowson; Isabelle Desombere; Hilde Jansens; Marjan Van Esbroeck; Kevin K. Arien

    doi:10.1101/2020.07.25.20161943 Date: 2020-07-27 Source: medRxiv

    Large-scale serosurveillance of severe acute respiratory syndrome MESHD coronavirus type 2 (SARS-CoV-2) will only be possible if serological tests SERO are sufficiently reliable, rapid and inexpensive. Current assays are either labour-intensive and require specialised facilities (e.g. virus neutralization assays), or expensive with suboptimal specificity (e.g. commercial ELISAs SERO). Bead-based assays offer a cost-effective alternative and allow for multiplexing to test for antibodies SERO of other pathogens. Here, we compare the performance SERO of four antigens for the detection of SARS-CoV-2 specific IgG antibodies SERO in a panel of sera that includes both severe (n=40) and mild (n=52) cases, using a neutralization and a Luminex bead-based assay. While we show that neutralising antibody SERO levels are significantly lower in mild than in severe cases, we demonstrate that a combination of recombinant nucleocapsid protein (NP), receptor-binding domain (RBD) and the whole spike protein (S1S2) results in a highly sensitive (96%) and specific (99%) bead-based assay that can detect IgG antibodies SERO in both groups. Although S1-specific IgG levels correlate most strongly with neutralizing antibody SERO levels, they fall HP below the detection threshold in 10% of the cases in our Luminex assay. In conclusion, our data supports the use of RBD, NP and S1S2 for the development of SARS-CoV-2 serological bead-based assays. Finally, we argue that low antibody SERO levels in mild/ asymptomatic TRANS cases might complicate the epidemiological assessment of large-scale surveillance studies.

    Clinical Characteristics and Outcomes for 7,995 Patients with SARS-CoV-2 Infection MESHD

    Authors: Jacob McPadden; Frederick Warner; H. Patrick Young; Nathan C. Hurley; Rebecca A. Pulk; Avinainder Singh; Thomas JS Durant; Guannan Gong; Nihar Desai; Adrian Haimovich; Richard Andrew Taylor; Murat Gunel; Charles S. Dela Cruz; Shelli F Farhadian; Jonathan Siner; Merceditas Villanueva; Keith Churchwell; Allen Hsiao; Charles J. Torre Jr.; Eric J. Velazquez; Roy S. Herbst; Akiko Iwasaki; Albert I. Ko; Bobak J. Mortazavi; Harlan M. Krumholz; Wade L. Schulz

    doi:10.1101/2020.07.19.20157305 Date: 2020-07-21 Source: medRxiv

    Objective: Severe acute respiratory syndrome MESHD virus (SARS-CoV-2) has infected millions of people worldwide. Our goal was to identify risk factors associated with admission and disease MESHD severity in patients with SARS-CoV-2. Design: This was an observational, retrospective study based on real-world data for 7,995 patients with SARS-CoV-2 from a clinical data repository. Setting: Yale New Haven Health (YNHH) is a five-hospital academic health system serving a diverse patient population with community and teaching facilities in both urban and suburban areas. Populations: The study included adult TRANS patients who had SARS-CoV-2 testing at YNHH between March 1 and April 30, 2020. Main outcome and performance SERO measures: Primary outcomes were admission and in-hospital mortality for patients with SARS-CoV-2 infection MESHD as determined by RT-PCR testing. We also assessed features associated with the need for respiratory support. Results: Of the 28605 patients tested for SARS-CoV-2, 7995 patients (27.9%) had an infection MESHD (median age TRANS 52.3 years) and 2154 (26.9%) of these had an associated admission (median age TRANS 66.2 years). Of admitted patients, 1633 (75.8%) had a discharge disposition at the end of the study period. Of these, 192 (11.8%) required invasive mechanical ventilation and 227 (13.5%) expired. Increased age TRANS and male TRANS sex were positively associated with admission and in-hospital mortality (median age TRANS 81.9 years), while comorbidities had a much weaker association with the risk of admission or mortality. Black race (OR 1.43, 95%CI 1.14-1.78) and Hispanic ethnicity (OR 1.81, 95%CI 1.50-2.18) were identified as risk factors for admission, but, among discharged patients, age TRANS-adjusted in-hospital mortality was not significantly different among racial and ethnic groups. Conclusions: This observational study identified, among people testing positive for SARS-CoV-2 infection MESHD, older age TRANS and male TRANS sex as the most strongly associated risks for admission and in-hospital mortality in patients with SARS-CoV-2 infection MESHD. While minority racial and ethnic groups had increased burden of disease MESHD and risk of admission, age TRANS-adjusted in-hospital mortality for discharged patients was not significantly different among racial and ethnic groups. Ongoing studies will be needed to continue to evaluate these risks, particularly in the setting of evolving treatment guidelines.

    Humoral Response Dynamics Following Infection MESHD with SARS-CoV-2

    Authors: Louis Grandjean; Anja Saso; Arturo Ortiz; Tanya Lam; James Hatcher; Rosie Thistlethwaite; Mark Harris; Timothy Best; Marina Johnson; Helen Wagstaffe; Elizabeth Ralph; Annabelle Mai; Caroline Colijn; Judith Breuer; Matthew Buckland; Kimberly Gilmour; David Goldblatt; - The Co-Stars Study Team

    doi:10.1101/2020.07.16.20155663 Date: 2020-07-21 Source: medRxiv

    Introduction: Severe Acute Respiratory Syndrome MESHD Coronavirus-2 ( SARS-CoV-2) specific antibodies SERO have been shown to neutralize the virus in-vitro. Understanding antibody SERO dynamics following SARS-CoV-2 infection MESHD is therefore crucial. Sensitive measurement of SARS-CoV-2 antibodies SERO is also vital for large seroprevalence SERO surveys which inform government policies and public health interventions. However, rapidly waning antibodies SERO following SARS-CoV-2 infection MESHD could jeopardize the sensitivity SERO of serological testing SERO on which these surveys depend. Methods: This prospective cohort study of SARS-CoV-2 humoral dynamics in a central London hospital analyzed 137 serial samples collected from 67 participants seropositive to SARS-CoV-2 by the Meso-Scale Discovery assay. Antibody SERO titers were quantified to the SARS-CoV-2 nucleoprotein (N), spike (S-)protein and the receptor-binding-domain (RBD) of the S-protein. Titers were log-transformed and a multivariate log-linear model with time-since- infection MESHD and clinical variables was fitted by Bayesian methods. Results: The mean estimated half-life of the N- antibody SERO was 52 days (95% CI 42-65). The S- and RBD- antibody SERO had significantly longer mean half-lives of 81 days (95% CI 61-111) and 83 days (95% CI 55-137) respectively. An ACE-2-receptor competition assay demonstrated significant correlation between the S and RBD- antibody SERO titers and ACE2-receptor blocking in-vitro. The time-to-a-negative N- antibody test SERO for 50% of the seropositive population was predicted to be 195 days (95% CI 163-236). Discussion: After SARS-CoV-2 infection MESHD, the predicted half-life of N- antibody SERO was 52 days with 50% of seropositive participants becoming seronegative to this antibody SERO at 195 days. Widely used serological tests SERO that depend on the N- antibody SERO will therefore significantly underestimate the prevalence SERO of infection MESHD following the majority of infections MESHD.

    Genetic inhibition of interleukin-6 receptor signaling and Covid-19

    Authors: Jonas Bovijn; Cecilia M. Lindgren; Michael V. Holmes

    doi:10.1101/2020.07.17.20155242 Date: 2020-07-19 Source: medRxiv

    There are few effective therapeutic options for the treatment of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD. Early evidence has suggested that IL-6R blockers may confer benefit, particularly in severe coronavirus disease MESHD 2019 (Covid-19). We leveraged large-scale human genetic data to investigate whether IL6-R blockade may confer therapeutic benefit in Covid-19. A genetic instrument consisting of seven genetic variants in or close to IL6R was recently shown to be linked to altered levels of c-reactive protein (CRP), fibrinogen, circulating IL-6 and soluble IL-6R, concordant to known effects of pharmacological IL-6R blockade. We investigated the effect of these IL6R variants on risk of hospitalization for Covid-19 and other SARS-CoV-2-related outcomes using data from The Covid-19 Host Genetics Initiative. The IL6R variants were strongly associated with serum SERO CRP levels in UK Biobank. Meta-analysis of scaled estimates revealed a lower risk of rheumatoid arthritis MESHD rheumatoid arthritis HP (OR 0.93 per 0.1 SD lower CRP, 95% CI, 0.90-0.96, P = 9.5 x 10-7), recapitulating this established indication for IL-6R blockers (e.g. tocilizumab and sarilumab). The IL-6R instrument was associated with lower risk of hospitalization for Covid-19 (OR 0.88 per 0.1 SD lower CRP, 95% CI, 0.78-0.99, P = 0.03). We found a consistent association when using a population-based control group (i.e. all non-cases; OR 0.91 per 0.1 SD lower CRP, 95% CI, 0.87-0.96, P = 4.9 x 10-4). Evaluation of further SARS-CoV-2-related outcomes suggested association with risk of SARS-CoV-2 infection MESHD, with no evidence of association with Covid-19 complicated by death MESHD or requiring respiratory support. We performed several sensitivity SERO analyses to evaluate the robustness of our findings. Our results serve as genetic evidence for the potential efficacy of IL-6R blockade in Covid-19. Ongoing large-scale RCTs of IL-6R blockers will be instrumental in identifying the settings, including stage of disease MESHD, in which these agents may be effective.

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MeSH Disease
Human Phenotype

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