Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Serology assessment of antibody SERO response to SARS-CoV-2 in patients with COVID-19 by rapid IgM/IgG antibody test SERO

    Authors: Yang De Marinis; Torgny Sunnerhagen; Pradeep Bompada; Anna Blackberg; Runtao Yang; Joel Svensson; Ola Ekstrom; Karl-Fredrik Eriksson; Ola Hansson; Leif Groop; Isabel Goncalves; Magnus Rasmussen

    doi:10.1101/2020.08.05.20168815 Date: 2020-08-06 Source: medRxiv

    The coronavirus disease MESHD 2019 (COVID-19) pandemic has created a global health- and economic crisis. Lifting confinement restriction and resuming to normality depends greatly on COVID-19 immunity screening. Detection of antibodies SERO to severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection MESHD. In this study, we applied a rapid COVID-19 IgM/IgG antibody test SERO and performed serology assessment of antibody SERO response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n=45), the total antibody SERO detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. We also studied antibody SERO response in relation to time after symptom onset TRANS and disease MESHD severity, and observed an increase in antibody SERO reactivity and distinct distribution patterns of IgM and IgG following disease progression MESHD. The total IgM and IgG detection is 63% in patients with < 2 weeks from disease MESHD onset; 85% in non-hospitalized patients with > 2 weeks disease MESHD duration; and 91% in hospitalized patients with > 2 weeks disease MESHD duration. We also compared different blood SERO sample types and suggest a potentially higher sensitivity SERO by serum SERO/ plasma SERO comparing with whole blood SERO measurement. To study the specificity of the test, we used 69 sera/ plasma SERO samples collected between 2016-2018 prior to the COVID-19 pandemic, and obtained a test specificity of 97%. In summary, our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody SERO detection patterns in association with disease MESHD progress and hospitalization. Our study supports that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level.

    Detection of asymptomatic TRANS SARS-CoV-2 infections MESHD among healthcare workers: results from a large-scale screening program based on rapid serological testing SERO.

    Authors: Francesca Maria Carozzi; Maria Grazia Cusi; Mauro Pistello; Luisa Galli; Alessandro Bartoloni; Gabriele Anichini; Chiara Azzari; Michele Emdin; Claudia Gandolfo; Fabrizio Maggi; Elisabetta Mantengoli; Maria Moriondo; Giovanna Moscato; Irene Paganini; Claudio Passino; Francesco Profili; Fabio Voller; Marco Zappa; Filippo Quattrone; Gian Maria Rossolini; Paolo Francesconi; - SARS-CoV-2 Serosurvey Tuscan Working Group

    doi:10.1101/2020.07.30.20149567 Date: 2020-08-04 Source: medRxiv

    Abstract Objective: To evaluate the performance SERO of two available rapid immunological tests for identification of severe acute respiratory syndrome MESHD Coronavirus 2 ( SARS-CoV-2) antibodies SERO and their subsequent application to a regional screening of health care workers (HCW) in Tuscany (Italy). Design: measures of accuracy and HCW serological surveillance Setting: 6 major health facilities in Tuscany, Italy. Participants: 17,098 HCW of the Tuscany Region. Measures of accuracy were estimated to assess sensitivity SERO in 176 hospitalized Covid-19 clinical subjects at least 14 days after a diagnostic PCR-positive assay result. Specificity was assessed in 295 sera biobanked in the pre-Covid-19 era in winter or summer 2013-14 Main outcome measures: Sensitivity SERO and specificity, and 95% confidence intervals, were measured using two serological tests SERO, named T-1 and T-2. Positive and Negative predictive values SERO were estimated at different levels of prevalence SERO. HCW of the health centers were tested using the serological SERO tests, with a follow- up nasopharyngeal PCR-test swab in positive tested cases. Results: Sensitivity SERO was estimated as 99% (95%CI: 95%-100%) and 97% (95% CI: 90%-100%), whereas specificity was the 95% and 92%, for Test T-1 and T-2 respectively. In the historical samples IgM cross-reactions were detected in sera collected during the winter period, probably linked to other human coronaviruses. Out of the 17,098 tested, 3.1% have shown the presence of SARS-CoV-2 IgG antibodies SERO, among them 6.8% were positive at PCR follow-up test on nasopharyngeal swabs. Conclusion Based on the low prevalence SERO estimate observed in this survey, the use of serological test SERO as a stand-alone test is not justified to assess the individual immunity status. Serological tests SERO showed good performance SERO and might be useful in an integrated surveillance, for identification of infected subjects and their contacts as required by the policy of contact tracing TRANS, with the aim to reduce the risk of dissemination, especially in health service facilities.

    Assessment of a Laboratory-Based SARS-CoV-2 Antibody SERO Test Among Hemodialysis Patients: A Quality Improvement Initiative

    Authors: Dena E Cohen; Gilbert Marlowe; Gabriel Contreras; Marie Ann Sosa; Jair Munoz Mendoza; Oliver Lenz; Zain Mithani; Pura Margarita Teixeiro; Nery Queija; Araceli Moneda; Jean S Jeanty; Katherine Swanzy; Misha Palecek; Mahesh Krishnan; Jeffery Giullian; Steven M Brunelli

    doi:10.1101/2020.08.03.20163642 Date: 2020-08-04 Source: medRxiv

    Abstract Introduction: The coronavirus disease MESHD 2019 (COVID -19) pandemic is caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS -CoV -2) infection MESHD. Although tests to detect anti - SARS -CoV-2 antibodies SERO have been developed, their sensitivity SERO and specificity in hemodialysis patients have not been previously assessed. Methods: As part of a quality improvement (QI) initiative, nasopharyngeal swabs and predialysis blood SERO samples were collected on the same day from adult TRANS patients receiving routine hemodialysis care at clinics managed by a large dialysis organization in the greater Miami, Florida region (23 - 30 Apr 2020). Polymerase chain reaction (PCR) tests for SARS -CoV -2 and chemiluminescence immunoassays SERO for anti -SARS -CoV2 antibodies SERO were performed according to manufacturer-specified protocols. Results: Of 715 participants in the QI initiative, 38 had symptomatology consistent with COVID -19 prior to or during the initiative. Among these, COVID -19 was PCR -confirmed in 14 and ruled out in 20, with the remaining 4 being inconclusive. Among the 34 patients with known COVID -19 status, the sensitivity SERO and specificity of the antibody test SERO were 57.1% and 85.0% when either antibody SERO was considered. The remaining 677 patients had no record of symptoms consistent with COVID -19, nor any known exposure. Of these, 38 patients (5.6%) tested positive for anti- SARS-CoV-2 antibodies SERO. Conclusions: The operational characteristics of the laboratory-based antibody test SERO make it sufficient to rule in, but not rule out, SARS -CoV -2 infection MESHD in the appropriate clinical circumstance. A substantial proportion of dialysis patients may have had asymptomatic TRANS SARS -CoV -2 infection MESHD.

    Discovery of Natural Phenol Catechin as a Multitargeted Agent Against SARS-CoV-2 For the Plausible Therapy of COVID-19

    Authors: Chandra Bhushan Mishra; Preeti Pandey; Ravi Datta Sharma; Raj Kumar Mongre; Andrew M Lynn; Rajendra Prasad; Raok Jeon; Amresh Prakash

    doi:10.26434/chemrxiv.12752402.v1 Date: 2020-08-04 Source: ChemRxiv

    The global pandemic crisis, COVID-19 caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 SERO drugs or vaccines, are not turned to be realistic in the timeframe needed to combat this pandemic. Thus, rigorous efforts are still ongoing for the drug repurposing as a clinical treatment strategy to control COVID-19. Here we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, which are crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression MESHD and transmission TRANS of coronavirus infection MESHD. Virtual screening of 72 FDA approved potential antiviral drugs against the target proteins: Spike (S) glycoprotein, human angiotensin-converting enzyme 2 (hACE2), 3-chymotrypsin-like cysteine protease (3CLpro), Cathepsin L, Nucleocapsid protein, RNA-dependent RNA polymerase (RdRp) and nonstructural protein 6 (NSP6) resulted in the selection of seven drugs which preferentially binds to the target proteins. Further, the molecular interactions determined by MD simulation, free energy landscape and the binding free energy estimation, using MM-PBSA revealed that among 72 drug molecules, catechin (flavan-3-ol) can effectively bind to 3CLpro, Cathepsin L, RBD of S protein, NSP-6, and Nucleocapsid protein. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol (Cathepsin L) to -26.09 kcal/mol (NSP6). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favourable molecular interaction of catechin towards multiple target proteins, signifies that catechin can be potentially explored as a multitargeted agent in the rational design of effective therapies against COVID-19.

    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.

    Kinetics of SARS-CoV-2 Antibody SERO Avidity Maturation and Association with Disease MESHD Severity

    Authors: Yiqi Ruben Luo; Indrani Chakraborty; Cassandra Yun; Alan H.B. Wu; Kara Lake Lynch

    doi:10.1101/2020.07.30.20165522 Date: 2020-08-02 Source: medRxiv

    The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD was studied. The IgG avidity assay used a novel label-free immunoassay SERO technology to test IgG against the virus spike protein receptor-binding domain (RBD). The technology, thin-film interferometry (TFI), is able to sense the formation of immune complex on a sensing probe without attaching a reporter (enzyme, fluorophore, etc.). It was found that there was a strong correlation between IgG antibody SERO avidity and days since symptom onset TRANS (p < 0.0001). In addition, peak readings were significantly higher for specimens from ICU than non-ICU patients for the first month after symptom onset TRANS (1-4 weeks) and thereafter (p<0.0001). The findings are consistent for what has been reported for SARS-CoV. Given that SARS-CoV-2 specific IgG avidity is strong in ICU patients after 1 month, this suggests that antibody SERO-mediated immune enhancement triggered by suboptimal antibodies SERO may not play a role in COVID-19 disease progression MESHD and severity.

    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.

    High SARS-CoV-2 seroprevalence SERO in Health Care Workers but relatively low numbers of deaths MESHD in urban Malawi

    Authors: Marah Grace Chibwana; Khuzwayo Chidiwa Jere; Jonathan Mandolo; Vincent Katunga-Phiri; Dumizulu Tembo; Ndaona Mitole; Samantha Musasa; Simon Sichone; Agness Lakudzala; Lusako Sibale; Prisca Matambo; Innocent Kadwala; Rachel Louise Byrne; Alice Mbewe; Marc Y.R. Henrion; Ben Morton; Chimota Phiri; Jane Mallewa; Henry C Mwandumba; Emily R Adams; Stephen B Gordon; Kondwani Charles Jambo

    doi:10.1101/2020.07.30.20164970 Date: 2020-08-01 Source: medRxiv

    Background In low-income countries, like Malawi, important public health measures including social distancing or a lockdown, have been challenging to implement owing to socioeconomic constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. However, due to limited capacity to test for severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD, there are no reliable estimates of the true burden of infection MESHD and death MESHD. We, therefore, conducted a SARS-CoV-2 serosurvey amongst health care workers (HCW) in Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection MESHD in urban Malawi. Methods Five hundred otherwise asymptomatic TRANS HCWs were recruited from Blantyre City (Malawi) from 22nd May 2020 to 19th June 2020 and serum samples SERO were collected all participants. A commercial ELISA SERO was used to measure SARS-CoV-2 IgG antibodies SERO in serum SERO. We run local negative samples (2018 - 2019) to verify the specificity of the assay. To estimate the seroprevalence SERO of SARS CoV-2 antibodies SERO, we adjusted the proportion of positive results based on local specificity of the assay. Results Eighty-four participants tested positive for SARS-CoV-2 antibodies SERO. The HCW with a positive SARS-CoV-2 antibody SERO result came from different parts of the city. The adjusted seroprevalence SERO of SARS-CoV-2 antibodies SERO was 12.3% [CI 9.0-15.7]. Using age TRANS-stratified infection MESHD fatality estimates reported from elsewhere, we found that at the observed adjusted seroprevalence SERO, the number of predicted deaths MESHD was 8 times the number of reported deaths MESHD. Conclusion The high seroprevalence SERO of SARS-CoV-2 antibodies SERO among HCW and the discrepancy in the predicted versus reported deaths MESHD, suggests that there was early exposure but slow progression of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of locally parameterised mathematical models to more accurately predict the trajectory of the epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health response planning.

    Longitudinal COVID-19 Surveillance and Characterization in the Workplace with Public Health and Diagnostic Endpoints

    Authors: Manjula Gunawardana; Jessica Breslin; John M Cortez; Sofia Rivera; Simon Webster; F Javier Ibarrondo; Otto O Yang; Richard B Pyles; Christina M Ramirez; Amy P Adler; Peter A Anton; Marc M Baum

    doi:10.1101/2020.07.25.20160812 Date: 2020-07-28 Source: medRxiv

    Background The rapid spread of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease MESHD 2019 (COVID-19) have precipitated a global pandemic heavily challenging our social behavior, economy, and healthcare infrastructure. Public health practices currently represent the primary interventions for managing the spread of the pandemic. We hypothesized that frequent, longitudinal workplace disease MESHD surveillance would represent an effective approach to controlling SARS-CoV-2 transmission TRANS among employees and their household members, reducing potential economic consequences and loss of productivity of standard isolation methods, while providing new insights into viral-host dynamics. Methodology and Findings On March 23, 2020 a clinical study (OCIS-05) was initiated at a small Southern California organization. Results from the first 3 months of the ongoing study are presented here. Study participants (27 employees and 27 household members) consented to provide frequent nasal or oral swab samples that were analyzed by RT-qPCR for SARS-CoV-2 RNA using CDC protocols. Only participants testing negative were allowed to enter the "safe zone" workplace facility. Optional blood SERO samples were collected at baseline and throughout the 3-month study. Serum SERO virus-specific antibody SERO concentrations (IgG, IgM, and IgA) were measured using a selective, sensitive, and quantitative ELISA assay SERO developed in house. A COVID-19 infection MESHD model, based on traditional SEIR compartmental models combined with Bayesian non-linear mixed models and modern machine learning, was used to predict the number of employees and household members who would have become infected in the absence of workplace surveillance. Two study participants were found to be infected by SARS-CoV-2 during the study. One subject, a household member, tested positive clinically by RT-qPCR prior to enrollment and experienced typical COVID-19 symptoms that did not require hospitalization. While on study, the participant was SARS-CoV-2 RNA positive for at least 71 days and had elevated virus-specific antibody SERO concentrations (medians: IgM, 9.83 ug mL-1; IgG, 11.5 ug mL-1; IgA, 1.29 ug mL-1) in serum samples SERO collected at three timepoints. A single, unrelated employee became positive for SARS-CoV-2 RNA over the course of the study, but remained asymptomatic TRANS with low associated viral RNA copy numbers. The participant did not have detectable serum SERO IgM and IgG concentrations, and IgA concentrations decayed rapidly (half-life: 1.3 d). The employee was not allowed entry to the safe zone workplace until testing negative three consecutive times over 7 d. No other employees or household members contracted COVID-19 over the course of the study. Our model predicted that under the current prevalence SERO in Los Angeles County without surveillance intervention, up to 7 employees (95% CI = 3-10) would have become infected with at most 1 of them requiring hospitalizations and 0 deaths MESHD. Conclusions Our clinical study met its primary objectives by using intense longitudinal testing to provide a safe work environment during the COVID-19 pandemic, and elucidating SARS-CoV-2 dynamics in recovering and asymptomatic TRANS participants. The surveillance plan outlined here is scalable and transferrable. The study represents a powerful example on how an innovative public health initiative can be dovetailed with scientific discovery.

    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.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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