scholarly journals A Novel Diagnostic Test to Screen SARS-CoV-2 Variants Containing E484K and N501Y Mutations

2021 ◽  
Author(s):  
Yanan Zhao ◽  
Annie Lee ◽  
Kaelea Composto ◽  
Marcus H. Cunningham ◽  
Jose R. Mediavilla ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Screening Tool ◽  
Unmet Need ◽  
Nasopharyngeal Swab ◽  
Slow Speed ◽  
Epidemiological Monitoring ◽  
Fast Spreading ◽  
Viral Sequencing ◽  
Simultaneous Identification ◽  
Efficient Screening

ABSTRACTSpike protein mutations E484K and N501Y carried by SARS-CoV-2 variants have been associated with concerning changes of the virus, including resistance to neutralizing antibodies and increased transmissibility. While the concerning variants are fast spreading in various geographical areas, identification and monitoring of these variants is lagging far behind, due in large part to the slow speed and insufficient capacity of viral sequencing. In response to the unmet need for a fast and efficient screening tool, we developed a single-tube duplex molecular assay for rapid and simultaneous identification of E484K and N501Y mutations from nasopharyngeal swab (NS) samples within 2.5 h from sample preparation to report. Using this tool, we screened a total of 435 clinical NS samples collected from COVID patients at 8 hospitals within the Hackensack Meridian Health network in New Jersey. While B.1.351 and P.1 variants were absent from the current study, our data revealed a dramatic increase in the frequency of E484K over time, underscoring the need for continuous epidemiological monitoring.

INNV-35. A MULTI-DISCIPLINARY REVIEW OF NEWLY DIAGNOSED HIGH GRADE GLIOMA REFERRALS TO THERAPIES, AND IMPLEMENTATION OF A SCREENING TOOL TO IMPROVE ACCESS TO THERAPIES AT THE ROYAL MARSDEN HOSPITAL (RMH)

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi113-vi113
Author(s):  
Joanne Jethwa ◽  
Charmaine Jagger ◽  
Leanne Williams ◽  
Lizzy Jenkins ◽  
Kate Ashforth
Keyword(s):  
Screening Tool ◽  
Unmet Need ◽  
Clinical Excellence ◽  
High Grade Glioma ◽  
Outpatient Rehabilitation ◽  
Language Therapy ◽  
Oncological Treatment ◽  
Patient Tolerance ◽  
Royal Marsden Hospital ◽  
Therapy Intervention

Abstract Brain tumours make up 3% of all cancers. The disease and treatment have significant impact on function and quality of life (QoL). Early outpatient rehabilitation can improve function. National Institute of Clinical Excellence recommends patients have access to rehabilitation across the pathway, but unmet need is prevalent in this population. We recognised late referrals in our Trust and poor patient awareness of Therapies, resulting in reduced access to rehabilitation. METHOD: A retrospective notes review of new neuro-oncology patients (n=56) referred to RMH from July - December 2018 was undertaken to identify therapy needs and timeliness of referrals. A therapy screening tool was devised and piloted from July – December 2019. Additionally, an MDT questionnaire was circulated to gain feedback regarding this service. RESULTS: Retrospective review revealed that of those patients with identified therapy needs, 16% of physiotherapy (PT), 10% of Occupational Therapy (OT) and 9% of Speech and Language Therapy (SLT) were referred late. Additionally, referrals were not received for 40% of patients with OT needs, 32% for PT and 30% for SLT. Following implementation of the screening tool, referrals occurred earlier in the pathway, and rates increased by 60% in SLT, 59% in PT, and 25% in OT. An MDT questionnaire revealed 100% consensus that screening was beneficial to patients and the MDT with improved access to therapies. CONCLUSION: Brain tumour patients require prompt therapy intervention to improve and maintain function and QoL. We identified high levels of unmet need which was eliminated by a screening tool and subsequently increased referral rates. Patients and the MDT had improved awareness of the role of Therapies, as well as earlier access. The neuro-oncology MDT benefitted from the effects of therapy intervention improving patient tolerance to oncological treatment. Therapists were able to identify and manage impairments earlier, improving QoL.

scholarly journals Determination of Morphine in Human Urine by the Novel Competitive Fluorescence Immunoassay

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Cao ◽  
Xiao-Ying Chen ◽  
Wu-Rong Zhao
Keyword(s):  
Monoclonal Antibodies ◽  
Human Urine ◽  
Screening Tool ◽  
Fluorescein Isothiocyanate ◽  
Cross Reactivity ◽  
The Novel ◽  
Fluorescence Immunoassay ◽  
Coated Plate ◽  
Efficient Screening

A competitive fluorescence immunoassay for the identification and quantification of morphine has been developed on the basis of hapten-coated plate format. Hapten was prepared through covalent conjugating a morphine derivative with albumin bovine. In the immunoassay, the hapten was inoculated on a 96-well plate and then bound with monoclonal antibodies labeled with a signal indicating dye, fluorescein isothiocyanate (FITC). Unbound FITC-antibodies were rinsed off from the plate. The fluorescein intensity decreases in the presence of morphine molecules due to the competitively binding to antibodies against hapten. The intensity is inversely correlated with the concentration of morphine. In quantitative analysis for urine samples, we obtained a linearity range of 0.2 μg/mL∼2.5 μg/mL, along with a detection limit of c.a. 1 ng/mL. The fluorescence immunoassay shows low cross-reactivity (below 10%) to 6-acetylmorphine, 3-acetylmorphine, and heroine. The developed method produced comparable results to the standard GC-MS/MS method. In conclusion, a rapid and efficient screening tool for morphine in clinical human urine has been established.

scholarly journals A Human TREK-1/HEK Cell Line: A Highly Efficient Screening Tool for Drug Development in Neurological Diseases

PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e25602 ◽  
Author(s):  
Hamid Moha ou Maati ◽  
Rémi Peyronnet ◽  
Christelle Devader ◽  
Julie Veyssiere ◽  
Fabien Labbal ◽  
...  
Keyword(s):  
Drug Development ◽  
Cell Line ◽  
Screening Tool ◽  
Neurological Diseases ◽  
Highly Efficient ◽  
Efficient Screening

scholarly journals Copper Oxide Nanoparticle-Based Immunosensor for Zearalenone Analysis by Combining Automated Sample Pre-Processing and High-Throughput Terminal Detection

Sensors ◽  
2021 ◽  
Vol 21 (19) ◽  
pp. 6538
Author(s):  
Zhihong Xuan ◽  
Yanxiang Wu ◽  
Hongmei Liu ◽  
Li Li ◽  
Jin Ye ◽  
...  
Keyword(s):  
High Throughput ◽  
Screening Tool ◽  
Detection Method ◽  
Sample Pretreatment ◽  
Fluorescence Signal ◽  
Signal Conversion ◽  
Cuo Nps ◽  
Acidic Conditions ◽  
Oxide Nanoparticle ◽  
Efficient Screening

A rapid and high-throughput fluorescence detection method for zearalenone (ZEN) based on a CuO nanoparticle (NP)-assisted signal amplification immunosensor was developed using an automated sample pretreatment and signal conversion system. CuO NPs with high stability and biocompatibility were used as carriers to immobilize anti-ZEN antibodies. The obtained CuO NP-anti-ZEN can maintain the ability to recognize target toxins and act as both a signal source and carrier to achieve signal conversion using automated equipment. In this process, target toxin detection is indirectly transformed to Cu2+ detection because of the large number of Cu2+ ions released from CuO NPs under acidic conditions. Finally, a simple and high-throughput fluorescence assay based on a fluorescent tripeptide molecule was employed to detect Cu2+, using a multifunctional microporous plate detector. A good linear relationship was observed between the fluorescence signal and the logarithm of ZEN concentration in the range of 16.0–1600.0 μg/kg. Additionally, excellent accuracy with a high recovery yield of 99.2–104.9% was obtained, which was concordant with the results obtained from LC-MS/MS of naturally contaminated samples. The CuO NP-based assay is a powerful and efficient screening tool for ZEN detection and can easily be modified to detect other mycotoxins.

scholarly journals Penilaian gizi sederhana: alat penilaian praktis untuk menentukan status gizi pasien rawat inap di rumah sakit

2005 ◽  
Vol 1 (3) ◽  
pp. 137
Author(s):  
Ida Mardalena ◽  
Bambang Suprapto ◽  
Widarto Widarto ◽  
Bhisma Murti
Keyword(s):  
Nutritional Status ◽  
Screening Tool ◽  
Nutritional Assessment ◽  
High Sensitivity ◽  
Hospitalized Patients ◽  
Simple Method ◽  
High Incidence ◽  
Time Required ◽  
Sensitivity Specificity ◽  
Efficient Screening

Background: Absence of effective and efficient screening tool for assessment of nutritional status have lead to high incidence of malnutrition among hospitalized patients.Objective: To develope practical screening tool for assessing nutritional status of hospitalized patients.Method: A simple method of nutritional assessment, called The Simple Nutritional Assessment, was compared to albumin serum as the gold standard. This study involved 50 nurses and 50 hospitalized patients in Dr. Moewardi General Hospital, Surakarta.Result: There was significant concordance of nutritional status assessed by the Simple Nutritional Assessment and the level of albumin serum (k=0,92). Sensitivity, specificity, and likelihood ratio of the Simple Nutritional Assessment compared to serum albumin were 92%, 67–75%, and 3.8, respectively. Internal consistence of the Simple Nutritional ssessment is high (Alpha=0.80). Average time required for doing the assessment was only 5 minutes.Conclusion: The Simple Nutritional Assessment can be used for quick screening of nutritional status of hospitalized patients with high sensitivity and reliability.

scholarly journals Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants

Science ◽  
2021 ◽  
pp. eabi9745
Author(s):  
Yongfei Cai ◽  
Jun Zhang ◽  
Tianshu Xiao ◽  
Christy L. Lavine ◽  
Shaun Rawson ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Neutralizing Antibodies ◽  
Viral Fitness ◽  
Structural Basis ◽  
Amino Acid Substitutions ◽  
Receptor Binding Domain ◽  
Angiotensin Converting Enzyme 2 ◽  
Antigenic Properties ◽  
Structural Details ◽  
Fast Spreading

Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, making it resistant to some potent neutralizing antibodies. These findings provide structural details on how SARS-CoV-2 has evolved to enhance viral fitness and immune evasion.

scholarly journals An optimized stepwise algorithm combining rapid antigen and RT-qPCR for screening of COVID-19 patients

2021 ◽  
Author(s):  
Philippe Halfon ◽  
Guillaume Penaranda ◽  
Hacène Khiri ◽  
Vincent Garcia ◽  
Hortense Drouet ◽  
...  
Keyword(s):  
Case Management ◽  
Diagnostic Accuracy ◽  
Treatment Decisions ◽  
Screening Procedure ◽  
Nasopharyngeal Swab ◽  
Cycle Threshold ◽  
Negative Results ◽  
Stepwise Procedure ◽  
Sensitivity Specificity ◽  
Efficient Screening

AbstractBackgroundDiagnosing SARS CoV-2 infection with certainty is essential for appropriate case management. We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19.MethodsFrom August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates.ResultsThe overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT- qPCR were 72% (95%CI 62%–81%), 99% (95% CI95%–100%), 99% (95%CI 93%–100%), and 78% (95%CI 70%–85%), 0.28 (95%CI 0.21-0.39), and 72 (95%CI 10-208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%–99%), TSO > 4 days 100% (95%CI 54%–100%), and asymptomatic 100% (95%CI 78-100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed.ConclusionThis study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. Thus, negative results from RAD needs to be confirmed by RT-qPCR prior to making treatment decisions. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.

scholarly journals Contamination of Hospital Surfaces with Bacterial Pathogens under the Current COVID-19 Outbreak

2021 ◽  
Vol 18 (17) ◽  
pp. 9042
Author(s):  
Andrei A. Pochtovyi ◽  
Daria V. Vasina ◽  
Daria D. Kustova ◽  
Elizaveta V. Divisenko ◽  
Nadezhda A. Kuznetsova ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogens ◽  
Herd Immunity ◽  
Comorbid Conditions ◽  
Antimicrobial Drugs ◽  
Vaccination Rates ◽  
Epidemiological Monitoring ◽  
Microbiome Diversity ◽  
Global Health Issue

The SARS-CoV-2 pandemic remains a global health issue for several reasons, such as the low vaccination rates and a lack of developed herd immunity to the evolution of SARS-CoV-2, as well as its potential inclination to elude neutralizing antibodies. It should be noted that the severity of the COVID-19 disease is significantly affected by the presence of co-infections. Comorbid conditions are caused not only by pathogenic and opportunistic microorganisms but also by some representatives of the environmental microbiome. The presence of patients with moderate and severe forms of the disease in hospitals indicates the need for epidemiological monitoring of (1) bacterial pathogens circulating in hospitals, especially the ESKAPE group pathogens, and (2) the microbiome of various surfaces in hospitals. In our study, we used combined methods based on PCR and NGS sequencing, which are widely used for epidemiological monitoring. Through this approach, we identified the DNA of pathogenic bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, CoNS, and Achromobacter spp.) on various surfaces. We also estimated the microbiome diversity of surfaces and identified the potential reservoirs of infections using 16S rRNA profiling. Although we did not assess the viability of identified microorganisms, our results indicate the possible risks of insufficient regular disinfection of surfaces, regardless of department, at the Infectious Diseases Hospital. Controlling the transmission of nosocomial diseases is critical to the successful treatment of COVID-19 patients, the rational use of antimicrobial drugs, and timely decontamination measures.

scholarly journals A rapid and efficient screening system for neutralizing antibodies and its application for the discovery of potent neutralizing antibodies to SARS-CoV-2 S-RBD

2020 ◽  
Author(s):  
Xiaojian Han ◽  
Yingming Wang ◽  
Shenglong Li ◽  
Chao Hu ◽  
Tingting Li ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Inhibitory Concentration ◽  
Emerging Infectious Diseases ◽  
Receptor Binding Domain ◽  
Screening System ◽  
High Potency ◽  
Preliminary Screening ◽  
Neutralization Activity ◽  
Prevention And Treatment ◽  
Efficient Screening

AbstractNeutralizing antibodies (Abs) have been considered as promising therapeutics for the prevention and treatment of pathogens. After the outbreak of COVID-19, potent neutralizing Abs to SARS-CoV-2 were promptly developed, and a few of those neutralizing Abs are being tested in clinical studies. However, there were few methodologies detailly reported on how to rapidly and efficiently generate neutralizing Abs of interest. Here, we present a strategically optimized method for precisive screening of neutralizing monoclonal antibodies (mAbs), which enabled us to identify SARS-CoV-2 receptor-binding domain (RBD) specific Abs within 4 days, followed by another 2 days for neutralization activity evaluation. By applying the screening system, we obtained 198 Abs against the RBD of SARS-CoV-2. Excitingly, we found that approximately 50% (96/198) of them were candidate neutralizing Abs in a preliminary screening of SARS-CoV-2 pseudovirus and 20 of these 96 neutralizing Abs were confirmed with high potency. Furthermore, 2 mAbs with the highest neutralizing potency were identified to block authentic SARS-CoV-2 with the half-maximal inhibitory concentration (IC50) at concentrations of 9.88 ng/ml and 11.13 ng/ml. In this report, we demonstrated that the optimized neutralizing Abs screening system is useful for the rapid and efficient discovery of potent neutralizing Abs against SARS-CoV-2. Our study provides a methodology for the generation of preventive and therapeutic antibody drugs for emerging infectious diseases.

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