scholarly journals A 2-Gene Host Signature for Improved Accuracy of COVID-19 Diagnosis Agnostic to Viral Variants

2022 ◽  
Author(s):  
Jack Albright ◽  
Eran Mick ◽  
Estella Sanchez-Guerrero ◽  
Jack Kamm ◽  
Anthea Mitchell ◽  
...  
Keyword(s):  
Characteristic Curve ◽  
False Negative ◽  
Support Vector ◽  
Nasopharyngeal Swab ◽  
Test Results ◽  
Rna Seq ◽  
Respiratory Illnesses ◽  
Improving Accuracy ◽  
Improved Accuracy ◽  
Positive Results

The continued emergence of SARS-CoV-2 variants is one of several factors that may cause false negative viral PCR test results. Such tests are also susceptible to false positive results due to trace contamination from high viral titer samples. Host immune response markers provide an orthogonal indication of infection that can mitigate these concerns when combined with direct viral detection. Here, we leverage nasopharyngeal swab RNA-seq data from patients with COVID-19, other viral acute respiratory illnesses and non-viral conditions (n=318) to develop support vector machine classifiers that rely on a parsimonious 2-gene host signature to predict COVID-19. Optimal classifiers achieve an area under the receiver operating characteristic curve (AUC) greater than 0.9 when evaluated on an independent RNA-seq cohort (n=553). We show that a classifier relying on a single interferon-stimulated gene, such as IFI6 or IFI44, measured in RT-qPCR assays (n=144) achieves AUC values as high as 0.88. Addition of a second gene, such as GBP5, significantly improves the specificity compared to other respiratory viruses. The performance of a clinically practical 2-gene RT-qPCR classifier is robust across common SARS-CoV-2 variants, including Omicron, and is unaffected by cross-contamination, demonstrating its utility for improving accuracy of COVID-19 diagnostics.

scholarly journals A 2-Gene Host Signature for Improved Accuracy of COVID-19 Diagnosis Agnostic to Viral Variants

2022 ◽  
Author(s):  
Jack Albright ◽  
Eran Mick ◽  
Estella Sanchez-Guerrero ◽  
Jack Kamm ◽  
Anthea Mitchell ◽  
...  
Keyword(s):  
Characteristic Curve ◽  
False Negative ◽  
Support Vector ◽  
Nasopharyngeal Swab ◽  
Test Results ◽  
Rna Seq ◽  
Respiratory Illnesses ◽  
Improving Accuracy ◽  
Improved Accuracy ◽  
Positive Results

Abstract The continued emergence of SARS-CoV-2 variants is one of several factors that may cause false negative viral PCR test results. Such tests are also susceptible to false positive results due to trace contamination from high viral titer samples. Host immune response markers provide an orthogonal indication of infection that can mitigate these concerns when combined with direct viral detection. Here, we leverage nasopharyngeal swab RNA-seq data from patients with COVID-19, other viral acute respiratory illnesses and non-viral conditions (n=318) to develop support vector machine classifiers that rely on a parsimonious 2-gene host signature to predict COVID-19. Optimal classifiers achieve an area under the receiver operating characteristic curve (AUC) greater than 0.9 when evaluated on an independent RNA-seq cohort (n=553). We show that a classifier relying on a single interferon-stimulated gene, such as IFI6 or IFI44, measured in RT-qPCR assays (n=144) achieves AUC values as high as 0.88. Addition of a second gene, such as GBP5, significantly improves the specificity compared to other respiratory viruses. The performance of a clinically practical 2-gene RT-qPCR classifier is robust across common SARS-CoV-2 variants, including Omicron, and is unaffected by cross-contamination, demonstrating its utility for improving accuracy of COVID-19 diagnostics.

Three Years of Experience With Random Urinary Homovanillic and Vanillylmandelic Acid Levels in the Diagnosis of Neuroblastoma

PEDIATRICS ◽  
1987 ◽  
Vol 79 (2) ◽  
pp. 203-205
Author(s):  
Mendel Tuchman ◽  
Margaret L. R. Ramnaraine ◽  
William G. Woods ◽  
William Krivit
Keyword(s):  
False Positive ◽  
Homovanillic Acid ◽  
False Negative ◽  
False Negative Rate ◽  
Urine Samples ◽  
Vanillylmandelic Acid ◽  
Test Results ◽  
Upper Limit ◽  
Positive Results ◽  
Rule Out

During the last 3 years, random urine samples from 408 patients were tested for elevated homovanillic acid (HVA) and vanillylmandelic acid (VMA) levels to rule out the diagnosis of neuroblastoma. Thirty-seven of these patients had elevated HVA and/or VMA levels, and neuroblastoma was subsequently diagnosed. In three additional patients with negative test results (normal HVA and VMA levels), tumors were subsequently diagnosed (false-negative rate of 7.5%). Ten percent of the patients with neuroblastoma had normal HVA and 27.5% had normal VMA levels at the time of diagnosis. Only one patient (2.5%) with neuroblastoma had elevated VMA levels in the presence of normal HVA levels. More than 60% of the patients with neuroblastoma had urinary HVA and/or VMA levels higher than twice the upper limit of normal. No false-positive results were encountered. Age and stage distributions of the patients are shown, and the significance of the results is discussed.

scholarly journals COVID-19 pneumonia: Significance of diagnostic approaches other than PCR testing

2020 ◽  
Vol 4 (7) ◽  
pp. 25-28
Author(s):  
Jovan Javorac ◽  
Dejan Živanović ◽  
Ana Milenković ◽  
Zvonko Dimoski
Keyword(s):  
False Negative ◽  
Fatal Outcome ◽  
High Sensitivity ◽  
Lung Parenchyma ◽  
Diagnostic Methods ◽  
Pcr Analysis ◽  
Nasopharyngeal Swab ◽  
Test Results ◽  
Radiological Findings ◽  
Diagnostic Approaches

The infection by SARS-CoV-2 virus leads to the development of COVID-19 disease, which can manifest asymptomatically, or cause pneumonia caracterised by mild to severe symptoms, with potential fatal outcome. The gold diagnostic standard for COVID-19 disease is the PCR analysis of biological materials sampled by nasopharyngeal swab. However, despite the high sensitivity of this diagnostic method, our clinical experience has shown that in some cases, false-negative PCR test results can be obtained. This paper reports a case of a patient with developed pneumonia that could be related to COVID-19 disease based on the clinical picture, laboratory and radiological findings, but two nasopharyngeal swabs were negative for SARS-CoV-2 after PCR analysis. The patient was treated with the therapy recommended for COVID-19, achieving both clinical and radiological improvement, which indicates that the infection by SARS-CoV-2 virus was probably the UN-derlying factor of of the inflammatory process in the lung parenchyma. Therefore, the aim of this paper is to highlight the importance of other diagnostic methods in diagnosing COVID-19, not only PCR testing.

scholarly journals Machine learning techniques as an efficient alternative diagnostic tool for COVID-19 cases

2021 ◽  
Keyword(s):  
Machine Learning ◽  
Deep Learning ◽  
Sensitivity And Specificity ◽  
Predictive Power ◽  
Characteristic Curve ◽  
False Negative ◽  
Machine Learning Techniques ◽  
Support Vector ◽  
X Ray ◽  
Learning Techniques

Background: The SARS-CoV-2 virus has demonstrated the weakness of many health systems worldwide, creating a saturation and lack of access to treatments. A bottleneck to fight this pandemic relates to the lack of diagnostic infrastructure for early detection of positive cases, particularly in rural and impoverished areas of developing countries. In this context, less costly and fast machine learning (ML) diagnosis-based systems are helpful. However, most of the research has focused on deep-learning techniques for diagnosis, which are computationally and technologically expensive. ML models have been mainly used as a benchmark and are not entirely explored in the existing literature on the topic of this paper. Objective: To analyze the capabilities of ML techniques (compared to deep learning) to diagnose COVID-19 cases based on X-ray images, assessing the performance of these techniques and using their predictive power for such a diagnosis. Methods: A factorial experiment was designed to establish this power with X-ray chest images of healthy, pneumonia, and COVID-19 infected patients. This design considers data-balancing methods, feature extraction approaches, different algorithms, and hyper-parameter optimization. The ML techniques were evaluated based on classification metrics, including accuracy, the area under the receiver operating characteristic curve (AUROC), F1-score, sensitivity, and specificity. Results: The design of experiment provided the mean and its confidence intervals for the predictive capability of different ML techniques, which reached AUROC values as high as 90% with suitable sensitivity and specificity. Among the learning algorithms, support vector machines and random forest performed best. The down-sampling method for unbalanced data improved the predictive power significantly for the images used in this study. Conclusions: Our investigation demonstrated that ML techniques are able to identify COVID-19 infected patients. The results provided suitable values of sensitivity and specificity, minimizing the false-positive or false-negative rates. The models were trained with significantly low computational resources, which helps to provide access and deployment in rural and impoverished areas.

Laboratory Testing Strategies

2017 ◽  
Author(s):  
Thomas P. Young
Keyword(s):  
Clinical Judgment ◽  
False Negative ◽  
Preliminary Test ◽  
Test Results ◽  
Testing Strategies ◽  
Laboratory Confirmation ◽  
Health Fairs ◽  
Hiv Antibodies ◽  
Positive Results

Laboratory confirmation of HIV infection is primarily through the detection of HIV antibodies in an individual. Using the current immunoassays and confirmatory testing, false-positive results are exceedingly rare. However, providers should use clinical judgment when interpreting test results and consider additional follow-up testing when appropriate. False-negative immunoassays are also exceedingly rare except for individuals who are early in their infection and have yet to produce HIV antibodies that are detectable by current assays. Rapid HIV tests have similar testing accuracies as compared to those of currently available immunoassays and can be useful testing options for settings such as health fairs, nonclinical locations, and other situations in which quickly receiving preliminary test results would be beneficial.

scholarly journals Evaluation of antigen detection and antibody detection tests for Trypanosoma evansi infections of buffaloes in Indonesia

1999 ◽  
Vol 123 (1) ◽  
pp. 149-155 ◽  
Author(s):  
H. C. DAVISON ◽  
M. V. THRUSFIELD ◽  
S. MUHARSINI ◽  
A. HUSEIN ◽  
S. PARTOUTOMO ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
False Negative ◽  
Trypanosoma Evansi ◽  
Antibody Detection ◽  
Test Results ◽  
Likelihood Ratios ◽  
Significant Difference ◽  
Post Test ◽  
Positive Results ◽  
Rule Out

Two Ag-ELISAs, an IgG-specific antibody detection ELISA (IgG ELISA) and a card agglutination test (CATT) for the detection of Trypanasoma evansi infections in buffaloes in Indonesia, were compared. Diagnostic sensitivity estimates were obtained by testing sera from 139 Indonesian buffaloes which had been found to be infected by parasitological tests. Diagnostic specificity was estimated by testing sera from 263 buffaloes living in Australia. Response-operating characteristic curves were constructed, and optimal ELISA cut-off values, which minimized the number of false–negative and false–positive results, were chosen. The IgG ELISA had the highest sensitivity (89%) and the CATT had the highest specificity (100%). There was a significant difference between the sensitivities (71 and 81%), but not between the specificities (75 and 78%), of the two Ag-ELISAs. The four tests were further compared by calculation of post-test probabilities of infection for positive and negative test results using a range of prevalence values, and likelihood ratios. The results suggested that the CATT was the best test to ‘rule-in’ infection (i.e. the highest probability of infection in test-positive animals) and the IgG ELISA was the best test to ‘rule-out’ infection (i.e. the lowest probability of infection in test-negative animals).

scholarly journals New Meconium Biomarkers of Prenatal Methamphetamine Exposure Increase Identification of Affected Neonates

2010 ◽  
Vol 56 (5) ◽  
pp. 856-860 ◽  
Author(s):  
Teresa R Gray ◽  
Tamsin Kelly ◽  
Linda L LaGasse ◽  
Lynne M Smith ◽  
Chris Derauf ◽  
...  
Keyword(s):  
False Negative ◽  
Screening Tests ◽  
Test Results ◽  
Third Trimester ◽  
Self Reports ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectrometric ◽  
New Biomarkers ◽  
Related Compounds ◽  
Positive Results

Abstract Background: Prenatal methamphetamine (MAMP) exposure is poorly reflected in neonatal meconium. Often, maternal self-reported MAMP use is not corroborated by positive results in amphetamines immunoassays of meconium, and even if initial test results are positive, they frequently are not confirmed for MAMP or amphetamine (AMP) by chromatographic analysis. The presence of the MAMP metabolites p-hydroxymethamphetamine (pOHMAMP), p-hydroxyamphetamine (pOHAMP), and norephedrine (NOREPH) in meconium may improve the identification of MAMP- and AMP-exposed neonates. Methods: Immunoassay-positive and -negative meconium samples were subjected to liquid chromatography– tandem mass spectrometric reanalysis for these recently identified metabolites. Results: pOHAMP and NOREPH were detected only when MAMP and/or AMP were present and thus do not appear to be promising biomarkers of prenatal MAMP exposure. pOHMAMP, in contrast, identified 6 additional neonates whose mothers reported MAMP exposure, yet had a meconium sample screened as negative; pOHMAMP was more likely to be present if maternal MAMP use continued into the third trimester. Although the pOHMAMP results for meconium samples corroborated the maternal self-reports, the confirmation rate for positive meconium screening results did not improve with the inclusion of these new biomarkers. Conclusions: pOHMAMP identified additional MAMP- exposed neonates; therefore, MAMP, AMP, and pOHMAMP should be included in meconium chromatographic analyses. Maximizing the identification of MAMP-exposed children requires improvement in immunoassay screening tests to reduce false-negative and false-positive results. Additional research will help clarify which AMP-related compounds, if any, contribute to unconfirmed positive results in screening tests. Furthermore, nonamphetamine compounds endogenous to the complex meconium matrix also may cross-react, making chromatographic confirmation of screening results essential.

scholarly journals Optimal Insertion Depth for Nasal Mid-Turbinate and Nasopharyngeal Swabs

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1257
Author(s):  
Rasmus Eið Callesen ◽  
Cecilie Mullerup Kiel ◽  
Lisette Hvid Hovgaard ◽  
Kathrine Kronberg Jakobsen ◽  
Michael Papesch ◽  
...  
Keyword(s):  
Nasal Swab ◽  
False Negative ◽  
Inferior Turbinate ◽  
Nasopharyngeal Swab ◽  
Test Results ◽  
Insertion Depth ◽  
Specimen Collection ◽  
The Mean ◽  
Current Guidelines ◽  
Virus Testing

Millions of people are tested for COVID-19 daily during the pandemic, and a lack of evidence to guide optimal nasal swab testing can increase the risk of false-negative test results. This study aimed to determine the optimal insertion depth for nasal mid-turbinate and nasopharyngeal swabs. The measurements were made with a flexible endoscope during the collection of clinical specimens with a nasopharyngeal swab at a public COVID-19 test center in Copenhagen, Denmark. Participants were volunteer adults undergoing a nasopharyngeal SARS-CoV-2 rapid antigen test. All 109 participants (100%) completed the endoscopic measurements; 52 (48%) women; 103 (94%) white; mean age 34.39 (SD, 13.2) years; and mean height 176.7 (SD, 9.29) cm. The mean swab length to the posterior nasopharyngeal wall was 9.40 (SD, 0.64) cm. The mean endoscopic distance to the anterior and posterior end of the inferior turbinate was 1.95 (SD, 0.61) cm and 6.39 (SD, 0.62) cm, respectively. The mean depth to nasal mid-turbinate was calculated as 4.17 (SD, 0.48) cm. The optimal depths of insertion for nasal mid-turbinate swabs are underestimated in current guidelines compared with our findings. This study provides clinical evidence to guide the performance of anatomically correct nasal and nasopharyngeal swab specimen collection for virus testing.

scholarly journals Detection of SARS-CoV-2 infection by rapid antigen test in comparison with RT-PCR in a public setting

2021 ◽  
Author(s):  
Kathrine Kronberg Jakobsen ◽  
Jakob Schmidt Jensen ◽  
Tobias Todsen ◽  
Freddy Lippert ◽  
Cyril Jean-Marie Martel ◽  
...  
Keyword(s):  
False Negative ◽  
Pcr Analysis ◽  
Nasopharyngeal Swab ◽  
Test Results ◽  
Antigen Test ◽  
Rt Pcr ◽  
Predictive Values ◽  
Public Setting ◽  
Antigen Tests ◽  
Sensitivity Specificity

AbstractBackgroundRapid and accurate detection of SARS-CoV-2 infection is essential in limiting the spread of infection during the ongoing COVID-19 pandemic. The aim of this study was to determine the accuracy of the STANDARD Q COVID-19 Ag test (SD BIOSENSOR) by comparison with RT-PCR in a public setting.MethodIndividuals aged 18 years or older who had booked an appointment for a RT-PCR test on December 26-31, 2020 at a public test center in Copenhagen, Denmark, were invited to participate. An oropharyngeal swab was collected for RT-PCR analysis, immediately followed by a nasopharyngeal swab examined by the STANDARD Q COVID-19 Ag test (SD BIOSENSOR). Sensitivity, specificity, positive and negative predictive values of the antigen test were calculated with test results from RT-PCR as reference.ResultsOverall, 4697 individuals were included (female n=2456, 53.3%; mean age: 44.7 years, SD: 16.9 years); 196 individuals were tested twice or more. Among 4811 paired conclusive test results from the RT-PCR and antigen tests, 221 (4.6%) RT-PCR tests were positive. The overall sensitivity and specificity of the antigen test were 69.7% and 99.5%, the positive and negative predictive values were 87.0% and 98.5%. Ct values were significantly higher among individuals with false negative antigen tests compared to true positives.ConclusionThe sensitivity, specificity, and predictive values found indicate that the STANDARD Q COVID-19 Ag is a good supplement to RT-PCR testing.

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