scholarly journals Serological immunochromatographic approach in diagnosis with SARS-CoV-2 infected COVID-19 patients

2020 ◽  
Author(s):  
Yunbao Pan ◽  
Xinran Li ◽  
Gui Yang ◽  
Junli Fan ◽  
Yueting Tang ◽  
...  
Keyword(s):  
Real Time ◽  
Early Stage ◽  
False Negative ◽  
False Negative Rate ◽  
Intermediate Stage ◽  
Rt Pcr ◽  
Igg Antibody ◽  
Blood Samples ◽  
Icg Strip ◽  
Stage 1

AbstractAn outbreak of new coronavirus SARS-CoV-2 was occurred in Wuhan, China and rapidly spread to other cities and nations. The standard diagnostic approach that widely adopted in the clinic is nuclear acid detection by real-time RT-PCR. However, the false-negative rate of the technique is unneglectable and serological methods are urgently warranted. Here, we presented the colloidal gold-based immunochromatographic (ICG) strip targeting viral IgM or IgG antibody and compared it with real-time RT-PCR. The sensitivity of ICG assay with IgM and IgG combinatorial detection in nuclear acid confirmed cases were 11.1%, 92.9% and 96.8% at the early stage (1-7 days after onset), intermediate stage (8-14 days after onset), and late stage (more than 15 days), respectively. The ICG detection capacity in nuclear acid-negative suspected cases was 43.6%. In addition, the consistencies of whole blood samples with plasma were 100% and 97.1% in IgM and IgG strips, respectively. In conclusion, serological ICG strip assay in detecting SARS-CoV-2 infection is both sensitive and consistent, which is considered as an excellent supplementary approach in clinical application.

scholarly journals Pooling of Upper Respiratory Specimens Using a SARS-CoV-2 Real-time RT-PCR Assay Authorized for Emergency Use in Low-Prevalence Populations for High-Throughput Testing

2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Gwynngelle A Borillo ◽  
Ron M Kagan ◽  
Russell E Baumann ◽  
Boris M Fainstein ◽  
Lamela Umaru ◽  
...  
Keyword(s):  
Real Time ◽  
False Negative ◽  
False Negative Rate ◽  
Nucleic Acid Amplification ◽  
Rt Pcr ◽  
Pooled Testing ◽  
Negative Results ◽  
Single Positive ◽  
Upper Respiratory ◽  
Respiratory Specimens

Abstract Background Nucleic acid amplification testing is a critical tool for addressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Specimen pooling can increase throughput and conserve testing resources but requires validation to ensure that reduced sensitivity does not increase the false-negative rate. We evaluated the performance of a real-time reverse transcription polymerase chain reaction (RT-PCR) test authorized by the US Food and Drug Administration (FDA) for emergency use for pooled testing of upper respiratory specimens. Methods Positive specimens were selected from 3 prevalence groups, 1%–3%, >3%–6%, and >6%–10%. Positive percent agreement (PPA) was assessed by pooling single-positive specimens with 3 negative specimens; performance was assessed using Passing-Bablok regression. Additionally, we assessed the distributions of RT-PCR cycle threshold (Ct) values for 3091 positive specimens. Results PPA was 100% for the 101 pooled specimens. There was a linear relationship between Ct values for pooled and single-tested specimens (r = 0.96–0.99; slope ≈ 1). The mean pooled Ct shifts at 40 cycles were 2.38 and 1.90, respectively, for the N1 and N3 targets. The median Cts for 3091 positive specimens were 25.9 (N1) and 24.7 (N3). The percentage of positive specimens with Cts between 40 and the shifted Ct was 1.42% (N1) and 0.0% (N3). Conclusions Pooled and individual testing of specimens positive for SARS-CoV-2 demonstrated 100% agreement, which demonstrates the viability of pooled specimens for SARS-COV-2 testing using a dual-target RT-PCR system. Pooled specimen testing can help increase testing capacity for SARS-CoV-2 with a low risk of false-negative results.

EVALUATION OF PERFORMANCE OF NINE SEROLOGICALASSAYS FOR THE DETECTION OF SARS-COV-2 ANTIBODIES.

2021 ◽  
pp. 60-62
Author(s):  
Tagajdid Mohamed Rida ◽  
Konzi Clémence ◽  
El Kochri Safae ◽  
Elannaz Hicham ◽  
Abi Rachid ◽  
...  
Keyword(s):  
Clinical Performance ◽  
Current Knowledge ◽  
False Negative ◽  
Antibody Test ◽  
Antibody Detection ◽  
Rt Pcr ◽  
Igg Antibody ◽  
Serological Tests ◽  
Blood Samples ◽  
Test Kit

Introduction: Currently, polymerase chain reaction (PCR) based viral RNAdetection is the standard for COVID-19 diagnosis [2]. Though, RNA testing based on throat or nasopharyngeal swabs has shown a number of false-negative results. Antibody detection tests have been developed to detect specic antibodies, IgM and IgG, to SRAS-CoV-2 virus. The clinical relevance of these tests is still under evaluation and is highly related to their clinical performance. Our objective is to assess analytical performances of nine SARS-CoV-2 antibodies immunoassays. Materiel and Method: We collected 80 blood samples from PCR-conrmed COVID-19 patients diagnosed in our Virology department (20 samples collected at day 10 after the onset of symptoms, 60 collected after day 14 following the onset of symptoms) and 20 blood samples from patients SARS-CoV-2 RT-PCR negative. All sera were tested with nine SARS-CoV-2 antibodies immunoassays ARCHITECT SARS-CoV-2 IgG® (Abbott), COVID-19 VIRCLIA® IgG MONOTEST (Vircell), COVID-19 VIRCLIA® IgM+IgA MONOTEST (Vircell), COVID-19 ELISA IgG® (Vircell), COVID-19 ELISA IgM+IgA® (Vircell), Elecsys® Anti-SARS-CoV-2 (Roche), FREND® COVID-19 IgG/IgM Duo (NanoEntek), COVID-PRESTO® (AAZ) and COVID-19 (SARS-CoV-2) IgM/IgG Antibody Test Kit® (Labnovation Technologies). Results: Sensitivity of tests increases once the seroconversion to anti-SARS-CoV-2 IgG positive in most individuals occurs toward the end of week 2 post-infection. COVID-19 PRESTO had the best accuracy in our study showing 100% sensitivity after day 14 following the onset of symptoms. All of the tests had a specicity of 100%. Conclusion: Serological tests are sensitive for the latest stages of COVID-19 infection. Recommendations on using SRAS-COV-2 antibody detection tests are continuously improving based on current knowledge of host antibody responses during infection. They are of great value in cases presenting COVID-19 symptoms with negative RT-PCR.

scholarly journals Proteome-wide analysis of differentially-expressed SARS-CoV-2 antibodies in early COVID-19 infection

2020 ◽  
Author(s):  
Xiaomei Zhang ◽  
Xian Wu ◽  
Dan Wang ◽  
Minya Lu ◽  
Xin Hou ◽  
...  
Keyword(s):  
Early Stage ◽  
False Negative ◽  
False Negative Rate ◽  
Antibody Detection ◽  
Igg Antibodies ◽  
Protein Subunit ◽  
Igg Antibody ◽  
S Protein ◽  
N Protein ◽  
Acute Myocardial Injury

AbstractRapid and accurate tests that detect IgM and IgG antibodies to SARS-CoV-2 proteins are essential in slowing the spread of COVID-19 by identifying patients who are infected with COVID-19. Using a SARS-CoV-2 proteome microarray developed in our lab, we comprehensively profiled both IgM and IgG antibodies in forty patients with early-stage COVID-19, influenza, or non-influenza who had similar symptoms. The results revealed that the SARS-CoV-2 N protein is not an ideal biomarker for COVID-19 diagnosis because of its low immunogenicity, thus tests that rely on this marker alone will have a high false negative rate. Our data further suggest that the S protein subunit 1 receptor binding domain (S1-RBD) might be the optimal antigen for IgM antibody detection, while the S protein extracellular domain (S1+S2ECD) would be the optimal antigen for both IgM and IgG antibody detection. Notably, the combination of all IgM and IgG biomarkers can identify 87% and 73.3% COVID-19 patients, respectively. Finally, the COVID-19-specific antibodies are significantly correlated with the clinical indices of viral infection and acute myocardial injury (p≤0.05). Our data may help understand the function of anti-SARS-CoV-2 antibodies and improve serology tests for rapid COVID-19 screening.

scholarly journals The comparative superiority of IgM-IgG antibody test to real-time reverse transcriptase PCR detection for SARS-CoV-2 infection diagnosis

2020 ◽  
Author(s):  
Rui Liu ◽  
Xinghui Liu ◽  
Huan Han ◽  
Muhammad Adnan Shereen ◽  
Zhili Niu ◽  
...  
Keyword(s):  
Real Time ◽  
False Negative ◽  
Antibody Test ◽  
Pcr Detection ◽  
Antibody Detection ◽  
Rt Pcr ◽  
Igg Antibody ◽  
Positive Ratio ◽  
Infection Diagnosis ◽  
Significant Difference

AbstractBackgroundAs the increasing number of Corona Virus Disease 2019 (COVID-19) patients caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2), which caused an outbreak initiated from Wuhan, China in December, 2019, the clinical features and treatment of COVID-19 patients have been understood. However, it is urgent to need the rapid and accurate detection for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based and nucleic acid-based tests (NAT) for SARS-CoV-2-infected patients.MethodWe retrospectively and observationally studied 133 patients diagnosed with SARS-CoV-2 and admitted in Renmin Hospital of Wuhan University, China, from Feb 17 to Mar 1, 2020. Demographic data, symptoms, clinical examination, laboratory tests, and clinical outcomes were collected. Data were compared between IgM-IgG antibody test and real-time RT-PCR detection for COVID-19 patients.ResultsOf 133 patients with SARS-CoV-2 infection, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no significant difference of gender and age among three subgroups. Overall, the positive ratio in IgM antibody test was higher than in RT-PCR detection. In RT-PCR detection, the positive ratio was 65.91%, 71.15%, and 67.57% in moderate, severe, and critical cases, respectively. Whereas, the positive ratio of IgM/IgG antibody detection in patients was 79.55%/93.18%, 82.69%/100%, and 72.97%/97.30% in moderate, severe, and critical cases, respectively. Moreover, the concentrations of antibodies were also measured in three subgroups.ConclusionThe IgM-IgG antibodies-based test exhibited a comparative superiority to the NAT for COVID-19 diagnosis, which provides an effective complement to the false negative results from NAT for SARS-CoV-2 infection diagnosis.

scholarly journals Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1091
Author(s):  
Ali A. Rabaan ◽  
Raghavendra Tirupathi ◽  
Anupam A Sule ◽  
Jehad Aldali ◽  
Abbas Al Mutair ◽  
...  
Keyword(s):  
Viral Load ◽  
Real Time ◽  
Disease Severity ◽  
False Negative ◽  
Influential Factors ◽  
Confirmatory Test ◽  
Acid Extraction ◽  
Rt Pcr ◽  
Viral Kinetics ◽  
Ct Value

Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.

scholarly journals Incorporating false negative tests in epidemiological models for SARS-CoV-2 transmission and reconciling with seroprevalence estimates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rupam Bhattacharyya ◽  
Ritoban Kundu ◽  
Ritwik Bhaduri ◽  
Debashree Ray ◽  
Lauren J. Beesley ◽  
...  
Keyword(s):  
False Negative ◽  
Population Based ◽  
Training Data ◽  
Epidemiological Models ◽  
Rt Pcr ◽  
Antibody Prevalence ◽  
Igg Antibody ◽  
False Negatives ◽  
Seir Model ◽  
Study Population

AbstractSusceptible-Exposed-Infected-Removed (SEIR)-type epidemiologic models, modeling unascertained infections latently, can predict unreported cases and deaths assuming perfect testing. We apply a method we developed to account for the high false negative rates of diagnostic RT-PCR tests for detecting an active SARS-CoV-2 infection in a classic SEIR model. The number of unascertained cases and false negatives being unobservable in a real study, population-based serosurveys can help validate model projections. Applying our method to training data from Delhi, India, during March 15–June 30, 2020, we estimate the underreporting factor for cases at 34–53 (deaths: 8–13) on July 10, 2020, largely consistent with the findings of the first round of serosurveys for Delhi (done during June 27–July 10, 2020) with an estimated 22.86% IgG antibody prevalence, yielding estimated underreporting factors of 30–42 for cases. Together, these imply approximately 96–98% cases in Delhi remained unreported (July 10, 2020). Updated calculations using training data during March 15-December 31, 2020 yield estimated underreporting factor for cases at 13–22 (deaths: 3–7) on January 23, 2021, which are again consistent with the latest (fifth) round of serosurveys for Delhi (done during January 15–23, 2021) with an estimated 56.13% IgG antibody prevalence, yielding an estimated range for the underreporting factor for cases at 17–21. Together, these updated estimates imply approximately 92–96% cases in Delhi remained unreported (January 23, 2021). Such model-based estimates, updated with latest data, provide a viable alternative to repeated resource-intensive serosurveys for tracking unreported cases and deaths and gauging the true extent of the pandemic.

scholarly journals False Negative Mitigation in Group Testing for COVID-19 Screening

2021 ◽  
Vol 8 ◽  
Author(s):  
Amir Reza Alizad Rahvar ◽  
Safar Vafadar ◽  
Mehdi Totonchi ◽  
Mehdi Sadeghi
Keyword(s):  
Viral Load ◽  
False Negative ◽  
Group Testing ◽  
False Negative Rate ◽  
Screening Strategy ◽  
Web Interface ◽  
Rt Pcr ◽  
Promising Candidate ◽  
Testing Method ◽  
High False Negative Rate

After lifting the COVID-19 lockdown restrictions and opening businesses, screening is essential to prevent the spread of the virus. Group testing could be a promising candidate for screening to save time and resources. However, due to the high false-negative rate (FNR) of the RT-PCR diagnostic test, we should be cautious about using group testing because a group's false-negative result identifies all the individuals in a group as uninfected. Repeating the test is the best solution to reduce the FNR, and repeats should be integrated with the group-testing method to increase the sensitivity of the test. The simplest way is to replicate the test twice for each group (the 2Rgt method). In this paper, we present a new method for group testing (the groupMix method), which integrates two repeats in the test. Then we introduce the 2-stage sequential version of both the groupMix and the 2Rgt methods. We compare these methods analytically regarding the sensitivity and the average number of tests. The tradeoff between the sensitivity and the average number of tests should be considered when choosing the best method for the screening strategy. We applied the groupMix method to screening 263 people and identified 2 infected individuals by performing 98 tests. This method achieved a 63% saving in the number of tests compared to individual testing. Our experimental results show that in COVID-19 screening, the viral load can be low, and the group size should not be more than 6; otherwise, the FNR increases significantly. A web interface of the groupMix method is publicly available for laboratories to implement this method.

scholarly journals Optimal remote access trojans detection based on network behavior

2019 ◽  
Vol 9 (3) ◽  
pp. 2177
Author(s):  
Khin Swe Yin ◽  
May Aye Khine
Keyword(s):  
Early Stage ◽  
False Negative ◽  
False Negative Rate ◽  
Remote Access ◽  
Network Behavior ◽  
Random Forest Algorithm ◽  
Detection Model ◽  
Negative Rate ◽  
Confidential Data ◽  
Unbalanced Dataset

<p>RAT is one of the most infected malware in the hyper-connected world. Data is being leaked or disclosed every day because new remote access Trojans are emerging and they are used to steal confidential data from target hosts. Network behavior-based detection has been used to provide an effective detection model for Remote Access Trojans. However, there is still short comings: to detect as early as possible, some False Negative Rate and accuracy that may vary depending on ratio of normal and malicious RAT sessions. As typical network contains large amount of normal traffic and small amount of malicious traffic, the detection model was built based on the different ratio of normal and malicious sessions in previous works. At that time false negative rate is less than 2%, and it varies depending on different ratio of normal and malicious instances. An unbalanced dataset will bias the prediction model towards the more common class. In this paper, each RAT is run many times in order to capture variant behavior of a Remote Access Trojan in the early stage, and balanced instances of normal applications and Remote Access Trojans are used for detection model. Our approach achieves 99 % accuracy and 0.3% False Negative Rate by Random Forest Algorithm.</p>

Letters to the Editor

PEDIATRICS ◽  
1981 ◽  
Vol 68 (1) ◽  
pp. 144-145
Author(s):  
Lachlan Ch De Crespigny ◽  
Hugh P. Robinson
Keyword(s):  
Real Time ◽  
Linear Array ◽  
False Positive Rate ◽  
False Negative ◽  
False Negative Rate ◽  
Letters To The Editor ◽  
Premature Babies ◽  
Computed Tomography Scans ◽  
Positive Rate ◽  
Time Linear

We read with interest the report which suggested that the diagnosis of cerebroventricular hemorrhage ([CVH] including both subependymal [SEH] and intraventricular) with real time ultrasound was unreliable.1 Ultrasound, when compared with computed tomography scans, had a 35% false-positive rate and a 21% false-negative rate. In our institution over a 12-month period more than 200 premature babies have been examined (ADR real time linear array scanner with a 7-MHz transducer).

scholarly journals Evaluation of endometrial polymerase chain reaction in diagnosis of female genital tuberculosis

2019 ◽  
Vol 8 (11) ◽  
pp. 4424
Author(s):  
Manvi Dua ◽  
Kiran Pandey ◽  
Sangeeta Arya ◽  
Anil Verma
Keyword(s):  
Diagnostic Criteria ◽  
Peritoneal Fluid ◽  
Early Stage ◽  
False Negative ◽  
False Negative Rate ◽  
Clinical History ◽  
Standard Test ◽  
Genital Tuberculosis ◽  
Group B ◽  
Dna Pcr

Background: Genital tuberculosis also known as tuberculous pelvic inflammatory disease can affect any age group, most common being reproductive women of 20-40 years. Clinical diagnosis of genital tuberculosis is a big challenge as the disease is either asymptomatic or has varied presentations. Conventional methods for diagnosis including AFB smear, endometrial histopathology and culture have limitations of low detection rate because of paucibacillary nature of disease. Laparoscopy generally detects macroscopic changes such as peritubal adhesions, tubercles and tubo-ovarian mass but it fails to diagnose disease at early stage. The objective of this study was to evaluate efficacy of TB DNA PCR in diagnosis of genital tuberculosis.Methods: A total of 127 patients (between 2013-2016) who presented in gynecologic OPD with symptoms suggestive of tuberculosis were included in the study. All patients were subjected to endometrial histopathology and TB DNA PCR of endometrial tissue and peritoneal fluid. Since there is no gold standard test available for diagnosis of genital tuberculosis, a diagnostic criteria was adopted in the study based on laparoscopic findings, clinical history and other investigations. Patients were divided in two groups. Group A included patients positive of tuberculosis based on diagnostic criteria. Group B included patients negative for tuberculosis based on diagnostic criteria.Results: In our study sensitivity of endometrial PCR, peritoneal PCR and endometrial histopathology were 73.8%,17.8% and 10.7% respectively. Endometrial histopathology and peritoneal fluid PCR was found to be highly specific (100%) while endometrial PCR was found to be 93% specific. Endometrial PCR although has highest sensitivity and specificity amongst the groups evaluated but high false negative rate was its major limitation.Conclusions: No single test fulfills all criteria to emerge as sole diagnostic test, hence a high degree of suspicion with a detailed history and investigating with a variety of tests is all that is required to diagnose geniatal tuberculosis.

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