scholarly journals Multi-Platform Comparison of SARS-CoV-2 Serology Assays for the Detection of COVID-19

2020 ◽  
Vol 5 (6) ◽  
pp. 1324-1336 ◽  
Author(s):  
Raymond T Suhandynata ◽  
Melissa A Hoffman ◽  
Michael J Kelner ◽  
Ronald W McLawhon ◽  
Sharon L Reed ◽  
...  
Keyword(s):  
Predictive Value ◽  
False Positive Rate ◽  
Disease Prevalence ◽  
Percentage Agreement ◽  
Chain Reaction ◽  
Acute Infections ◽  
Positive Rate ◽  
Platform Comparison ◽  
Polymerase Chain ◽  
Time Frames

Abstract Background COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel beta-coronavirus that is responsible for the 2019 coronavirus pandemic. Acute infections should be diagnosed by polymerase chain reaction (PCR) based tests, but serology tests can demonstrate previous exposure to the virus. Methods We compared the performance of the Diazyme, Roche, and Abbott SARS-CoV-2 serology assays using 179 negative participants to determine negative percentage agreement (NPA) and in 60 SARS-CoV-2 PCR-confirmed positive patients to determine positive percentage agreement (PPA) at 3 different time frames following a positive SARS-CoV-2 PCR result. Results At ≥15 days, the PPA (95% CI) was 100 (86.3–100)% for the Diazyme IgM/IgG panel, 96.0 (79.7–99.9)% for the Roche total Ig assay, and 100 (86.3–100)% for the Abbott IgG assay. The NPA (95% CI) was 98.3 (95.2–99.7)% for the Diazyme IgM/IgG panel, 99.4 (96.9–100)% for the Roche total Ig assay, and 98.9 (96.0–99.9)% for the Abbott IgG assay. When the Roche total Ig assay was combined with either the Diazyme IgM/IgG panel or the Abbott IgG assay, the positive predictive value was 100% while the negative predictive value remained greater than 99%. Conclusions Our data demonstrates that the Diazyme, Roche, and Abbott SARS-CoV-2 serology assays have similar clinical performances. We demonstrated a low false-positive rate across all 3 platforms and observed that false positives observed on the Roche platform are unique compared to those observed on the Diazyme or Abbott assays. Using multiple platforms in tandem increases the PPVs, which is important when screening populations with low disease prevalence.

scholarly journals Longitudinal Monitoring of SARS-CoV-2 IgM and IgG Seropositivity to Detect COVID-19

2020 ◽  
Vol 5 (5) ◽  
pp. 908-920 ◽  
Author(s):  
Raymond T Suhandynata ◽  
Melissa A Hoffman ◽  
Michael J Kelner ◽  
Ronald W McLawhon ◽  
Sharon L Reed ◽  
...  
Keyword(s):  
False Positive Rate ◽  
The United States ◽  
Performance Parameters ◽  
Chain Reaction ◽  
Viral Antibodies ◽  
Positive Rate ◽  
Polymerase Chain ◽  
First Time ◽  
Kinetics Of ◽  
Disease Free

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel beta-coronavirus that has recently emerged as the cause of the 2019 coronavirus pandemic (COVID-19). Polymerase chain reaction (PCR) based tests are optimal and recommended for the diagnosis of an acute SARS-CoV-2 infection. Serology tests for viral antibodies provide an important tool to diagnose previous exposure to the virus. Here we evaluate the analytical performance parameters of the Diazyme SARS-CoV-2 IgM/IgG serology assays and describe the kinetics of IgM and IgG seroconversion observed in patients with PCR-confirmed COVID-19 who were admitted to our hospital. Methods We validated the performance of the Diazyme assay in 235 presumed SARS-CoV-2 negative subjects to determine specificity. Subsequently, we evaluated the SARS-CoV-2 IgM and IgG seroconversion of 54 PCR-confirmed COVID-19 patients and determined sensitivity of the assay at three different timeframes. Result Sensitivity and specificity for detecting seropositivity at ≥15 days following a positive SARS-CoV-2 PCR result, was 100.0% and 98.7% when assaying for the panel of IgM and IgG. The median time to seropositivity observed for a reactive IgM and IgG result from the date of a positive PCR was 5 days (IQR: 2.75–9 days) and 4 days (IQR: 2.75–6.75 days), respectively. Conclusions Our data demonstrate that the Diazyme IgM/IgG assays are suited for the purpose of detecting SARS-CoV-2 IgG and IgM in patients with suspected SARS-CoV-2 infections. For the first time, we report longitudinal data showing the evolution of seroconversion for both IgG and IgM in a cohort of acutely ill patients in the United States. We also demonstrate a low false positive rate in patients who were presumed to be disease free.

scholarly journals A meta-analysis of accuracy and sensitivity of chest CT and RT-PCR in COVID-19 diagnosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fatemeh Khatami ◽  
Mohammad Saatchi ◽  
Seyed Saeed Tamehri Zadeh ◽  
Zahra Sadat Aghamir ◽  
Alireza Namazi Shabestari ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Reverse Transcriptase ◽  
Ct Scan ◽  
Predictive Value ◽  
Meta Analysis ◽  
Chest Ct ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Chest Ct Scan

AbstractNowadays there is an ongoing acute respiratory outbreak caused by the novel highly contagious coronavirus (COVID-19). The diagnostic protocol is based on quantitative reverse-transcription polymerase chain reaction (RT-PCR) and chests CT scan, with uncertain accuracy. This meta-analysis study determines the diagnostic value of an initial chest CT scan in patients with COVID-19 infection in comparison with RT-PCR. Three main databases; PubMed (MEDLINE), Scopus, and EMBASE were systematically searched for all published literature from January 1st, 2019, to the 21st May 2020 with the keywords "COVID19 virus", "2019 novel coronavirus", "Wuhan coronavirus", "2019-nCoV", "X-Ray Computed Tomography", "Polymerase Chain Reaction", "Reverse Transcriptase PCR", and "PCR Reverse Transcriptase". All relevant case-series, cross-sectional, and cohort studies were selected. Data extraction and analysis were performed using STATA v.14.0SE (College Station, TX, USA) and RevMan 5. Among 1022 articles, 60 studies were eligible for totalizing 5744 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value of chest CT scan compared to RT-PCR were 87% (95% CI 85–90%), 46% (95% CI 29–63%), 69% (95% CI 56–72%), and 89% (95% CI 82–96%), respectively. It is important to rely on the repeated RT-PCR three times to give 99% accuracy, especially in negative samples. Regarding the overall diagnostic sensitivity of 87% for chest CT, the RT-PCR testing is essential and should be repeated to escape misdiagnosis.

scholarly journals EXPRESS: Clinical performance of the Elecsys® Anti-SARS-CoV-2 combined in an algorithm with two specific anti-IgG immunoassays for the evaluation of the serological response of patients with COVID-19 in a population with a high prevalence of infection

2021 ◽  
pp. 000456322110380
Author(s):  
Xavier Gabaldó-Barrios ◽  
Simona Iftimie ◽  
Anna Hernández-Aguilera ◽  
Isabel Pujol ◽  
Frederic Ballester ◽  
...  
Keyword(s):  
Immune Response ◽  
Polymerase Chain Reaction ◽  
Predictive Value ◽  
Clinical Performance ◽  
Polymerase Chain Reaction Test ◽  
Serological Response ◽  
Chain Reaction ◽  
Automated Assay ◽  
High Prevalence ◽  
Polymerase Chain

Background: Anti-SARS-CoV-2 antibodies have been used in the study of the immune response in infected patients. However, differences in sensitivity and specificity have been reported, depending on the method of analysis. The aim of the present study was to evaluate the diagnostic accuracy of an algorithm in which a high-throughput automated assay for total antibodies was used for screening and two semi-automated IgG-specific methods were used to confirm the results, and also to correlate the analytical results with the clinical data and the time elapsed since infection. Methods: We studied 306 patients, some hospitalized and some outpatients, belonging to a population with a high prevalence of COVID-19. One-hundred and ten patients were classified as SARS-CoV-2 negative and 196 as positive by polymerase chain reaction. Results: The algorithm and automated assay alone had a specificity and a positive predictive value of 100%, although the sensitivity and negative predictive value of the algorithm was higher. Both methods showed a good sensitivity from day 11 of the onset of symptoms in asymptomatic and symptomatic patients. The absorbance of the total antibodies was significantly higher in severely symptomatic than in asymptomatic or mildly symptomatic patients, which suggests the antibody level was higher. We found 15 patients that did not present seroconversion at 12 days from the onset of symptoms or the first polymerase chain reaction test. Conclusion: This study highlights the proper functioning of algorithms in the diagnosis of the immune response to COVID-19, which can help to define testing strategies against this disease.

scholarly journals Peripheral Blood Leukocytes and Serum Nested Polymerase Chain Reaction Are Complementary Methods for Monitoring Active Cytomegalovirus Infection in Transplant Patients

2013 ◽  
Vol 24 (3) ◽  
pp. e69-e74 ◽  
Author(s):  
PD Andrade ◽  
MT Fioravanti ◽  
EBV Anjos ◽  
C De Oliveira ◽  
DM Albuquerque ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Positive Predictive Value ◽  
Predictive Value ◽  
Cytomegalovirus Infection ◽  
Clinical Symptoms ◽  
Peripheral Blood Leukocytes ◽  
Active Infection ◽  
Chain Reaction ◽  
Blood Leukocytes ◽  
Polymerase Chain

BACKGROUND: Human cytomegalovirus is an important cause of morbidity and mortality in immunocompromised patients. Qualitative polymerase chain reaction (PCR) has proven to be a sensitive and effective technique in defining active cytomegalovirus infection, in addition to having low cost and being a useful test for situations in which there is no need for quantification. Real-time PCR has the advantage of quantification; however, the high cost of this methodology makes it impractical for routine use.OBJECTIVE: To apply a nested PCR assay to serum (sPCR) and to evaluate its efficiency to diagnose active cytomegalovirus infection compared with PCR of peripheral blood leukocytes (L-PCR).METHODS: Samples of 37 patients were prospectively evaluated. An internal control was created and applied to sPCR to exclude false-negative results.RESULTS: In total, 21 patients (57%) developed active cytomegalovirus infection. After analyzing the two methods for the diagnosis of active infection, higher sensitivity and negative predictive value of the L-PCR versus sPCR (100% versus 62%), and higher specificity and positive predictive value of sPCR versus L-PCR (81% versus 50% and 72%, respectively) were observed. Discordant results were observed in 11 patients who were L-PCR-positive but sPCR-negative for active cytomegalovirus infection, five of whom developed clinical symptoms of cytomegalovirus. Clinical symptoms were observed in 14 patients, 12 of whom were diagnosed with active infection by nested L-PCR (P=0.007) and seven by nested sPCR (P=0.02). Higher specificity and a positive predictive value for sPCR were observed.CONCLUSION: Nested L-PCR and sPCR were considered to be complementary methods for the diagnosis and management of symptomatic cytomegalovirus infection.

scholarly journals Performance of the Innova SARS-CoV-2 antigen rapid lateral flow test in the Liverpool asymptomatic testing pilot: population based cohort study

BMJ ◽  
2021 ◽  
pp. n1637 ◽  
Author(s):  
Marta García-Fiñana ◽  
David M Hughes ◽  
Christopher P Cheyne ◽  
Girvan Burnside ◽  
Mark Stockbridge ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Viral Load ◽  
Predictive Value ◽  
High Viral Load ◽  
Test Results ◽  
Chain Reaction ◽  
Viral Loads ◽  
Flow Test ◽  
Polymerase Chain ◽  
Lateral Flow Test

Abstract Objective To assess the performance of the SARS-CoV-2 antigen rapid lateral flow test (LFT) versus polymerase chain reaction testing in the asymptomatic general population attending testing centres. Design Observational cohort study. Setting Community LFT pilot at covid-19 testing sites in Liverpool, UK. Participants 5869 asymptomatic adults (≥18 years) voluntarily attending one of 48 testing sites during 6-29 November 2020. Interventions Participants were tested using both an Innova LFT and a quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) test based on supervised self-administered swabbing at testing sites. Main outcome measures Sensitivity, specificity, and predictive values of LFT compared with RT-qPCR in an epidemic steady state of covid-19 among adults with no classic symptoms of the disease. Results Of 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of <18.3 (approximate viral loads >10 6 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>10 4 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<10 4 RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load. Conclusions The Innova LFT can be useful for identifying infections among adults who report no symptoms of covid-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.

scholarly journals Identification of newborns at risk for autism using electronic medical records and machine learning

2019 ◽  
Author(s):  
Rayees Rahman ◽  
Arad Kodesh ◽  
Stephen Z Levine ◽  
Sven Sandin ◽  
Abraham Reichenberg ◽  
...  
Keyword(s):  
Machine Learning ◽  
Autism Spectrum Disorder ◽  
Positive Predictive Value ◽  
Electronic Medical Records ◽  
Predictive Value ◽  
False Positive ◽  
Medical Records ◽  
False Positive Rate ◽  
Autism Spectrum ◽  
Positive Rate

AbstractImportanceCurrent approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, where most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and outcome.ObjectiveDevelop a machine learning (ML) method predicting the diagnosis of ASD in offspring in a general population sample, using parental electronic medical records (EMR) available before childbirthDesignPrognostic study of EMR data within a single Israeli health maintenance organization, for the parents of 1,397 ASD children (ICD-9/10), and 94,741 non-ASD children born between January 1st, 1997 through December 31st, 2008. The complete EMR record of the parents was used to develop various ML models to predict the risk of having a child with ASD.Main outcomes and measuresRoutinely available parental sociodemographic information, medical histories and prescribed medications data until offspring’s birth were used to generate features to train various machine learning algorithms, including multivariate logistic regression, artificial neural networks, and random forest. Prediction performance was evaluated with 10-fold cross validation, by computing C statistics, sensitivity, specificity, accuracy, false positive rate, and precision (positive predictive value, PPV).ResultsAll ML models tested had similar performance, achieving an average C statistics of 0.70, sensitivity of 28.63%, specificity of 98.62%, accuracy of 96.05%, false positive rate of 1.37%, and positive predictive value of 45.85% for predicting ASD in this dataset.Conclusion and relevanceML algorithms combined with EMR capture early life ASD risk. Such approaches may be able to enhance the ability for accurate and efficient early detection of ASD in large populations of children.Key pointsQuestionCan autism risk in children be predicted using the pre-birth electronic medical record (EMR) of the parents?FindingsIn this population-based study that included 1,397 children with autism spectrum disorder (ASD) and 94,741 non-ASD children, we developed a machine learning classifier for predicting the likelihood of childhood diagnosis of ASD with an average C statistic of 0.70, sensitivity of 28.63%, specificity of 98.62%, accuracy of 96.05%, false positive rate of 1.37%, and positive predictive value of 45.85%.MeaningThe results presented serve as a proof-of-principle of the potential utility of EMR for the identification of a large proportion of future children at a high-risk of ASD.

The bovine sex-determining region Y (Sry) gene and its mRNA transcript are present in Y sperm but not X sperm of bulls

2018 ◽  
Vol 68 (3) ◽  
pp. 321-332 ◽  
Author(s):  
Chun-Mei Han ◽  
Rong Chen ◽  
Tao Li ◽  
Xiao-Li Chen ◽  
Yong-Fu Zheng ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Fish Analysis ◽  
Mrna Transcript ◽  
Rt Pcr ◽  
Sry Gene ◽  
Chain Reaction ◽  
Dna And Rna ◽  
Positive Rate ◽  
Polymerase Chain

AbstractThe aims of this study were to establish whether the sex-determining region Y gene and its mRNA transcript are present in the Y sperm and X sperm of bulls and, if present, determine their cellular localization. Semen was collected from three bulls and sorted by flow cytometry into X- and Y-chromosome populations. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determineSrymRNA expression in X sperm and Y sperm. The presence and localization ofSryDNA and RNA were investigated by fluorescence in situ hybridization (FISH). RT-PCR detected a singleSrytranscript of 142 bp in Y sperm but not in X sperm. In Y sperm, the FISH-positive rates forSryDNA andSryRNA did not differ significantly from the re-analyzed Y sperm purity. In further experiments, there were no significant differences between the FISH-positive rate forSryRNA and the re-analyzed Y sperm purity for X-sorted, Y-sorted, or unsorted sperm. In conclusion, FISH analysis revealed thatSrytranscripts are present at the edges of the sperm heads of Y sperm but are absent from X sperm.

Venous Flow Coupler in Head and Neck Free Flap Reconstruction

2020 ◽  
pp. 019459982095309
Author(s):  
Scott H. Troob ◽  
Quinn Self ◽  
Deniz Gerecci ◽  
Macgregor Hodgson ◽  
Javier González-Castro ◽  
...  
Keyword(s):  
Free Flap ◽  
Predictive Value ◽  
False Positive ◽  
False Positive Rate ◽  
Case Series ◽  
Arterial Flow ◽  
Retrospective Case ◽  
Venous Flow ◽  
Retrospective Case Series ◽  
Positive Rate

Objective To describe the utility of venous flow couplers in monitoring free tissue flaps in the immediate postoperative setting. Study Design Retrospective case series. Setting Otolaryngology department at a single tertiary care institution. Methods A retrospective case series of free flap reconstructions in which venous flow couplers were employed to supplement flap monitoring. All free flap cases performed over the past 4 years were reviewed. Inclusion criteria were venous flow coupler and arterial flow Doppler monitored for 5 days postoperatively. Results From July 2014 through May 2018, the venous flow coupler was used with the arterial flow Doppler and clinical monitoring in 228 cases. Eleven cases did not meet criteria for inclusion; thus, 217 cases were analyzed. Twenty cases (9.2%) returned to the operating room with concern for flap compromise, and 16 were salvaged. The combination of venous flow coupler and arterial flow Doppler identified 19 of these flaps. Venous flow couplers identified 5 compromised flaps before there was an arterial signal change, and all were salvaged. Additionally, there was a 24.1% false-positive rate when 2 venous flow couplers were used in parallel. For the venous flow coupler, the positive predictive value was 64.3% and the negative predictive value, 98.9%. The false-positive rate in the series was 5.1%. The sensitivity was 90% and the specificity, 94.9%. Conclusion The venous flow coupler is able to detect venous thrombosis in the absence of arterial thrombosis and may contribute to improved flap salvage rates.

scholarly journals What Is the Predictive Value of a Single Nasopharyngeal SARS-CoV-2 PCR Swab Test in a Patient With COVID-Like Symptoms and/or Significant COVID-19 Exposure?

2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Blessen George ◽  
James McGee ◽  
Eileen Giangrasso ◽  
Sheila Finkelstein ◽  
Susan Wu ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Severe Acute Respiratory Syndrome ◽  
Predictive Value ◽  
Hospital Workers ◽  
Chain Reaction ◽  
Pcr Screening ◽  
Test Characteristics ◽  
Antibody Titers ◽  
Polymerase Chain ◽  
Pcr Test

Abstract Utilizing results of polymerase chain reaction (PCR) testing and subsequent antibody titers, we report on the test characteristics of a PCR screening test for severe acute respiratory syndrome coronavirus 2 among hospital workers. The PCR test was found to be 87% sensitive and 97% specific, with a positive predictive value of 0.98 and a negative predictive value of 0.80.

Prognostic Value of Circulating Melanoma Cells Detected by Reverse Transcriptase–Polymerase Chain Reaction

2003 ◽  
Vol 21 (5) ◽  
pp. 767-773 ◽  
Author(s):  
Giuseppe Palmieri ◽  
Paolo A. Ascierto ◽  
Francesco Perrone ◽  
Sabrina M.R. Satriano ◽  
Alessandro Ottaiano ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Subgroup Analysis ◽  
Peripheral Blood ◽  
Predictive Value ◽  
Prognostic Value ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Blood Samples ◽  
Stage Of Disease ◽  
Polymerase Chain

Purpose: Factors that are predictive of prognosis in patients who are diagnosed with malignant melanoma (MM) are widely awaited. Detection of circulating melanoma cells (CMCs) by reverse transcriptase-polymerase chain reaction (RT-PCR) has recently been postulated as a possible negative prognostic factor. Two main questions were addressed: first, whether the presence of CMCs, defined as the patient being positive for any of the three markers, had a prognostic role; and second, what the predictive value of each individual marker was. Patients and Methods: A consecutive series of 200 melanoma patients observed between January 1997 and December 1997, with stage of disease ranging from I to IV, was analyzed by semiquantitative RT-PCR. Tyrosinase, p97, and MelanA/MART1 were used as markers to CMCs on baseline peripheral blood samples. Progression-free survival (PFS) was used as a unique end point and was described by the product limit method. Multivariable analysis was applied to verify whether the auspicated prognostic value of these markers was independent of the stage of disease, and a subgroup analysis was performed that excluded patients with stage IV disease. Results: Overall, 32% (64 of 200) of patients progressed, and a median PFS of 52 months in the whole series was observed. The presence of CMCs and the markers individually or combined was predictive of prognosis in the univariate analysis but did not provide additional prognostic information to the stage of disease in multivariable models. In the subgroup analysis of stage (ie, I–III subgroup), similar results were observed. Conclusion: Detection of CMCs in peripheral blood samples at the time of MM diagnosis by semiquantitative RT-PCR does not add any significant predictive value to the stage of disease. Thus, this approach should not be used in clinical practice, and further studies are required to determine its usefulness.

Sign in / Sign up

Export Citation Format

Share Document