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 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 Changes in SARS-CoV-2 Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies

2020 ◽  
Author(s):  
Craig Fenwick ◽  
Antony Croxatto ◽  
Alix T. Coste ◽  
Florence Pojer ◽  
Cyril Andre ◽  
...  
Keyword(s):  
General Population ◽  
Acute Infection ◽  
Population Based ◽  
Antibody Responses ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Igg Antibody ◽  
S Protein ◽  
N Protein ◽  
Total Cohort

We have determined SARS-CoV-2-specific antibody responses in a cohort of 96 individuals with acute infection and in 578 individuals enrolled in a seroprevalence population study in Switzerland including three groups, i.e. subjects with previous RT-PCR confirmed SARS-CoV-2 infections (n=90), positive patient contacts (n=177) and random selected subjects (n=311). SARS-CoV-2 antibody responses specific to the Spike (S), in the monomeric and native trimeric forms, and/or the nucleocapsid (N) proteins were equally sensitive in the acute infection phase. Interestingly, as compared to anti-S antibody responses, those against the N protein appear to wane in the post-infection and substantially underestimated the proportion of SARS-CoV-2 infections in the groups of patient positive contacts, i.e. 10.9 to 32.2% reduction and in the random selected general population, i.e. up to 45% reduction. The overall reduction in seroprevalence targeting only anti-N IgG antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was more sensitive as compared to monomeric S proteins. These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies.

scholarly journals Application of Immunosignatures for Diagnosis of Valley Fever

2014 ◽  
Vol 21 (8) ◽  
pp. 1169-1177 ◽  
Author(s):  
Krupa Arun Navalkar ◽  
Stephen Albert Johnston ◽  
Neal Woodbury ◽  
John N. Galgiani ◽  
D. Mitchell Magee ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Random Sequence ◽  
False Negative ◽  
False Negative Rate ◽  
Peptide Array ◽  
Igg Antibodies ◽  
False Negatives ◽  
Peptide Microarray ◽  
Valley Fever ◽  
Antibody Levels

ABSTRACTValley fever (VF) is difficult to diagnose, partly because the symptoms of VF are confounded with those of other community-acquired pneumonias. Confirmatory diagnostics detect IgM and IgG antibodies against coccidioidal antigens via immunodiffusion (ID). The false-negative rate can be as high as 50% to 70%, with 5% of symptomatic patients never showing detectable antibody levels. In this study, we tested whether the immunosignature diagnostic can resolve VF false negatives. An immunosignature is the pattern of antibody binding to random-sequence peptides on a peptide microarray. A 10,000-peptide microarray was first used to determine whether valley fever patients can be distinguished from 3 other cohorts with similar infections. After determining the VF-specific peptides, a small 96-peptide diagnostic array was created and tested. The performances of the 10,000-peptide array and the 96-peptide diagnostic array were compared to that of the ID diagnostic standard. The 10,000-peptide microarray classified the VF samples from the other 3 infections with 98% accuracy. It also classified VF false-negative patients with 100% sensitivity in a blinded test set versus 28% sensitivity for ID. The immunosignature microarray has potential for simultaneously distinguishing valley fever patients from those with other fungal or bacterial infections. The same 10,000-peptide array can diagnose VF false-negative patients with 100% sensitivity. The smaller 96-peptide diagnostic array was less specific for diagnosing false negatives. We conclude that the performance of the immunosignature diagnostic exceeds that of the existing standard, and the immunosignature can distinguish related infections and might be used in lieu of existing diagnostics.

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>

Development of Dual Fluorescent Microsphere Immunological Assay for Detection of Pseudorabies Virus gE and gB IgG Antibodies

2020 ◽  
Author(s):  
chihai ji ◽  
Jingyu Wang ◽  
Yuchen Zeng ◽  
Haoming Pan ◽  
Yingfang Wei ◽  
...  
Keyword(s):  
Pseudorabies Virus ◽  
High Specificity ◽  
Antibody Detection ◽  
Economic Losses ◽  
Igg Antibodies ◽  
Wild Type ◽  
Swine Industry ◽  
Igg Antibody ◽  
Fluorescent Microsphere ◽  
Specificity And Sensitivity

Abstract Background Pseudorabies, also known as Aujezsky’s disease, is an acute viral infection caused by pseudorabies virus (PRV). Swine are one of the natural hosts of pseudorabies, therefore, the disease brings huge economic losses to the swine industry. Establishment of a differential diagnosis technique that can distinguish between wild-type infected and vaccinated pigs, and monitor vaccine-induced IgG is crucial for eventual eradication of pseudorabies.Results The aim of this study was to develop a rapid dual detection method for PRV gE and gB protein IgG antibodies with high specificity and sensitivity. PRV gE codons at amino acid residues (aa) 52–238 and gB codons at aa 539–741 were expressed to obtain recombinant PRV gE and gB proteins by pMAL-c5x vector. After purification with Qiagen Ni–NTA agarose affinity, the two proteins were analyzed by SDS-PAGE and immunoblotting assay. Two single fluorescent-microsphere immunoassays (FMIA) were established by coupling two recombinant proteins (gE and gB) with two magnetic microbeads and an effective dual FMIA was developed by integrating the two single assays. Optimal serum dilution for each assay, correlation with other common swine virus-positive sera and comparison with ELISA for two PRV antigens were tested for validation. Compared with ELISA, the specificity and sensitivity were 99.26% and 92.3% for gE IgG antibody detection and 95.74% and 96.3% for gB IgG antibody detection by dual-FMIA.Conclusion We provide a new method for monitoring PRV protective antibody in vaccinated pigs and differentiating wild-type-PRV-infected from vaccinated pigs

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.

scholarly journals Outbreak of Kawasaki disease in children during COVID-19 pandemic: a prospective observational study in Paris, France

2020 ◽  
Author(s):  
Julie Toubiana ◽  
Clement Poirault ◽  
Alice Corsia ◽  
Fanny Bajolle ◽  
Jacques Fourgeaud ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Early Stage ◽  
African Ancestry ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Sub Saharan Africa ◽  
University Hospital ◽  
Antibody Detection ◽  
Rt Pcr ◽  
Igg Antibody

Background: Acute clinical manifestations of SARS-CoV-2 infection are less frequent and less severe in children than in adults. However, recent observations raised concerns about potential post-viral severe inflammatory reactions in children infected with SARS-CoV-2. Methods: We describe an outbreak of cases of Kawasaki disease (KD) admitted between April 27 and May 7, 2020, in the general paediatrics department of a university hospital in Paris, France. All children prospectively underwent nasopharyngeal swabs for SARS-CoV-2 RT-PCR, SARS-CoV-2 IgG serology testing, and echocardiography. The number of admissions for KD during the study period was compared to that observed since January 1, 2018, based on discharge codes, using Poisson regression. Results: A total of 17 children were admitted for KD over an 11-day period, in contrast with a mean of 1.0 case per 2-week period over 2018-2019 (Poisson incidence rate ratio: 13.2 [95% confidence interval: 7.3-24.1], p <0.001). Their median age was 7.5 (range, 3.7-16.6) years, and 59% of patients originated from sub-Saharan Africa or Caribbean islands. Eleven patients presented with KD shock syndrome (KDSS) requiring intensive care support, and 12 had myocarditis. All children had marked gastrointestinal symptoms at the early stage of illness and high levels of inflammatory markers. Fourteen patients (82%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR 7/17, positive IgG antibody detection 14/16). All patients received immunoglobulins and some received corticosteroids (5/17). The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 cases (29%) during hospitalisation. Conclusions: The ongoing outbreak of KD in the Paris might be related to SARS-CoV2, and shows an unusually high proportion of children with gastrointestinal involvement, KDSS and African ancestry.

scholarly journals Seroepidemiological Study of Novel Corona Virus (CoVID-19) in Tehran, Iran

2021 ◽  
Author(s):  
Zeinab Tabanejad ◽  
Sorena Darvish ◽  
Zeinab Borjian Boroujeni ◽  
Seyed Saeed Asadi ◽  
Morteza Mesri ◽  
...  
Keyword(s):  
False Negative ◽  
Underlying Disease ◽  
Population Based ◽  
Immunological Methods ◽  
Age Group ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Igg Antibody ◽  
Cross Sectional ◽  
Exposed Population

AbstractA novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to all countries of the world, including Iran. Although new anti-coronavirus antibodies in patients may be identified by immunological methods with sufficient sensitivity and specificity, the conclusive diagnosis of the disease is by the molecular RT-PCR process. We used a population-based seroepidemiological survey to quantify the proportion of the exposed population with SARS-CoV-2 antibodies and evaluated whether the antibodies are a marker of total or partial immunity to the proportion of the population that remains susceptible to the virus. This cross-sectional study was conducted to investigate the seroprevalence of CoVID-19 in Tehran, the capital of Iran, between April and end of October 2020. Specimens of clotted and heparinized blood (2ml) were collected from the patients. The serum and plasma were separated and stored at − 80LJ°C until use. We examined serum anti-SARS-CoV-2 IgG and IgM antibodies from 1375 in-patients admitted to our hospitals using ELISA kits. In total, 1375 participants were enrolled in this study, and SARS-CoV-2 antibodies were detected using IgM-IgG antibody assay in 291 patients. Among the seropositive patients studied, 187 were men (64.3%), and 104 were women (35.7%) (P<0.05). The mean age of the patients was 49±8.4 years; the majority (27%) were in age group 31-40 years. Also, the lowest frequency of cases was reported in the age group of 1-10 years (P <0.05). We determined the seroprevalence of SARS-CoV-2 for IgM or IgG antibodies to be 21.2%. Diabetes mellitus was the most common underlying disease among SARS-CoV-2 patients [P=0.05; Odd Ratio=1.61(0.90-2.91)]. Conventional serological assays in SARS-CoV-2 cases, such as the enzyme-linked immunoassay (ELISA) for specific IgM and IgG antibodies, have a high-throughput advantage and minimize false-negative rates that occur with the RT-PCR method. This study determined the seroprevalence of SARS-CoV-2 antibodies to be 21%. Control of diabetes among other cases factors shall play important role in management and control of COVID-19.

scholarly journals Highlighted Prospects of an IgM/IgG Antibodies Test in Identifying Individuals With Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

2020 ◽  
Vol 145 (1) ◽  
pp. 39-45
Author(s):  
Yaqing Li ◽  
Qiang He ◽  
Rizhen Yu ◽  
Hui Jiang ◽  
Weizhong Wang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Ct Scanning ◽  
Immunoglobulin M ◽  
Antibody Detection ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Imaging Results ◽  
Close Contacts ◽  
Nucleic Acid Tests

Context.— Covert severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections could be seeding new outbreaks. How to identify asymptomatic SARS-CoV-2 infections early has become a global focus. Objective.— To explore the roles of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies detection, nucleic acid tests, and computed tomography (CT) scanning to identify asymptomatic SARS-CoV-2 infection. Design.— The clinical data of 389 individuals with close contacts, including in general characteristics, SARS-CoV-2 etiology, serum-specific IgM and IgG antibody detection and CT imaging results, were systematically analyzed. Results.— The present study showed that only 89 of 389 individuals with close contacts were positive after the first nucleic acid test, while 300 individuals were still negative after 2 nucleic acid tests. Among the 300 individuals, 75 did not have pneumonia, and the other 225 individuals had pulmonary imaging changes. A total of 143 individuals were eventually diagnosed as having asymptomatic infection through IgM antibody and IgG antibody detection. The sensitivity, specificity, and false-negative rate of IgM and IgG antibody detection were approximately 97.1% (347 of 357), 95.3% (204 of 214), and 4.67% (10 of 214), respectively. It also indicated that during approximately 2 weeks, most individuals were both IgM positive and IgG positive, accounting for 68.57% (72 of 105). During approximately 3 weeks, the proportion of IgM-positive and IgG-positive individuals decreased to 8.57% (9 of 105), and the proportion of IgM-negative and IgG-positive individuals increased to 76.19% (80 of 105). Conclusions.— There are highlighted prospects of IgM/IgG antibody detection as a preferred method in identifying the individuals with asymptomatic SARS-CoV-2 infection, especially combined with nucleic acid tests and pulmonary CT scanning.

scholarly journals Optimize Clinical Laboratory Diagnosis of COVID-19 from Suspect Cases by Likelihood Ratio of SARS-CoV-2 IgM and IgG antibody

2020 ◽  
Author(s):  
Feng Yangchun
Keyword(s):  
Nucleic Acid ◽  
Likelihood Ratio ◽  
Posterior Probability ◽  
Clinical Laboratory ◽  
Laboratory Diagnosis ◽  
Antibody Detection ◽  
Nucleic Acid Detection ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Antibody Tests

ObjectiveTo optimize clinical laboratory diagnosis of COVID-19 from suspect cases by Likelihood Ratio of SARS-CoV-2 IgM and IgG antibody.MethodsBy reinterpreting the data in the article “Diagnostic Value of Combined Detection of Serum 2019 novel coronavirus IgM and IgG Antibodies in novel coronavirusin Infection”, the positive likelihood ratio of IgM and IgG antibody in diagnosis of COVID-19 (nucleic acid positive patients) was calculated, and the posterior probability of IgM and IgG antibodies and their tandem detection to diagnose was finally calculated.ResultsThe positive likelihood ratios of single IgM and IgG antibody were 18.50 and 12.65 respectively, and the posterior probabilities were 90.18% and 86.26% respectively. However, the posterior probability of the two antibodies tandem detection is 99.15%, which can give clinicians quantitative confidence in the diagnosis of COVID-19 from suspected cases. According to the results of this study, combining the advantages and disadvantages of nucleic acid detection and antibody detection, the clinical pathway for clinicians to diagnose COVID-19 is found.ConclusionFor suspected cases, IgM and IgG antibody tests should be firstly done at the same time. If the antibody tests are all positive, COVID-19 can be confirmed. If not, nucleic acid detection (one or more times) is performed, and in extreme cases, high-throughput viral genome sequencing is performed.

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