scholarly journals Stringent thresholds for SARS-CoV-2 IgG assays result in under-detection of cases reporting loss of taste/smell

2020 ◽  
Author(s):  
David W Eyre ◽  
Sheila F Lumley ◽  
Denise O'Donnell ◽  
Nicole E Stoesser ◽  
Philippa C Matthews ◽  
...  
Keyword(s):  
Asymptomatic Infection ◽  
Negative Results ◽  
Diagnostic Thresholds ◽  
Assay Performance ◽  
Hospitalised Patients ◽  
Antibody Assays ◽  
Antibody Titres ◽  
Chemiluminescent Microparticle Immunoassay ◽  
Test Probability ◽  
Abbott Architect

Thresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. Assay performance following mild/asymptomatic infection is unclear. We assessed IgG responses in asymptomatic healthcare workers with a high pre-test probability of Covid-19, e.g. 807/9292(8.9%) reported loss of smell/taste. The proportion reporting anosmia/ageusia increased at antibody titres below diagnostic thresholds for both an in-house ELISA and the Abbott Architect chemiluminescent microparticle immunoassay (CMIA): 424/903(47%) reported anosmia/ageusia with a positive ELISA, 59/387(13.2%) with high-negative titres, and 324/7943(4.1%) with low-negative results. Adjusting for the proportion of staff reporting anosmia/ageusia suggests the sensitivity of both assays is lower than previously reported: Oxford ELISA 90.8% (95%CI 86.1-92.1%) and Abbott CMIA 80.9% (77.5-84.3%). However, the sensitivity may be lower if some anosmia/ageusia in those with low-negative titres is Covid-19-associated. Samples from individuals with mild/asymptomatic infection should be included in SARS-CoV-2 immunoassay evaluations. Reporting equivocal SARS-CoV-2 antibody results should be considered.

scholarly journals Stringent thresholds in SARS-CoV-2 IgG assays lead to under-detection of mild infections

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
David W. Eyre ◽  
Sheila F. Lumley ◽  
Denise O’Donnell ◽  
Nicole E. Stoesser ◽  
Philippa C. Matthews ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Antibody Assay ◽  
Diagnostic Thresholds ◽  
Assay Performance ◽  
Hospitalised Patients ◽  
Antibody Assays ◽  
Chemiluminescent Microparticle Immunoassay ◽  
Result Interpretation ◽  
Test Probability ◽  
Abbott Architect

Abstract Background Thresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. In this setting the sensitivity and specificity of the best performing assays can both exceed 98%. However, antibody assay performance following mild infection is less clear. Methods We assessed quantitative IgG responses in a cohort of healthcare workers in Oxford, UK, with a high pre-test probability of Covid-19, in particular the 991/11,475(8.6%) who reported loss of smell/taste. We use anosmia/ageusia and other risk factors as probes for Covid-19 infection potentially undiagnosed by immunoassays by investigating their relationship with antibody readings either side of assay thresholds. Results The proportion of healthcare workers reporting anosmia/ageusia increased at antibody readings below diagnostic thresholds using an in-house ELISA (n = 9324) and the Abbott Architect chemiluminescent microparticle immunoassay (CMIA; n = 11,324): 426/906 (47%) reported anosmia/ageusia with a positive ELISA, 59/449 (13.1%) with high-negative and 326/7969 (4.1%) with low-negative readings. Similarly, by CMIA, 518/1093 (47.4%) with a positive result reported anosmia/ageusia, 106/686 (15.5%) with a high-negative and 358/9563 (3.7%) with a low-negative result. Adjusting for the proportion of staff reporting anosmia/ageusia suggests the sensitivity of both assays in mild infection is lower than previously reported: Oxford ELISA 89.8% (95%CI 86.6–92.8%) and Abbott CMIA 79.3% (75.9–82.7%). Conclusion Following mild SARS-CoV-2 infection 10–30% of individuals may have negative immunoassay results. While lowered diagnostic thresholds may result in unacceptable specificity, our findings have implications for epidemiological analyses and result interpretation in individuals with a high pre-test probability. Samples from mild PCR-confirmed infections should be included in SARS-CoV-2 immunoassay evaluations.

scholarly journals Kinetics and performance of the Abbott Architect SARS-CoV-2 IgG antibody assay

2020 ◽  
Author(s):  
Fergus Hamilton ◽  
Peter Muir ◽  
Marie Attwood ◽  
Alan Noel ◽  
Barry Vipond ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Clinical Settings ◽  
Antibody Testing ◽  
Antibody Assay ◽  
Igg Antibody ◽  
Negative Results ◽  
Hospitalised Patients ◽  
And Performance ◽  
Negative Controls ◽  
Abbott Architect

ObjectivesTo assess the performance (sensitivity and specificity) of the Abbott Architect SARS-CoV-2 IgG antibody assay across three clinical settings.MethodsAntibody testing was performed on three clinical cohorts of COVID-19 disease: hospitalised patients with PCR confirmation, hospitalized patients with a clinical diagnosis but negative PCR, and symptomatic healthcare workers (HCW’s). Pre-pandemic respiratory infection sera were tested as negative controls. The sensitivity of the assay was calculated at different time points (<5 days, 5-9 days, 10-14 days, 15-19 days, >20 days, >42 days), and compared between cohorts.ResultsPerformance of the Abbot Architect SARS-CoV-2 assay varied significantly between cohorts. For PCR confirmed hospitalised patients (n = 114), early sensitivity was low: <5 days: 44.4% (95%CI: 18.9%-73.3%), 5-9 days: 32.6% (95%CI, 20.5%-47.5%), 10-14 days: 65.2% (95% CI 44.9%-81.2%), 15-20 days: 66.7% (95% CI: 39.1%-86.2%) but by day 20, sensitivity was 100% (95%CI, 86.2-100%).In contrast, 17 out of 114 symptomatic healthcare workers tested at >20 days had negative results, generating a sensitivity of 85.1% (95%CI, 77.4% - 90.5%). All pre-pandemic sera were negative, a specificity of 100%. Seroconversion rates were similar for PCR positive and PCR negative hospitalised cases.ConclusionsThe sensitivity of the Abbot Architect SARS-CoV-2 IgG assay increases over time, with sensitivity not peaking until 20 days post symptoms. Performance varied markedly by setting, with sensitivity significantly worse in symptomatic healthcare workers than in the hospitalised cohort. Clinicians, policymakers, and patients should be aware of the reduced sensitivity in this setting.

scholarly journals Impact of thyroglobulin and thyroglobulin antibody assay performance on the differential classification of DTC patients

2021 ◽  
Author(s):  
Lise Schoonen ◽  
Marjolein Neele ◽  
Hans van Toor ◽  
Caroline M J van Kinschot ◽  
Charlotte van Noord ◽  
...  
Keyword(s):  
Poor Correlation ◽  
Antibody Assay ◽  
Thyroglobulin Antibody ◽  
Assay Performance ◽  
Upper Limits ◽  
Antibody Assays ◽  
The Impact ◽  
Storage Temperatures

Abstract Context Measurements of thyroglobulin (Tg) and Tg antibodies are crucial in the follow-up of treated differentiated thyroid cancer (DTC) patients. Inter-assay differences may significantly impact follow-up. Objective The aim of this multicenter study was to explore the impact of Tg and Tg antibody assay performance on the differential classification of DTC patients, as described in national and international guidelines. Design Four commonly used Tg and Tg antibody assays were technically compared to reflect possible effects on patients with DTC follow-up. Storage stability at different storage temperatures was also investigated for LIAISON® and Kryptor assays, as this is an underexposed topic in current literature. Results B.R.A.H.M.S. assays yield approximately 50% lower Tg values over the whole range compared to the DiaSorin and Roche assays investigated. These differences between assays may result in potential misclassification in up to 7% of patients if fixed cut-offs (e.g. 1 ng/mL) are applied. Poor correlation was also observed between the Tg antibody assays, when the method-specific upper limits of normal are used as cut-offs. Storage of Tg and Tg antibodies was possible for three to four weeks at -20 °C and -80 °C. Calibration of the assays, however, was found to be crucial for stable results over time. Conclusions Technical aspects of Tg and Tg antibody assays, including inter-assay differences, calibration and standardization, and cut-off values, may have a significant clinical impact on the follow-up of DTC patients.

scholarly journals Repetition of microbiological tests in suspect of SARS-CoV-2 infection: utility of a score based on clinical probability

2020 ◽  
Vol 33 (6) ◽  
pp. 410-414
Author(s):  
Javier Pardo Lledias ◽  
Laura Ayarza ◽  
Pablo González-García ◽  
Zaida Salmón González ◽  
Jorge Calvo Montes ◽  
...  
Keyword(s):  
False Negative ◽  
Serum Lactate ◽  
University Hospital ◽  
Serum Lactate Dehydrogenase ◽  
Sampling Errors ◽  
Rt Pcr ◽  
Negative Results ◽  
Clinical Probability ◽  
Clinical Scenarios ◽  
Test Probability

Background. The diagnosis of SARS-CoV-2 infection presents some limitations. RT-PCR in nasopharyngeal swabs is considered the gold standard for the diagnosis, although it can have false negative results. We aimed to analyze the accuracy of repeating nasopharyngeal swabs based on different clinical probabilities. Methods. Retrospective observational study of the first patients admitted to a two COVID Internal Medicine wards at the University Hospital Marqués de Valdecilla, Santander, from March to April 2020. RT-PCR targering E, N, RdRP and ORFab1 genes and antibody tests detecting IgG. Results. A total of 145 hospitalized patients with suspected SARS-Cov2 infection were admitted and in 98 (67.5%) diagnosis was confirmed. The independent predictive variables for SARS-CoV-2 infection were: epidemiological contact, clinical presentation as pneumonia, absence of pneumonia in the last year, onset of symptoms > 7 days, two or more of the following symptoms -dyspnea, cough or fever- and serum lactate dehydrogenase levels >350 U/L (p<0.05). A score based on these variables yielded an AUC-ROC of 0.89 (CI95%, 0.831-0.946; p<0.001). The accuracy of the first nasopharyngeal swabs was 54.9%. Repeating nasopharyngeal swabs two or three times allows to detect an additional 16% of positive cases. The overall accuracy of successive RT-PCR tests in patients with low pre-test probability was <5%. Conclusions. We have defined a pre-test probability score based on epidemiological and clinical data with a high accuracy for diagnosis of SARS-CoV-2. Repeating nasopharyngeal swabs avoids sampling errors, but only in medium of high probability pre-test clinical scenarios.

scholarly journals Clinical utility of targeted SARS-CoV-2 serology testing to aid the diagnosis and management of suspected missed, late or post-COVID-19 infection syndromes: Results from a pilot service implemented during the first pandemic wave

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249791
Author(s):  
Nicola Sweeney ◽  
Blair Merrick ◽  
Rui Pedro Galão ◽  
Suzanne Pickering ◽  
Alina Botgros ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Performance Characteristics ◽  
Direct Care ◽  
Serological Testing ◽  
Internal Validation ◽  
Assay Performance ◽  
Adults And Children ◽  
Test Probability

During the first wave of the global COVID-19 pandemic the clinical utility and indications for SARS-CoV-2 serological testing were not clearly defined. The urgency to deploy serological assays required rapid evaluation of their performance characteristics. We undertook an internal validation of a CE marked lateral flow immunoassay (LFIA) (SureScreen Diagnostics) using serum from SARS-CoV-2 RNA positive individuals and pre-pandemic samples. This was followed by the delivery of a same-day named patient SARS-CoV-2 serology service using LFIA on vetted referrals at central London teaching hospital with clinical interpretation of result provided to the direct care team. Assay performance, source and nature of referrals, feasibility and clinical utility of the service, particularly benefit in clinical decision-making, were recorded. Sensitivity and specificity of LFIA were 96.1% and 99.3% respectively. 113 tests were performed on 108 participants during three-week pilot. 44% participants (n = 48) had detectable antibodies. Three main indications were identified for serological testing; new acute presentations potentially triggered by recent COVID-19 e.g. pulmonary embolism (n = 5), potential missed diagnoses in context of a recent COVID-19 compatible illness (n = 40), and making infection control or immunosuppression management decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n = 6). We demonstrate acceptable performance characteristics, feasibility and clinical utility of using a LFIA that detects anti-spike antibodies to deliver SARS-CoV-2 serology service in adults and children. Greatest benefit was seen where there is reasonable pre-test probability and results can be linked with clinical advice or intervention. Experience from this pilot can help inform practicalities and benefits of rapidly implementing new tests such as LFIAs into clinical service as the pandemic evolves.

scholarly journals GROUND GLASS OPACITY- (GGO) MIMICS AND ITS CHAMELEONS IN THE ED A LITERATURE REVIEW

2021 ◽  
pp. 11-14
Author(s):  
Mamatha Reddy Chanduputla ◽  
Vishwa Reddy Gankidi ◽  
Rakesh C Reddy
Keyword(s):  
Health Care ◽  
Care Delivery ◽  
Point Of Care ◽  
Ground Glass Opacity ◽  
Asymptomatic Infection ◽  
Viral Pneumonia ◽  
Ground Glass ◽  
Upper Respiratory Tract ◽  
Negative Results ◽  
The Common

Background : The COVID-19 pandemic has created an unprecedented health care crisis with, disruptions in both routine and emergency health care delivery and immense strain on health care resources . The clinical spectrum of disease with coronavirus disease (COVID-19) infection is variable and ranges from an asymptomatic infection or mild upper respiratory tract illness to severe viral pneumonia with respiratory failure and occasionally death. In a resourceconstrained environment with a high community burden of the disease and rapid point-of-care testing either unavailable or showing negative results, CT has been used to rapidly triage patients into non COVID-19, possible COVID-19, or most likely COVID-19 . As per the Fleischner Society consensus statement, CT is appropriate in certain scenarios, including for patients who are at risk for and/or develop clinical worsening .The common chest CT findings of COVID-19 are multiple ground glass opacity(most common), consolidation and interlobular septal thickening in both lungs, which are mostly distributed under the pleura. The ground-glass opacities are usually peripherally located with the lower lobes being commonly involved. Imaging differentiation is important for management and isolation purposes and for appropriate disposition of patients . (1,7) The purpose of this article is to discuss the common presentations of emergency department with ground glass opacities and to review the differential diagnosis of typical imaging findings of COVID-19. Ground glass opacities appear in a variety of disease processes of emergenc Conclusion : y department presentations . Not all presentations with GGO” s have SARS COV2 or Covid -19 viral pneumonia .

scholarly journals Assessment of Commercial SARS-CoV-2 Antibody Assays, Jamaica

2020 ◽  
Author(s):  
Tiffany R Butterfield ◽  
Alrica Bruce-Mowatt ◽  
Yakima Z R Phillips ◽  
Nicole Brown ◽  
Keisha Francis ◽  
...  
Keyword(s):  
Viral Infections ◽  
Nasopharyngeal Swab ◽  
Serum Samples ◽  
Rapid Assays ◽  
Wide Range ◽  
Antibody Assays ◽  
Sample Testing ◽  
English Speaking ◽  
Caribbean Population ◽  
Abbott Architect

The performance of the Roche Elecsys® Anti-SARS-CoV-2, Abbott Architect SARS-CoV-2 IgG, Euroimmun SARS-CoV-2 IgA, Euroimmun SARS-CoV-2 IgG ELISA, and Trillium IgG/IgM rapid assays was evaluated in Jamaica, the largest country of the English-speaking Caribbean. Diagnostic sensitivities of the assays were assessed by testing serum samples from SARS-CoV-2 PCR-confirmed persons. Serum samples collected ≥14 days after onset of symptoms, or ≥14 days after an initial SARS-CoV-2 RT-PCR positive test for asymptomatics, showed diagnostic sensitivities ranging from 67.9-75.0% when including all possible disease severities and increased to 90.0-95.0% when examining those with moderate to critical disease. Grouping moderate to critical disease showed a significant association with a SARS-CoV-2 antibody positive result for all assays. Diagnostic specificity, assessed by testing serum samples collected during 2018-2019 from healthy persons and from persons with antibodies to a wide range of viral infections, ranged from 96.7-100.0%. For all assays examined, SARS-CoV-2 real-time PCR cycle threshold (Ct) values of the initial nasopharyngeal swab sample testing positive were significantly different for samples testing antibody positive versus negative. These data from a predominantly African descent Caribbean population shows comparable diagnostic sensitivities and specificities for all testing platforms assessed and limited utility of these tests for persons with asymptomatic and mild infections.

scholarly journals Typically asymptomatic but with robust antibody formation: Childrens unique humoral immune response to SARS-CoV-2

2021 ◽  
Author(s):  
Hanna Renk ◽  
Alex Dulovic ◽  
Matthias Becker ◽  
Dorit Fabricius ◽  
Maria Zernickel ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Age Groups ◽  
Asymptomatic Infection ◽  
Serological Response ◽  
Vaccination Programs ◽  
Humoral Immune ◽  
Viral Spread ◽  
Antibody Assays

Background: Long-term persistence of antibodies against SARS-CoV-2, particularly the SARS-CoV-2 Spike Trimer, determines individual protection against infection and potentially viral spread. The quality of children's natural humoral immune response following SARS-CoV-2 infection is yet incompletely understood but crucial to guide pediatric SARS-CoV-2 vaccination programs. Methods: In this prospective observational multi-center cohort study, we followed 328 households, consisting of 548 children and 717 adults, with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. The serological response was assessed at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Results: Overall, 33.76% of SARS-CoV-2 exposed children and 57.88% adults were seropositive. Children were five times more likely to have seroconverted without symptoms compared to adults. Despite the frequently asymptomatic course of infection, children had higher specific antibody levels, and their antibodies persisted longer than in adults (96.22% versus 82.89% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induced similar humoral responses in all age groups. In symptomatic children, only dysgeusia was found as diagnostic indicator of COVID-19. SARS-CoV-2 infections occurred independent of HCoV serostatus. Antibody binding responses to VOCs were similar in children and adults, with reduced binding for the Beta variant in both groups. Conclusions: The long-term humoral immune response to SARS-CoV-2 infection in children is robust and may provide long-term protection even after asymptomatic infection. (Study ID at German Clinical Trials Register: 00021521)

Sign in / Sign up

Export Citation Format

Share Document