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Mary Gaeddert

Other affiliations: University Hospital Heidelberg
Bio: Mary Gaeddert is an academic researcher from Heidelberg University. The author has contributed to research in topics: Rapid diagnostic test & Antibody titer. The author has an hindex of 8, co-authored 15 publications receiving 198 citations. Previous affiliations of Mary Gaeddert include University Hospital Heidelberg.

Papers
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Posted ContentDOI
01 Mar 2021-medRxiv
TL;DR: In this article, a systematic review and meta-analysis of commercially available rapid diagnostic tests (Ag-RDTs) is presented, where the clinical accuracy (sensitivity and specificity) of these tests are assessed.
Abstract: Background SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. Methods We registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FINDdx) for publications up until December 11th, 2020. Descriptive analyses of all studies were performed and when more than four studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcriptase polymerase chain reaction testing. We assessed heterogeneity by subgroup analyses ((1) performed con-form with manufacturer’s instructions for use (IFU) or not, (2) symptomatic vs. asymptomatic, (3) duration of symptoms less than seven days vs. more than seven days, (4) Ct-value Results From a total of 11,715 articles, we extracted 98 analytical and clinical data sets. 74 clinical accuracy data sets were evaluated that included 31,202 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 73.8% (CI 68.6 to 78.5). If analysis was restricted to studies that followed the Ag-RDT manufacturers’ instructions using fresh upper respiratory swab samples, the sensitivity increased to 79.1% (95%CI 75.0 to 82.8). The SD Biosensor Standard Q and Abbott Panbio showed the highest sensitivity with 81.7% and 72.7%, respectively. The best Ag-RDT performance was found with nasopharyngeal sampling (77.3%, CI 72.0 to 81.9) in comparison to other sample types (e.g., anterior nasal or mid turbinate 63.5%, CI 49.5 to 75.5). Testing in the first week from symptom onset resulted in higher sensitivity (87.5%, CI 86.0 to 89.1) compared to testing after one week (64.1%, CI 54.4 to 73.8). The tests performed markedly better on samples with lower Ct-values, i.e., Conclusion As Ag-RDTs detect most cases within the first week of symptom onset and those with high viral load, they can have high utility for screening purposes in the early phase of disease, and thus can be a valuable tool to fight the spread of SARS-CoV-2. Standardization of conduct and reporting of clinical accuracy studies would improve comparability and use of data. Summary In this living systematic review we analyzed 98 data sets for performance of SARS-CoV-2 Ag-RDTs compared to RT-PCR. Best-performing tests achieved a sensitivity of 81.7%. Highest sensitivity was found in patients within seven days of symptom onset when NP swabs were utilized.

166 citations

Posted ContentDOI
04 Oct 2020-medRxiv
TL;DR: There is large variability in performance of Ag-RDT tests with one test showing promise and these tests are likely to have impact despite imperfect sensitivity; however further research and modelling are needed.
Abstract: Background Reliable point-of-care (POC) diagnostics not requiring laboratory infrastructure could be a game changer in the COVID-19 pandemic, particularly in the Global South. We assessed performance, limit of detection and ease-of-use of three antigen-detecting, rapid POC tests (Ag-RDT) for SARS-CoV-2. Methods This prospective, multi-centre diagnostic accuracy study recruited participants suspected to have SARS-CoV-2 in Germany and the UK. Paired nasopharyngeal swabs (NP) or NP and/or oropharyngeal swabs (OP) were collected from participants (one for clinical RT-PCR and one for Ag-RDT). Performance of each of three Ag-RDTs was compared to RT-PCR overall, and according to predefined subcategories e.g. cycle threshold (CT)-value, days from symptoms onset, etc. In addition, limited verification of the analytical limit-of-detection (LOD) was determined. To understand the usability a System Usability Scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed. Results Between April 17th and August 25th, 2020, 2417 participants were enrolled, with 70 (3.0%) testing positive by RT-PCR. The best-performing test (SD Biosensor, Inc. STANDARD Q) was 76×6% (95% Confidence Interval (CI) 62×8-86×4) sensitive and 99×3% (CI 98×6-99×6) specific. A sub-analysis showed all samples with RT-PCR CT-values Conclusion There is large variability in performance of Ag-RDT with SD Biosensor showing promise. Given the usability at POC, this test is likely to have impact despite imperfect sensitivity; however further research and modelling are needed.

82 citations

Journal ArticleDOI
01 May 2021-PLOS ONE
TL;DR: In this paper, the authors evaluated the performance and ease-of-use of the Abbott PanBio antigen-detecting rapid diagnostic test (Ag-RDT) for SARS-CoV-2 testing.
Abstract: OBJECTIVES: Diagnostics are essential for controlling the pandemic. Identifying a reliable and fast diagnostic device is needed for effective testing. We assessed performance and ease-of-use of the Abbott PanBio antigen-detecting rapid diagnostic test (Ag-RDT). METHODS: This prospective, multi-centre diagnostic accuracy study enrolled at two sites in Germany. Following routine testing with reverse-transcriptase polymerase chain reaction (RT-PCR), a second study-exclusive swab was performed for Ag-RDT testing. Routine swabs were nasopharyngeal (NP) or combined NP/oropharyngeal (OP) whereas the study-exclusive swabs were NP. To evaluate performance, sensitivity and specificity were assessed overall and in predefined sub-analyses accordingly to cycle-threshold values, days after symptom onset, disease severity and study site. Additionally, an ease-of-use assessment (EoU) and System Usability Scale (SUS) were performed. RESULTS: 1108 participants were enrolled between Sept 28 and Oct 30, 2020. Of these, 106 (9.6%) were PCR-positive. The Abbott PanBio detected 92/106 PCR-positive participants with a sensitivity of 86.8% (95% CI: 79.0% - 92.0%) and a specificity of 99.9% (95% CI: 99.4%-100%). The sub-analyses indicated that sensitivity was 95.8% in Ct-values <25 and within the first seven days from symptom onset. The test was characterized as easy to use (SUS: 86/100) and considered suitable for point-of-care settings. CONCLUSION: The Abbott PanBio Ag-RDT performs well for SARS-CoV-2 testing in this large manufacturer independent study, confirming its WHO recommendation for Emergency Use in settings with limited resources.

44 citations

Journal ArticleDOI
TL;DR: In this article, a head-to-head comparison of diagnostic accuracy of patient self-testing with professional testing using a SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) was performed.

36 citations

Posted ContentDOI
27 Oct 2020-medRxiv
TL;DR: Supervised self-sampling from the anterior nose is a reliable alternative to professional nasopharyngeal sampling using a WHO-listed SARS-CoV-2 Ag-RDT, STANDARD Q COVID-19 Ag Test (SD Biosensor), which is also being distributed by Roche.
Abstract: Background Two antigen-detecting rapid diagnostic tests (Ag-RDTs) are now approved through the WHO Emergency Use Listing procedure and can be performed at the point-of-care. However, both tests use nasopharyngeal (NP) swab samples. NP swab samples must be collected by trained healthcare personnel with protective equipment and are frequently perceived as uncomfortable by patients. Methods This was a manufacturer-independent, prospective diagnostic accuracy study with comparison of a supervised, self-collected anterior nose (AN) swab sample with a professional-collected NP swab sample, using a WHO-listed SARS-CoV-2 Ag-RDT, STANDARD Q COVID-19 Ag Test (SD Biosensor), which is also being distributed by Roche. The reference standard was RT-PCR from an oro-/nasopharyngeal swab sample. Percent positive and negative agreement as well as sensitivity and specificity were calculated. Results Among the 289 participants, 39 (13.5%) tested positive for SARS-CoV-2 by RT-PCR. The positive percent agreement of the two different sampling techniques for the Ag-RDT was 90.6% (CI 75.8-96.8). The negative percent agreement was 99.2% (CI 97.2-99.8). The Ag-RDT with AN sampling showed a sensitivity of 74.4% (29/39 PCR positives detected; CI 58.9-85.4) and specificity of 99.2% (CI 97.1-99.8) compared to RT-PCR. The sensitivity with NP sampling was 79.5% (31/39 PCR positives detected; CI 64.5-89.2) and specificity was 99.6% (CI 97.8-100). In patients with high viral load (>7.0 log 10 RNA SARS-CoV2/swab), the sensitivity of the Ag-RDT with AN sampling was 96% and 100% with NP sampling. Conclusion Supervised self-sampling from the anterior nose is a reliable alternative to professional nasopharyngeal sampling using a WHO-listed SARS-CoV-2 Ag-RDT. Considering the ease-of-use of Ag-RDTs, self-sampling and potentially patient self-testing at home may be a future use case.

36 citations


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Journal ArticleDOI
07 Apr 2021
TL;DR: The sensitivity range of most AgPOCTs overlaps with SARS-CoV-2 viral loads typically observed in the first week of symptoms, which marks the infectious period in most patients.
Abstract: Summary Background Antigen point-of-care tests (AgPOCTs) can accelerate SARS-CoV-2 testing. As some AgPOCTs have become available, interest is growing in their utility and performance. Here we aimed to compare the analytical sensitivity and specificity of seven commercially available AgPOCT devices. Methods In a single-centre, laboratory evaluation study, we compared AgPOCT products from seven suppliers: the Abbott Panbio COVID-19 Ag Rapid Test, the RapiGEN BIOCREDIT COVID-19 Ag, the Healgen Coronavirus Ag Rapid Test Cassette (Swab), the Coris BioConcept COVID-19 Ag Respi-Strip, the R-Biopharm RIDA QUICK SARS-CoV-2 Antigen, the nal von minden NADAL COVID-19 Ag Test, and the Roche-SD Biosensor SARS-CoV Rapid Antigen Test. Tests were evaluated on recombinant SARS-CoV-2 nucleoprotein, cultured endemic and emerging coronaviruses, stored respiratory samples with known SARS-CoV-2 viral loads, stored samples from patients with respiratory pathogens other than SARS-CoV-2, and self-sampled swabs from healthy volunteers. We estimated analytical sensitivity in terms of approximate viral concentrations (quantified by real-time RT-PCR) that yielded positive AgPOCT results, and specificity in terms of propensity to generate false-positive results. Findings In 138 clinical samples with quantified SARS-CoV-2 viral load, the 95% limit of detection (concentration at which 95% of test results were positive) in six of seven AgPOCT products ranged between 2·07 × 106 and 2·86 × 107 copies per swab, with an outlier (RapiGEN) at 1·57 × 1010 copies per swab. The assays showed no cross-reactivity towards cell culture or tissue culture supernatants containing any of the four endemic human coronaviruses (HCoV‑229E, HCoV‑NL63, HCoV‑OC43, or HCoV‑HKU1) or MERS-CoV, with the exception of the Healgen assay in one repeat test on HCoV-HKU1 supernatant. SARS-CoV was cross-detected by all assays. Cumulative specificities among stored clinical samples with non-SARS-CoV-2 infections (n=100) and self-samples from healthy volunteers (n=35; cumulative sample n=135) ranged between 98·5% (95% CI 94·2–99·7) and 100·0% (97·2–100·0) in five products, with two outliers at 94·8% (89·2–97·7; R-Biopharm) and 88·9% (82·1–93·4; Healgen). False-positive results did not appear to be associated with any specific respiratory pathogen. Interpretation The sensitivity range of most AgPOCTs overlaps with SARS-CoV-2 viral loads typically observed in the first week of symptoms, which marks the infectious period in most patients. The AgPOCTs with limit of detections that approximate virus concentrations at which patients are infectious might enable shortcuts in decision making in various areas of health care and public health. Funding EU's Horizon 2020 research and innovation programme, German Ministry of Research, German Federal Ministry for Economic Affairs and Energy, German Ministry of Health, and Bill & Melinda Gates Foundation.

218 citations

Journal ArticleDOI
TL;DR: In this paper, the authors systematically searched PubMed, Google Scholar, medRxiv, and bioRXiv (last retrieval 1 October 2020) for comparative studies of alternative sample types (saliva, oropharyngeal [OP], and nasal [NS] swabs) versus NP swabs for SARS-CoV-2 diagnosis using nucleic acid amplification testing (NAAT).
Abstract: Nasopharyngeal (NP) swabs are considered the highest-yield sample for diagnostic testing for respiratory viruses, including SARS-CoV-2. The need to increase capacity for SARS-CoV-2 testing in a variety of settings, combined with shortages of sample collection supplies, have motivated a search for alternative sample types with high sensitivity. We systematically reviewed the literature to understand the performance of alternative sample types compared to NP swabs. We systematically searched PubMed, Google Scholar, medRxiv, and bioRxiv (last retrieval 1 October 2020) for comparative studies of alternative specimen types (saliva, oropharyngeal [OP], and nasal [NS] swabs) versus NP swabs for SARS-CoV-2 diagnosis using nucleic acid amplification testing (NAAT). A logistic-normal random-effects meta-analysis was performed to calculate % positive alternative-specimen, % positive NP, and % dual positives overall and in subgroups. The QUADAS 2 tool was used to assess bias. From 1,253 unique citations, we identified 25 saliva, 11 NS, 6 OP, and 4 OP/NS studies meeting inclusion criteria. Three specimen types captured lower % positives (NS [82%, 95% CI: 73 to 90%], OP [84%, 95% CI: 57 to 100%], and saliva [88%, 95% CI: 81 to 93%]) than NP swabs, while combined OP/NS matched NP performance (97%, 95% CI: 90 to 100%). Absence of RNA extraction (saliva) and utilization of a more sensitive NAAT (NS) substantially decreased alternative-specimen yield of positive samples. NP swabs remain the gold standard for diagnosis of SARS-CoV-2, although alternative specimens are promising. Much remains unknown about the impact of variations in specimen collection, processing protocols, and population (pediatric versus adult, late versus early in disease course), such that head-to head studies of sampling strategies are urgently needed.

184 citations

Journal ArticleDOI
TL;DR: A systematic review and meta-analysis of commercially available rapid diagnostic tests (Ag-RDTs) for SARS-CoV-2 up until 30 April 2021 was conducted in this paper.
Abstract: Background SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. Methods and findings We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers’ instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies’ heterogeneity in design and reporting. Conclusions In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.

181 citations

Posted ContentDOI
01 Mar 2021-medRxiv
TL;DR: In this article, a systematic review and meta-analysis of commercially available rapid diagnostic tests (Ag-RDTs) is presented, where the clinical accuracy (sensitivity and specificity) of these tests are assessed.
Abstract: Background SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. Methods We registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FINDdx) for publications up until December 11th, 2020. Descriptive analyses of all studies were performed and when more than four studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcriptase polymerase chain reaction testing. We assessed heterogeneity by subgroup analyses ((1) performed con-form with manufacturer’s instructions for use (IFU) or not, (2) symptomatic vs. asymptomatic, (3) duration of symptoms less than seven days vs. more than seven days, (4) Ct-value Results From a total of 11,715 articles, we extracted 98 analytical and clinical data sets. 74 clinical accuracy data sets were evaluated that included 31,202 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 73.8% (CI 68.6 to 78.5). If analysis was restricted to studies that followed the Ag-RDT manufacturers’ instructions using fresh upper respiratory swab samples, the sensitivity increased to 79.1% (95%CI 75.0 to 82.8). The SD Biosensor Standard Q and Abbott Panbio showed the highest sensitivity with 81.7% and 72.7%, respectively. The best Ag-RDT performance was found with nasopharyngeal sampling (77.3%, CI 72.0 to 81.9) in comparison to other sample types (e.g., anterior nasal or mid turbinate 63.5%, CI 49.5 to 75.5). Testing in the first week from symptom onset resulted in higher sensitivity (87.5%, CI 86.0 to 89.1) compared to testing after one week (64.1%, CI 54.4 to 73.8). The tests performed markedly better on samples with lower Ct-values, i.e., Conclusion As Ag-RDTs detect most cases within the first week of symptom onset and those with high viral load, they can have high utility for screening purposes in the early phase of disease, and thus can be a valuable tool to fight the spread of SARS-CoV-2. Standardization of conduct and reporting of clinical accuracy studies would improve comparability and use of data. Summary In this living systematic review we analyzed 98 data sets for performance of SARS-CoV-2 Ag-RDTs compared to RT-PCR. Best-performing tests achieved a sensitivity of 81.7%. Highest sensitivity was found in patients within seven days of symptom onset when NP swabs were utilized.

166 citations

Journal ArticleDOI
TL;DR: In this article, a nanobody-functionalized organic electrochemical transistors with a modular architecture for the rapid quantification of single-molecule-to-nanomolar levels of specific antigens in complex bodily fluids is presented.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid and sensitive protein detection and quantification in simple and robust formats for widespread point-of-care applications. Here, we report on nanobody-functionalized organic electrochemical transistors with a modular architecture for the rapid quantification of single-molecule-to-nanomolar levels of specific antigens in complex bodily fluids. The sensors combine a solution-processable conjugated polymer in the transistor channel and high-density and orientation-controlled bioconjugation of nanobody–SpyCatcher fusion proteins on disposable gate electrodes. The devices provide results after 10 min of exposure to 5 μl of unprocessed samples, maintain high specificity and single-molecule sensitivity in human saliva and serum, and can be reprogrammed to detect any protein antigen if a corresponding specific nanobody is available. We used the sensors to detect green fluorescent protein, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV) spike proteins, and for the COVID-19 screening of unprocessed clinical nasopharyngeal swab and saliva samples with a wide range of viral loads. Organic electrochemical transistors functionalized with antigen-specific nanobodies can rapidly detect attomolar-to-nanomolar levels of the antigens in complex bodily fluids.

161 citations