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Virus mutations have the potential to impact the accuracy of diagnostic tests. The SARS-CoV-2 B.1.1.7 lineage is defined by a large number of mutations in the spike gene and four in the nucleocapsid (N) gene. Most commercially available SARS-CoV-2 antigen-detecting rapid tests (Ag-RDTs) target the viral N-protein, encoded by the N-gene. We conducted a manufacturer-independent, prospective diagnostic accuracy study of three SARS-CoV-2 Ag-RDTs that are currently under review by the WHO Emergency Use Listing Procedure (Espline -Fujirebio Inc.; Sure Status -Premier Medical Corporation Private Limited; Mologic -Mologic Ltd.) and report here on an additional sub-analysis regarding the B.1.1.7 lineage. During the study, in Berlin and Heidelberg, Germany, from 20 January to 15 April 2021, B.1.1.7 rapidly became the dominant SARS-CoV-2 lineage at the testing sites and was detected in 220 (62%) of SARS-CoV-2 RT-PCR positive patients. All three Ag-RDTs yielded comparable sensitivities irrespective of an infection with the B.1.1.7 lineage or not. There is only limited data on how N-gene mutations in variants of concern may impact Ag-RDTs. Currently, no major changes to test performance are anticipated. However, test developers and health authorities should assess and monitor the impact of emerging variants on the accuracy of Ag-RDTs.
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Summary/AbstractO_ST_ABSIntroductionC_ST_ABSContainment of the COVID-19 pandemic requires broad-scale testing. Laboratory capacities for real-time-PCR were increased, and are complemented by Ag-tests. However, sample-collection still requires qualified personnel and protective equipement, may produce transmission to others during conduct and travel, and is perceived uncomfortable. We tested sensitivity of three simplified self-sampling techniques compared to professional-collected combined oro-nasopharyngeal samples (cOP/NP). MethodsFrom 62 symptomatic COVID-19 outpatients, we obtained simultaneously three self- and one professional-collected sample after initial confirmation in a testing centre: (i) combination swab (tongue, cheek, both nasal vestibula, MS, (ii) saliva sponge combined with both nasal vestibula, SN, and (iii) gargled tap water, GW, (iv) professionally-collected cOP/NP (standard). We compared the results of SARS-CoV-2 PCR-assays detecting E-gene and ORF1ab for the different sample types and performed bivariate statistical analysis to determine the variables reducing sensitivity of the self-collecting procedures. ResultsSARS-CoV-2 RNA was detected in all 62 professionally-collected cOP/NP. MS and SN samples showed a sensitivity of 95.2% (95%CI 86.5-99.0) and GW samples of 88.7% (78.1-95.3). Compared to the median ct-values of cOP/NP samples for E-gene (20.7) and ORF1ab (20.2) these were higher for MS (22.6 and 21.8), SN (23.3 and 22.3), and for GW (30.3 and 29.8). For MS and SN samples but not for GW specimens, false negativity in bivariate analysis was associated with non-German mother-tongue, number of sampling errors, and with symptom duration. For symptom duration of [≤]8 days, test sensitivity for SN samples was 98.2% (95%CI 90.4-100.0) and for MS 96.4% (95%CI 87.7-99.6) and drops after day 8 below 90%. DiscussionThe study is limited to sensitivity of self-collection in symptomatic patients. Still, in this group, self-collected oral/nasal/saliva samples are reliable alternatives to professional-collected cOP/NP samples, if symptom duration does not exceed eight days and operational errors are minimized. Self-sampling could contribute to up-scaling of safe and efficient testing.
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BackgroundIn 2020, the World Health Organization (WHO) recommended two SARS-CoV-2 lateral flow antigen detecting rapid diagnostics tests (Ag-RDTs), both initially with nasopharyngeal (NP) sample collection. Independent head-to-head studies demonstrated for SARS-CoV-2 Ag-RDTs nasal sampling to be a comparable and reliable alternative for nasopharyngeal (NP) sampling. MethodsWe conducted a head-to-head comparison study of a supervised, self-collected nasal mid-turbinate (NMT) swab and a professional-collected NP swab, using the Panbio Ag-RDT (the second WHO-listed SARS-CoV-2 Ag-RDT, distributed by Abbott). We calculated positive and negative percent agreement and, compared to the reference standard reverse transcription polymerase chain reaction (RT-PCR), sensitivity and specificity for both sampling techniques. ResultsA SARS-CoV-2 infection could be diagnosed by RT-PCR in 45 of 290 participants (15.5%). Comparing the NMT and NP sampling the positive percent agreement of the Ag-RDT was 88.1% (37/42 PCR positives detected; CI 75.0% - 94.8%). The negative percent agreement was 98.8% (245/248; CI 96.5% - 99.6%). The overall sensitivity of Panbio with NMT sampling was 84.4% (38/45; CI 71.2% - 92.3%) and 88.9% (40/45; CI 76.5% - 95.5%) with NP sampling. Specificity was 99.2% (243/245; CI 97.1% - 99.8%) for both, NP and NMT sampling. The sensitivity of the Panbio test in participants with high viral load (> 7 log10 SARS-CoV-2 RNA copies/mL) was 96.3% (CI 81.7% - 99.8%) for both, NMT and NP sampling. ConclusionFor the Panbio Ag-RDT supervised NMT self-sampling yields to results comparable to NP sampling. This suggests that nasal self-sampling could be used for scale-up population testing.
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ObjectivesThe aim of this diagnostic accuracy study was direct comparison of two different nasal sampling methods for an antigen-based rapid diagnostic test (Ag-RDT) that detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, the accuracy and feasibility of self-sampling was evaluated. MethodsThis manufacturer-independent, prospective diagnostic accuracy study, compared professional anterior nasal (AN) and nasal mid-turbinate (NMT) sampling for a WHO-listed SARS-CoV-2 Ag-RDT. A second group of participants collected a NMT sample themselves and underwent a professional nasopharyngeal swab for comparison. The reference standard was real-time polymerase chain reaction (RT-PCR) using combined oro-/nasopharyngeal sampling. Individuals with high suspicion of SARS-CoV-2 infection were tested. Sensitivity, specificity, and percent agreement were calculated. Self-sampling was observed without intervention. Feasibility was evaluated by observer and participant questionnaires. ResultsAmong 132 symptomatic adults, both professional AN- and NMT-sampling yielded a sensitivity of 86.1% (31/36 RT-PCR positives detected; 95%CI: 71.3-93.9) and a specificity of 100.0% (95%CI: 95.7-100). The positive percent agreement (PPA) was 100% (95%CI: 89.0-100). Among 96 additional adults, self NMT- and professional NP-sampling yielded an identical sensitivity of 91.2% (31/34; 95%CI 77.0-97.0). Specificity was 98.4% (95%CI: 91.4-99.9) with NMT- and 100.0% (95%CI: 94.2-100) with NP-sampling. The PPA was 96.8% (95%CI: 83.8-99.8). Most participants (85.3%) considered self-sampling as easy to perform. ConclusionProfessional AN- and NMT-sampling are of equivalent accuracy for an Ag-RDT in ambulatory symptomatic adults. Participants were able to reliably perform the NMT-sampling themselves, following written and illustrated instructions. Nasal self-sampling will likely facilitate scaling of SARS-CoV-2 antigen testing.
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BackgroundAntigen-detecting rapid diagnostic tests (Ag-RDTs) have been widely recommended as a complement to RT-PCR. Considering the possibility of nasal self-sampling and the ease-of-use in performing the test, self-testing may be an option. Methods and FindingsWe performed a manufacturer-independent, prospective diagnostic accuracy study of nasal mid-turbinate self-sampling and self-testing when using a WHO-listed SARS-CoV-2 Ag-RDT. Symptomatic participants suspected to have COVID-19 received written and illustrated instructions. Procedures were observed without intervention. For comparison, Ag-RDTs with nasopharyngeal sampling were professionally performed. Estimates of agreement, sensitivity, and specificity relative to RT-PCR on a combined oro-/nasopharyngeal sample were calculated. Feasibility was evaluated by observer and participant questionnaires. Among 146 symptomatic adults, 40 (27.4%) were RT-PCR-positive for SARS-CoV-2. Sensitivity with self-testing was 82.5% (33/40 RT-PCR positives detected; 95% CI 68.1-91.3), and 85.0% (34/40; 95% CI 70.9-92.9) with professional testing. The positive percent agreement between self-testing and professional testing on Ag-RDT was 91.4% (95% CI 77.6-97.0), and negative percent agreement 99.1% (95% CI 95.0-100). At high viral load (>7.0 log10 SARS-CoV-2 RNA copies/ml), sensitivity was 96.6% (28/29; 95% CI 82.8-99.8) for both self- and professional testing. Deviations in sampling and testing (incomplete self-sampling or extraction procedure, or imprecise volume applied on the test device) were observed in 25 out of the 40 PCR-positives. Participants were rather young (mean age 35 years) and educated (59.6% with higher education degree). Most participants (80.9%) considered the Ag-RDT as rather easy to perform. ConclusionsAmbulatory participants suspected for SARS-CoV-2 infection were able to reliably perform the Ag-RDT and test themselves. Procedural errors might be reduced by refinement of the Ag-RDTs for self-testing, such as modified instructions for use or product design/procedures. Self-testing may result in more wide-spread and more frequent testing. Paired with the appropriate information and education of the general public about the benefits and risks, self-testing may therefore have significant impact on the pandemic.
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BackgroundNasopharyngeal (NP) swab samples for antigen-detecting rapid diagnostic tests (Ag-RDTs) require qualified healthcare professionals and are frequently perceived as uncomfortable by patients. MethodsWe performed a manufacturer-independent, prospective diagnostic accuracy study, comparing professional-collected nasal mid-turbinate (NMT) to nasopharyngeal swab, using the test kits of a WHO-listed SARS-CoV-2 Ag-RDT (STANDARD Q COVID-19 Ag Test, SD Biosensor), which is also being distributed by Roche. Individuals with high suspicion for COVID-19 infection were tested. The reference standard was RT-PCR using a combined oro-/nasopharyngeal swab sample. Percent positive and negative agreement, as well as sensitivity and specificity were calculated. ResultsAmong the 179 participants, 41 (22.9%) tested positive for SARS-CoV-2 by RT-PCR. The positive percent agreement of the two different sampling techniques for the Ag-RDT was 93.5% (CI 79.3-98.2). The negative percent agreement was 95.9% (CI 91.4-98.1). The Ag-RDT with NMT-sampling showed a sensitivity of 80.5% (33/41 PCR positives detected; CI 66.0-89.8) and specificity of 98.6% (CI 94.9-99.6) compared to RT-PCR. The sensitivity with NP-sampling was 73.2% (30/41 PCR positives detected; CI 58.1-84.3) and specificity was 99.3% (CI 96.0-100). In patients with high viral load (>7.0 log10 SARS-CoV-2 RNA copies/swab), the sensitivity of the Ag-RDT with NMT-sampling was 100% and 94.7% with NP-sampling. ConclusionThis study demonstrates that sensitivity of a WHO-listed SARS-CoV-2 Ag-RDT using a professional nasal-sampling kit is at least equal to that of the NP-sampling kit, although confidence intervals overlap. Of note, differences in the IFUs of the test procedures could have contributed to different sensitivities. NMT-sampling can be performed with less training, reduces patient discomfort, and it enables scaling of antigen testing strategies. Additional studies of patient self-sampling should be considered to further facilitate the scaling-up of Ag-RDT testing.
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BackgroundDiagnostics are essential for controlling the pandemic. Identifying a reliable and fast diagnostic is needed to support testing. We assessed performance and ease-of-use of the Abbott PanBio antigen-detecting rapid diagnostic test (Ag-RDT). MethodsThis prospective, multi-centre diagnostic accuracy study enrolled at two sites in Germany. Following routine testing with 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 of symptoms, disease severity and study site. Additionally, an ease-of-use assessment and System Usability Scale (SUS) were performed. Findings1108 participants were enrolled between Sept 28 and Oct 30, 2020. Of these, 106 (9{middle dot}6%) were PCR-positive. The Abbott PanBio detected 92/106 PCR-positive participants with a sensitivity of 86{middle dot}8% (95% CI: 79{middle dot}0% - 92{middle dot}0%) and a specificity of 99{middle dot}9% (95% CI: 99{middle dot}4%-100%). The sub analyses indicated that sensitivity was 95{middle dot}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. InterpretationThe 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. FundingThe Foundation of Innovative New Diagnostics supplied the test kits for the study. The internal funds from the Heidelberg University as well as the Charite Berlin supported this study.
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BackgroundTwo 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. MethodsThis 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. ResultsAmong 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. ConclusionSupervised 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.
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BackgroundLiving conditions in homeless shelters may facilitate the transmission of COVID-19. Social determinants and pre-existing health conditions place homeless people at increased risk of severe disease. Described outbreaks in homeless shelters resulted in high proportions of infected residents and staff members. In addition to other infection prevention strategies, regular shelter-wide (universal) testing for COVID-19 may be valuable, depending on the level of community transmission and when resources permit. MethodsThis was a prospective feasibility cohort study to evaluate universal testing for COVID-19 at a homeless shelter with 106 beds in Berlin, Germany. Co-researchers were recruited from the shelter staff. A PCR analysis of saliva or self-collected nasal/oral swab was performed weekly over a period of 3 weeks in July 2020. Acceptability and implementation barriers were analyzed by process evaluation using mixed methods including evaluation sheets, focus group discussion and a structured questionnaire. ResultsNinety-three out of 124 (75%) residents were approached to participate in the study. Fifty-one out of the 93 residents (54.8%) gave written informed consent. High retention rates (88.9% - 93.6%) of a weekly respiratory specimen were reached, but repeated collection attempts, as well as assistance were required. A self-collected nasal/oral swab was considered easier and more hygienic to collect than a saliva specimen. No resident was tested positive. Language barriers were the main reason for non-participation. Flexibility of sample collection schedules, the use of video and audio materials, and concise written information were the main recommendations of the co-researchers for future implementation. ConclusionVoluntary universal testing for COVID-19 is feasible in homeless shelters. Universal testing of high-risk facilities will require flexible approaches, considering the level of the community transmission, the available resources, and the local recommendations. Lack of human resources and laboratory capacity may be a major barrier for implementation of universal testing, requiring adapted approaches compared to standard individual testing. Assisted self-collection of specimens and barrier free communication may facilitate implementation in homeless shelters. Program planning must consider homeless peoples needs and life situation, and guarantee confidentiality and autonomy.
