Comparison of fourteen Rapid Point-of-Care Antigen Tests for SARS-CoV-2: Use & Sensitivity

Abstract Fast sensitive techniques are advisable for SARS-CoV-2 detection. Various rapid SARS-CoV-2 antigen detection tests have been developed, but type and quality of the sample, stage of the disease and viral load can all have an impact on their sensitivity. For this study, a total of 486 swabs were processed and checked with various commercially available tests, and then compared with q(RT)-PCR (the gold-standard method). Total sensitivity varied considerably, for example, 42.10% (nal von minden and Tody Laboratories), 68.42% (Cahnos) and 84.78% (PCL). Sensitivity reached 100% when cycle threshold (Ct) was lower than 22 in almost all tests, although this dropped considerably when Ct was higher above 30, where only three tests identified 40% or more positive samples and in 5 cases it was 0%. What is more, only two cases were 100% accurate when viral load was higher than 5 log/103 cells and accuracy was 0% in 12 cases where viral load was lower than 4 log/103 cells. These results, particularly taking into consideration the fact they used normalized viral load, suggest that antigen detection tests have their role in the fast triage of positive patients, but that considerable care should be taken with negative results, which is even more important if they are used for massive screening.

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Handling and accuracy of four rapid antigen tests for the diagnosis of SARS-CoV-2 compared to RT-qPCR

10.1101/2020.12.05.20244673 ◽

2020 ◽

Author(s):

Flaminia Olearo ◽

Dominik Nörz ◽

Fabian Heinrich ◽

Jan Peter Sutter ◽

Kevin Rödel ◽

...

Keyword(s):

Viral Load ◽

Point Of Care ◽

Significant Risk ◽

Relative Sensitivity ◽

High Viral Load ◽

Careful Consideration ◽

Lower Sensitivity ◽

Clinical Implementation ◽

Rt Pcr ◽

Antigen Tests

AbstractBackgroundSARS-CoV-2 molecular diagnostics is facing material shortages and long turnaround times due to exponential increase of testing demand.ObjectiveWe evaluated the analytic performance and handling of four rapid Antigen Point of Care Tests (AgPOCTs) I-IV (Distributors: (I) Roche, (II) Abbott, (III) MEDsan and (IV) Siemens).Methods100 RT-PCR negative and 84 RT-PCR positive oropharyngeal swabs were prospectively collected and used to determine performance and accuracy of these AgPOCTs. Handling was evaluated by 10 healthcare workers/users through a questionnaire.ResultsThe median duration from symptom onset to sampling was 6 days (IQR 2-12 days). The overall relative sensitivity was 49.4%, 44.6%, 45.8% and 54.9 % for tests I, II, III and IV, respectively. In the high viral load subgroup (containing >106 copies of SARS-CoV-2 /swab, n=26), AgPOCTs reached sensitivities of 92.3% or more (range 92.3%-100%). Specificity was 100% for tests I, II and IV and 97% for test III. Regarding handling, test I obtained the overall highest scores, while test II was considered to have the most convenient components. Of note, users considered all assays, with the exception of test I, to pose a significant risk for contamination by drips or spills.DiscussionBesides some differences in sensitivity and handling, all four AgPOCTs showed acceptable performance in high viral load samples. However, due to the significantly lower sensitivity compared to RT-qPCR, a careful consideration of pro and cons of AgPOCT has to be taken into account before clinical implementation.

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Assessment of SARS-CoV-2 rapid antigen tests

Journal of Laboratory Medicine ◽

10.1515/labmed-2021-0036 ◽

2021 ◽

Vol 45 (3) ◽

pp. 143-148

Author(s):

Mustafa Özcürümez ◽

Antonios Katsounas ◽

Stefan Holdenrieder ◽

Alexander von Meyer ◽

Harald Renz ◽

...

Keyword(s):

Point Of Care ◽

Low Cost ◽

Sources Of Information ◽

Package Inserts ◽

Evaluation Of Performance ◽

Specificity And Sensitivity ◽

Performance Specifications ◽

Antigen Tests ◽

Minimum Criteria ◽

Almost All

Abstract Objectives Point-of-care antigen tests (PoC-AgTs) for the rapid detection of SARS-CoV-2 infection enable screening of additional populations with less effort, independent of laboratories and at a low cost. PoC-AgTs have therefore been included in national testing strategies with additional quality requirements to address limitations in specificity and sensitivity. Information given in the package inserts of the test providers should enable the user to evaluate the performance of a PoC-AgT in advance. The quality of this information has been independently assessed since the Corona Test Ordinance came into force in Germany in October 2020. Methods The completeness of analytical and diagnostic performance specifications was assessed for all package inserts publicly available via the Paul Ehrlich Institute (PEI). It was ascertained whether the minimum criteria, recommendations, and extended criteria of the PEI were comprehensibly fulfilled. The number of tests removed from the list by March 2021 was determined. Results By the closing date of the survey (17.11.2020), the PEI had listed 165 PoC-AgTs that formally fulfilled the minimum criteria and were thus reimbursed. A total of 78 identical systems were identified. Almost all providers were found to have gaps in the information on the validation results of their tests, meaning that an evaluation of performance is only possible to a limited extent. Until March 2021, 25 non-identical PoC-AgTs have been removed from the list. Conclusions Many PoC-AgTs could not be comprehensively evaluated based on the information provided by the provider. Users are therefore dependent on provider-independent sources of information.

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Evaluation of the performance of the COVID-19 rapid antigen tests in a tertiary level hospital in Bangladesh.

10.21203/rs.3.rs-1056525/v1 ◽

2021 ◽

Author(s):

Mohammad Jahidur Rahman Khan ◽

Md. Shahadat Hossain ◽

Samshad Jahan Shumu ◽

Md. Selim Reza ◽

Farzana Mim ◽

...

Keyword(s):

Viral Load ◽

Real Time ◽

Sensitivity And Specificity ◽

Detection Rate ◽

High Sensitivity ◽

Rt Pcr ◽

College Hospital ◽

Medical College ◽

Qrt Pcr ◽

Antigen Tests

Abstract Background: While the COVID-19 pandemic is a worldwide crisis, tests with high sensitivity and specificity are essential for identifying and managing COVID-19 patients. Globally, several rapid antigen tests RATs for COVID-19 have been developed, but their clinical efficacy has not been well established. This study aimed to evaluate the performance of several rapid antigen tests (RATs) to diagnose SARS-CoV-2 infection.Methods: This prospective observational study was conducted at Shaheed Suhrawardy Medical College hospital from February 2021 to April 2021 in Dhaka, Bangladesh. This study included the patients admitted in this hospital at the COVID-19 isolation unit or referred from the triage facility of the outdoor department of this hospital suspected as COVID-19 case. Two nasopharyngeal samples were collected simultaneously. one sample was used on the spot for the RAT. The other was sent to the adjacent Shaheed Suhrawardy Medical College COVID-19 RT-PCR laboratory for real-time reverse transcription-polymerase chain reaction (qRT-PCR). The performance of the RAT was evaluated using the results of qRT-PCR as a reference.Results: A total of 223 patients were included in this study, and the real-time RT-PCR detected SARS-CoV-2 in 84 (37.7%) patients. Of these 84 patients, 9 (10.7%) were asymptomatic. The overall sensitivity and specificity of RATs were 78.6% and 99.3%, respectively. The sensitivity was 81.3% in symptomatic cases and 55.6% in asymptomatic cases. False-negatives were observed in 18 patients, 3 of whom were asymptomatic and had a low viral load (cycle threshold (Ct) > 30). The detection rate of RATs was 100% when the Ct value was up to 24. The detection rate was 42.3% when the Ct was >29. The detection rate of RATs was 92.3% when the onset of symptoms was within three days. The detection rate was 33.3% when the onset of symptoms was >7 days.Conclusions: RATs for COVID-19 used in this study delivered an acceptable performance in patients with high viral load and within the first week of the onset of symptoms. They can be used as a supplementary method to RT-PCR for the diagnosis of COVID-19 patients.

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Distribution of SARS-CoV-2 PCR Cycle Threshold Values Provide Practical Insight Into Overall and Target-Specific Sensitivity Among Symptomatic Patients

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa133 ◽

2020 ◽

Vol 154 (4) ◽

pp. 479-485 ◽

Cited By ~ 4

Author(s):

Blake W Buchan ◽

Jessica S Hoff ◽

Cameron G Gmehlin ◽

Adriana Perez ◽

Matthew L Faron ◽

...

Keyword(s):

Viral Load ◽

Limit Of Detection ◽

False Negative ◽

Age Group ◽

Rt Pcr ◽

Patient Age ◽

Cycle Threshold ◽

Negative Results ◽

Patient Âgé ◽

False Negative Results

Abstract Objectives We examined the distribution of reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (CT) values obtained from symptomatic patients being evaluated for coronavirus disease 2019 (COVID-19) to determine the proportion of specimens containing a viral load near the assay limit of detection (LoD) to gain practical insight to the risk of false-negative results. We also examined the relationship between CT value and patient age to determine any age-dependent difference in viral load or test sensitivity. Methods We collected CT values obtained from the cobas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay corresponding to 1,213 combined nasopharyngeal-oropharyngeal specimens obtained from symptomatic individuals that were reported as positive or presumptive positive for SARS-CoV-2. CT values were stratified by SARS-CoV target and patient age group. Results In total, 93.3% to 98.4% of specimens demonstrated CT values greater than 3× the assay LoD, at which point false-negative results would not be expected. The mean of CT values between age groups was statistically equivalent with the exception of patients in age group 80 to 89 years, which demonstrated slightly lower CTs. Conclusions Based on the distribution of observed CT values, including the small proportion of specimens with values near the assay LoD, there is a low risk of false-negative RT-PCR results in combined nasopharyngeal-oropharyngeal specimens obtained from symptomatic individuals.

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Optimization of Lyophilized LAMP and RT-PCR Reaction Mixes for Detection of Tuberculosis

The EuroBiotech Journal ◽

10.2478/ebtj-2020-0027 ◽

2020 ◽

Vol 4 (4) ◽

pp. 230-236

Author(s):

Esra Agel ◽

Hasan Sagcan

Keyword(s):

Rural Areas ◽

Point Of Care ◽

Culture Method ◽

Molecular Techniques ◽

Cold Chain ◽

Clinical Samples ◽

Rt Pcr ◽

Gold Standard Method ◽

Tuberculosis Diagnosis ◽

Peg 8000

AbstractUndoubtedly, one of the most infectious diseases in the world is tuberculosis. Key factor for tuberculosis control is to prevent possible contagion with rapid diagnosis and effective treatment. The culture method, which it takes several weeks to obtain results, is the gold standard method for laboratory diagnosis of tuberculosis. In order to prevent possible contagion of tuberculosis, diagnosis must be made in short time and treatment should be started as soon as possible. Normally, clinical samples are studied in advanced laboratories designed for this purpose. However, especially after the screening in rural areas, the transmission of the samples to the centers has many negative effects on the clinical material. Therefore, the latest trend molecular techniques in microbiological diagnosis are developing into point of care systems that can be applied in the field without laboratory infrastructure. The major challenge for molecular-based point-of-care tests is the need to store polymerase enzymes and some of the ingredients used in the cold chain. The aim of this study is to increase the resistance of the amplification reaction mixtures by lyophilizing the tuberculosis diagnosis. Lyophilization was performed on Loop-mediated isothermal amplification (LAMP) and Real-time PCR mixtures. For the lyophilization of LAMP and RT-PCR mixtures, two different experimental setups were tried from the literature except for the developed content. Chemicals such as stachyose, trehalose, glycerol and PEG 8000 are widely using as cryoprotectants. As a result, the developed content (0.5% PEG 8000, 2.0 % Stachyose) was determined the best cryoprotectant mixture. Accordingly, amplification mixtures can be produced with the developed lyophilization method and point of care kits can be developed.

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The Performance of Two Rapid Antigen Tests During Population-Level Screening for SARS-CoV-2 Infection

Frontiers in Medicine ◽

10.3389/fmed.2021.797109 ◽

2021 ◽

Vol 8 ◽

Author(s):

Mohammad Alghounaim ◽

Hamad Bastaki ◽

Farah Bin Essa ◽

Hoda Motlagh ◽

Salman Al-Sabah

Keyword(s):

Positive Predictive Value ◽

Prospective Study ◽

Predictive Value ◽

Point Of Care ◽

Population Level ◽

Lower Sensitivity ◽

Rt Pcr ◽

Antigen Tests ◽

A Prospective Study ◽

Antigen Testing

Background: SARS-CoV-2 antigen assays offer a rapid mean to diagnose and isolate infected individuals. However, their utility in population-level screening is unknown.Objectives: The performance of two antigen tests in detecting SARS-CoV-2 was assessed among individuals randomly selected in the community.Study Design: A prospective study that performed head-to-head comparison of two SARS-CoV-2 antigen assays. Individuals were recruited during community SARS-CoV-2 screening over 10 working days. Demographic and clinical data were collected. Standard Q COVID-19 Ag test, a point-of-care chromatographic assay, was conducted immediately, and then the sample was transported to the virology laboratory to perform PCR and the LIAISON SARS-CoV-2 Ag chemiluminesence immunoassay.Results: respiratory samples from 991 individuals were collected, and 62 were positive by PCR. Inconclusive PCR results were observed in 19 samples and were excluded. The median age of participants was 40.2 years (IQR 32.3–47.8), and 932 (94%) were males. Most (77.4%) of infections were asymptomatic. The sensitivity and the specificity of the LIAISON assay were 43.3% (95%CI 30.6–56.8) and 99.9% (95%CI 99.3–100). The Standard Q assay had lower sensitivity (30.6%, 95%CI 19.6–43.7) but similar specificity (98.8%, 95%CI, 97.8–99.4). Similarly, the LIAISON assay had higher positive predictive value (96.3%, 95%CI 81–99.9% vs. 63.3%, 95%CI, 43.9–80.1%). Both assays performed better in symptomatic patients and among samples with a low-cycle threshold (Ct < 25).Conclusion: In our setting of random community surveillance, rapid antigen testing of nasopharyngeal swabs by either LIAISON SARS-CoV-2 Ag (DiaSorin) or Standard Q COVID-19 Ag (SD Biosensor) was less sensitive to detecting SARS-CoV-2 than the TaqPath COVID-19 RT-PCR.

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A novel RT-LAMP workflow for rapid salivary diagnostics of COVID-19 and effects of age, gender and time from symptom onset

10.1101/2021.06.07.21258288 ◽

2021 ◽

Author(s):

Gerson Shigeru Kobayashi ◽

Luciano Abreu Brito ◽

Danielle De Paula Moreira ◽

Angela May Suzuki ◽

Gabriella Shih Ping Hsia ◽

...

Keyword(s):

Viral Load ◽

Symptom Onset ◽

Clinical Performance ◽

Point Of Care ◽

Rapid Diagnostics ◽

Rt Pcr ◽

Point Of Care Testing ◽

Viral Loads ◽

Peak Viral Load ◽

Salivary Diagnostics

Objectives: Rapid diagnostics is pivotal to curb SARS-CoV-2 transmission, and saliva has emerged as a practical alternative to naso/oropharyngeal (NOP) specimens. We aimed to develop a direct RT-LAMP workflow for viral detection in saliva, and to provide more information regarding its potential in COVID-19 diagnostics. Methods: Clinical and contrived specimens were used to screen/optimize formulations and sample processing protocols. Salivary viral load was determined in symptomatic patients to evaluate clinical performance (n = 90) and to characterize saliva based on age, gender and time from onset of symptoms (n = 49). Results: The devised workflow achieved 93.2% sensitivity, 97% specificity, and 0.895 Kappa for salivas containing >102 copies/μL. Further analyses in saliva showed peak viral load in the first days of symptoms and lower viral loads in females, particularly among young individuals (<38 years). NOP RT-PCR data did not yield relevant associations. Conclusions: This novel saliva RT-LAMP workflow can be applied to point-of-care testing. This work reinforces that saliva better correlates with transmission dynamics than NOP specimens, and reveals gender differences that may reflect higher transmission by males. To maximize detection, testing should be done immediately after symptom onset, especially in females.

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Real-World Clinical Performance of the Abbott Panbio with Nasopharyngeal, Throat and Saliva Swabs Among Symptomatic Individuals with COVID-19

10.1101/2021.01.02.21249138 ◽

2021 ◽

Author(s):

William Stokes ◽

Byron Berenger ◽

Danielle Portnoy ◽

Brittney Scott ◽

Jonas Szelewicki ◽

...

Keyword(s):

Symptom Onset ◽

Clinical Performance ◽

Point Of Care ◽

Community Setting ◽

Poor Performance ◽

Community Assessment ◽

Rt Pcr ◽

United States Food ◽

States Food ◽

Antigen Tests

BACKGROUND Point of Care Testing (POCT) SARS-CoV-2 antigen tests, such as the Abbott Panbio, have great potential to help combat the COVID-19 pandemic. The Panbio is United States Food and Drug Administration (FDA) approved for the detection of SARS-CoV-2 in symptomatic individuals within the first 7 days of COVID-19 symptom onset(s). METHODS Symptomatic adults recently diagnosed with COVID-19 in the community were recruited into the study. Paired nasopharyngeal (NP), throat, and saliva swabs were collected, with one paired swab tested immediately with the Panbio, and the other transported in universal transport media and tested using reverse-transcriptase polymerase chain reaction (RT-PCR). Positive percent agreement (PPA) was calculated. Subsequently, individuals within 7 days of symptom onset who presented to community assessment centres for SARS-CoV-2 testing had Panbio testing completed and paired with RT-PCR results from parallel NP or throat swabs. RESULTS 145 individuals were included in the study. Collection of throat and saliva was stopped early due to poor performance (throat PPA 57.7%, n=61, and saliva PPA 2.6%, n=41). NP swab PPA was 87.7% [n=145, 95% confidence interval 81.0% - 92.7%]. There were 1,641 symptomatic individuals tested by Panbio in community assessment centres, with 268/1641 (16.3%) positive for SARS-CoV-2. There were 37 false negatives, corresponding to a PPA of 86.2% [81.5% - 90.1%]. CONCLUSIONS The Panbio test reliably detects most cases of SARS-CoV-2 from adults in the POCT community setting presenting within 7 days of symptom onset using nasopharyngeal swabs. Throat and saliva swabs are not reliable specimens for the Panbio.

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Characteristics of children and antigen test performance at a SARS-CoV-2 community testing site

10.1101/2021.07.06.21259792 ◽

2021 ◽

Author(s):

Laura Ford ◽

Melissa J. Whaley ◽

Melisa M. Shah ◽

Phillip P. Salvatore ◽

Hannah E. Segaloff ◽

...

Keyword(s):

Test Performance ◽

Point Of Care ◽

Lower Sensitivity ◽

Antigen Test ◽

Rt Pcr ◽

Culture Methods ◽

Viral Culture ◽

Asymptomatic Children ◽

Testing Site ◽

Antigen Tests

Background: Performance characteristics of SARS-CoV-2 antigen tests among children are limited despite the need for point-of-care testing in school and childcare settings. We describe children seeking SARS-CoV-2 testing at a community site and compare antigen test performance to real-time reverse transcription-polymerase chain reaction (RT-PCR) and viral culture. Methods: Two anterior nasal specimens were self-collected for BinaxNOW antigen and RT-PCR testing, along with demographics, symptoms, and exposure information from individuals ≥5 years at a community testing site. Viral culture was attempted on residual antigen or RT-PCR positive specimens. Demographic and clinical characteristics, and the performance of SARS-CoV-2 antigen tests, were compared among children (<18 years) and adults. Results: About one in ten included specimens were from children (225/2110); 16.4% (37/225) were RT-PCR positive. Cycle threshold values were similar among RT-PCR positive specimens from children and adults (22.5 vs 21.3, p=0.46) and among specimens from symptomatic and asymptomatic children (22.5 vs 23.2, p=0.39). Sensitivity of antigen test compared to RT-PCR was 73.0% (27/37) among specimens from children and 80.8% (240/297) among specimens from adults; among specimens from children, specificity was 100% (188/188), positive and negative predictive value were 100% (27/27) and 94.9% (188/198) respectively. Virus was isolated from 51.4% (19/37) of RT-PCR positive pediatric specimens; all 19 had positive antigen test results. Conclusions : With lower sensitivity relative to RT-PCR, antigen tests may not diagnose all positive COVID-19 cases; however, antigen testing identified children with live SARS-CoV-2 virus.

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Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™ - Antigen-detecting point-of-care device for SARS-CoV-2

10.1101/2021.03.02.21252430 ◽

2021 ◽

Author(s):

Lisa Johanna Krüger ◽

Julian A.F. Klein ◽

Frank Tobian ◽

Mary Gaeddert ◽

Federica Lainati ◽

...

Keyword(s):

Viral Load ◽

Limit Of Detection ◽

Point Of Care ◽

Scale Up ◽

Cross Reactivity ◽

Ease Of Use ◽

Analytical Sensitivity ◽

Rt Pcr ◽

Clinical Sensitivity ◽

Lateral Flow Assays

Background: Rapid antigen-detecting tests (Ag-RDTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transform pandemic control. Thus far, sensitivity (≤85%) of lateral-flow assays has limited scale-up. Conceivably, microfluidic immunofluorescence Ag-RDTs could increase sensitivity for SARS-CoV-2 detection. Materials and Methods: This multi-centre diagnostic accuracy study investigated performance of the microfluidic immunofluorescence LumiraDx™ assay, enrolling symptomatic and asymptomatic participants with suspected SARS-CoV-2 infection. Participants collected a supervised nasal mid-turbinate (NMT) self-swab for Ag-RDT testing, in addition to a professionally-collected nasopharyngeal (NP) swab for routine testing with reverse transcriptase polymerase chain reaction (RT-PCR). Results were compared to calculate sensitivity and specificity. Sub-analyses investigated the results by viral load, symptom presence and duration. An analytical study assessed exclusivity and limit-of-detection (LOD). In addition, we evaluated ease-of-use. Results: Study conduct was between November 2nd 2020 and January 21st 2021. 761 participants were enrolled, with 486 participants reporting symptoms on testing day. 120 out of 146 RT-PCR positive cases were detected positive by LumiraDx™, resulting in a sensitivity of 82.2% (95% CI: 75.2%-87.5%). Specificity was 99.3% (CI: 98.3-99.7%). Sensitivity was increased in individuals with viral load ≥ 7 log10 SARS-CoV2 RNA copies/ml (93.8%; CI: 86.2%-97.3%). Testing against common respiratory commensals and pathogens showed no cross-reactivity and LOD was estimated to be 2-56 PFU/mL. The ease-of-use-assessment was favourable for lower throughput settings. Conclusion: The LumiraDx™ assay showed excellent analytical sensitivity, exclusivity and clinical specificity with good clinical sensitivity using supervised NMT self-sampling.

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