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

Abstract BACKGROUND Point of Care SARS-CoV-2 antigen tests, such as the Abbott Panbio, have great potential to help combat the COVID-19 pandemic. The Panbio is Health Canada 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). We also prospectively evaluated results from assessment centres. For those individuals, an NP swab was collected for Panbio testing 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 poorer performance (throat sensitivity 57.7%, n = 61, and saliva sensitivity 2.6%, n = 41). NP swab sensitivity was 87.7% [n = 145, 95% confidence interval (CI) 81.0% − 92.7%]. There were 1,641 symptomatic individuals tested by Panbio in assessment centres, with 268/1641 (16.3%) positive for SARS-CoV-2. There were 37 false negatives and 2 false positives, corresponding to a sensitivity and specificity of 86.1% [95% CI 81.3% − 90.0%] and 99.9% [95% CI 99.5% − 100.0%], respectively. CONCLUSIONS The Panbio test reliably detects most cases of SARS-CoV-2 from adults in the 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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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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Estimating false-negative detection rate of SARS-CoV-2 by RT-PCR

10.1101/2020.04.05.20053355 ◽

2020 ◽

Cited By ~ 46

Author(s):

Paul Wikramaratna ◽

Robert S Paton ◽

Mahan Ghafari ◽

José Lourenço

Keyword(s):

Symptom Onset ◽

Detection Rate ◽

False Negative ◽

Rt Pcr ◽

Chain Reaction ◽

False Negatives ◽

Clinical Stages ◽

Polymerase Chain ◽

Pcr Assays ◽

Negative Detection

AbstractReverse transcription-polymerase chain reaction (RT-PCR) assays are used to test patients and key workers for infection with the causative SARS-CoV-2 virus. RT-PCR tests are highly specific and the probability of false positives is low, but false negatives can occur if the sample contains insufficient quantities of the virus to be successfully amplified and detected. The amount of virus in a swab is likely to vary between patients, sample location (nasal, throat or sputum) and through time as infection progresses. Here, we analyse publicly available data from patients who received multiple RT-PCR tests and were identified as SARS-CoV-2 positive at least once. We identify that the probability of a positive test decreases with time after symptom onset, with throat samples less likely to yield a positive result relative to nasal samples. Empirically derived distributions of the time between symptom onset and hospitalisation allowed us to comment on the likely false negative rates in cohorts of patients who present for testing at different clinical stages. We further estimate the expected numbers of false negative tests in a group of tested individuals and show how this is affected by the timing of the tests. Finally, we assessed the robustness of these estimates of false negative rates to the probability of false positive tests. This work has implications both for the identification of infected patients and for the discharge of convalescing patients who are potentially still infectious.

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Point-of-Care PCR Assays for COVID-19 Detection

Biosensors ◽

10.3390/bios11050141 ◽

2021 ◽

Vol 11 (5) ◽

pp. 141

Author(s):

Niharika Gupta ◽

Shine Augustine ◽

Tarun Narayan ◽

Alan O’Riordan ◽

Asmita Das ◽

...

Keyword(s):

Point Of Care ◽

Digital Pcr ◽

Rt Pcr ◽

Chain Reaction ◽

Polymerase Chain ◽

Pcr Assays ◽

Antigen Tests ◽

Distinct Features ◽

The Impact ◽

Higher Sensitivity

Molecular diagnostics has been the front runner in the world’s response to the COVID-19 pandemic. Particularly, reverse transcriptase-polymerase chain reaction (RT-PCR) and the quantitative variant (qRT-PCR) have been the gold standard for COVID-19 diagnosis. However, faster antigen tests and other point-of-care (POC) devices have also played a significant role in containing the spread of SARS-CoV-2 by facilitating mass screening and delivering results in less time. Thus, despite the higher sensitivity and specificity of the RT-PCR assays, the impact of POC tests cannot be ignored. As a consequence, there has been an increased interest in the development of miniaturized, high-throughput, and automated PCR systems, many of which can be used at point-of-care. This review summarizes the recent advances in the development of miniaturized PCR systems with an emphasis on COVID-19 detection. The distinct features of digital PCR and electrochemical PCR are detailed along with the challenges. The potential of CRISPR/Cas technology for POC diagnostics is also highlighted. Commercial RT–PCR POC systems approved by various agencies for COVID-19 detection are discussed.

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Performance of qualitative and quantitative antigen tests for SARS-CoV-2 in early symptomatic patients using saliva

10.1101/2020.11.06.20227363 ◽

2020 ◽

Author(s):

Isao Yokota ◽

Takayo Sakurazawa ◽

Junichi Sugita ◽

Sumio Iwasaki ◽

Keiko Yasuda ◽

...

Keyword(s):

Symptom Onset ◽

Gold Standard ◽

Rapid Detection ◽

Disease Outbreaks ◽

Nasopharyngeal Swab ◽

Chain Reaction ◽

Qualitative And Quantitative ◽

Polymerase Chain ◽

Antigen Tests ◽

Chemiluminescent Enzyme Immunoassay

AbstractBackgroundThe rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent need for the prevention and containment of disease outbreaks in communities. Although the gold standard is polymerase chain reaction (PCR), antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) that can yield results within 30 minutes.MethodsWe evaluated performance of ICA and CLEIA using 34 frozen PCR-positive specimens (17 saliva and 17 nasopharyngeal swab) and 307 PCR-negative samples.ResultsICA detected SARS-CoV-2 in only 14 (41%) samples, with positivity of 24% in saliva and 59% in NPS. Notably, ICA detected SARS-CoV-2 in 5 (83%) of 6 samples collected within 4 days after symptom onset. CLEIA detected SARS-CoV-2 in 31 (91%) samples, with positivity of 82% in saliva and 100% in NPS. CLEIA was negative in 3 samples with low viral load by PCR.ConclusionsThese results suggest that use of ICA should be limited to earlier time after symptom onset and CLEIA is more sensitive and can be used in situations where quick results are required.

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Detecting SARS-CoV-2 at point of care: preliminary data comparing loop-mediated isothermal amplification (LAMP) to polymerase chain reaction (PCR)

BMC Infectious Diseases ◽

10.1186/s12879-020-05484-8 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Marc F. Österdahl ◽

Karla A. Lee ◽

Mary Ni Lochlainn ◽

Stuart Wilson ◽

Sam Douthwaite ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Reverse Transcription ◽

Predictive Value ◽

Point Of Care ◽

Isothermal Amplification ◽

Service Improvement ◽

Rt Pcr ◽

Chain Reaction ◽

Loop Mediated Isothermal Amplification ◽

Polymerase Chain

Abstract Background A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting. Methods This prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines. Results The novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a “gold standard”, the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19. Conclusions RT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.

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Head-to-Head Comparison of Rapid and Automated Antigen Detection Tests for the Diagnosis of SARS-CoV-2 Infection

Journal of Clinical Medicine ◽

10.3390/jcm10020265 ◽

2021 ◽

Vol 10 (2) ◽

pp. 265

Author(s):

Julien Favresse ◽

Constant Gillot ◽

Maxime Oliveira ◽

Julie Cadrobbi ◽

Marc Elsen ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Clinical Performance ◽

Antigen Detection ◽

Clinical Validation ◽

Rt Pcr ◽

Chain Reaction ◽

Viral Loads ◽

Automated Assay ◽

Polymerase Chain ◽

Asymptomatic Subjects

(1) Background: The detection of SARS-CoV-2 RNA in nasopharyngeal samples through real-time reverse transcription-polymerase chain reaction (RT-PCR) is considered the standard gold method for the diagnosis of SARS-CoV-2 infection. Antigen detection (AD) tests are more rapid, less laborious, and less expensive alternatives but still require clinical validation. (2) Methods: This study compared the clinical performance of five AD tests, including four rapid AD (RAD) tests (biotical, Panbio, Healgen, and Roche) and one automated AD test (VITROS). For that purpose, 118 (62.8%) symptomatic patients and 70 (37.2%) asymptomatic subjects were tested, and results were compared to RT-PCR. (3) Results: The performance of the RAD tests was modest and allowed us to identify RT-PCR positive patients with higher viral loads. For Ct values ≤25, the sensitivity ranged from 93.1% (95% CI: 83.3–98.1%) to 96.6% (95% CI: 88.1–99.6%), meaning that some samples with high viral loads were missed. Considering the Ct value proposed by the CDC for contagiousness (i.e., Ct values ≤33) sensitivities ranged from 76.2% (95% CI: 65.4–85.1%) to 88.8% (95% CI: 79.7–94.7%) while the specificity ranged from 96.3% (95% CI: 90.8–99.0%) to 99.1% (95% CI: 95.0–100%). The VITROS automated assay showed a 100% (95% CI: 95.5–100%) sensitivity for Ct values ≤33, and had a specificity of 100% (95% CI: 96.6–100%); (4) Conclusions: Compared to RAD tests, the VITROS assay fully aligned with RT-PCR for Ct values up to 33, which might allow a faster, easier and cheaper identification of SARS-CoV-2 contagious patients.

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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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Logistic advantage of two-step screening strategy for SARS-CoV-2 at airport quarantine

10.1101/2021.01.25.21250509 ◽

2021 ◽

Author(s):

Isao Yokota ◽

Peter Y Shane ◽

Takanori Teshima

Keyword(s):

Point Of Care ◽

High Accuracy ◽

Screening Strategy ◽

Nucleic Acid Amplification ◽

Point Of Care Testing ◽

Chain Reaction ◽

False Negatives ◽

Imported Cases ◽

Polymerase Chain ◽

Antigen Testing

SummaryBackgroundAirport quarantine is required to reduce the risk of entry of travelers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is challenging for both high accuracy and rapid turn-around time to coexist in testing; polymerase chain reaction (PCR) is time-consuming with high accuracy, while antigen testing is rapid with less accuracy.Methods88,924 (93.2%) of 95,457 arrivals at three international airports in Japan were tested for SARS-CoV-2 using self-collected saliva by a screening strategy with initial chemiluminescent enzyme immunoassay (CLEIA) followed by confirmatory nucleic acid amplification tests (NAAT) only for intermediate range antigen concentrations.Results254 (0.27%) persons were found to be SARS-CoV-2 antigen positive (≥ 4.0 pg/mL) by CLEIA. NAAT was required for confirmatory testing in 513 (0.54%) persons with intermediate antigen concentrations (0.67-4.0 pg/mL) whereby the virus was detected in 34 (6.6%) persons. This two-step strategy dramatically reduced the utilization of NAAT to approximately one out of every 200 test subjects.Estimated performance of this strategy did not show significant increase in false negatives as compared to performing NAAT in all subjects. Further reduction in imported cases may be achieved by post-screening quarantine.ConclusionsPoint of care testing by quantitative CLEIA using self-collected saliva is less labor-intensive and yields results rapidly, thus suitable as an initial screening test. Reserving NAAT for CLEIA indeterminate cases may prevent compromising accuracy while significantly improving the logistics of administering mass-screening at large venues.

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Comparison of clinical and serological features of RT-PCR positive and negative COVID-19 patients

Journal of International Medical Research ◽

10.1177/0300060520972658 ◽

2021 ◽

Vol 49 (2) ◽

pp. 030006052097265

Author(s):

Caiqin Li ◽

Qi Su ◽

Jun Liu ◽

Lei Chen ◽

Yuting Li ◽

...

Keyword(s):

Symptom Onset ◽

Retrospective Cohort ◽

Time Window ◽

Clinical Symptoms ◽

Rt Pcr ◽

Chain Reaction ◽

Serological Tests ◽

Global Epidemic ◽

Polymerase Chain ◽

Demographic Features

Background In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan, China, and led to a global epidemic. We aimed to compare the clinical and serological features of COVID-19 patients with positive and negative reverse transcriptase polymerase chain reaction (RT-PCR) tests. Methods This was a retrospective cohort study conducted from 9 February to 4 April 2020. COVID-19 patients at Leishenshan Hospital in Wuhan, China (125 total cases; 87 RT-PCR positive and 38 RT-PCR negative) were included. COVID-19 serology was assessed by colloidal gold assay. All cases were analyzed for demographic, clinical, and serological features. Results There were no significant differences in most demographic features, clinical symptoms, complications or treatments of RT-PCR positive and negative COVID-19 patients. Serum IgM/IgG was positive in 82 (94%) and 33 (87%) RT-PCR positive and negative cases, respectively. IgM was detectable as early as 3 days after symptom onset and was undetectable 60 days after symptom onset. By contrast, IgG could be detected only 10 days after symptom onset and reached its peak 60 days after symptom onset. Conclusions Serological tests performed during the appropriate time window of disease progression could be valuable auxiliary methods to RT-PCR in COVID-19 patients.

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The Comparative Clinical Performance of Four SARS-CoV-2 Rapid Antigen Tests and Their Correlation to Infectivity In Vitro

Journal of Clinical Medicine ◽

10.3390/jcm10020328 ◽

2021 ◽

Vol 10 (2) ◽

pp. 328 ◽

Cited By ~ 1

Author(s):

Niko Kohmer ◽

Tuna Toptan ◽

Christiane Pallas ◽

Onur Karaca ◽

Annika Pfeiffer ◽

...

Keyword(s):

Cell Culture ◽

Large Scale ◽

Clinical Performance ◽

Immunofluorescence Assay ◽

Clinical Samples ◽

Chain Reaction ◽

Lateral Flow Assays ◽

Polymerase Chain ◽

Antigen Tests

Due to globally rising numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resources for real-time reverse-transcription polymerase chain reaction (rRT-PCR)-based testing have been exhausted. In order to meet the demands of testing and reduce transmission, SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) are being considered. These tests are fast, inexpensive, and simple to use, but whether they detect potentially infectious cases has not been well studied. We evaluated three lateral flow assays (RIDA®QUICK SARS-CoV-2 Antigen (R-Biopharm), SARS-CoV-2 Rapid Antigen Test (Roche)), and NADAL® COVID-19 Ag Test (Nal von Minden GmbH, Regensburg, Germany) and one microfluidic immunofluorescence assay (SARS-CoV-2 Ag Test (LumiraDx GmbH, Cologne, Germany)) using 100 clinical samples. Diagnostic rRT-PCR and cell culture testing as a marker for infectivity were performed in parallel. The overall Ag-RDT sensitivity for rRT-PCR-positive samples ranged from 24.3% to 50%. However, for samples with a viral load of more than 6 log10 RNA copies/mL (22/100), typically seen in infectious individuals, Ag-RDT positivity was between 81.8% and 100%. Only 51.6% (33/64) of the rRT-PCR-positive samples were infectious in cell culture. In contrast, three Ag-RDTs demonstrated a more significant correlation with cell culture infectivity (61.8–82.4%). Our findings suggest that large-scale SARS-CoV-2 Ag-RDT-based testing can be considered for detecting potentially infective individuals and reducing the virus spread.

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