Multicenter evaluation of the Panbio™ COVID-19 Rapid Antigen-Detection Test for the diagnosis of SARS-CoV-2 infection

AbstractThe standard RT-PCR assay for COVID-19 is laborious and time-consuming, limiting the availability of testing. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the reliability of the PanbioTM COVID-19 Ag Rapid Test Device (PanbioRT) (Abbott) for SARS-CoV-2 in nasopharyngeal swab specimens. This was a prospective multicenter study in ten Spanish university hospitals of patients from hospital units with clinical symptoms or epidemiological criteria for COVID-19. Patients whose onset of symptoms or exposure was more than 7 days earlier were excluded. Two nasopharyngeal exudate samples were taken to perform the PanbioRT and a diagnostic RT-PCR test. Among the 958 patients studied, 359 (37.5%) were positive by RT-PCR and 325 (33.9%) were also positive by the PanbioRT. Agreement was 95.7% (kappa score: 0.90). All 34 false-negative PanbioRT results were in symptomatic patients, with 23.5% of them at 6–7 days since the onset of symptoms and 58.8% presenting CT >30 values for RT-PCR, indicating a low viral load. Overall sensitivity and specificity for the PanbioRT were 90.5% and 98.8%, respectively. The PanbioRT provides good clinical performance as a point-of-care test, with even more reliable results for patients with a shorter clinical course of the disease or a higher viral load. While this study has had a direct impact on the national diagnostic strategy for COVID-19 in Spain, the results must be interpreted based on the local epidemiological context.

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Scoring System for the Diagnosis of COVID-19

The Open Public Health Journal ◽

10.2174/1874944502013010413 ◽

2020 ◽

Vol 13 (1) ◽

pp. 413-414 ◽

Cited By ~ 1

Author(s):

Mohamed Farouk Allam

Keyword(s):

Scoring System ◽

Clinical Symptoms ◽

False Negative ◽

Nasopharyngeal Swab ◽

Rt Pcr ◽

Pcr Assay ◽

Negative Results ◽

False Negative Results ◽

Symptoms And Signs

Due to the international spread of COVID-19, the difficulty of collecting nasopharyngeal swab specimen from all suspected patients, the costs of RT-PCR and CT, and the false negative results of RT-PCR assay in 41% of COVID-19 patients, a scoring system is needed to classify the suspected patients in order to determine the need for follow-up, home isolation, quarantine or the conduction of further investigations. A scoring system is proposed as a diagnostic tool for suspected patients. It includes Epidemiological Evidence of Exposure, Clinical Symptoms and Signs, and Investigations (if available). This scoring system is simple, could be calculated in a few minutes, and incorporates the main possible data/findings of any patient.

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Clinical evaluation of the Roche/SD Biosensor rapid antigen test with symptomatic, non-hospitalized patients in a municipal health service drive-through testing site

10.1101/2020.11.18.20234104 ◽

2020 ◽

Cited By ~ 5

Author(s):

Zsὁfia Iglὁi ◽

Jans Velzing ◽

Janko van Beek ◽

David van de Vijver ◽

Georgina Aron ◽

...

Keyword(s):

Viral Load ◽

Rapid Test ◽

Contact Tracing ◽

Gene Copy ◽

Nasopharyngeal Swab ◽

List Type ◽

Antigen Test ◽

Rt Pcr ◽

Outbreak Management ◽

Testing Site

AbstractBackgroundRapid detection of infectious individuals is essential in stopping the further spread of SARS-CoV-2. Although rapid antigen test is not as sensitive as the gold standard RT-PCR, the time to result is decreased by day(s), strengthening the effectiveness of contact tracing.MethodsThe Roche/SD Biosensor lateral flow antigen rapid test was evaluated in a mild symptomatic population at a large drive through testing site. A second nasopharyngeal swab was directly tested with the rapid test on site and results were compared to RT-PCR and virus culture. Date of onset and symptoms were analysed using data from a clinical questionnaire.ResultsWe included 970 persons with complete data. Overall sensitivity and specificity were 84.9% (CI95% 79.1-89.4) and 99.5% (CI95% 98.7-99.8) which translated into a positive predictive value of 97.5% (CI95% 94.0-99.5) under the current regional PCR positivity of 19.2%. Sensitivity for people with high loads of viral RNA (ct <30, 2.17E+05 E gene copy/ml) and who presented within 7 days since symptom onset increased to 95.8% (CI95% 90.5-98.2). Band intensity and time to result correlated strongly with viral load thus strong positive bands could be read before the recommended time. Around 98% of all viable specimen with ct <30 were detected successfully indicating that the large majority of infectious people can be captured with this test.ConclusionAntigen rapid tests can detect mildly symptomatic cases in the early phase of disease thereby identifying the most infectious individuals. Using this assay can have a significant value in the speed and effectiveness of SARS-CoV-2 outbreak management.SummaryPeople with early onset and high viral load were detected with 98.2% sensitivity.97% of individuals in which virus could be cultured were detected by the rapid test.This test is suitable to detect mild symptomatic cases.

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Lumipulse G SARS-CoV-2 Ag Assay Evaluation for SARS-CoV-2 Antigen Detection Using 594 Nasopharyngeal Swab Samples from Different Testing Groups

10.1101/2021.01.26.21250533 ◽

2021 ◽

Author(s):

Giulia Menchinelli ◽

Licia Bordi ◽

Flora Marzia Liotti ◽

Ivana Palucci ◽

Maria Rosaria Capobianchi ◽

...

Keyword(s):

Positive Result ◽

Limit Of Detection ◽

False Negative ◽

Antigen Detection ◽

Nasopharyngeal Swab ◽

Repeated Testing ◽

Rt Pcr ◽

Subgenomic Rna ◽

Negative Results ◽

Percent Agreement

ABSTRACTCompared to RT-PCR, lower performance of antigen detection assays, including the Lumipulse G SARS-CoV-2 Ag assay, may depend on specific testing scenarios. We tested 594 nasopharyngeal swab samples from individuals with COVID-19 (RT-PCR cycle threshold [Ct] values ≤40) or non-COVID-19 (Ct values ≤40) diagnoses. RT-PCR positive samples were assigned to diagnostic, screening, or monitoring groups of testing. With a limit of detection of 1.2 × 104 SARS-CoV-2 RNA copies/ml, Lumipulse showed positive percent agreement (PPA) of 79.9% (155/194) and negative percent agreement of 99.3% (397/400), whereas PPAs were 100% for samples with Ct values of <18 or 18–<25 and 92.5% for samples with Ct values of 25–<30. By three groups, Lumipulse showed PPA of 87.0% (60/69), 81.1% (43/53), or 72.2% (52/72), respectively, whereas PPA was 100% for samples with Ct values of <18 or 18–<25, and was 94.4%, 80.0%, or 100% for samples with Ct values of 25–<30, respectively. RT-PCR positive samples were also tested for SARS-CoV-2 subgenomic RNA and, by three groups, testing showed that PPA was 63.8% (44/69), 62.3% (33/53), or 33.3% (24/72), respectively. PPAs dropped to 55.6%, 20.0%, or 41.7% for samples with Ct values of 25–<30, respectively. All 101 samples with a subgenomic RNA positive result had a Lumipulse assay’s antigen positive result, whereas only 54 (58.1%) of remaining 93 samples had a Lumipulse assay’s antigen positive result. In conclusion, Lumipulse assay was highly sensitive in samples with low RT-PCR Ct values, implying repeated testing to reduce consequences of false-negative results.

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Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

Diagnostics ◽

10.3390/diagnostics11061091 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1091

Author(s):

Ali A. Rabaan ◽

Raghavendra Tirupathi ◽

Anupam A Sule ◽

Jehad Aldali ◽

Abbas Al Mutair ◽

...

Keyword(s):

Viral Load ◽

Real Time ◽

Disease Severity ◽

False Negative ◽

Influential Factors ◽

Confirmatory Test ◽

Acid Extraction ◽

Rt Pcr ◽

Viral Kinetics ◽

Ct Value

Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.

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Performance of Self-Collected Saliva Testing Compared with Nasopharyngeal Swab Testing for the Detection of SARS-CoV-2

Viruses ◽

10.3390/v13050895 ◽

2021 ◽

Vol 13 (5) ◽

pp. 895

Author(s):

Florence Carrouel ◽

Martine Valette ◽

Hervé Perrier ◽

Maude Bouscambert-Duchamp ◽

Claude Dussart ◽

...

Keyword(s):

Viral Load ◽

Quantitative Pcr ◽

Statistical Analyses ◽

Fair Agreement ◽

Quantitative Detection ◽

Nasopharyngeal Swab ◽

Rt Pcr ◽

Noninvasive Techniques ◽

Concordance Probability ◽

Salivary Test

The aim of this study was to determine whether self-collected pure saliva (SCPS) is comparable to nasopharyngeal (NP) swabs in the quantitative detection of SARS-CoV-2 by RT-PCR in asymptomatic, mild patients with confirmed COVID-19. Thirty-one patients aged from 18 to 85 years were included between 9 June and 11 December 2020. A SCPS sample and a NP sample were taken for each patient. Quantitative PCR was performed to detect SARS-CoV-2 viral load. Results of SCPS vs NP samples testing were compared. Statistical analyses were performed. Viral load was significantly correlated (r = 0.72). The concordance probability was estimated at 73.3%. In symptomatic adults, SCPS performance was similar to that of NP swabs (Percent Agreement = 74.1%; p = 0.11). Thus, the salivary test based on pure oral saliva samples easily obtained by noninvasive techniques has a fair agreement with the nasopharyngeal one in asymptomatic, mild patients with a confirmed diagnosis of COVID-19.

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Evaluation of SARS-CoV-2 antigen-based rapid diagnostic kits in Pakistan: formulation of COVID-19 national testing strategy

Virology Journal ◽

10.1186/s12985-021-01505-3 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Umar Saeed ◽

Sara Rizwan Uppal ◽

Zahra Zahid Piracha ◽

Azhar Rasheed ◽

Zubair Aftab ◽

...

Keyword(s):

Gold Standard ◽

Injection Drug Users ◽

Drug Users ◽

Diagnostic Testing ◽

False Negative ◽

Cross Sectional Study ◽

Nasopharyngeal Swab ◽

Rt Pcr ◽

Cross Sectional ◽

Negative Results

AbstractRapid diagnosis of SARS-CoV-2 during pandemic enables timely treatment and prevention of COVID-19. Evaluating the accuracy and reliability of rapid diagnostic testing kits is crucial for surveillance and diagnosis of SARS-CoV-2 infections in general population, injection drug users, multi-transfused populations, healthcare workers, prisoners, barbers and other high risk populations. The aim of this study was to evaluate performance and effectiveness of nasopharyngeal swab (NSP) and saliva based rapid antigen detection testing kits in comparison with USFDA approved triple target gold standard real-time polymerase chain reaction. A cross-sectional study was conducted on 33,000 COVID-19 suspected patients. From RT-PCR positive patients, nasopharyngeal swab (NSP) and saliva samples were obtained for evaluation of rapid COVID-19 testing kits (RDT). 100/33,000 (0.3%) of specimens were RT-PCR positive for SARS-CoV-2. Among RT-PCR positive, 62% were males, 34% were females, and 4% were children. The NSP-RDT (Lepu Medical China) analysis revealed 53% reactivity among males, 58% reactivity among females, and 25% reactivity among children. However saliva based RDT (Lepu Medical China) analysis showed 21% reactivity among males and 23% among females, and no reactivity in children. False negative results were significantly more pronounced in saliva based RDT as compared to NSP-RDT. The sensitivity of these NSP-RDT and saliva based RDT were 52% and 21% respectively. The RDTs evaluated in this study showed limited sensitivities in comparison to gold standard RT-PCR, indicating that there is a dire need in Pakistan for development of suitable testing to improve accurate COVID-19 diagnosis in line with national demands.

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SARS-CoV-2 in peritoneal swabs from asymptomatic patients undergoing emergency abdominal surgery

Journal of Surgical Case Reports ◽

10.1093/jscr/rjab116 ◽

2021 ◽

Vol 2021 (4) ◽

Author(s):

Jasim AlAradi ◽

Rawan A Rahman AlHarmi ◽

Mariam AlKooheji ◽

Sayed Ali Almahari ◽

Mohamed Abdulla Isa ◽

...

Keyword(s):

Peritoneal Fluid ◽

Case Series ◽

Rapid Test ◽

Nasopharyngeal Swab ◽

Rt Pcr ◽

Protective Measures ◽

The Public ◽

Asymptomatic Patients ◽

Number Of Patients ◽

Viral Transfer

Abstract This is a case series of five patients with acute abdomen requiring surgery who tested positive for coronavirus disease 2019 (COVID-19) and were asymptomatic, with the purpose of detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in peritoneal fluid. Nasopharyngeal swab was done as a prerequisite for admission or prior to admission as part of random testing. Two methods of viral testing were employed: Xpert® Xpress SARS-CoV-2 (rapid test) and real-time reverse transcription polymerase chain reaction (RT-PCR). Either or both tests were done, with the former performed for patients requiring surgery immediately. Surgery was performed within 24–36 h from admission. Peritoneal fluid swabs were obtained for the detection of SARS-CoV-2 using RT-PCR test. Swabs were immediately placed in viral transfer media and delivered to the public health laboratory in an ice bag. SARS-CoV-2 was not detected in peritoneal swabs. Due to the limited number of patients, further studies are required; yet, protective measures should still be taken by surgeons when dealing with COVID-19 cases.

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False Negative Mitigation in Group Testing for COVID-19 Screening

Frontiers in Medicine ◽

10.3389/fmed.2021.661277 ◽

2021 ◽

Vol 8 ◽

Author(s):

Amir Reza Alizad Rahvar ◽

Safar Vafadar ◽

Mehdi Totonchi ◽

Mehdi Sadeghi

Keyword(s):

Viral Load ◽

False Negative ◽

Group Testing ◽

False Negative Rate ◽

Screening Strategy ◽

Web Interface ◽

Rt Pcr ◽

Promising Candidate ◽

Testing Method ◽

High False Negative Rate

After lifting the COVID-19 lockdown restrictions and opening businesses, screening is essential to prevent the spread of the virus. Group testing could be a promising candidate for screening to save time and resources. However, due to the high false-negative rate (FNR) of the RT-PCR diagnostic test, we should be cautious about using group testing because a group's false-negative result identifies all the individuals in a group as uninfected. Repeating the test is the best solution to reduce the FNR, and repeats should be integrated with the group-testing method to increase the sensitivity of the test. The simplest way is to replicate the test twice for each group (the 2Rgt method). In this paper, we present a new method for group testing (the groupMix method), which integrates two repeats in the test. Then we introduce the 2-stage sequential version of both the groupMix and the 2Rgt methods. We compare these methods analytically regarding the sensitivity and the average number of tests. The tradeoff between the sensitivity and the average number of tests should be considered when choosing the best method for the screening strategy. We applied the groupMix method to screening 263 people and identified 2 infected individuals by performing 98 tests. This method achieved a 63% saving in the number of tests compared to individual testing. Our experimental results show that in COVID-19 screening, the viral load can be low, and the group size should not be more than 6; otherwise, the FNR increases significantly. A web interface of the groupMix method is publicly available for laboratories to implement this method.

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Inappropriate Nasopharyngeal Sampling for SARS-CoV-2 Detection Is a Relevant Cause of False-Negative Reports

Otolaryngology ◽

10.1177/0194599820931793 ◽

2020 ◽

Vol 163 (3) ◽

pp. 459-461 ◽

Cited By ~ 12

Author(s):

Antonio Piras ◽

Davide Rizzo ◽

Sergio Uzzau ◽

Giacomo De Riu ◽

Salvatore Rubino ◽

...

Keyword(s):

Nasal Obstruction ◽

Negative Impact ◽

Present Report ◽

False Negative ◽

Nasopharyngeal Swab ◽

Rt Pcr ◽

Radiologic Findings ◽

Negative Findings ◽

Current Outbreak ◽

Polymerase Chain

Reverse transcriptase polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 mRNA on nasopharyngeal swab is the standard for diagnosing active COVID-19 disease in asymptomatic cases and in symptomatic patients without the typical radiologic findings. For the present COVID-19 outbreak in Italy, we describe 4 symptomatic patients with negative RT-PCR results at the first nasopharyngeal swab, which became positive when collected a few hours later by an otolaryngologist. All the patients showed nasal obstruction. The present report suggests that inadequate nasopharyngeal sampling performed by untrained operators in the presence of nasal obstruction can be a relevant case of false-negative findings at RT-PCR, with a clear negative impact on the efforts to contain the current outbreak.

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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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