Evaluation and clinical implications of the time to a positive results of antigen testing for SARS-CoV-2

Akashi, Yusaku; Kiyasu, Yoshihiko; Takeuchi, Yuto; Kato, Daisuke; Kuwahara, Masaki; Muramatsu, Shino; Ueda, Atsuo; Notake, Shigeyuki; Nakamura, Koji; Ishikawa, Hiroichi; Suzuki, Hiromichi

doi:10.1101/2021.06.09.21258157

Cited by 4 publications

(6 citation statements)

References 13 publications

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“…At the end of the data extraction process, 21 studies were still in preprint form [20,21,25,51,54,59,62,69,73,78,88,104,120,125,133,164,171,172,177,178,190]. All studies included were written in English, except for 3 in Spanish [57,66,138], 1 in Turkish [99], and 1 in French [157].…”

Section: Summary Of Studiesmentioning

confidence: 99%

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: An updated systematic review and meta-analysis with meta-regression analyzing influencing factors

et al. 2022

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Background Comprehensive information about the accuracy of antigen rapid diagnostic tests (Ag-RDTs) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is essential to guide public health decision makers in choosing the best tests and testing policies. In August 2021, we published a systematic review and meta-analysis about the accuracy of Ag-RDTs. We now update this work and analyze the factors influencing test sensitivity in further detail. Methods and findings We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched preprint and peer-reviewed databases for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 until August 31, 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 with reverse transcription polymerase chain reaction (RT-PCR) testing as a reference. To evaluate factors influencing test sensitivity, we performed 3 different analyses using multivariable mixed-effects meta-regression models. We included 194 studies with 221,878 Ag-RDTs performed. Overall, the pooled estimates of Ag-RDT sensitivity and specificity were 72.0% (95% confidence interval [CI] 69.8 to 74.2) and 98.9% (95% CI 98.6 to 99.1). When manufacturer instructions were followed, sensitivity increased to 76.3% (95% CI 73.7 to 78.7). Sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values (97.9% [95% CI 96.9 to 98.9] and 90.6% [95% CI 88.3 to 93.0] for Ct-values <20 and <25, compared to 54.4% [95% CI 47.3 to 61.5] and 18.7% [95% CI 13.9 to 23.4] for Ct-values ≥25 and ≥30) and was estimated to increase by 2.9 percentage points (95% CI 1.7 to 4.0) for every unit decrease in mean Ct-value when adjusting for testing procedure and patients’ symptom status. Concordantly, we found the mean Ct-value to be lower for true positive (22.2 [95% CI 21.5 to 22.8]) compared to false negative (30.4 [95% CI 29.7 to 31.1]) results. Testing in the first week from symptom onset resulted in substantially higher sensitivity (81.9% [95% CI 77.7 to 85.5]) compared to testing after 1 week (51.8%, 95% CI 41.5 to 61.9). Similarly, sensitivity was higher in symptomatic (76.2% [95% CI 73.3 to 78.9]) compared to asymptomatic (56.8% [95% CI 50.9 to 62.4]) persons. However, both effects were mainly driven by the Ct-value of the sample. With regards to sample type, highest sensitivity was found for nasopharyngeal (NP) and combined NP/oropharyngeal samples (70.8% [95% CI 68.3 to 73.2]), as well as in anterior nasal/mid-turbinate samples (77.3% [95% CI 73.0 to 81.0]). Our analysis was limited by the included studies’ heterogeneity in viral load assessment and sample origination. Conclusions Ag-RDTs detect most of the individuals infected with SARS-CoV-2, and almost all (>90%) when high viral loads are present. With viral load, as estimated by Ct-value, being the most influential factor on their sensitivity, they are especially useful to detect persons with high viral load who are most likely to transmit the virus. To further quantify the effects of other factors influencing test sensitivity, standardization of clinical accuracy studies and access to patient level Ct-values and duration of symptoms are needed.

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Section: Summary Of Studiesmentioning

confidence: 99%

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: An updated systematic review and meta-analysis with meta-regression analyzing influencing factors

et al. 2022

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“…At the end of the data extraction process, 21 studies were still in preprint form [16, 17, 21, 47, 50, 55, 58, 65, 69, 74, 84, 100, 116, 121, 129, 160, 167, 168, 173, 174, 186]. All studies were written in English, except for 3 in Spanish [53, 62, 134], 1 in Turkish [95], and 1 in French [153].…”

Section: Resultsmentioning

confidence: 99%

“…All studies were written in English, except for 3 in Spanish [53, 62, 134], 1 in Turkish [95], and 1 in French [153]. Out of the 196 studies, 26 conducted a case-control study [21, 32, 34, 66, 67, 72, 81, 84, 88-90, 93, 94, 96, 103, 108, 135, 140, 144, 145, 151, 156, 166, 168, 182, 184], while the remaining 168 were cross-sectional or cohort studies. The reference method was RT-PCR in all except 1 study, which used viral culture [135].…”

Section: Resultsmentioning

confidence: 99%

“…Further 20 studies were included from the FIND website [190][191][192][193][194][195][196][197][198][199][200][201][202][203][204][205][206][207][208][209] (Fig 1). At the end of the data extraction process, 21 studies were still in preprint form [16,17,21,47,50,55,58,65,69,74,84,100,116,121,129,160,167,168,173,174,186]. All studies were written in English, except for 3 in Spanish [53,62,134], 1 in Turkish [95], and 1 in French [153].…”

Section: Summary Of Studiesmentioning

confidence: 99%

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Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: an updated systematic review and meta-analysis with meta regression analyzing influencing factors

Brümmer

Katzenschlager

McGrath

et al. 2022

Preprint

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Background Comprehensive information about the accuracy of antigen rapid diagnostic tests (Ag-RDTs) for SARS-CoV-2 is essential to guide public health decision makers in choosing the best tests and testing policies. In August 2021, we published a systematic review and meta-analysis about the accuracy of Ag-RDTs. We now update this work and analyze the factors influencing test sensitivity in further detail. 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 until August 31, 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 with reverse transcription polymerase chain reaction (RT-PCR) testing as a reference. To evaluate factors influencing test sensitivity, we performed 3 different analyses using multivariate mixed-effects meta-regression models. We included 194 studies with 221,878 Ag-RDTs performed. Overall, the pooled estimates of Ag-RDT sensitivity and specificity were 72.0% (95% confidence interval [CI] 69.8 to 74.2) and 98.9% (95% CI 98.6 to 99.1), respectively. When manufacturer instructions were followed, sensitivity increased to 76.4% (95%CI 73.8 to 78.8). Sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values (sensitivity of 97.9% [95% CI 96.9 to 98.9] and 90.6% [95% CI 88.3 to 93.0] for Ct-values <20 and <25, compared to 54.4% [95% CI 47.3 to 61.5] and 18.7% [95% CI 13.9 to 23.4] for Ct-values ≥25 and ≥30) and was estimated to increase by 2.9 percentage points (95% CI 1.7 to 4.0) for every unit decrease in mean Ct-value when adjusting for testing procedure and patients symptom status. Concordantly, we found the mean Ct-value to be lower for true positive (22.2 [95% CI 21.5 to 22.8]) compared to false negative (30.4 [95% CI 29.7 to 31.1]) results. Testing in the first week from symptom onset resulted in substantially higher sensitivity (81.9% [95% CI 77.7 to 85.5]) compared to testing after 1 week (51.8%, 95% CI 41.5 to 61.9). Similarly, sensitivity was higher in symptomatic (76.2% [95% CI 73.3 to 78.9]) compared to asymptomatic (56.8% [95% CI 50.9 to 62.4]) persons. However, both effects were mainly driven by the Ct-value of the sample. With regards to sample type, highest sensitivity was found for nasopharyngeal (NP) and combined NP/oropharyngeal samples (70.8% [95% CI 68.3 to 73.2]), as well as in anterior nasal/mid-turbinate samples (77.3% [95% CI 73.0 to 81.0]). Conclusion Ag-RDTs detect most of the individuals infected with SARS-CoV-2, and almost all when high viral loads are present (>90%). With viral load, as estimated by Ct-value, being the most influential factor on their sensitivity, they are especially useful to detect persons with high viral load who are most likely to transmit the virus. To further quantify the effects of other factors influencing test sensitivity, standardization of clinical accuracy studies and access to patient level Ct-values and duration of symptoms are needed.

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“…NP and saliva samples were simultaneously obtained from participants. The sample collection was performed as previously described [2,[8][9][10][11][12][13][14][15][16][17][18][19]. All antigen tests for saliva were immediately performed on site after sample collection.…”

Section: Study Processmentioning

confidence: 99%

A prospective evaluation of three saliva qualitative antigen testing kits for the detection of SARS-CoV-2 in Japan

Terada

Akashi

Takeuchi

et al. 2022

Preprint

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Introduction: Rapid qualitative antigen testing has been widely used for the laboratory diagnosis of COVID-19 with nasopharyngeal samples. Saliva samples have been used as alternative samples, but the analytical performance of those samples for qualitative antigen testing has not been sufficiently evaluated. Methods: A prospective observational study evaluated the analytical performance of three In Vitro Diagnostics (IVD) approved COVID-19 rapid antigen detection kits for saliva between June 2022 and July 2022 in Japan using real-time reverse transcription polymerase chain reaction (RT-PCR) as a reference. A nasopharyngeal sample and a saliva sample were simultaneously obtained, and RT-PCR was performed. Results: In total, saliva samples and nasopharyngeal samples were collected from 471 participants (140 RT-PCR-positive saliva samples and 143 RT-PCR-positive nasopharyngeal samples) for the analysis. The median Ct values were 25.5 (interquartile range [IQR]: 21.9-28.8) for saliva samples and 17.1 (IQR: 15.5-18.7) for nasopharyngeal samples (p<0.001). Compared with saliva samples of RT-PCR, the sensitivity and specificity were 46.4% and 99.7% for ImunoAce SARS-CoV-2 Saliva, 59.3% and 99.1% for Espline SARS-CoV-2 N, and 61.4% and 98.8% for QuickChaser Auto SARS-CoV-2, respectively. The sensitivity is >90% for saliva samples with a moderate-to-high viral load (Ct<25), whereas the sensitivity is <70% for high-viral-load nasopharyngeal samples (Ct<20). Conclusion: COVID-19 rapid antigen detection kits with saliva showed high specificities, but the sensitivities varied among kits, and the analytical performance of saliva qualitative antigen detection kits was much worse than that of kits using nasopharyngeal samples.

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Evaluation and clinical implications of the time to a positive results of antigen testing for SARS-CoV-2

Cited by 4 publications

References 13 publications

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: An updated systematic review and meta-analysis with meta-regression analyzing influencing factors

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: An updated systematic review and meta-analysis with meta-regression analyzing influencing factors

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: an updated systematic review and meta-analysis with meta regression analyzing influencing factors

A prospective evaluation of three saliva qualitative antigen testing kits for the detection of SARS-CoV-2 in Japan

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