scaling up covid 19 rapid antigen tests promises and challenges CORD-Papers-2022-06-02 (Version 1)

Title: Scaling up COVID-19 rapid antigen tests: promises and challenges
Abstract: WHO recommends a minimum of 80% sensitivity and 97% specificity for antigen-detection rapid diagnostic tests (Ag-RDTs) which can be used for patients with symptoms consistent with COVID-19. However after the acute phase when viral load decreases use of Ag-RDTs might lead to high rates of false negatives suggesting that the tests should be replaced by a combination of molecular and serological tests. When the likelihood of having COVID-19 is low such as for asymptomatic individuals in low prevalence settings for travel return to schools workplaces and mass gatherings Ag-RDTs with high negative predictive values can be used with confidence to rule out infection. For those who test positive in low prevalence settings the high false positive rate means that mitigation strategies such as molecular testing to confirm positive results are needed. Ag-RDTs when used appropriately are promising tools for scaling up testing and ensuring that patient management and public health measures can be implemented without delay.
Published: 2021-02-23
Journal: Lancet Infect Dis
DOI: 10.1016/s1473-3099(21)00048-7
DOI_URL: http://doi.org/10.1016/s1473-3099(21)00048-7
Author Name: Peeling Rosanna W
Author link: https://covid19-data.nist.gov/pid/rest/local/author/peeling_rosanna_w
Author Name: Olliaro Piero L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/olliaro_piero_l
Author Name: Boeras Debrah I
Author link: https://covid19-data.nist.gov/pid/rest/local/author/boeras_debrah_i
Author Name: Fongwen Noah
Author link: https://covid19-data.nist.gov/pid/rest/local/author/fongwen_noah
sha: 30c4b7e99190f0a17eacecc6e2ec8d1c53b6a91e
license: no-cc
license_url: [no creative commons license associated]
source_x: Elsevier; Medline; PMC
source_x_url: https://www.elsevier.com/https://www.medline.com/https://www.ncbi.nlm.nih.gov/pubmed/
pubmed_id: 33636148
pubmed_id_url: https://www.ncbi.nlm.nih.gov/pubmed/33636148
pmcid: PMC7906660
pmcid_url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906660
url: https://www.sciencedirect.com/science/article/pii/S1473309921000487 https://doi.org/10.1016/s1473-3099(21)00048-7 https://www.ncbi.nlm.nih.gov/pubmed/33636148/ https://api.elsevier.com/content/article/pii/S1473309921000487
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Keywords Extracted from Text Content: COVID-19 patient patients SARS-CoV-2 antigen Patients PLO Yap Boum II sample-to-answer centre PPVs COVID-19 antigen FDA SAR-CoV-2 serum travellers samples SARS-CoV-2 RDTs self-isolate SARS-CoV-2 viral proteins antigen 1-2·5 specimens lateral COVID-19 Tedros Food people SARS-CoV-2 antibodies appendix p 1 NF patients patient Ag-RDT Wellcome [215091/Z/18/Z UK Foreign PLO
Extracted Text Content in Record: First 5000 Characters:WHO recommends a minimum of 80% sensitivity and 97% specificity for antigen-detection rapid diagnostic tests (Ag-RDTs), which can be used for patients with symptoms consistent with COVID-19. However, after the acute phase when viral load decreases, use of Ag-RDTs might lead to high rates of false negatives, suggesting that the tests should be replaced by a combination of molecular and serological tests. When the likelihood of having COVID-19 is low, such as for asymptomatic individuals in low prevalence settings, for travel, return to schools, workplaces, and mass gatherings, Ag-RDTs with high negative predictive values can be used with confidence to rule out infection. For those who test positive in low prevalence settings, the high false positive rate means that mitigation strategies, such as molecular testing to confirm positive results, are needed. Ag-RDTs, when used appropriately, are promising tools for scaling up testing and ensuring that patient management and public health measures can be implemented without delay. Lancet Infect Dis 2021 It has been nearly 1 year since the COVID-19 pandemic started and most countries still face major challenges in scaling up testing capacity, coupled with a lack of understanding of the different types of tests and how they can be used. To combat the COVID-19 pandemic, Tedros Adhanom Ghebreyesusm, the director-general of WHO, urged countries to "test, test, test.". 1 Yet, few countries have managed to scale up testing capacity to gather sufficient population-level data to inform public health decisions on reopening of schools, return to work, mass gatherings, and travel, to allow easing of restrictions. The consequences for individuals, public health, and the economy are substantial. Molecular assays to diagnose COVID-19 were quickly developed once the genetic sequence of SAR-CoV-2 was published in January, 2020. 2 These assays typically use PCR to amplify and detect viral RNA, and are highly sensitive and specific. Most assays require laboratory facilities with robust infrastructure and highly trained staff. Normally, results are available in less than 2 h, but many countries are seeing delays of up to 7 days. 3 Delays in obtaining molecular testing results can increase the risk of virus transmission. The longer patients wait, the more likely they will not self-isolate at the time that they are most infectious and will resume daily activities before receiving test results. Although rapid technological advances in automated portable sample-to-answer molecular testing platforms have allowed testing to be deployed outside laboratory settings, and provide results in less than 1 h, these technologies are still equipmentdependent and the manufacture and scale up takes time. Hence the supply of devices and cartridges is short of global demand, especially for countries with weak or scarce laboratory infrastructure. Another limitation of molecular testing is the global competition for reagents and supplies, which has severely slowed down testing capacity, particularly in resource-constrained settings. The con sequences of these limi tations include continued restrictions and delays in confirming or excluding SARS-CoV-2 infection at the individual-level for case management or isolation, and at population-level for surveillance and response purposes. Molecular testing is inherently difficult to scale up. Pooling samples for molecular testing has been suggested as a cost-effective way of scaling up the number of samples tested per day. Although pooling might be useful for large scale surveys, for individual detection there is a risk of false negative results due to sample dilution in the pooling process. Furthermore, batching a large number of samples followed by testing individual samples of positive pools would result in delays in getting the test results sent back. These limitations show the need for well thought out options in addition to molecular assays. An alternative assay that can alleviate some of the bottlenecks created by molecular testing would be antigen testing. COVID-19 antigen tests diagnose active infection by detecting SARS-CoV-2 viral proteins in various specimen types. They are available as a single use, lateral flow, antigen-detection rapid diagnostic tests (Ag-RDTs) that can be visually read or processed and read using a small portable device (table 1) . Both can be done outside the laboratory and provide a result within 15-20 min. These rapid tests can be produced much faster and cheaper in larger quantities for large scale deployment. Although these tests can be highly specific, they are generally not as sensitive as molecular tests. As of Nov 27, 2020, six Ag-RDTs have received US Food and Drug Administration (FDA) Emergency Use Authorization and two have received WHO Emergency Use Listing and are undergoing independent evaluation. 2, 4, 5 Understanding the limitations of these Ag-RDTs is important when trying to scale up testing to detect cases of CO
Keywords Extracted from PMC Text: antibody tests.6 appendix p 1).2 Patients Studies8, 9 centre Food antigen patients FDA people sample-to-answer 104–105 test.".1 self-isolate COVID-19.12 travellers Tedros SARS-CoV-2 antibodies specimens patient SARS-CoV-2 viral proteins COVID-19 antigen 25–30 Studies14 serum Ag-RDT Studies19 SARS-CoV-2 SARS-CoV-2 antigen Yap Boum II COVID-19 guidance,7 FIND2 SAR-CoV-2 RDTs samples 15–20 PPVs PanelExamples lateral individuals area.21
Extracted PMC Text Content in Record: First 5000 Characters:It has been nearly 1 year since the COVID-19 pandemic started and most countries still face major challenges in scaling up testing capacity, coupled with a lack of understanding of the different types of tests and how they can be used. To combat the COVID-19 pandemic, Tedros Adhanom Ghebreyesusm, the director-general of WHO, urged countries to "test, test, test.".1 Yet, few countries have managed to scale up testing capacity to gather sufficient population-level data to inform public health decisions on reopening of schools, return to work, mass gatherings, and travel, to allow easing of restrictions. The consequences for individuals, public health, and the economy are substantial. Molecular assays to diagnose COVID-19 were quickly developed once the genetic sequence of SAR-CoV-2 was published in January, 2020.2 These assays typically use PCR to amplify and detect viral RNA, and are highly sensitive and specific. Most assays require laboratory facilities with robust infrastructure and highly trained staff. Normally, results are available in less than 2 h, but many countries are seeing delays of up to 7 days.3 Delays in obtaining molecular testing results can increase the risk of virus transmission. The longer patients wait, the more likely they will not self-isolate at the time that they are most infectious and will resume daily activities before receiving test results. Although rapid technological advances in automated portable sample-to-answer molecular testing platforms have allowed testing to be deployed outside laboratory settings, and provide results in less than 1 h, these technologies are still equipment-dependent and the manufacture and scale up takes time. Hence the supply of devices and cartridges is short of global demand, especially for countries with weak or scarce laboratory infrastructure. Another limitation of molecular testing is the global competition for reagents and supplies, which has severely slowed down testing capacity, particularly in resource-constrained settings. The consequences of these limitations include continued restrictions and delays in confirming or excluding SARS-CoV-2 infection at the individual-level for case management or isolation, and at population-level for surveillance and response purposes. Molecular testing is inherently difficult to scale up. Pooling samples for molecular testing has been suggested as a cost-effective way of scaling up the number of samples tested per day. Although pooling might be useful for large scale surveys, for individual detection there is a risk of false negative results due to sample dilution in the pooling process. Furthermore, batching a large number of samples followed by testing individual samples of positive pools would result in delays in getting the test results sent back. These limitations show the need for well thought out options in addition to molecular assays. An alternative assay that can alleviate some of the bottlenecks created by molecular testing would be antigen testing. COVID-19 antigen tests diagnose active infection by detecting SARS-CoV-2 viral proteins in various specimen types. They are available as a single use, lateral flow, antigen-detection rapid diagnostic tests (Ag-RDTs) that can be visually read or processed and read using a small portable device (table 1 ). Both can be done outside the laboratory and provide a result within 15–20 min. These rapid tests can be produced much faster and cheaper in larger quantities for large scale deployment. Although these tests can be highly specific, they are generally not as sensitive as molecular tests. As of Nov 27, 2020, six Ag-RDTs have received US Food and Drug Administration (FDA) Emergency Use Authorization and two have received WHO Emergency Use Listing and are undergoing independent evaluation.2, 4, 5 Understanding the limitations of these Ag-RDTs is important when trying to scale up testing to detect cases of COVID-19 and provide data to inform public health measures, and ease restrictions. Here we explore the use of Ag-RDTs across different populations with various risks of acquiring and transmitting COVID-19 for a more informed public health approach. When considering which test to use and how to interpret results, two components should be considered: the test sensitivity and specificity, which provide information on its performance to accurately measure the presence or absence of the disease. Test sensitivity and specificity are inherent characteristics of a test and do not change when used in different populations. However, the usefulness of a test for a particular population is defined by the positive predictive value (PPV) and negative predictive value (NPV) of the test result for that particular population. The PPV is defined as the probability that a person with a positive test result truly has the disease. The NPV is defined as the probability that a person with a negative test result truly does not have the disease. Both measures vary depending on
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