Evaluation of Rapid Antigen Tests Using Nasal Samples to Diagnose SARS-CoV-2 in Symptomatic Patients

IntroductionThe best way to mitigate an outbreak besides mass vaccination is via early detection and isolation of infected cases. As such, a rapid, cost-effective test for the early detection of COVID-19 is required.MethodsThe study included 4,183 mildly symptomatic patients. A nasal and nasopharyngeal sample obtained from each patient was analyzed to determine the diagnostic ability of the rapid antigen detection test (RADT, nasal swab) in comparison with the current gold-standard (RT-PCR, nasopharyngeal swab).ResultsThe calculated sensitivity and specificity of the RADT was 82.1 and 99.1%, respectively. Kappa's coefficient of agreement between the RADT and RT-PCR was 0.859 (p < 0.001). Stratified analysis showed that the sensitivity of the RADT improved significantly when lowering the cut-off RT-PCR Ct value to 24.ConclusionOur study's results support the potential use of nasal swab RADT as a screening tool in mildly symptomatic patients, especially in patients with higher viral loads.

Model-based evaluation of alternative reactive class closure strategies against COVID-19

There are contrasting results concerning the effect of reactive school closure on SARS-CoV-2 transmission. To shed light on this controversy, we developed a data-driven computational model of SARS-CoV-2 transmission. We found that by reactively closing classes based on syndromic surveillance, SARS-CoV-2 infections are reduced by no more than 17.3% (95%CI: 8.0–26.8%), due to the low probability of timely identification of infections in the young population. We thus investigated an alternative triggering mechanism based on repeated screening of students using antigen tests. Depending on the contribution of schools to transmission, this strategy can greatly reduce COVID-19 burden even when school contribution to transmission and immunity in the population is low. Moving forward, the adoption of antigen-based screenings in schools could be instrumental to limit COVID-19 burden while vaccines continue to be rolled out.

Implementation of a COVID-19 Screening Testing Program in a Rural, Tribal Nation: Experience of the San Carlos Apache Tribe, January–February 2021

The COVID-19 pandemic has disproportionately affected tribal populations, including the San Carlos Apache Tribe. Universal screening testing in a community using rapid antigen tests could allow for near–real-time identification of COVID-19 cases and result in reduced SARS-CoV-2 transmission. Published experiences of such testing strategies in tribal communities are lacking. Accordingly, tribal partners, with support from the Centers for Disease Control and Prevention, implemented a serial testing program using the Abbott BinaxNOW rapid antigen test in 2 tribal casinos and 1 detention center on the San Carlos Apache Indian Reservation for a 4-week pilot period from January to February 2021. Staff members at each setting, and incarcerated adults at the detention center, were tested every 3 or 4 days with BinaxNOW. During the 4-week period, 3834 tests were performed among 716 participants at the sites. Lessons learned from implementing this program included demonstrating (1) the plausibility of screening testing programs in casino and prison settings, (2) the utility of training non–laboratory personnel in rapid testing protocols that allow task shifting and reduce the workload on public health employees and laboratory staff, (3) the importance of building and strengthening partnerships with representatives from the community and public and private sectors, and (4) the need to implement systems that ensure confidentiality of test results and promote compliance among participants. Our experience and the lessons learned demonstrate that a serial rapid antigen testing strategy may be useful in work settings during the COVID-19 pandemic as schools and businesses are open for service.

Quantitative comparison of SARS-CoV-2 nucleic acid amplification test and antigen testing algorithms: a decision analysis simulation model

Background Antigen tests for SARS-CoV-2 offer advantages over nucleic acid amplification tests (NAATs, such as RT-PCR), including lower cost and rapid return of results, but show reduced sensitivity. Public health organizations recommend different strategies for utilizing NAATs and antigen tests. We sought to create a framework for the quantitative comparison of these recommended strategies based on their expected performance. Methods We utilized a decision analysis approach to simulate the expected outcomes of six testing algorithms analogous to strategies recommended by public health organizations. Each algorithm was simulated 50,000 times in a population of 100,000 persons seeking testing. Primary outcomes were number of missed cases, number of false-positive diagnoses, and total test volumes. Outcome medians and 95% uncertainty ranges (URs) were reported. Results Algorithms that use NAATs to confirm all negative antigen results minimized missed cases but required high NAAT capacity: 92,200 (95% UR: 91,200-93,200) tests (in addition to 100,000 antigen tests) at 10% prevalence. Selective use of NAATs to confirm antigen results when discordant with symptom status (e.g., symptomatic persons with negative antigen results) resulted in the most efficient use of NAATs, with 25 NAATs (95% UR: 13-57) needed to detect one additional case compared to exclusive use of antigen tests. Conclusions No single SARS-CoV-2 testing algorithm is likely to be optimal across settings with different levels of prevalence and for all programmatic priorities. This analysis provides a framework for selecting setting-specific strategies to achieve acceptable balances and trade-offs between programmatic priorities and resource constraints.

Combining Rapid Antigen Testing and Syndromic Surveillance Improves Community-Based COVID-19 Detection in Low-to-Middle-Income Countries

Diagnostics for COVID-19 detection are limited in many settings. Syndromic surveillance is often the only means to identify cases, but lacks specificity. Rapid antigen testing is inexpensive and easy-to-deploy but concerns remain about sensitivity. We examine how combining these approaches can improve surveillance for guiding interventions in low-income communities in Dhaka, Bangladesh. Rapid-antigen-tests and PCR validation was performed on 1172 symptomatically-identified individuals at home. Statistical models were fit to predict PCR status using rapid-antigen-test results, syndromic data, and their combination. Model predictive and classification performance was examined under contrasting epidemiological scenarios to evaluate their potential for improving diagnoses. Models combining rapid-antigen-test and syndromic data yielded equal-to-better performance to rapid-antigen-test-only models across all scenarios. These results show that drawing on complementary strengths across two rapid diagnostics, improves COVID-19 detection, and reduces false-positive and -negative diagnoses to match local requirements; improvements achievable without additional expense, or changes for patients or practitioners.

Analytic sensitivity of the Abbott BinaxNOW lateral flow immunochromatographic assay for the SARS-CoV-2 Omicron variant

The emergence of the SARS-CoV-2 Omicron variant has motivated a re-evaluation of the test characteristics for lateral flow immunochromatographic assays (LFIAs), commonly referred to as rapid antigen tests. To address this need, we evaluated the analytic sensitivity of one of the most widely used LFIAs in the US market, the Abbott BinaxNOW COVID-19 Ag At-Home Card using 32 samples of Omicron and 30 samples of the Delta variant. Samples were chosen to intentionally over-represent the range of viral loads where differences are most likely to appear. We found no changes in the analytic sensitivity of the BinaxNOW assay by variant even after controlling for variation in cycle threshold values in the two populations. Similar to prior studies, the sensitivity of the assay is highly dependent on the amount of virus present in the sample. While the analytic sensitivity of the BinaxNOW LFIA remains intact versus the Omicron variant, its clinical sensitivity is influenced by the interaction between viral replication, the dynamics of tissue tropism and the timing of sampling. Further research is necessary to optimally adapt current testing strategies to robustly detect early infection by the Omicron variant to prevent transmission.

High Sensitivity and NPV for BinaxNOW Rapid Antigen Test in Children at a Mass Testing Site During Prevalent Delta Variant

SARS-CoV-2 continues to develop new, increasingly infectious variants, such as delta and omicron. Here, we evaluate the efficacy of the Abbott BinaxNOW Rapid Antigen Test against the gold standard of Reverse Transcription Polymerase Chain Reaction (RT-PCR) in 1054 pediatric participants presenting to a state-owned high-volume Coronavirus Disease 2019 (COVID-19) testing site. During the testing period, the delta variant was predominant. Prior to sample collection, symptomatic and exposure status was collected for all participants based on Centers for Disease Control (CDC) criteria. RT-PCR results demonstrated an overall prevalence rate of 5.2%. For all participants, the sensitivity of the rapid antigen tests was 92.7% (95% CI 82.4% - 98.0%) and specificity was 98.0% (95% CI 97.0%-98.8%). For symptomatic participants, the sensitivity was 92.3% (95% CI 74.9% - 99.1%), specificity was 96.6% (95% CI 93.6%- 98.4%), positive predictive value (PPV) was 72.7% (95% CI 54.5% - 86.7%) and negative predictive value (NPV) was 99.2% (95% CI 98.2% - 100%). Among asymptomatic participants, the sensitivity was 92.6% (95% CI 75.7% - 99.1%), specificity was 98.6% (95% CI 97.5% - 99.3%) the PPV was 71.4% (95% CI 53.7% - 85.4%) and the NPV was 99.7% (95% CI 99.0% - 100%). Our reported sensitivity and NPV are higher than other pediatric studies, but specificity and PPV are lower. Importance Children are especially impacted by the disease and its ability to disrupt educational opportunities. Although vaccinations have been approved for children 5 years and older, many children remain unvaccinated. Widespread testing may improve the ability for children to remain in in-person activities, minimizing absences from school and extracurriculars. Highly accurate rapid antigen tests may be vital to containing future COVID-19 waves while mitigating detrimental effects.

Should rapid antigen tests be government funded in Australia? An economic evaluation

Objective: Easy and equitable access to testing is a cornerstone of the public health response to COVID-19. Currently in Australia, testing using Polymerase Chain Reaction (PCR) tests for COVID-19 is free-to-the-user, but the public purchase their own Rapid Antigen Tests (RATs). We conduct an economic analysis of government-funded RATs in Australia. Design: An interactive decision tree model was developed to compare one policy in which government-funded RATs are free-to-the-user, and one in which individuals purchase their own RATs. The decision tree represents RAT and PCR testing pathways for a cohort of individuals without COVID-19-like symptoms, to estimate the likelihood of COVID-19 positive individuals isolating prior to developing symptoms and the associated costs of testing, from a government perspective. Data sources: Test costs and detection rates were informed by published studies, other input parameter values are unobservable and uncertain, for which a range of scenario analyses are presented. Data synthesis: Assuming 10% prevalence of COVID-19 in a cohort of 10,000 individuals who would use government-funded RATs, the model estimates an additional 464 individuals would isolate early at a cost to the government of around $52,000. Scenario analyses indicate that the incremental cost per additional COVID-19 positive individual isolating with no symptoms remains at a few hundred dollars at 5% prevalence, rising to $2,052 at 1% prevalence. Conclusions: Based on the presented decision tree model, even only minor reductions in COVID-19 transmission rates due to early isolation would justify the additional costs associated with a policy of government-funded RATs.

Discordant SARS-CoV-2 PCR and Rapid Antigen Test Results When Infectious: A December 2021 Occupational Case Series

The performance of Covid-19 diagnostic tests must continue to be reassessed with new variants of concern. The objective of this study was to describe the discordance in saliva SARS-CoV-2 PCR and nasal rapid antigen test results during the early infectious period. We identified a high-risk occupational case cohort of 30 individuals with daily testing during an Omicron outbreak in December 2021. Based on viral load and transmissions confirmed through epidemiological investigation, most Omicron cases were infectious for several days before being detectable by rapid antigen tests.