Detection of SARS-CoV-2 Omicron, Delta, Alpha and Gamma variants using a rapid antigen test (preprint)

Throughout the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged with different infection and disease dynamics. Testing strategies, including clinical diagnosis, surveillance, and screening, have been deployed to help limit the spread of SARS-CoV-2 variants. Rapid antigen tests, in particular, have been approved for self-testing in many countries and governments are supporting their manufacturing and distribution. However, studies demonstrating the accuracy of rapid antigen tests in detecting SARS-CoV-2 variants, especially the new Omicron variant, are limited. We determined the analytical sensitivity of a CE-marked rapid antigen test against the Omicron, Delta, Alpha and Gamma variants. The rapid antigen test had the most sensitive limit of detection (10 plaque forming units [PFU]/mL) when tested with the Alpha and Gamma variants, followed by the Omicron (100 PFU/mL) and Delta (1,000 PFU/mL) variants. Given the increasing numbers of breakthrough infections and the need to surveil infectiousness, rapid antigen tests are effective public health tools to detect SARS-CoV-2 variants.

Comparative evaluation of rapid isothermal amplification and antigen assays for screening testing of SARS-CoV-2 (preprint)

Human transmission of SARS-CoV-2 and emergent variants of concern has continued to occur globally, despite mass vaccination campaigns. Public health strategies to reduce virus spread should therefore rely, in part, on frequent screening with rapid, inexpensive, and sensitive tests. We evaluated two digitally integrated rapid tests and assessed their performance using stored nasal swab specimens collected from individuals with or without COVID-19. An isothermal amplification assay combined with a lateral flow test had a limit of detection of 10 RNA copies per reaction, and a positive percent agreement (PPA)/negative percent agreement (NPA) during the asymptomatic and symptomatic phases of 100%/100% and 95.83/100%, respectively. Comparatively, an antigen-based lateral flow test, had a limit of detection of 30,000 copies, and a PPA/NPA during the asymptomatic and symptomatic phases of 82.86%/98.68% and 91.67/100%, respectively. Both the isothermal amplification and antigen-based lateral flow tests had optimized detection of SARS-CoV-2 during the peak period of transmission; however, the antigen-based test had reduced sensitivity in clinical samples with qPCR Ct values greater than 29.8. Low-cost, high-throughput screening enabled by isothermal amplification or antigen-based techniques have value for outbreak control.

Pooling of samples for SARS-CoV-2 detection using rapid antigen tests (preprint)

While molecular assays, such as RT-PCR, have been widely used throughout the COVID-19 pandemic, the technique is costly and resource intensive. As a means to reduce costs and increase diagnostic efficiency, pooled testing for RT-PCR has been implemented. However, pooling samples for antigen testing has not been evaluated. We propose a pooling strategy for antigen testing that would significantly expand SARS-CoV-2 surveillance, especially for low-to-middle income countries, schools, and workplaces. Our data demonstrate that combining of up to 20 nasal swab specimens per pool can expand surveillance with antigen tests, even if a pool contains only one positive sample.

Validating and modeling the impact of high-frequency rapid antigen screening on COVID-19 spread and outcomes (preprint)

High frequency screening of populations has been proposed as a strategy in facilitating control of the COVID-19 pandemic. We use computational modeling, coupled with clinical data from rapid antigen tests, to predict the impact of frequent viral antigen rapid testing on COVID-19 spread and outcomes. Using patient nasal or nasopharyngeal swab specimens, we demonstrate that the sensitivity/specificity of two rapid antigen tests compared to quantitative real-time polymerase chain reaction (qRT-PCR) are 80.0%/91.1% and 84.7%/85.7%, respectively; moreover, sensitivity correlates directly with viral load. Based on COVID-19 data from three regions in the United States and São José do Rio Preto, Brazil, we show that high frequency, strategic population-wide rapid testing, even at varied accuracy levels, diminishes COVID-19 infections, hospitalizations, and deaths at a fraction of the cost of nucleic acid detection via qRT-PCR. We propose large-scale antigen-based surveillance as a viable strategy to control SARS-CoV-2 spread and to enable societal re-opening.

The impact of high frequency rapid viral antigen screening on COVID-19 spread and outcomes: a validation and modeling study (preprint)

High frequency screening of populations has been proposed as a strategy in facilitating control of the COVID-19 pandemic. Here we develop a model to evaluate the impact of rapid testing on COVID-19 spread and outcomes, inspired by our clinically validated direct antigen rapid test (DART) for detection of SARS-CoV-2 spike glycoprotein. Using patient nasopharyngeal swab specimens we demonstrate that the DART sensitivity and specificity are 84.7% and 85.7%, respectively; moreover, sensitivity increases proportionally with higher viral loads. Based on surveillance data on COVID-19 from the United States and Sao Jose do Rio Preto, Brazil we show that frequent and strategic population-wide rapid testing, even at varied accuracy levels, is more effective than virus detection via polymerase chain reaction at reducing COVID-19 infections, hospitalizations, and deaths. While current policy emphasizes testing accuracy, we propose large-scale antigen-based surveillance as a vital strategy to control SARS-CoV-2 spread and to enable societal re-opening.