key: cord-0706070-u7xrm1iz
authors: Shah, M. M.; Salvatore, P. P.; Ford, L.; Kamitani, E.; Whaley, M. J.; Mitchell, K.; Currie, D. W.; Morgan, C. N.; Segaloff, H. E.; Lecher, S.; Somers, T.; Van Dyke, M. E.; Bigouette, J. P.; Delaney, A.; DaSilva, J.; O'Hegarty, M.; Boyle-Estheimer, L.; Abdirizak, F.; Karpathy, S. E.; Meece, J.; Ivanic, L.; Goffard, K.; Gieryn, D.; Sterkel, A.; Bateman, A.; Kahrs, J.; Langolf, K.; Zochert, T.; Knight, N. W.; Hsu, C. H.; Kirking, H. L.; Tate, J. E.
title: Performance of Repeat BinaxNOW SARS-CoV-2 Antigen Testing in a Community Setting, Wisconsin, November-December 2020
date: 2021-04-09
journal: nan
DOI: 10.1101/2021.04.05.21254834
sha: 770168bc049beb4d7ec66749169c4d7cc59d2bd8
doc_id: 706070
cord_uid: u7xrm1iz

Repeating the BinaxNOW antigen test for SARS-CoV-2 by two groups of readers within 30 minutes resulted in high concordance (98.9%) in 2,110 encounters. BinaxNOW test sensitivity was 77.2% (258/334) compared to real-time reverse transcription-polymerase chain reaction. Same day antigen testing did not significantly improve test sensitivity while specificity remained high.

second BinaxNOW test was done by a separate group of trained CDC staff, both according to manufacturer's instructions. All swabs were supervised, self-collected, and from the anterior nares. Participants completed a questionnaire on demographics, exposures, and symptoms. Approximately 30 minutes after the initial swab was taken, each participant provided documentation of their initial BinaxNOW test result and two additional self-collected swabs were taken by CDC staff. Participants were instructed to simultaneously insert one swab into the left nostril and one swab into the right nostril, rotate five times, swap nostrils, and rotate five times again. One swab was used to perform the second BinaxNOW test immediately, and the other swab was placed in viral transport medium and transported to the Marshfield Clinical Research Institute laboratory for RT-PCR testing within two to five days. BinaxNOW results were considered invalid/indeterminate if no lines were seen in the results window or if only the sample line was seen. A three viral target RT-PCR assay (S gene, N gene, Orf1Ab)

for SARS-CoV-2 was conducted. Positive specimens were defined as having at least two targets with a threshold cycle (Ct) value ≤ 37 per manufacturer's instructions [7] .

MagMAX Viral/Pathogen Nucleic Acid Isolation Kit (REF A48310) was used for RNA extraction. Specimens with inconclusive results (defined as one of three positive targets) were re-tested. Symptomatic participants were defined as reporting one or more of 15 symptom criteria at enrollment [8] . RT-PCR was the gold standard for defining antigen test performance. Ninety-five percent confidence intervals (CI) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the Clopper-Pearson method. The Mann-Whitney-U test was used to test rank differences for Ct values; chi-square tests were used to test for for use under a CC0 license. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Table 1 ). Asymptomatic antigen positive participants had a higher false positive proportion (5/38, 13.2%) compared to symptomatic antigen positive participants (2/223, 0.9%).

In this investigation of the BinaxNOW test, the overall sensitivity and sensitivity compared to RT-PCR among people with symptom onset within seven days were consistent with performance reported to the Federal Drug Administration (FDA) by the manufacturer [1] . Among asymptomatic individuals, sensitivity was lower consistent with other reports [2] [3] [4] This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 9, 2021. ; https://doi.org/10.1101/2021.04.05.21254834 doi: medRxiv preprint combinations using a repeated test strategy and to identify the ideal frequency of repeat BinaxNOW testing.

This investigation supports foregoing confirmatory RT-PCR testing in symptomatic antigen test positive individuals per current guidelines, given <1% false positive BinaxNOW test results among symptomatic cases [9] . The FDA has warned healthcare workers of the potential for false positive antigen tests particularly in lowprevalence settings [10]. The BinaxNOW had overall high specificity regardless of symptom status (>99%) and high positive predictive value (97.4%) in a population with high prevalence (15.8%). Prevalence among asymptomatic individuals was lower (5.8%), but this population also had a relatively high positive predictive value (86.8%). In moderate-to-high pretest probability settings, foregoing a RT-PCR confirmatory test in asymptomatic antigen-positive individuals could be considered if resources are limited.

The trade-off would be a relatively small but non-trivial increase in false positive results and the associated consequences (e.g., missed work/school, increased stress, unnecessary contact tracing).

False negative antigen tests are often consequential given the risk of furthering transmission due to perceived lack of infection. The significantly higher RT-PCR Ct values among BinaxNOW antigen-negative individuals suggest that nasal specimens from this group had less viral RNA (and possibly lower viral load) compared to antigen positive specimens. Others have shown reduced sensitivity of BinaxNOW antigen testing in asymptomatic individuals, and one explanation is that this group may be in the early infectious period or recovery period when viral load is lower [5, 11, 12] .

for use under a CC0 license. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 9, 2021. ; https://doi.org/10.1101/2021.04.05.21254834 doi: medRxiv preprint There are several limitations to this investigation. The population was largely white, non-Hispanic, and older, and the findings may not be generalizable to other settings. Lack of swabbing supervision in other settings could alter test performance.

Among asymptomatic individuals, a larger sample size is needed for more precise sensitivity estimates. RT-PCR was used as the gold standard for SARS-CoV-2 detection; however, since post-infectious individuals recovering from COVID-19 may have prolonged detectable viral shedding, the performance of BinaxNOW assays for detecting contagiousness may vary from these results. This investigation is specific to the BinaxNOW test, and the findings cannot be applied directly to other antigen tests. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 9, 2021. ; https://doi.org/10.1101/2021.04.05.21254834 doi: medRxiv preprint 

US Department of Health and Human Services, Food and Drug Administration

Vitro Diagnostics Emergency Use Authorization. Silver Spring, MD. 2020

Performance of the BinaxNOW COVID-19 Antigen Card test relative to the SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction assay among symptomatic and asymptomatic healthcare employees

Performance Characteristics of BinaxNOW COVID-19 Antigen Card for Screening Asymptomatic Individuals in a University Setting

Evaluation of Abbott BinaxNOW Rapid Antigen Test for SARS-CoV-2 Infection at Two Community-Based Testing Sites-Pima County

Performance characteristics of a rapid SARS-CoV-2 antigen detection assay at a public plaza testing site in San Francisco

UW-Madison offers surge testing to community amid rise in cases

MD: US Department of Health and Human Services, Food and Drug Administration

Council of State and Territorial Epidemiologists (CSTE) Interim Position Statement

COVID-19): interim guidance for antigen testing for SARS-CoV-2

Letter to Health Care Providers. Potential for False Positive Results with Antigen Tests

Analytical Sensitivity of the Abbott BinaxNOW COVID-19 Ag CARD

Quantitative detection and viral load analysis of SARS-CoV

The authors thank the participants in Wisconsin for contributing to