Implementation and Accuracy of BinaxNOW Rapid Antigen COVID-19 Test in Asymptomatic and Symptomatic Populations in a High-Volume Self-Referred Testing Site

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to threaten global public health. Easily accessible and widely distributed SARS-CoV-2 testing is a cornerstone of limiting the spread of the virus globally even as vaccines are distributed. The U.S. federal government continues to invest in SARS-CoV-2 testing, which remains essential as we begin to emerge from the pandemic (1).

Reverse transcription–PCR (RT-PCR) remains the “gold standard” for identifying infected individuals (2). However, such testing can take more than 48 h to yield results (3). According to a large, nationally representative survey sample, median test result wait times are longer for African Americans (5 days) and Hispanic Americans (4.6 days) compared with white Americans (3.9 days) (3). Rapid lateral flow antigen (herein, “rapid antigen”) tests detect viral proteins and many have a 15-min turnaround time for results, which can enable individuals who test positive to quickly self-isolate to prevent transmission and can accelerate assessment of individuals at high risk for severe COVID-19 for possible monoclonal antibody treatment. Fourteen brands of such tests have received emergency use authorization by the U.S. Food and Drug Administration for clinical use in symptomatic individuals, and three have been approved for home use (4, 5). During February 2021, the U.S. government invested more than $800 million to increase the production of point-of-care tests, such as rapid antigen tests (1, 6).

Although studies have evaluated the performance of rapid antigen testing, to our knowledge only a few have been evaluated in high-throughput settings, and results from these studies have been inconsistent (7–9). Manufacturer-reported data are based on symptomatic patients and small sample sizes and, until recently, lacked transparency regarding exact RT-PCR test used as the comparator (10). Therefore, we evaluated sensitivity and specificity, as well as our implementation of a rapid antigen test (BinaxNOW COVID-19 Antigen Test [herein, “BinaxNOW rapid antigen test”], Abbott Laboratories, Abbott Park, IL) at a high-volume COVID-19 testing site and compared its performance in symptomatic versus asymptomatic patients, as well as by self-reported COVID-19 exposure in asymptomatic individuals.

A total of 9,866 adults underwent RT-PCR testing between December 23, 2020 and January 11, 2021. Of these, 6,099 (61%) enrolled in this study of which 6,061 had valid rapid antigen testing and RT-PCR results. Among the study sample, 3,223 participants (53%) were female, 3,743 (61%) were white, 1,110 (18%) were African American, and the median age was 31 years (interquartile range [IQR], 26–41 years). We obtained symptom status data from 6,098 participants, 5,452 (89%) of whom were asymptomatic. Symptomatic participants were slightly younger (34 vs. 35 years) (P  =  0.04) and more frequently non-white Hispanic (5.9% vs. 3.7%) (P  <  0.01) (Table 1).

Among asymptomatic participants, 145 (2.7%) reported living with someone with confirmed or suspected COVID, 498 (9.1%) reported being within 6 feet of someone with confirmed or suspected COVID-19 for >15 min, and 248 (4.5%) reported other exposure types. The COVID-19 prevalence rate was 3.7% (222/6,061) overall, 1.6% (87/5,418) for asymptomatic individuals, and 21% (135/642) for symptomatic individuals. Among those reporting any exposure, the median number of days since exposure was 5 (IQR, 3–7). For symptomatic participants, the median number of days since symptom onset was 3 (IQR, 4–5), and 89% (573/642) of participants were tested ≤7 days after symptom onset.

This prospective study at a high-throughput, state-owned, self-referred walk-up COVID-19 testing site represents, to our knowledge, the largest evaluation of a rapid antigen test using BinaxNOW tests performed by health care workers. We demonstrated that mass testing sites can deploy rapid antigen test with minimal increase in staff. The BinaxNOW rapid antigen test had high accuracy in symptomatic individuals and adequate accuracy in some asymptomatic individuals. The sensitivity was 87% and, despite low COVID-19 prevalence, positive predictive value was 95% for symptomatic individuals, with the vast majority of symptomatic participants being tested within 7 days after symptom onset. The test sensitivity was 71% for asymptomatic individuals and the specificity was >99% for all individuals. The sensitivity was even higher for asymptomatic individuals who reported COVID-19 exposure and for participants who were considered more infectious based on their RT-PCR CT count. A total of 0.5% of the tests were indeterminate, which could be related to poor sampling or test kit–related issues. Our study demonstrates rapid antigen test sensitivity in symptomatic individuals above the 80% threshold set by the U.S. Food and Drug Administration for emergency use authorization (11). While rapid antigen test sensitivity is below this threshold in asymptomatic individuals, the test could still be considered for screening with serial testing. The U.S. Food and Drug Administration suggests, regarding emergency use authorization, “strategies for serial testing with less sensitive tests, such as 70% sensitivity, could increase overall sensitivity and be considered cumulatively rather than based on one-time testing” (11). Despite the high negative predictive value, patients with negative results represent a large proportion of total positive cases. Hence, a negative result does not preclude infection from a clinical and public health perspective.

Two large studies of BinaxNOW found lower sensitivity than we did, despite higher rates of asymptomatic COVID-19 prevalence (8, 12). However, Okoye et al. (12) reported results for samples that were self-collected by college students under supervision of trained nonmedical staff. Pollock et al. (8) reported accuracy results similar to ours. They also noted significantly lower test accuracy at temperatures below the manufacturer recommendations, and that all false positives were clustered in a single lot in the pediatric arm of the study. Their findings are consistent with ours in showing better sensitivity with lower CT counts. Hence, testing in the appropriate population (e.g., testing within 7 days after developing symptoms per the emergency use authorization) is important. A negative rapid test should be followed up with an RT-PCR test for symptomatic individuals with high clinical suspicion (7–9, 12–14).

Our study benefitted from a rigorous expert tester-driven training protocol for all testing providers, which could have contributed to the high level of accuracy. Sample collection technique, ambient conditions (such as temperature and humidity) of the storage and test site, variation in test kit quality between lots, and differences in patient characteristics may also explain differences in accuracy reported by the studies. Some of these factors, such as test administration by untrained individuals, may also play a role in test accuracy for the BinaxNOW COVID-19 Ag Card 2 Home Test (Abbott Laboratories), which was recently authorized for emergency use.

The accuracy of the rapid antigen test in the asymptomatic population suggests that repeat testing can be useful among asymptomatic individuals in congregate settings. Twice-per-week antigen testing has shown 95% sensitivity in detecting COVID-19 infection (15). Modeling by Paltiel et al. (16) of a hypothetical cohort of 5,000 college-age students suggested that frequent screening every 2 days using a test with a minimum 70% sensitivity and 98% specificity could contain outbreaks and support safe reopening. Our study found that the BinaxNOW rapid antigen test meets this 70% threshold and may offer a practical alternative to RT-PCR in this population when RT-PCR is unavailable.

Finally, our results indicate that rapid testing may facilitate timely referral for clinical evaluation, monitoring, or monoclonal antibody therapy. Such treatments (bamlanivimab/etesevimab; casirivimab/imdevimab) currently have emergency use authorization for individuals with mild disease and high risk of progression to severe disease and hospitalization. Monoclonal antibody treatments are authorized for administration only within a 10-day window after symptom onset and are likely of the greatest benefit during the first couple of days after symptom onset (17). A rapid antigen test could facilitate timely referral and treatment.

This study was performed at one high-volume center. Any potential systematic errors in testing administration or interpretation may have been missed by our quality control measures. Furthermore, our sample population was limited to adults and one urban location with a low SARS-CoV-2 prevalence of 3.7% among those tested. Importantly, we included individuals of diverse racial backgrounds. Additionally, because our testing staff has administered nearly 70,000 tests, our findings may not be generalizable to lower-volume centers with less skilled testing staff, such as schools or colleges. Not all tests were interpreted by two independent test readers. However, the concurrence rate in samples reviewed by a second tester was 100%, and our quality control mechanisms exceeded the manufacturer’s recommended process. An additional limitation is the narrow age range of the study participants (interquartile range, 26–41 years).

As one of a few large-scale studies assessing the performance of a rapid antigen test, our study provides guidance for public health practice and future research related to COVID testing. Our study further supports the utility of rapid antigen tests to meet volume targets needed to contain outbreaks and to safely reopen the economy (8, 9). Rapid antigen tests could be considered for screening asymptomatic people when a 24-h turnaround RT-PCR is unavailable, especially for repeat testing in congregate settings. When screening asymptomatic individuals, rapid antigen testing can help enable early identification and isolation, as well as enable timely referral for monoclonal antibody treatment in symptomatic individuals. Rapid antigen tests may also have a role in narrowing disparities in access to testing and RT-PCR testing wait times for patients of color if deployed in underserved communities. Further studies are needed to better understand variation in test accuracy across different conditions and home tests. Additional studies in pediatric populations will also be helpful in guiding testing in schools.

For their editorial assistance, we thank Jenni Weems, Kerry Kennedy, and Rachel Box, in the editorial services group of The Johns Hopkins Department of Orthopaedic Surgery.

For their support of this study, we thank Jonathan Weinstein and MDH COVID-19 Testing Task Force. For assistance with regulatory process, we thank Mary Catherine Beach and Megan Singleton.

No funding support was received for this study. BinaxNOW test kits were provided by the Maryland Department of Health, free of cost.