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

Pima County, Arizona, November 3-17, 2020

Jessica L. Prince-Guerra, PhD; Olivia Almendares, MSPH; Leisha D. Nolen, MD, PhD; Jayleen K. L. Gunn, PhD; Ariella P. Dale, PhD; Sean A. Buono, PhD; Molly Deutsch-Feldman, PhD; Suganthi Suppiah, PhD; LiJuan Hao, MD; Yan Zeng, MS; Valerie A. Stevens; Kristen Knipe, MS; Justine Pompey, PhD; Christine Atherstone, PhD; David P. Bui, PhD; Tracy Powell, PhD; Azaibi Tamin, PhD; Jennifer L. Harcourt, PhD; Patricia L. Shewmaker, PhD; Magdalena Medrzycki, PhD; Phili Wong, MS; Shilpi Jain, PhD; Alexandra Tejada-Strop, MS; Shannon Rogers, MS; Brian Emery; Houping Wang, PhD; Marla Petway, MPH; Caitlin Bohannon, PhD; Jennifer M. Folster, PhD; Adam MacNeil, PhD; Reynolds Salerno, PhD; Wendi Kuhnert-Tallman, PhD; Jacqueline E. Tate, PhD; Natalie J. Thornburg, PhD; Hannah L. Kirking, MD; Khalilullah Sheiban, MD; Julie Kudrna, MPA; Theresa Cullen, MD; Kenneth K. Komatsu, MPH; Julie M. Villanueva, PhD; Dale A. Rose, PhD; John C. Neatherlin, MPH; Mark Anderson, MD; Paul A. Rota, PhD; Margaret A. Honein, PhD; William A. Bower, MD

Disclosures

Morbidity and Mortality Weekly Report. 2021;70(3):100-105. 

In This Article

Abstract and Introduction

Introduction

Rapid antigen tests, such as the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW), offer results more rapidly (approximately 15–30 minutes) and at a lower cost than do highly sensitive nucleic acid amplification tests (NAATs).[1] Rapid antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in symptomatic persons,[2] but data are lacking on test performance in asymptomatic persons to inform expanded screening testing to rapidly identify and isolate infected persons.[3] To evaluate the performance of the BinaxNOW rapid antigen test, it was used along with real-time reverse transcription–polymerase chain reaction (RT-PCR) testing to analyze 3,419 paired specimens collected from persons aged ≥10 years at two community testing sites in Pima County, Arizona, during November 3–17, 2020. Viral culture was performed on 274 of 303 residual real-time RT-PCR specimens with positive results by either test (29 were not available for culture). Compared with real-time RT-PCR testing, the BinaxNOW antigen test had a sensitivity of 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons, with near 100% specificity in specimens from both groups. Virus was cultured from 96 of 274 (35.0%) specimens, including 85 (57.8%) of 147 with concordant antigen and real-time RT-PCR positive results, 11 (8.9%) of 124 with false-negative antigen test results, and none of three with false-positive antigen test results. Among specimens positive for viral culture, sensitivity was 92.6% for symptomatic and 78.6% for asymptomatic individuals. When the pretest probability for receiving positive test results for SARS-CoV-2 is elevated (e.g., in symptomatic persons or in persons with a known COVID-19 exposure), a negative antigen test result should be confirmed by NAAT.[1] Despite a lower sensitivity to detect infection, rapid antigen tests can be an important tool for screening because of their quick turnaround time, lower costs and resource needs, high specificity, and high positive predictive value (PPV) in settings of high pretest probability. The faster turnaround time of the antigen test can help limit transmission by more rapidly identifying infectious persons for isolation, particularly when used as a component of serial testing strategies.

Paired upper respiratory swabs were collected at the same timepoint from persons aged ≥10 years receiving testing for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), at two Pima County Health Department community testing sites during November 3–17 (site A) and November 8–16 (site B). The sites offered SARS-CoV-2 testing to anyone in the community who wanted testing. A questionnaire capturing demographic information and current and past–14-day symptoms was administered to all participants. At both sites, a health care professional first collected a bilateral anterior nasal swab, using a swab provided in the BinaxNOW kit, immediately followed by a bilateral nasopharyngeal (NP) swab for real-time RT-PCR testing. Anterior nasal swabs were immediately tested on-site using the BinaxNOW antigen test according to the manufacturer's instructions.[4] NP swabs were stored in phosphate buffered saline at 39°F (4°C) and analyzed within 24–48 hours by real-time RT-PCR using either the CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel for detection of SARS-CoV-2[5] (2,582 swabs) or the Fosun COVID-19 RT-PCR Detection Kit[6] (837 swabs). Viral culture*,† was attempted on 274 of 303 residual real-time RT-PCR specimens if either the real-time RT-PCR or BinaxNOW antigen test result was positive (the remaining 29 were not available for viral culture). Results from real-time RT-PCR and the BinaxNOW antigen test were compared to evaluate sensitivity, specificity, negative predictive value (NPV), and PPV. Statistical analyses were performed using SAS (version 9.4; SAS Institute). Cycle threshold (Ct) values from real-time RT-PCR were compared using a Mann-Whitney U Test; 95% confidence intervals (CIs) were calculated using the exact binomial method. The investigation protocol was reviewed by CDC and determined to be nonresearch and was conducted consistent with applicable federal law and CDC policy.§

Paired upper respiratory swabs were collected from 3,419 persons, including 1,458 (42.6%) from site A and 1,961 (57.4%) from site B (Table 1). Participants ranged in age from 10 to 95 years (median = 41 years) with 236 (6.9%) aged 10–17 years, 1,885 (55.1%) aged 18–49 years, 743 (21.7%) aged 50–64 years, and 555 (16.2%) aged ≥65 years. Approximately one third (31.4%) of participants identified as Hispanic or Latino, and three quarters (75.1%) identified as White.

At the time of testing, 827 (24.2%) participants reported at least one COVID-19–compatible sign or symptom, and 2,592 (75.8%) were asymptomatic. Among symptomatic participants, 113 (13.7%) received a positive BinaxNOW antigen test result, and 176 (21.3%) received a positive real-time RT-PCR test result. Among asymptomatic participants, 48 (1.9%) received a positive BinaxNOW antigen test result, and 123 (4.7%) received a positive real-time RT-PCR test result.

Testing among symptomatic participants indicated the following for the BinaxNOW antigen test (with real-time RT-PCR as the standard): sensitivity, 64.2%; specificity, 100%; PPV, 100%; and NPV, 91.2% (Table 2); among asymptomatic persons, sensitivity was 35.8%; specificity, 99.8%; PPV, 91.7%; and NPV, 96.9%. For participants who were within 7 days of symptom onset, the BinaxNOW antigen test sensitivity was 71.1% (95% CI = 63.0%–78.4%), specificity was 100% (95% CI = 99.3%–100%), PPV was 100% (95% CI = 96.4%–100%), and NPV was 92.7% (95% CI = 90.2%–94.7%). Using real-time RT-PCR as the standard, four false-positive BinaxNOW antigen test results occurred, all among specimens from asymptomatic participants. Among 299 real-time RT-PCR positive results, 142 (47.5%) were false-negative BinaxNOW antigen test results (63 in specimens from symptomatic persons and 79 in specimens from asymptomatic persons).

Virus was recovered from 96 (35.0%) of 274 analyzed specimens that were positive by either test, including 85 (57.8%) of 147 with concordant positive results and 11 (8.9%) of 124 with false-negative BinaxNOW antigen test results. Virus was not recovered from any of the three available specimens with false-positive BinaxNOW antigen test results. Among the 224 specimens undergoing viral culture that were analyzed with the CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel for detection of SARS-CoV-2, median Ct values** were significantly higher for specimens with false-negative BinaxNOW antigen test results, indicating lower viral RNA levels than in those with concordant positive results (33.9 versus 22.0 in specimens from symptomatic persons [p<0.001] and 33.9 versus 22.5 in specimens from asymptomatic persons [p<0.001]) (Figure). Median Ct values for SARS-CoV-2 culture-positive specimens (22.1) were significantly lower than were those for culture-negative specimens (32.8) (p<0.001), indicating higher levels of viral RNA in culture-positive specimens. Among specimens with positive viral culture, the sensitivity of the BinaxNOW antigen test compared with real-time RT-PCR in specimens from symptomatic participants was 92.6% (95% CI = 83.7%–97.6%) and in those from asymptomatic participants was 78.6% (95% CI = 59.1%–91.7%).

Figure.

Abbott BinaxNOW COVID-19 Ag Card Point of Care Diagnostic Test (antigen test) results, N1 cycle threshold (Ct) values,* and viral culture results among A) symptomatic (N = 136)§ and B) asymptomatic (N = 88) participants receiving positive SARS-CoV-2 real-time reverse transcription–polymerase chain reaction (RT-PCR) test results at two community-based testing sites — Pima County, Arizona, November 2020
*Only those specimens that were analyzed using the CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel for detection of SARS-CoV-2 and that were analyzed using viral culture are included in the graph.
Twenty specimens with Ct values <18 had positive antigen and real-time RT-PCR results but were culture negative. The culture showed evidence of cytopathic effects and had presence of SARS-CoV-2 RNA as detected by real-time RT-PCR in the first passage culture, but viral recovery was not two Ct values lower than the corresponding clinical specimen Ct.
§Antigen test results: 88 positive and 48 negative; median Ct values indicated with black line: 22.0 for antigen-positive specimens and 33.9 for antigen-negative specimens.
Antigen test results: 37 positive and 51 negative; median Ct values indicated with black line: 22.5 for antigen-positive specimens and 33.9 for antigen-negative specimens.

*Specimens were used to perform a limiting-dilution inoculation of Vero CCL-81 cells, and cultures showing evidence of cytopathic effect were tested by real-time RT-PCR for the presence of SARS-CoV-2 RNA. Viral recovery was defined as any culture in which the first passage had an N1 Ct value at least two Ct values lower than the corresponding clinical specimen.
https://www.biorxiv.org/content/10.1101/2020.03.02.972935v1.
§45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
Participants were asked whether they had each sign or symptom from a list based on Council for State and Territorial Epidemiologists clinical criteria for COVID-19 that included fever, cough, shortness of breath, fatigue, sore throat, headache, muscle aches, chills, nasal congestion, difficulty breathing, diarrhea, nausea, vomiting, abdominal pain, rigors, loss of taste, and loss of smell. https://cdn.ymaws.com/www.cste.org/resource/resmgr/ps/positionstatement2020/Interim-20-ID-02_COVID-19.pdf.
**Ct values from the N1 viral nucleocapsid protein gene region from real-time RT-PCR were compared only for specimens that were analyzed with the CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel for detection of SARS-CoV-2. Lower Ct values represent higher levels of viral RNA in the specimen and higher Ct values represent lower levels of viral RNA.

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