The U.S. Food and Drug Administration (FDA) is alerting clinical laboratory staff and health care providers of a potential for false positive results due to the software associated with the Alinity m SARS-CoV-2 AMP Kit, List Number 09N78-095, and Alinity m Resp-4-Plex AMP Kit, List Number 09N79-096. False-positive results mean the test results show an infection when actually there isn't one. We performed rRT-PCR by using the ThermoFisher TaqPath COVID-19 Combo Kit, which targets 3 SARS-CoV-2 viral regions (nucleocapsid protein gene, spike protein gene, and open reading frame 1ab), and the Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument (ThermoFisher Scientific), according to the manufacturers instructions. Critical revision of the manuscript for important intellectual content: Goldfarb, Agrawal, Sennik, Stein, Rosella. Clin Infect Dis 2020. At the time of testing, 827 (24.2%) participants reported at least one COVID-19compatible sign or symptom, and 2,592 (75.8%) were asymptomatic. All participants provided written consent to participate in the screening program and to share their deidentified data with the CDL RSC, including for publication, and with public health authorities. Using real-time RT-PCR as the standard, four false-positive BinaxNOW antigen test results occurred, all among specimens from asymptomatic participants. Cells with no cytopathic effect or negative rRT-PCR results were passaged after 7 d onto fresh confluent Vero-81 and monitored for an additional 7 d before performing rRT-PCR again. BinaxNOW rapid antigen test results and viral culture results among 100 real-time reverse transcription PCRpositive specimens with cycle threshold <30 among staff at a horse racetrack, California, USA, NovemberDecember 2020. Of the 127 rRT-PCRpositive specimens, we attempted virus isolation and culture for all 100 specimens with Ct <30. The alert about false positives applies to both Alinity products. to sell a version of Alinity that tests for SARS-CoV-2, two types of influenza and respiratory syncytial virus. The false positive results may be related to current mixing parameters of the PCR reaction mixture that may result in potential overflow that could carry over into neighboring wells in the assay reagent tray. Because estimates suggest that over 50% of transmission occurs from persons who are presymptomatic or asymptomatic (9), expanded screening testing, potentially in serial fashion for reducing transmission in specific venues (e.g., institutions of higher education, schools, and congregate housing settings), is essential to interrupting transmission (3). The rapid turnaround time and high PPV of BinaxNOW enabled some SARS-CoV-2positive employees to be identified and isolated faster than if rRT-PCR had been used alone. Abbott first received FDA emergency use authorization for its Alinity m SARS-CoV-2 AMP test in May 2020. "True" and "false" refer to the accuracy of the test, while "positive" and "negative" refer to the outcome you receive, says Geoffrey Baird, M.D., Ph.D., professor and chair of the Department. University of California San Francisco School of Medicine, San Francisco (C. Stainken). Partial data from the company-funded study showed that . ** 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. The LHD decided to use BinaxNOW as a supplement to rRT-PCR to more quickly identify SARS-CoV-2positive employees for isolation. On January 19, 2021, this report was posted online as an MMWR Early Release. Positive viral culture is further evidence of the presence of infectious virus, so these findings might indicate that some BinaxNOW false-negative participants were not infectious at the time of specimen collection (i.e., they had low viral RNA load at the beginning or end of their infection trajectory) (12). Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website. Compared to the regular laboratory-based PCR test, the Panbio COVID-19 Ag Rapid Test has a higher risk of a false negative and a false positive result. This conversion might result in character translation or format errors in the HTML version. If you do not allow these cookies we will not know when you have visited our site, and will not be able to monitor its performance. Tests were most accurate when used in the first week after symptoms began (an average of 82% of confirmed cases had positive antigen tests). This low false-positive rate is consistent with results from Pilarowski et al. To register for email alerts, access free PDF, and more, Get unlimited access and a printable PDF ($40.00), 2023 American Medical Association. This study investigated the incidence of false-positive results in a large sample of rapid antigen tests used to serially screen asymptomatic workers throughout Canada. Abbott tests earlier this year in response to a risk of false results linked to its own product. False positives are much less common. Consider any positive result from tests using the Alinity m SARS-CoV-2 AMP and the Alinity m Resp-4-Plex AMP Kits to be presumptive until the company can implement updated software specification files to correct the issue at each laboratory site. One type is a sped-up, smaller version of the PCR tests. An erratumhas been published. But the MSU study showed something else that is troubling false positive. et al. However, the results reported by Haage et al. * 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. This cohort study examines the performance of direct antigen rapid tests compared with that of quantitative real-time polymerase chain reaction for analyzing self-collected nasal specimens for the presence of SARS-CoV-2. 552a; 44 U.S.C. All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. 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. Abbott's tests run on its Alinity automated molecular diagnostics analyzer. All rRT-PCRnegative results (n = Of 127 rRT-PCRpositive specimens, BinaxNOW detected 55, did not detect 72 (44 specimens with Ct <30, 5 specimens with Ct <20, and 6 specimens with positive viral cultures), and produced no false-positive results (Table 3). B, Schildgen The number of false-positive results was 462 (0.05% of screens and 42% of positive test results with PCR information). Epub June 29, 2020. These cookies may also be used for advertising purposes by these third parties. Another false-positive problem for a SARS-CoV-2 antigen test in Japan. Acquisition, analysis, or interpretation of data: Gans, Goldfarb, Agrawal, Sennik, Rosella. In contrast, our findings suggest that BinaxNOW negative results in an outbreak investigation should be confirmed with rRT-PCR, because false negatives do occur. US CDC real-time reverse transcription PCR panel for detection of severe acute respiratory syndrome coronavirus 2. The Food and Drug Administration (FDA) has expanded its recall of Ellume at-home COVID-19 tests due to potential false-positive results. The first mass testing dates (round 0) only used rRT-PCR testing, so no comparison with BinaxNOW was possible. actually correct (positive) but the PCR a false negative. False-positive results were matched to lot number and test manufacturer. Some antigen-negative, real-time RT-PCRpositive specimens possibly could represent noninfectious viral particles, but some might also represent infectious virus not detected by the antigen test. Cookies used to track the effectiveness of CDC public health campaigns through clickthrough data. The FDA first gave emergency use authorization for Abbott Labs ' rapid COVID-19 test for at-home, over-the-counter and non-prescription use in March. The investigation protocol was reviewed by CDC and determined to be nonresearch and was conducted consistent with applicable federal law and CDC policy.. Most staff identified as Hispanic (62.0%) (Table 1). You can review and change the way we collect information below. The prevalence of having SARS-CoV-2 real-time RT-PCR positive test results in this population was moderate (8.7% overall; 4.7% for asymptomatic participants); administering the test in a lower prevalence setting will likely result in a lower PPV. Among 11 participants with antigen-negative, real-time RT-PCRpositive specimens with positive viral culture, five were symptomatic and six asymptomatic. In a study published in the Journal of Clinical Virology, Haage et al. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page. 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%). Main results. 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. In outbreak situations in which access to laboratory rRT-PCR services is limited, it might be reasonable to act on BinaxNOW-positive results and forgo rRT-PCR confirmation. https://www.biorxiv.org/content/10.1101/2020.03.02.972935v1external icon. 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. Fierce Biotech. FDA used the warning to make two recommendations to users of Alinity tests. Emerg Infect Dis 2020;26:165465. The overall rate of false-positive results among the total rapid antigen test screens for SARS-CoV-2 was very low, consistent with other, smaller studies.3 The cluster of false-positive results from 1 batch was likely the result of manufacturing issues rather than implementation. A box containing a 5-minute test for COVID-19 from Abbott Laboratories is pictured during the daily briefing on the novel coronavirus, COVID-19, in the Rose Garden of the White House on March 30. The first limitation of our study is that, although other studies have demonstrated differential BinaxNOW test performance in symptomatic and asymptomatic persons (3,68), we were unable to examine test performance by symptom status, because symptom reporting might not have been reliable. The FDA is working with Abbott Molecular Inc. to resolve these issues. ** Based on one or more symptoms. Exposure was defined as close contact (within 6 ft for 15 min) in the 14 days before the day of testing with a person with diagnosed COVID-19. Received positive real-time RT-PCR or antigen test result. JAMA Netw Open 2020;3:e2016818. When the pretest probability for receiving positive SARS-CoV-2 test results is elevated (e.g. Evaluation of Abbott BinaxNOW rapid antigen test for SARS-CoV-2 infection at two community-based testing sitesPima County, Arizona, November 317, 2020. The risk of false-negative or false-positive test results depends on the type and sensitivity of the COVID-19 diagnostic test, thoroughness of the sample collection, and accuracy of the lab analysis. 45 C.F.R. You will be subject to the destination website's privacy policy when you follow the link. Why bother with a test that is not so different from flipping a coin? The results of the current evaluation differ from those of an evaluation of the BinaxNOW antigen test in a community screening setting in San Francisco (7), which found a BinaxNOW antigen test overall sensitivity of 89.0% among specimens from all 3,302 participants, regardless of the Ct value of the real-time RT-PCRpositive specimens. Positive Predictive Value depends upon prevalence of disease in community, Role of Rapid Antigen Detection Test (RADT) for Detection of SARS Cov-2 Variants. Abbreviation: COVID-19=coronavirus disease 2019. Abbott's BinaxNOW antigen test is one of two types of diagnostic tests. CDC. Brittany Murray/MediaNews Group/Long Beach Press-Telegram via Getty Images Rapid tests are a quick and convenient way to learn about your COVID-19 status. Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website. Of those specimens, 51 resulted in positive virus isolation. More complete paired-testing data could have provided better insight as to the usefulness of rapid antigen testing when used for the entire duration of an outbreak. Out of 955 patients, 23 were found to be positive for COVID-19 using a lab-based test. Interim data from Abbott's 1,003-participant study shows that its test, which can deliver results in under 15 minutes, correctly identified positive COVID-19 cases 95% of the time when used . The Abbott ID Now Rapid Molecular Test for COVID-19 is the first in-house lab testing available . Previous studies of BinaxNOW compared with rRT-PCR have demonstrated a high negative percent agreement (NPA) (99.4%100%) but variable positive percent agreement (PPA) (52.5%89.0%). The Powerful Link Between Connectivity and MedTech Innovation, FDA authorizes first at-home flu-COVID-19 combination test days after its developer files for bankruptcy, Henry Schein Q4 profit drops, hurt by falling sales of COVID test kits, PPE, Baxter, Abbott, Thermo Fisher among medtech firms cutting jobs on supply issues, slide in testing, Thermo Fisher cuts additional 230 jobs in California. Y, Aside from issues with the batch, false-positives are possible due to the timing of the test (ie, too early or too late in the infectious stage) or quality issues in how the self-test was completed. Coronavirus Disease 2019 (COVID-19): interim guidance for rapid antigen testing for SARS-CoV-2. When only rRT-PCR tests with Ct <30 were considered positive, BinaxNOW produced these results: PPA, 55.6% (95% CI45.2%65.6%); NPA, 100% (95% CI99.5%100%), PPV, 100.0% (95% CI93.5%100%); and NPV, 93.8% (95% CI91.8%95.5%) (Table 3). He was right. All specimen collection and antigen testing occurred outdoors in the parking lot of the facility. The kits can report false positives when wells in the assay reagent tray that contain positive samples overflow and contaminate neighboring specimens. Gans and colleagues found 1322 positive results in 903,408 rapid antigen tests conducted in 537 workplaces; with 1103 of the positive rapid tests followed by PCR testing.462 of the 1103 (42%) were determined to be false positive, with 278 of these (60%) at 2 workplaces, from the same lot-batch of Abbott's Panbio COVID-19 Ag Rapid Test Device. Furthermore, each round of testing was intended to capture all staff who had not yet tested positive; however, participant attrition occurred between testing rounds. even in this symptomatic group, the false negative rate is less than 1 out of 50 negative tests. Both Hostin and Navarro, who are fully vaccinated against. The authors assume that all RADT-positive/RTPCR-negative samples are false positives (42%). Fourth, the BinaxNOW antigen test characteristics might be different depending on whether an individual had previously tested positive. His research interests are workplace health and safety. Performance and implementation evaluation of the Abbott BinaxNOW rapid antigen test in a high-throughput drive-through community testing site in Massachusetts. This Medical News feature examines the debate about the value of frequent testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The FDA first gave emergency use authorization for Abbott Labs ' rapid COVID-19 test for at-home, over-the-counter and non-prescription use in March. Taken aback by the result, healthcare providers at BAH ordered another test, which was evaluated using the hospital's newly-acquired Abbott ID NOW testing machine, a rapid, molecular point-of . The relevant numbers are 462 rapid screens with false-positive results, or 42% of those with reference standard PCR information. Princeton, NJ: Fosun Pharma; 2020. A, Kossow By continuing to use our site, or clicking "Continue," you are agreeing to our, Kretschmer 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%. The FDA has classified the recall of the software for this test as a Class I recall, the most serious type of recall.