key: cord-0262046-0pgapwfu
authors: Sun, K. J.; Vaeth, M. J. E.; Robinson, M. L.; Elhabashy, M.; Gupta, I.; Purekal, S.; Hammershaimb, E. A. D.; Peralta, R.; Mitchell, A.; Foyez, M.; Johnson, J. K.; Ficke, J. R.; Manabe, Y. C.; Campbell, J. D.; Callahan, C. W.; Locke, C. F.; Kantsiper, M.; CONQUER COVID Consortium,; Siddiqui, Z. K.
title: High Sensitivity and NPV for BinaxNOW Rapid Antigen Test in Children at a Mass Testing Site During Prevalent Delta Variant
date: 2022-01-06
journal: nan
DOI: 10.1101/2022.01.05.22268788
sha: f1849421b51139f912a2ff8ef4b45ef1143a9a4b
doc_id: 262046
cord_uid: 0pgapwfu

SARS-CoV-2 continues to develop new, increasingly infectious variants, such as delta and omicron. Here, we evaluate the efficacy of the Abbott BinaxNOW Rapid Antigen Test against the gold standard of Reverse Transcription Polymerase Chain Reaction (RT-PCR) in 1054 pediatric participants presenting to a state-owned high-volume Coronavirus Disease 2019 (COVID-19) testing site. During the testing period, the delta variant was predominant. Prior to sample collection, symptomatic and exposure status was collected for all participants based on Centers for Disease Control (CDC) criteria. RT-PCR results demonstrated an overall prevalence rate of 5.2%. For all participants, the sensitivity of the rapid antigen tests was 92.7% (95% CI 82.4% - 98.0%) and specificity was 98.0% (95% CI 97.0%-98.8%). For symptomatic participants, the sensitivity was 92.3% (95% CI 74.9% - 99.1%), specificity was 96.6% (95% CI 93.6%- 98.4%), positive predictive value (PPV) was 72.7% (95% CI 54.5% - 86.7%) and negative predictive value (NPV) was 99.2% (95% CI 98.2% - 100%). Among asymptomatic participants, the sensitivity was 92.6% (95% CI 75.7% - 99.1%), specificity was 98.6% (95% CI 97.5% - 99.3%) the PPV was 71.4% (95% CI 53.7% - 85.4%) and the NPV was 99.7% (95% CI 99.0% - 100%). Our reported sensitivity and NPV are higher than other pediatric studies, but specificity and PPV are lower. Importance Children are especially impacted by the disease and its ability to disrupt educational opportunities. Although vaccinations have been approved for children 5 years and older, many children remain unvaccinated. Widespread testing may improve the ability for children to remain in in-person activities, minimizing absences from school and extracurriculars. Highly accurate rapid antigen tests may be vital to containing future COVID-19 waves while mitigating detrimental effects.

pediatric populations is critical to keeping children in classrooms, especially given the 56 transmissibility of newer variants (e.g. delta, omicron) among vaccinated individuals. 3, 4 The 57 impact of disrupted in-person learning has been substantial. Students are more behind in 58 foundational coursework, with the effect compounded for students with historical racial or 59 socioeconomic disadvantages. 5 60 61 One strategy to keep children safely in school is with routine testing. Challenges around testing 62 include delayed result reporting, high cost for reverse transcription polymerase chain reaction 63 ("RT-PCR") tests, and access disparities among marginalized populations. 6 Rapid antigen tests 64 offer an attractive alternative with results often returned in 15 minutes, lower cost, and ability to 65 predict patients harboring culturable, infectious virus. 7 Studies of the accuracy of these tests in 66 children are conflicting. Most were conducted before the more aggressive variants like delta 67 became prevalent. 8, 9 We evaluated the real-world characteristics of the Abbott BinaxNOW rapid 68 antigen test (Abbott Laboratories, Abbott Park, IL) in children presenting to a high-throughput 69 setting. Our study took place in the context of a high prevalence of the delta variant, between 70 May 7, 2021 and December 6, 2021.The prevalence of the delta variant rapidly increased from 71 All rights reserved. No reuse allowed without permission.

(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 January 6, 2022. ; https://doi.org/10.1101/2022.01.05.22268788 doi: medRxiv preprint less than 2.5% of COVID-19 cases to more than 99% in Maryland and surrounding states during 72 the first month of the study period. 10 (CDC) symptom checklist. 11 Participants who reported at least one symptom were considered 91 "symptomatic," while those who reported no symptoms were considered "asymptomatic." 92 Participant exposure status was obtained according to CDC risk stratification. Participants were 93 asked about living with someone with confirmed or suspected COVID-19; if they had been 94 All rights reserved. No reuse allowed without permission.

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The copyright holder for this preprint this version posted January 6, 2022. ; https://doi.org/10.1101/2022.01.05.22268788 doi: medRxiv preprint within 6 feet of someone with confirmed or suspected COVID-19 for more than 15 minutes; and 95 if they had any other exposure to anyone with confirmed or suspected COVID-19. Participants 96 were considered to have had high risk exposures if they lived with or were within 6 feet for more 97 than 15 minutes of someone with confirmed or suspected COVID-19. Date of symptom onset 98 and exposure were recorded. Test implementation, education, and training processes have been 99 previously described. 12 100 101 Sample collection. The rapid antigen and RT-PCR samples were collected sequentially for each 102 participant in the study by medical staff who were trained to perform rapid antigen tests. 103

Manufacturer's guidelines were followed in obtaining and processing rapid antigen samples. 13 predictive values [PPV, NPV respectively]) and 95% confidence intervals (CIs) were calculated 116 using the binomial exact method for the rapid antigen test for both symptomatic and 117 All rights reserved. No reuse allowed without permission.

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The copyright holder for this preprint this version posted January 6, 2022. after symptom onset. The prevalence rate was 20% for symptomatic participants with high-risk 138 exposure and 7.2% for asymptomatic with high-risk exposure (Table 1) . 139 140 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Mean CT values were similar for the asymptomatic and symptomatic groups (28. This single center prospective study at a state-owned walk-up testing site showed high 155 sensitivity, specificity, and NPV for the rapid antigen test in both symptomatic and 156 asymptomatic children. The sensitivity was 92.3% in symptomatic participants, and all but one 157 of these 26 RT-PCR positive participants were tested within 7 days of symptom onset. The 158 sensitivity in asymptomatic population was nearly identical at 92.6%, with an NPV of nearly 159 100%. Cycle threshold counts were similar for symptomatic and asymptomatic individuals and 160 rapid tests showed 100% sensitivity in both these groups at CT count less than 30, which signifies 161 higher viral loads and greater transmissibility. Our point estimate of BinaxNOW rapid antigen 162 test sensitivity in children is above the 80% threshold set by the US Food & Drug Administration 163 All rights reserved. No reuse allowed without permission.

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The copyright holder for this preprint this version posted January 6, 2022. ; https://doi.org/10.1101/2022.01.05.22268788 doi: medRxiv preprint (FDA) for Emergency Use Authorization (EUA) for both symptomatic and asymptomatic 164 children. 14 Our results show that rapid antigen tests provide a reliable means to diagnose and 165 screen for COVID-19 in children. The near 100% NPVs for both symptomatic and asymptomatic 166 children, including some children with recent high-risk exposures, should provide providers and 167 parents with assurance that a negative rapid antigen test with this product can be trusted. These 168 data also provide support to the use of these tests as part of a "test-to-stay" approach in schools. 15 169

Because our study showed that roughly 30% of positive antigen tests were false positives, it 170 would be prudent to confirm all positive antigen tests with a PCR test. 171 172 Our study shows higher sensitivity and NPV but lower specificity and PPV than other pediatric 173 studies. 8, 9 Differences could be related to higher viral load from prevalent delta variant during 174 the study period as most of the prior pediatric studies were conducted before the delta variant 175 became widespread. 16 Additionally, ambient conditions for kit storage and use, variation in 176 quality of the test kit between lots, and the skill of our experienced testers may also explain 177 higher sensitivity in our study. 17 178 179 Our study has a few limitations. The results from a single-site with over one-year of experience 180 in high volume testing may not be generalizable to all situations. However, with implementation 181 of best practices, similar accuracy would be expected. 12 Our study enrolled only a small number 182 of children with high-risk exposure and the estimates of accuracy had broad confidence interval. 183 However, the results are similar to overall symptomatic and asymptomatic groups. Additionally, 184 three of the four false negative tests in the high-risk exposure group were tested within 3 days of 185 exposure and samples were likely collected too early for detection by a rapid antigen test. 186 All rights reserved. No reuse allowed without permission.

(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 January 6, 2022. ; https://doi.org/10.1101/2022.01.05.22268788 doi: medRxiv preprint 187 Given the short turn-around-time, low cost, and ease of use, this test could play an important role 188 in allowing children to limit absence from school and other activities while in quarantine or 189 awaiting PCR test results especially for asymptomatic children. It may assist in implementing 190 test-to-stay strategies, where exposed school children are allowed to continue uninterrupted in-191 person learning given frequent testing for one week after exposure. 18 The higher accuracy 192 reported in our study also underscores the magnitude of missed opportunity in failing to make 193 this important tool widely available to schools. If further studies with the extremely transmissible 194 omicron variant show very high viral load and rapid antigen accuracy, these tests could become 195 one of most valuable tools used to fight current and future COVID-19 variants. 196 197 All rights reserved. No reuse allowed without permission.

(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 January 6, 2022. (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 January 6, 2022. (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 January 6, 2022. ; https://doi.org/10.1101/2022.01.05.22268788 doi: medRxiv preprint

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