Design and implementation of a digital site-less clinical study of serial rapid antigen testing to identify asymptomatic SARS-CoV-2 infection.

Background: Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Methods: This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Conclusions: The digital site-less approach employed in the "Test Us At Home" study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.

Comparison of Rapid Antigen Tests' Performance Between Delta and Omicron Variants of SARS-CoV-2 : A Secondary Analysis From a Serial Home Self-testing Study.

BACKGROUND: It is important to document the performance of rapid antigen tests (Ag-RDTs) in detecting SARS-CoV-2 variants. OBJECTIVE: To compare the performance of Ag-RDTs in detecting the Delta (B.1.617.2) and Omicron (B.1.1.529) variants of SARS-CoV-2. DESIGN: Secondary analysis of a prospective cohort study that enrolled participants between 18 October 2021 and 24 January 2022. Participants did Ag-RDTs and collected samples for reverse transcriptase polymerase chain reaction (RT-PCR) testing every 48 hours for 15 days. SETTING: The parent study enrolled participants throughout the mainland United States through a digital platform. All participants self-collected anterior nasal swabs for rapid antigen testing and RT-PCR testing. All Ag-RDTs were completed at home, whereas nasal swabs for RT-PCR were shipped to a central laboratory. PARTICIPANTS: Of 7349 participants enrolled in the parent study, 5779 asymptomatic persons who tested negative for SARS-CoV-2 on day 1 of the study were eligible for this substudy. MEASUREMENTS: Sensitivity of Ag-RDTs on the same day as the first positive (index) RT-PCR result and 48 hours after the first positive RT-PCR result. RESULTS: A total of 207 participants were positive on RT-PCR (58 Delta, 149 Omicron). Differences in sensitivity between variants were not statistically significant (same day: Delta, 15.5% [95% CI, 6.2% to 24.8%] vs. Omicron, 22.1% [CI, 15.5% to 28.8%]; at 48 hours: Delta, 44.8% [CI, 32.0% to 57.6%] vs. Omicron, 49.7% [CI, 41.6% to 57.6%]). Among 109 participants who had RT-PCR-positive results for 48 hours, rapid antigen sensitivity did not differ significantly between Delta- and Omicron-infected participants (48-hour sensitivity: Delta, 81.5% [CI, 66.8% to 96.1%] vs. Omicron, 78.0% [CI, 69.1% to 87.0%]). Only 7.2% of the 69 participants with RT-PCR-positive results for shorter than 48 hours tested positive by Ag-RDT within 1 week; those with Delta infections remained consistently negative on Ag-RDTs. LIMITATION: A testing frequency of 48 hours does not allow a finer temporal resolution of the analysis of test performance, and the results of Ag-RDTs are based on self-report. CONCLUSION: The performance of Ag-RDTs in persons infected with the SARS-CoV-2 Omicron variant is not inferior to that in persons with Delta infections. Serial testing improved the sensitivity of Ag-RDTs for both variants. The performance of rapid antigen testing varies on the basis of duration of RT-PCR positivity. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Feasibility of At-Home Serial Testing Using Over-the-Counter SARS-CoV-2 Tests With a Digital Smartphone App for Assistance: Longitudinal Cohort Study.

BACKGROUND: The ongoing SARS-CoV-2 pandemic necessitates the development of accurate, rapid, and affordable diagnostics to help curb disease transmission, morbidity, and mortality. Rapid antigen tests are important tools for scaling up testing for SARS-CoV-2; however, little is known about individuals' use of rapid antigen tests at home and how to facilitate the user experience. OBJECTIVE: This study aimed to describe the feasibility and acceptability of serial self-testing with rapid antigen tests for SARS-CoV-2, including need for assistance and the reliability of self-interpretation. METHODS: A total of 206 adults in the United States with smartphones were enrolled in this single-arm feasibility study in February and March 2021. All participants were asked to self-test for COVID-19 at home using rapid antigen tests daily for 14 days and use a smartphone app for testing assistance and to report their results. The main outcomes were adherence to the testing schedule, the acceptability of testing and smartphone app experiences, and the reliability of participants versus study team's interpretation of test results. Descriptive statistics were used to report the acceptability, adherence, overall rating, and experience of using the at-home test and MyDataHelps app. The usability, acceptability, adherence, and quality of at-home testing were analyzed across different sociodemographic, age, and educational attainment groups. RESULTS: Of the 206 enrolled participants, 189 (91.7%) and 159 (77.2%) completed testing and follow-up surveys, respectively. In total, 51.3% (97/189) of study participants were women, the average age was 40.7 years, 34.4% (65/189) were non-White, and 82% (155/189) had a bachelor's degree or higher. Most (n=133/206, 64.6%) participants showed high testing adherence, meaning they completed over 75% of the assigned tests. Participants' interpretations of test results demonstrated high agreement (2106/2130, 98.9%) with the study verified results, with a κ score of 0.29 (P<.001). Participants reported high satisfaction with self-testing and the smartphone app, with 98.7% (157/159) reporting that they would recommend the self-test and smartphone app to others. These results were consistent across age, race/ethnicity, and gender. CONCLUSIONS: Participants' high adherence to the recommended testing schedule, significant reliability between participants and study staff's test interpretation, and the acceptability of the smartphone app and self-test indicate that self-tests for SARS-CoV-2 with a smartphone app for assistance and reporting is a highly feasible testing modality among a diverse population of adults in the United States.

Use of a Digital Assistant to Report COVID-19 Rapid Antigen Self-test Results to Health Departments in 6 US Communities.

Importance: Widespread distribution of rapid antigen tests is integral to the US strategy to address COVID-19; however, it is estimated that few rapid antigen test results are reported to local departments of health. Objective: To characterize how often individuals in 6 communities throughout the United States used a digital assistant to log rapid antigen test results and report them to their local departments of health. Design, Setting, and Participants: This prospective cohort study is based on anonymously collected data from the beneficiaries of the Say Yes! Covid Test program, which distributed more than 3 000 000 rapid antigen tests at no cost to residents of 6 communities (Louisville, Kentucky; Indianapolis, Indiana; Fulton County, Georgia; O'ahu, Hawaii; Ann Arbor and Ypsilanti, Michigan; and Chattanooga, Tennessee) between April and October 2021. A descriptive evaluation of beneficiary use of a digital assistant for logging and reporting their rapid antigen test results was performed. Interventions: Widespread community distribution of rapid antigen tests. Main Outcomes and Measures: Number and proportion of tests logged and reported to the local department of health through the digital assistant. Results: A total of 313 000 test kits were distributed, including 178 785 test kits that were ordered using the digital assistant. Among all distributed kits, 14 398 households (4.6%) used the digital assistant, but beneficiaries reported three-quarters of their rapid antigen test results to their state public health departments (30 965 tests reported of 41 465 total test results [75.0%]). The reporting behavior varied by community and was significantly higher among communities that were incentivized for reporting test results vs those that were not incentivized or partially incentivized (90.5% [95% CI, 89.9%-91.2%] vs 70.5%; [95% CI, 70.0%-71.0%]). In all communities, positive tests were less frequently reported than negative tests (60.4% [95% CI, 58.1%-62.8%] vs 75.5% [95% CI, 75.1%-76.0%]). Conclusions and Relevance: These results suggest that application-based reporting with incentives may be associated with increased reporting of rapid tests for COVID-19. However, increasing the adoption of the digital assistant may be a critical first step.

Design and Preliminary Findings of Adherence to the Self-Testing for Our Protection From COVID-19 (STOP COVID-19) Risk-Based Testing Protocol: Prospective Digital Study.

BACKGROUND: Serial testing for SARS-CoV-2 is recommended to reduce spread of the virus; however, little is known about adherence to recommended testing schedules and reporting practices to health departments. OBJECTIVE: The Self-Testing for Our Protection from COVID-19 (STOP COVID-19) study aims to examine adherence to a risk-based COVID-19 testing strategy using rapid antigen tests and reporting of test results to health departments. METHODS: STOP COVID-19 is a 12-week digital study, facilitated using a smartphone app for testing assistance and reporting. We are recruiting 20,000 participants throughout the United States. Participants are stratified into high- and low-risk groups based on history of COVID-19 infection and vaccination status. High-risk participants are instructed to perform twice-weekly testing for COVID-19 using rapid antigen tests, while low-risk participants test only in the case of symptoms or exposure to COVID-19. All participants complete COVID-19 surveillance surveys, and rapid antigen results are recorded within the smartphone app. Primary outcomes include participant adherence to a risk-based serial testing protocol and percentage of rapid tests reported to health departments. RESULTS: As of February 2022, 3496 participants have enrolled, including 1083 high-risk participants. Out of 13,730 tests completed, participants have reported 13,480 (98.18%, 95% CI 97.9%-98.4%) results to state public health departments with full personal identifying information or anonymously. Among 622 high-risk participants who finished the study period, 35.9% showed high adherence to the study testing protocol. Participants with high adherence reported a higher percentage of test results to the state health department with full identifying information than those in the moderate- or low-adherence groups (high: 71.7%, 95% CI 70.3%-73.1%; moderate: 68.3%, 95% CI 66.0%-70.5%; low: 63.1%, 59.5%-66.6%). CONCLUSIONS: Preliminary results from the STOP COVID-19 study provide important insights into rapid antigen test reporting and usage, and can thus inform the use of rapid testing interventions for COVID-19 surveillance.