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BackgroundPerformance of Rapid Antigen Tests for SARS-CoV-2 (Ag-RDT) varies over the course of an infection, and their performance is not well established among asymptomatic individuals. ObjectiveEvaluate performance of Ag-RDT for detection of SARS-CoV-2 in relation to onset of infection for symptomatic and asymptomatic participants. Design, Setting, and ParticipantsProspective cohort study conducted from October 2021 to February 2022 among participants > 2 years-old from across the US who enrolled using a smartphone app. During each testing encounter, participants self-collected one nasal swab and performed Ag-RDT at home; at-least fifteen minutes later, a second nasal swab was self-collected and shipped for SARS-CoV-2 RT-PCR at a central lab. Both nasal swabs were collected 7 times at 48-hour intervals (over approximately 14 days) followed by an extra nasal swab collection with home Ag-RDT test 48-hours after their last PCR sample. Each participant was assigned to one of the three emergency use authorized (EUA) Ag-RDT tests used in this study. This analysis was limited to participants who were asymptomatic and tested negative by antigen and molecular test on their first day of study participation. ExposureSARS-CoV-2 positivity was determined by testing a single home-collected anterior nasal sample with three FDA EUA molecular tests, where 2 out 3 positive test results were needed to determine a SARS-CoV-2 positive result. Onset of infection was defined as day on which the molecular PCR comparator result was positive for the first time. Main Outcomes and MeasuresSensitivity of Ag-RDT was measured based on testing once (same-day), twice (at 48-hours) and thrice (at 96 hours). Analysis was repeated for different Days Post Index PCR Positivity (DPIPP) and stratified based on symptom-status on a given DPIPP. ResultsA total of 7,361 participants enrolled in the study and 5,609 were eligible for this analysis. Among 154 eligible participants who tested positive for SARS-CoV-2 infection based on RT-PCR, 97 were asymptomatic and 57 had symptoms at onset of infection (DPIPP 0). Serial testing with Ag-RDT twice over 48-hours resulted in an aggregated sensitivity of 93.4% (95% CI: 89.1-96.1%) among symptomatic participants on DPIPP 0-6. Among the 97 people who were asymptomatic at the onset of infection, 19 were singleton RT-PCR positive, i.e., their positive test was preceded and followed by a negative RT-PCR test within 48-hours. Excluding these singleton positives, aggregated sensitivity on DPIPP 0-6 for two-time serial-testing among asymptomatic participants was lower 62.7% (54.7-70.0%) but improved to 79.0% (71.0-85.3%) with serial testing three times at 48-hour interval. DiscussionPerformance of Ag-RDT within first week of infection was optimized when asymptomatic participants tested three-times at 48-hour intervals and when symptomatic participants tested two-times separated by 48-hours. Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the performance of serial rapid antigen testing (Ag-RDT) in the first week of infection among symptomatic and asymptomatic SARS-CoV-2 infections? FindingsSerial testing with Ag-RDT two-times separated by 48-hours resulted in detection of more than 90% of SARS-CoV-2 infections when symptomatic participants began testing within first week from onset of molecular positivity; participants who were asymptomatic when they began testing within the first-week of molecular positivity observed a sensitivity of 79.0% when they performed three rapid antigen-tests, 48 hours apart. MeaningTo optimize detection of SARS-CoV-2 infection with home antigen tests, people suspected to be infected with SARS-CoV-2 virus should test twice at least 48-hours apart if they are symptomatic and three times at 48-hour intervals if they do not have symptoms (asymptomatic). Key definitionsO_ST_ABSComparator positiveC_ST_ABScomposite definition of molecular positivity if majority of molecular assays were positive Days Past Index Comparator Positive (DPIPP)Number of calendar-days past the day when first Comparator positive was observed Onset of InfectionDPIPP 0, when first Comparator positive was observed Symptomatic and Asymptomatic CasesBased on presence or absence of self-reported symptoms on the day of testing. Sensitivity was measured for Symptomatic and Asymptomatic cases on DPIPP 0-10 First week of InfectionDPIPP 0 - 6
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BackgroundOver-the-counter rapid antigen tests for SARS-CoV-2 with an Emergency Use Authorization (EUA) in the United States generally include a condition of authorization to evaluate the tests performance in asymptomatic individuals when used serially. A goal of this study was to investigate the performance of SARS-CoV-2 antigen serial testing and generate data to support regulatory decisions. ObjectiveTo describe a novel study design to evaluate serial use of rapid antigen tests in detecting SARS-CoV-2 virus among asymptomatic individuals. DesignProspective cohort study using a decentralized approach. Eligible participants from across the U.S. could enroll and complete this study from their home environment through a study app. Participant enrollment was prioritized based on regional 7-day case rates, participants vaccination status, and sociodemographic characteristics prior to enrollment. Prioritization criteria were adjusted on a daily or weekly basis. Enrolled participants were mailed rapid antigen tests and molecular comparator collection kits and asked to test every 48 hours for 15 days. Three companies rapid antigen tests were used in the study; assignment of participant to a test was criteria-based and non-random, precluding head-to-head comparison between the tests. ParticipantsMainland United States residents over 2 years old with no reported COVID-19 symptoms in the 14 days prior to study enrollment. Main MeasuresParticipant demographics, COVID-19 vaccination status, and geographic distribution were used to understand the impact of the site-less recruitment and enrollment strategy. Key ResultsA total of 7,361 participants enrolled in the study between October 18, 2021 and February 15, 2022. Throughout the study, 369 participants tested positive for SARS-CoV-2, including 167 who were asymptomatic and tested negative on SARS-CoV-2 molecular assays to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 of the 48 mainland U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. ConclusionsThe novel, 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.
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The global effort to vaccinate people against SARS-CoV-2 in the midst of an ongoing pandemic has raised questions about the nature of vaccine breakthrough infections and the potential for vaccinated individuals to transmit the virus. These questions have become even more urgent as new variants of concern with enhanced transmissibility, such as Delta, continue to emerge. To shed light on how vaccine breakthrough infections compare with infections in immunologically naive individuals, we examined viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at varying stages of vaccination. The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. These data indicate that vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.
