Description
AbstractBackgroundPerformance 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 pointsQuestionWhat 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 definitionsComparator positivecomposite definition of molecular positivity if majority of molecular assays were positiveDays Past Index Comparator Positive (DPIPP)Number of calendar-days past the day when first Comparator positive was observedOnset of InfectionDPIPP 0, when first Comparator positive was observedSymptomatic 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 0-10First week of InfectionDPIPP 0 - 6
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