Performance of Rapid Antigen Tests Based on Symptom Onset and Close Contact Exposure: A secondary analysis from the Test Us At Home prospective cohort study
Authors: Herbert Carly , Wang Biqi , Lin Honghuang , Hafer Nathaniel , Pretz Caitlin , Stamegna Pamela , Tarrant Seanan , Hartin Paul , Ferranto Julia , Behar Stephanie , Wright Colton , Orwig Taylor , Suvarna Thejas , Harman Emma , Schrader Summer , Nowak Chris , Kheterpal Vik , Orvek Elizabeth , Wong Steven , Zai Adrian , Barton Bruce , Gerber Ben , Lemon Stephenie C , Filippaios Andreas , D’Amore Kylie , Gibson Laura , Greene Sharone , Howard-Wilson Sakeina , Colubri Andres , Achenbach Chad , Murphy Robert , Heetderks William , Manabe Yukari C , O’Connor Laurel , Fahey Nisha , Luzuriaga Katherine , Broach John , McManus David D , Soni Apurv 
Published: February 2023

AbstractBackgroundThe performance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) in temporal relation to symptom onset or exposure is unknown, as is the impact of vaccination on this relationship.ObjectiveTo evaluate the performance of Ag-RDT compared with RT-PCR based on day after symptom onset or exposure in order to decide on ‘when to test’.Design, Setting, and ParticipantsThe Test Us at Home study was a longitudinal cohort study that enrolled participants over 2 years old across the United States between October 18, 2021 and February 4, 2022. All participants were asked to conduct Ag-RDT and RT-PCR testing every 48 hours over a 15-day period. Participants with one or more symptoms during the study period were included in the Day Post Symptom Onset (DPSO) analyses, while those who reported a COVID-19 exposure were included in the Day Post Exposure (DPE) analysis.ExposureParticipants were asked to self-report any symptoms or known exposures to SARS-CoV-2 every 48-hours, immediately prior to conducting Ag-RDT and RT-PCR testing. The first day a participant reported one or more symptoms was termed DPSO 0, and the day of exposure was DPE 0. Vaccination status was self-reported.Main Outcome and MeasuresResults of Ag-RDT were self-reported (positive, negative, or invalid) and RT-PCR results were analyzed by a central laboratory. Percent positivity of SARS-CoV-2 and sensitivity of Ag-RDT and RT-PCR by DPSO and DPE were stratified by vaccination status and calculated with 95% confidence intervals.ResultsA total of 7,361 participants enrolled in the study. Among them, 2,086 (28.3%) and 546 (7.4%) participants were eligible for the DPSO and DPE analyses, respectively. Unvaccinated participants were nearly twice as likely to test positive for SARS-CoV-2 than vaccinated participants in event of symptoms (PCR+: 27.6% vs 10.1%) or exposure (PCR+: 43.8% vs. 22.2%). The highest proportion of vaccinated and unvaccinated individuals tested positive on DPSO 2 and DPE 5-8. Performance of RT-PCR and Ag-RDT did not differ by vaccination status. Ag-RDT detected 78.0% (95% Confidence Interval: 72.56-82.61) of PCR-confirmed infections by DPSO 4. For exposed participants, Ag-RDT detected 84.9% (95% CI: 75.0-91.4) of PCR-confirmed infections by day five post-exposure (DPE 5).Conclusions and RelevancePerformance of Ag-RDT and RT-PCR was highest on DPSO 0-2 and DPE 5 and did not differ by vaccination status. These data suggests that serial testing remains integral to enhancing the performance of Ag-RDT.