Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection
Apurv Soni, Carly Herbert, Honghuang Lin, Yan Yi, Caitlin Pretz, Pamela Stamegna, Biqi Wang, Taylor Orwig, Colton Wright, Seanan Tarrant, S. Behar, Thejas Suvarna, Summer Schrader, Emma Harman, Christopher Nowak, Vik Kheterpal, Lokinendi V. Rao, Lisa Cashman, Elizabeth Orvek, Didem Ayturk, Laura Gibson, Adrian Zai, Steven Wong, Péter Lázár, Ziyue Wang, Andreas Filippaios, Bruce Barton, Chad J. Achenbach, Robert L. Murphy, Matthew L. Robinson, Yukari C. Manabe, Shishir Pandey, Andrés Colubri, Laurel O’Connor, Stephenie C. Lemon, Nisha Fahey, Katherine Luzuriaga, Nathaniel Hafer, Kristian M. Roth, Toby Lowe, Timothy T. Stenzel, William Heetderks, John Broach, David D. McManus
Abstract
BACKGROUND: The performance of rapid antigen tests (Ag-RDTs) for screening asymptomatic and symptomatic persons for SARS-CoV-2 is not well established. OBJECTIVE: To evaluate the performance of Ag-RDTs for detection of SARS-CoV-2 among symptomatic and asymptomatic participants. DESIGN: This prospective cohort study enrolled participants between October 2021 and January 2022. Participants completed Ag-RDTs and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 every 48 hours for 15 days. SETTING: Participants were enrolled digitally throughout the mainland United States. They self-collected anterior nasal swabs for Ag-RDTs and RT-PCR testing. Nasal swabs for RT-PCR were shipped to a central laboratory, whereas Ag-RDTs were done at home. PARTICIPANTS: Of 7361 participants in the study, 5353 who were asymptomatic and negative for SARS-CoV-2 on study day 1 were eligible. In total, 154 participants had at least 1 positive RT-PCR result. MEASUREMENTS: The sensitivity of Ag-RDTs was measured on the basis of testing once (same-day), twice (after 48 hours), and thrice (after a total of 96 hours). The analysis was repeated for different days past index PCR positivity (DPIPPs) to approximate real-world scenarios where testing initiation may not always coincide with DPIPP 0. Results were stratified by symptom status. RESULTS: Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDTs twice 48 hours apart resulted in an aggregated sensitivity of 93.4% (95% CI, 90.4% to 95.9%) among symptomatic participants on DPIPPs 0 to 6. When singleton positive results were excluded, the aggregated sensitivity on DPIPPs 0 to 6 for 2-time serial testing among asymptomatic participants was lower at 62.7% (CI, 57.0% to 70.5%), but it improved to 79.0% (CI, 70.1% to 87.4%) with testing 3 times at 48-hour intervals. LIMITATION: Participants tested every 48 hours; therefore, these data cannot support conclusions about serial testing intervals shorter than 48 hours. CONCLUSION: The performance of Ag-RDTs was optimized when asymptomatic participants tested 3 times at 48-hour intervals and when symptomatic participants tested 2 times separated by 48 hours. PRIMARY FUNDING SOURCE: National Institutes of Health RADx Tech program.