Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection

Abstract

Background: Performance 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. Objective: Evaluate performance of Ag-RDT for detection of SARS-CoV-2 in relation to onset of infection for symptomatic and asymptomatic participants. Design, Setting, and Participants: Prospective 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. Exposure: SARS-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 Measures: Sensitivity 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. Results: A 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. Discussion: Performance 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.

SARS‐CoV‐2 indoor environment contamination with epidemiological and experimental investigations

“…As seroconversion seems an unreliable marker for viral clearance, other means, such as an antigen test, should be used to assess the infection risk before ending precaution protocols. 111,112 Showing viable virus from environmental is highly demanding. Previous studies have presented a few possibly positive findings.…”

“…In the view of infection control, we agree with Lei et al, 108 Tan et al 109 and Wölfel et al 110 that the risk for exposure can remain after the patient starts to seroconvert and possibly improve clinically. As seroconversion seems an unreliable marker for viral clearance, other means, such as an antigen test, should be used to assess the infection risk before ending precaution protocols 111,112 …”

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

“…However, more information is needed on the diagnostic capabilities and limitations of these tools to ensure that individuals interpret the implications of their test results properly [ 25 ]. Additionally, although participants were asked to adhere to a 14-day continuous testing schedule for the purpose of this study, it is important to investigate further optimal testing schedules for SARS-CoV-2 detection [ 11 ]. We must also continue to evaluate the accessibility of at-home testing and the MyDataHelps app among diverse communities, including non-English speakers [ 26 ].…”

“…Numerous Ag-RDTs for SARS-CoV-2 have received Emergency Use Authorization by the US Food and Drug Administration for point-of-care testing in the health care setting and, more recently, for at-home use, with evidence consistently showing the validity of self-collected specimens for SARS-CoV-2 testing [7,8]. Self-testing at home offers great opportunity for scaling up and implementing regular testing of both asymptomatic and symptomatic individuals, a key step toward controlling the COVID-19 pandemic [2,[9][10][11]. Furthermore, self-testing offers the opportunity to increase testing access across geographic, sociodemographic, and socioeconomic groups to improve health outcomes and reduce health care disparities [12][13][14].…”

Comparison of Rapid Antigen Tests' Performance Between Delta and Omicron Variants of SARS-CoV-2

“…This is not the prespecified study analysis but was subsequently developed to address an ancillary research question using this unique and comprehensive longitudinal data set ( 15 ). Specific analysis related to symptomatic status was not pursued because of overlap with the primary objectives of the parent study ( 16 ). Descriptive statistics were calculated at the participant level using tabulation of frequencies for categorical data, and differences were compared using χ 2 or Fisher exact tests, depending on the cell sample size.…”