Comparison of Home Antigen Testing With RT-PCR and Viral Culture During the Course of SARS-CoV-2 Infection

Abstract

IMPORTANCEAs self-collected home antigen tests become widely available, a better understanding of their performance during the course of SARS-CoV-2 infection is needed. OBJECTIVE To evaluate the diagnostic performance of home antigen tests compared with reverse transcription-polymerase chain reaction (RT-PCR) and viral culture by days from illness onset, as well as user acceptability. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study was conducted from January to May 2021 in San Diego County, California, and metropolitan Denver, Colorado. The convenience sample included adults and children with RT-PCR-confirmed infection who used self-collected home antigen tests for 15 days and underwent at least 1 nasopharyngeal swab for RT-PCR, viral culture, and sequencing. EXPOSURES SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES The primary outcome was the daily sensitivity of home antigen tests to detect RT-PCR-confirmed cases. Secondary outcomes included the daily percentage of antigen test, RT-PCR, and viral culture results that were positive, and antigen test sensitivity compared with same-day RT-PCR and cultures. Antigen test use errors and acceptability were assessed for a subset of participants. RESULTS This study enrolled 225 persons with RT-PCR-confirmed infection (median [range] age, 29 [1-83] years; 117 female participants [52%]; 10 [4%] Asian, 6 [3%] Black or African American, 50 [22%] Hispanic or Latino, 3 [1%] Native Hawaiian or Other Pacific Islander, 145[64%] White, and 11 [5%] multiracial individuals) who completed 3044 antigen tests and 642 nasopharyngeal swabs. Antigen test sensitivity was 50% (95% CI, 45%-55%) during the infectious period, 64% (95% CI, 56%-70%) compared with same-day RT-PCR, and 84% (95% CI, 75%-90%) compared with same-day cultures. Antigen test sensitivity peaked 4 days after illness onset at 77% (95% CI, 69%-83%). Antigen test sensitivity improved with a second antigen test 1 to 2 days later, particularly early in the infection. Six days after illness onset, antigen test result positivity was 61% (95% CI, 53%-68%). Almost all (216 [96%]) surveyed individuals reported that they would be more likely to get tested for SARS-CoV-2 infection if home antigen tests were available over the counter. CONCLUSIONS AND RELEVANCEThe results of this cohort study of home antigen tests suggest that sensitivity for SARS-CoV-2 was moderate compared with RT-PCR and high compared with viral culture. The results also suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity peaked several days after illness onset and improved with repeated testing.

Understanding the impact of rapid antigen tests on SARS-CoV-2 transmission in the fifth wave of COVID-19 in Hong Kong in early 2022

“…We should realize that the sensitivity of RAT kits, e.g. QuickVue At-Home OTC COVID-19 Test; Quidel Corporation, increases from 20% post the fifth day to 80% post the eighth day after infection [ 23 ]; the high-quality RT–PCR test reaches 80% post the fourth day after infection [ 23 ], while the molecular POC test has a high sensitivity with close to 100% post the third day after infection [ 24 , 25 ]. Testing an infected individual with two or three kinds of tests together at the same period of time could result in a high sensitivity close to 80% at least after the fourth day post infection ( Figure 4 ).…”

“… Sensitivity of nucleic acid tests, rapid antigen tests, and molecular point-of-care (POC) tests. The red, blue, and pink lines denote the sensitivity over days post infection of nucleic acid tests [ 23 ] and rapid antigen tests [ 23 ], molecular point of care tests, respectively [ 24–26 ]. The sensitivity denotes the probability of having a positive test result given SARS-CoV-2 infection.…”

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

“…Unlike previous reports, which used composite sampling methods and did not have sufficient longitudinal data to adequately evaluate performance of Ag-RDT from the onset of infection, we were able to approximate performance of Ag-RDT for symptomatic and asymptomatic users by comparing performance within the first week of infection to align with the indications listed in the EUA. 9,10 The finding of singleton RT-PCR positive testing needs to be further investigated to understand the clinical significance of this observation.…”

Why Daily SARS-CoV-2 Nasal Rapid Antigen Testing Poorly Detects Infected and Infectious Individuals

“…First, our results are generally consistent with a previous study of pre-Omicron variant infections: the performance of an ANS Ag-RDT to detect individuals positive by nasopharyngeal swab (NPS) RT-qPCR was <50% in the first days of infection, and rose to a maximum of 77% three days after symptom onset. 42 Although, our study is not directly comparable because that study assessed only one reference specimen type (NPS). Second, observed ANS Ag-RDT performance was in excellent agreement with the performance predicted based on ANS viral loads measured by RT-qPCR, which used a separate ANS swab and sample tube.…”

“…Moreover, studies evaluating low-analytical-sensitivity testing relative to infectiousness in only one specimen type will likely overestimate the performance of that test to detect the full infectious period. 42,43 Several outbreak models 16,20 have simulated the performance of low-analytical-sensitivity tests; test performance will be overestimated if infectiousness in only the specimen type used for testing is considered. Further, the simulated performance of tests with high LODs (such as low-analytical-sensitivity Ag-RDTs) will be drastically different depending on the IVLT used in outbreak models: if the IVLT is at or above the LOD of the simulated test, artificially high or even perfect performance will be calculated simply as a result of the chosen parameters.…”