Diagnostic accuracy of rapid antigen tests in asymptomatic and presymptomatic close contacts of individuals with confirmed SARS-CoV-2 infection: cross sectional study

Abstract

Objective: To assess the diagnostic test accuracy of two rapid antigen tests in asymptomatic and presymptomatic close contacts of people with SARS-CoV-2 infection on day 5 after exposure.

Design: Prospective cross sectional study.

Setting: Four public health service covid-19 test sites in the Netherlands.

Participants: 4274 consecutively included close contacts (identified through test-and-trace programme or contact tracing app) aged 16 years or older and asymptomatic for covid-19 when requesting a test.

Main outcome measures: Sensitivity, specificity, and positive and negative predictive values of Veritor System (Beckton Dickinson) and Biosensor (Roche Diagnostics) rapid antigen tests, with reverse-transcriptase polymerase chain reaction (RT-PCR) testing as reference standard. The viral load cut-off above which 95% of people with a positive RT-PCR test result were virus culture positive was used as a proxy of infectiousness.

Results: Of 2678 participants tested with Veritor, 233 (8.7%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 149 were also detected by the rapid antigen test (sensitivity 63.9%, 95% confidence interval 57.4% to 70.1%). Of 1596 participants tested with Biosensor, 132 (8.3%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 83 were detected by the rapid antigen test (sensitivity 62.9%, 54.0% to 71.1%). In those who were still asymptomatic at the time of sampling, sensitivity was 58.7% (51.1% to 66.0%) for Veritor (n=2317) and 59.4% (49.2% to 69.1%) for Biosensor (n=1414), and in those who developed symptoms were 84.2% (68.7% to 94.0%; n=219) for Veritor and 73.3% (54.1% to 87.7%; n=158) for Biosensor. When a viral load cut-off was applied for infectiouness (≥5.2 log10 SARS-CoV-2 E gene copies/mL), the overall sensitivity was 90.1% (84.2% to 94.4%) for Veritor and 86.8% (78.1% to 93.0%) for Biosensor, and 88.1% (80.5% to 93.5%) for Veritor and 85.1% (74.3% to 92.6%) for Biosensor, among those who remained asymptomatic throughout. Specificities were >99%, and positive and negative predictive values were >90% and >95%, for both rapid antigen tests in all analyses.

Conclusions: The sensitivities of both rapid antigen tests in asymptomatic and presymptomatic close contacts tested on day 5 onwards after close contact with an index case were more than 60%, increasing to more than 85% after a viral load cut-off was applied as a proxy for infectiousness.

Fig 1

Flow of study participants. RT-PCR=reverse-transcriptase polymerase chain reaction

Fig 2

Distribution of viral loads in participants with a positive reverse-transcriptase polymerase chain reaction (RT-PCR) test result, stratified by Biosensor rapid antigen test result (negative or positive) and ability to culture, or not culture, SARS-CoV-2

Fig 3

Diagnostic accuracy variables of both rapid antigen tests for different definitions of reverse-transcriptase polymerase chain reaction (RT-PCR) test positivity based on viral load cut-offs, where a positive RT-PCR test result with a viral load below the viral load cut-off threshold is considered a negative result. Points highlighted in red indicate a viral load cut-off of 5.2 log10 SARS-CoV-2 E gene copies/mL, which was considered the viral load cut-off for infectiousness as determined by viral culture. PPV=positive predictive value; NPV=negative predictive value