Performance of antigen testing for diagnosis of COVID-19: a direct comparison of a lateral flow device to nucleic acid amplification based tests

Maria Kahn,Ramona Frey,Alanna Ebigbo,Reinhard Hoffmann,Margit Heier,Christoph Römmele,Christian Denzel,Helmut Messmann,Stephan Zellmer,Marie Freitag,Lukas Schuierer,Markus Wehler,Christina Bartenschlager,Christine Dhillon,Elisabeth Kling,Selin Temizel

doi:10.1186/s12879-021-06524-7

Maria Kahn, Ramona Frey + Show 14 more

Open Access

https://doi.org/10.1186/s12879-021-06524-7

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Abstract

ObjectivesThe gold standard for diagnosing an infection with SARS-CoV-2 is detection of viral RNA by nucleic acid amplification techniques. Test capacities, however, are limited. Therefore, numerous easy-to-use rapid antigen tests based on lateral flow technology have been developed. Manufacturer-reported performance data seem convincing, but real-world data are missing.MethodsWe retrospectively analysed all prospectively collected antigen tests results performed between 23.06.2020 and 26.11.2020, generated by non-laboratory personnel at the point-of-care from oro- or nasopharyngeal swab samples at the University Hospital Augsburg and compared them to concomitantly (within 24 h.) generated results from molecular tests.ResultsFor a total of 3630 antigen tests, 3110 NAAT results were available. Overall, sensitivity, specificity, NPV and PPV of antigen testing were 59.4%, 99.0%, 98.7% and 64.8%, respectively. Sensitivity and PPV were lower in asymptomatic patients (47.6% and 44.4%, respectively) and only slightly higher in patients with clinical symptoms (66.7% and 85.0%, respectively). Some samples with very low Ct-values (minimum Ct 13) were not detected by antigen testing. 31 false positive results occurred. ROC curve analysis showed that reducing the COI cut-off from 1, as suggested by the manufacturer, to 0.9 is optimal, albeit with an AUC of only 0.66.ConclusionIn real life, performance of lateral-flow-based antigen tests are well below the manufacturer's specifications, irrespective of patient’s symptoms. Their use for detection of individual patients infected with SARS-CoV2 should be discouraged. This does not preclude their usefulness in large-scale screening programs to reduce transmission events on a population-wide scale.

Highlights

The initial local outbreak of the "coronavirus disease 2019" (COVID-19) in Wuhan in December 2019 has become a worldwide pandemic [1]
In real life, performance of lateral-flow-based antigen tests are well below the manufacturer’s specifications, irrespective of patient’s symptoms. Their use for detection of individual patients infected with SARS-CoV2 should be discouraged
Considering the low sensitivities achieved with Point-of-care antigen test (AgPOCT), we evaluated whether test performance could be improved by optimizing the COI threshold for calling a test result “positive”

Summary

Introduction

The initial local outbreak of the "coronavirus disease 2019" (COVID-19) in Wuhan in December 2019 has become a worldwide pandemic [1]. The gold standard for the diagnosis of an acute SARSCoV2 infection is the direct pathogen-specific detection of the RNA of SARS-CoV2 via nucleic acid amplification tests (NAAT) in samples from the respiratory tract [4]. Due to the worldwide spread of COVID-19 and the resulting high demand for test reagents, availability is limited. NAAT are often carried out in batches and take 6–8 h, resulting significant delays until results are reported. This has a huge impact on many processes in hospitals

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