Clinical performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR

Isabell Wagenhäuser; Kerstin Knies; Vera Rauschenberger; Michael Eisenmann; Miriam McDonogh; Nils Petri; Oliver Andres; Sven Flemming; Micha Gawlik; Michael Papsdorf; Regina Taurines; Hartmut Böhm; Johannes Forster; Dirk Weismann; Benedikt Weißbrich; Lars Dölken; Johannes Liese; Oliver Kurzai; Ulrich Vogel; Manuel Krone

doi:10.1016/j.ebiom.2021.103455

Clinical performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR

EBioMedicine. 2021 Jul:69:103455. doi: 10.1016/j.ebiom.2021.103455. Epub 2021 Jun 26.

Authors

Isabell Wagenhäuser¹, Kerstin Knies², Vera Rauschenberger³, Michael Eisenmann³, Miriam McDonogh⁴, Nils Petri⁵, Oliver Andres⁶, Sven Flemming⁷, Micha Gawlik⁸, Michael Papsdorf⁹, Regina Taurines¹⁰, Hartmut Böhm¹¹, Johannes Forster¹, Dirk Weismann⁵, Benedikt Weißbrich², Lars Dölken², Johannes Liese⁶, Oliver Kurzai¹², Ulrich Vogel¹³, Manuel Krone¹⁴

Affiliations

¹ Institute for Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Str. 2 / E1, Wuerzburg 97080, Germany.
² Institute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
³ Infection Control Unit, University Hospital Wuerzburg, Wuerzburg, Germany.
⁴ Department of Orthopaedic Trauma, Hand, Plastic and Reconstructive Surgery, University Hospital Wuerzburg, Wuerzburg, Germany.
⁵ Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany.
⁶ Department of Paediatrics, University Hospital Wuerzburg, Wuerzburg, Germany.
⁷ Department of General, Visceral, Transplantation, Vascular and Paediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany.
⁸ Department of Psychiatry and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany.
⁹ Department of Obstetrics and Gynaecology, University Hospital Wuerzburg, Wuerzburg, Germany.
¹⁰ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany.
¹¹ Department of Oral and Maxillofacial Surgery, University Hospital Wuerzburg, Wuerzburg, Germany.
¹² Institute for Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Str. 2 / E1, Wuerzburg 97080, Germany; Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute, Jena, Germany.
¹³ Institute for Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Str. 2 / E1, Wuerzburg 97080, Germany; Infection Control Unit, University Hospital Wuerzburg, Wuerzburg, Germany.
¹⁴ Institute for Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Str. 2 / E1, Wuerzburg 97080, Germany; Infection Control Unit, University Hospital Wuerzburg, Wuerzburg, Germany; Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany. Electronic address: krone_m@ukw.de.

Abstract

Background: Antigen rapid diagnostic tests (RDT) for SARS-CoV-2 are fast, broadly available, and inexpensive. Despite this, reliable clinical performance data from large field studies is sparse.

Methods: In a prospective performance evaluation study, RDT from three manufacturers (NADAL®, Panbio™, MEDsan®, conducted on different samples) were compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) in 5 068 oropharyngeal swabs for detection of SARS-CoV-2 in a hospital setting. Viral load was derived from standardised RT-qPCR Cycle threshold (C_t) values. The data collection period ranged from November 12, 2020 to February 28, 2021.

Findings: The sensitivity of RDT compared to RT-qPCR was 42·57% (95% CI 33·38%-52·31%). The specificity was 99·68% (95% CI 99·48%-99·80%). Sensitivity declined with decreasing viral load from 100% in samples with a deduced viral load of ≥10⁸ SARS-CoV-2 RNA copies per ml to 8·82% in samples with a viral load lower than 10⁴ SARS-CoV-2 RNA copies per ml. No significant differences in sensitivity or specificity could be observed between samples with and without spike protein variant B.1.1.7. The NPV in the study cohort was 98·84%; the PPV in persons with typical COVID-19 symptoms was 97·37%, and 28·57% in persons without or with atypical symptoms.

Interpretation: RDT are a reliable method to diagnose SARS-CoV-2 infection in persons with high viral load. RDT are a valuable addition to RT-qPCR testing, as they reliably detect infectious persons with high viral loads before RT-qPCR results are available.

Funding: German Federal Ministry for Education and Science (BMBF), Free State of Bavaria.

Keywords: Antigen rapid diagnostic test; COVID-19; Clinical evaluation; PCR; Performance evaluation; SARS-CoV-2.

Publication types

Comparative Study
Evaluation Study

MeSH terms

Adult
Aged
COVID-19 / diagnosis*
COVID-19 / immunology
COVID-19 / virology
COVID-19 Nucleic Acid Testing / methods
COVID-19 Nucleic Acid Testing / standards
COVID-19 Serological Testing / methods
COVID-19 Serological Testing / standards*
Female
Humans
Male
Middle Aged
Point-of-Care Testing / standards*
Reagent Kits, Diagnostic / standards
Sensitivity and Specificity
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology
Viral Load

Substances

Reagent Kits, Diagnostic
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2