Clinical performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR
Authors: Wagenhäuser Isabell , Knies Kerstin , Rauschenberger Vera , Eisenmann Michael , McDonogh Miriam , Petri Nils , Andres Oliver , Flemming Sven , Gawlik Micha , Papsdorf Michael , Taurines Regina , Böhm Hartmut , Forster Johannes , Weismann Dirk , Weißbrich Benedikt , Dölken Lars , Liese Johannes , Kurzai Oliver , Vogel Ulrich , Krone Manuel 
Published: March 2021

AbstractBackgroundAntigen rapid diagnostic tests (RDT) for SARS-CoV-2 are fast, broadly available, and inexpensive. Despite this, reliable clinical performance data is sparse.MethodsIn a prospective performance evaluation study, RDT from three manufacturers (NADAL®, Panbio™, MEDsan®) 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 standardized RT-qPCR Cycle threshold (Ct) values. The data collection period ranged from November 12, 2020 to February 28, 2021.FindingsOverall, sensitivity of RDT compared to RT-qPCR was 42·57% (95% CI 33·38%–52·31%), and specificity 99·68% (95% CI 99·48%–99·80%). Sensitivity declined with decreasing viral load from 100% in samples with a deduced viral load of ≥108SARS-CoV-2 RNA copies per ml to 8·82% in samples with a viral load lower than 104SARS-CoV-2 RNA copies per ml. No significant differences in sensitivity or specificity could be observed between the three manufacturers, or 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.InterpretationRDT 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.FundingGerman Federal Ministry for Education and Science (BMBF), Free State of BavariaResearch in contextEvidence before this studyWe searched PubMED an MedRxiv for articles including “COVID-19”, “COVID”, “SARS-CoV-2”, “coronavirus” as well as “antigen detection”, “rapid antigen test”, “Point-of-Care test” in title or abstract, published between January 1, 2020 and February 28, 2021. The more than 150 RDT on the market at the end of February 2021 represent a huge expansion of diagnostic possibilities.1Performance of currently available RDT is evaluated in several international studies, with heterogeneous results. Sensitivity values of RDT range from 0·0%2to 98·3%3, specificity from 19·4%4to 100·0%.2,5–14. Some of this data differs greatly from manufacturers’ data. However, these previously published performance evaluation studies were conducted under laboratory conditions using frozen swabs, or in small cohorts with middle-aged participants. Comparable RDT performance data from large-scale clinical usage is missing.5–19Added value of this studyBased on previous examinations the real life opportunities and limitations of SARS-CoV-2 RDT as an instrument of hospital infection detection and control are still unclear as well as further study results are limited in transferability to general public. Our findings show that RDT performance in daily clinical routine is reliable in persons with high viral for punctual detection and isolation of infectious persons before RT-qPCR become available. In persons with lower viral load, or in case of asymptomatic patients SARS-CoV2 detection by RDT was unsuccessful. The general sensitivity of 42·57% is too low to accept the RDT in clinical use as an alternative to RT-qPCR in diagnosis of COVID-19. Calculated specificity was 99.68%. The results are based on a huge study cohort with more than 5 000 participants including a representative ages structure with pediatric patients up to geriatric individuals, which portrays approximately the demographic structure of the local society.Implications of all the available evidenceDue to the low general sensitivity RDT in clinical use cannot be accepted as an alternative but as an addition to RT-qPCR in SARS-CoV-2 diagnosis. The benefit of early detection of highly infectious persons has to be seen in context of the effort of testing and isolation of false positive tested persons.