Performance evaluation of the QIAstat-Dx® Respiratory SARS-CoV-2 Panel

Graphical abstract


Introduction
Early identification of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection enables rapid isolation to prevent transmission (European Centre for Disease Prevention and Control, 2020; National Institutes of Health, 2020; The World Health Organization, 2020). Symptoms of coronavirus disease 2019  are common to a range of respiratory pathogens; therefore, accurate diagnostics are required for differential diagnosis.
The QIAstat-Dx 1 Respiratory SARS-CoV-2 Panel (QIAstat-SARS-CoV-2) is a closed, fully automated, multiplex assay that detects SARS-CoV-2 and 21 other respiratory pathogens. Prior independent validation studies of the SARS-CoV-2 assay demonstrated comparable performance with a WHO-recommended reversetranscription polymerase chain reaction (RT-PCR) assay . The remaining 21 targets in the panel have been previously validated (Boers et al., 2020).

Methods
This was an observational, retrospective study of specimens from patients with or suspected of having COVID-19. The primary objective was to compare the performance of QIAstat-SARS-CoV-2 with the WHO-Charité reference method (Corman et al., 2020), which was the standard-of-care test at the investigation site (acceptance criteria: positive percent agreement [PPA] and negative percent agreement [NPA] !90%). Secondary objectives were to evaluate failure rates and differences between methods in mean cycle threshold (Ct) values and time-to-results.
Collection of nasopharyngeal swab specimens and analysis was performed at Bichat-Claude Bernard Hospital, Paris, France. Deidentified, residual samples were tested, and only transport medium liquid samples were included. Further methodological details are provided in the Supplementary data.
The study was conducted following the ethical principles of the Declaration of Helsinki and regulations regarding Good Clinical Practice.

Results
The analysis took place between March 23 and June 04, 2020. 293 specimens were collected, and 16 samples were excluded from the analysis (Figure 1). The remaining 277 samples were tested using both QIAstat-SARS-CoV-2 and the reference method. An additional 25 results were excluded based on a failed QIAstat-SARS-CoV-2 (n = 13) or reference method test (n = 12; Figure 1). Patient age at hospital admission was available for 237 subjects (mean 58.2 years [range, 1-97 years; standard deviation, 20.24 years]).

Discussion
The QIAstat-SARS-CoV-2 panel demonstrated PPA and NPA with the WHO-recommended assay greater than 90%, both in this study and in another previous smaller study .
Near-patient multiplex tests allow testing multiple pathogens in a single assay, simplifying testing workflows and assisting in the timely differential diagnosis of infectious diseases. The utility of near-patient multiplex testing using the QIAstat-Dx 1 Respiratory Panel to reduce time to diagnosis and improve patient management has previously been demonstrated .
In this study, co-infections were identified in four samples, including two samples positive for SARS-CoV-2. Co-infections with SARS-CoV-2, at rates in-line with this study, have previously been reported in the literature (Lai et al., 2020;Lansbury et al., 2020).
In conclusion, QIAstat-SARS-CoV-2 produces concordant results with the WHO-Charité reference method, but in a significantly shorter time and in a near-patient setting.

Funding
This study has been funded by QIAGEN Manchester Ltd., Manchester, UK.

Conflict of interest
BG is a contractor for QIAGEN. MCC, AE, JP, JL, and DM are employees of QIAGEN. DD has received personal fees from Viiv Healthcare, Gilead Sciences, and Janssen Cilag. BV has received grants from QIAGEN, personal fees from QIAGEN, BioMérieux, Hologic and Gilead, and non-financial support from QIAGEN and BioMérieux. SL, AS, QH, GAT, and NHF do not declare any conflicts of interest.