Prospective, multi-site evaluation of the Cepheid Xpert Xpress CoV-2 plus test on nasal and nasopharyngeal swabs

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues its largely aseasonal spread with millions of cases per year. Highly sensitive, point-of-care testing is critical for rapid detection of coronavirus disease 2019 (COVID-19) cases and initiation of antiviral therapy to avert adverse health outcomes and reduce onward transmission of the virus. While hundreds of COVID-19 diagnostics received emergency use authorization from the FDA during the pandemic, significantly fewer have navigated the course to FDA clearance or approval. Here, we determined the clinical performance of the Cepheid Xpert Xpress CoV-2 plus for detection of SARS-CoV-2 in 3,750 anterior nasal swab (NS) specimens and nasopharyngeal swab (NPS) from 32 sites in comparison to the FDA-authorized BioFire Respiratory Panel 2.1. Three-quarters of specimens collected were tested on the Xpert Xpress CoV-2 plus in the point-of-care setting. Overall positive percent agreement (PPA) was 98.1% (95% CI: 96.7%-98.9%) and negative percent agreement (NPA) was 98.3% (97.7%-98.7%). Performance of the Xpert Xpress CoV-2 plus was slightly improved in NS compared to NPS specimens, with PPA of 99.3% versus 97.0% (Fisher's exact test, P = 0.06) and NPA of 98.3% versus 98.2% (P = 0.89), respectively. Assay PPA was similar between untrained and trained users (98.7% vs 97.3%, P = 0.75), while NPA was slightly improved for untrained users (99.0% vs 97.6%, P = 0.0003). This study showed that Cepheid Xpert Xpress COV-2 plus is highly sensitive and specific/has high PPA and NPA for detection of SARS-CoV-2 from both NS and NPS specimens.

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause millions of infections and tens of thousands of deaths per year in the United States. While the FDA authorized hundreds of SARS-CoV-2 tests during the public health emergency, significantly fewer have made the transition to being cleared or approved. There continues to be a need for FDA-authorized point-of-care SARS-CoV-2 testing that can be performed by untrained users. We conducted a large prospective study of the Cepheid Xpert Xpress CoV-2 plus test for detection of SARS-CoV-2 in both nasal and nasopharyngeal swabs by trained and untrained users. The assay demonstrated excellent clinical performance characteristics and, as a result of this study, was cleared by the FDA.

Keywords: COVID-19; Cepheid; SARS-CoV-2; Xpert Xpress; clinical study; point-of-care; rapid.

Fig 1

Specimen accountability in the clinical study. CONSORT-like diagram of specimens enrolled and included in the study.

Fig 2

Violin plot of the Ct distribution of Xpert Xpress CoV-2 plus test results for NPS and NS specimens compared to the qualitative results of BioFire RP 2.1 comparator. N2 gene target Ct values are depicted for positive Xpert Xpress CoV-2 plus test results based on BioFire RP 2.1 comparator results. Specimens testing positive on the Xpert Xpress CoV-2 plus test based on E or RdRp gene target detection but negative for the N2 target are plotted above the assay’s cutoff for the N2 target. Filled-in circles are considered outliers based on >1.5× interquartile range.