Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Test

Loeffelholz, Michael J.; Alland, David; Butler-Wu, Susan M.; Pandey, Utsav; Perno, Carlo Frederico; Nava, Alice; Carroll, Karen C.; Mostafa, Heba; Davies, Emma; McEwan, Ashley; Rakeman, Jennifer L.; Fowler, Randal C.; Pawlotsky, Jean-Michel; Fourati, Slim; Banik, Sukalyani; Banada, Padmapriya P.; Swaminathan, Shobha; Chakravorty, Soumitesh; Kwiatkowski, Robert W.; Chu, Victor C.; Kop, JoAnn; Gaur, Rajiv; Sin, Mandy L. Y.; Nguyen, Duy; Singh, Simranjit; Zhang, Na; Persing, David H.

Nucleic acid amplification tests (NAATs) are the primary means of identifying acute infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accurate and fast test results may permit more efficient use of protective and isolation resources and allow rapid therapeutic interventions. We evaluated the analytical and clinical performance characteristics of the Xpert Xpress SARS-CoV-2 (Xpert) test, a rapid, automated molecular test for SARS-CoV-2. Analytical sensitivity and specificity/interference were assessed with infectious SARS-CoV-2; other infectious coronavirus species, including SARS-CoV; and 85 nasopharyngeal swab specimens positive for other respiratory viruses, including endemic human coronaviruses (hCoVs). Clinical performance was assessed using 483 remnant upper- and lower-respiratory-tract specimens previously analyzed by standard-of-care (SOC) NAATs. The limit of detection of the Xpert test was 0.01 PFU/ml. Other hCoVs, including Middle East respiratory syndrome coronavirus, were not detected by the Xpert test. SARS-CoV, a closely related species in the subgenus Sarbecovirus, was detected by a broad-range target (E) but was distinguished from SARS-CoV-2 (SARS-CoV-2-specific N2 target). Compared to SOC NAATs, the positive agreement of the Xpert test was 219/220 (99.5%), and the negative agreement was 250/261 (95.8%). A third tie-breaker NAAT resolved all but three of the discordant results in favor the Xpert test. The Xpert test provided sensitive and accurate detection of SARS-CoV-2 in a variety of upper- and lower-respiratory-tract specimens. The high sensitivity and short time to results of approximately 45 min may impact patient management.