Relative Sensitivity of ID NOW and RT-PCR for Detection of SARS-CoV-2 in an Ambulatory Population: Clinical Evaluation, Systematic Review and Meta-analysis

Diagnosis of the SARS-CoV-2 (COVID-19) requires confirmation by Reverse-Transcription Polymerase Chain Reaction (RT-PCR). Abbott ID NOW provides fast results but has been criticized for low sensitivity. Here we determine the sensitivity of ID NOW in an ambulatory population presenting for testing. The study enrolled 785 symptomatic patients, 21 of whom were positive by both ID NOW and RT-PCR, and 2 only by RT-PCR. All 189 asymptomatic patients tested negative. The positive percent agreement between the ID NOW assay and the RT-PCR assay was 91.3%, and negative percent agreement was 100%. The results from the current study were included into a larger systematic review of literature where at least 20 subjects were simultaneously tested using ID NOW and RT-PCR. The overall sensitivity for ID NOW assay was calculated at 84% (95% CI 55-96%), and had the highest correlation to RT-PCR at viral loads most likely to be associated with transmissible infections. Objective: To determine the sensitivity of SARS-CoV-2 detection by ID NOW in an ambulatory population presenting for initial diagnostic testing. Design: Consecutive patients presenting at the Febrile Upper Respiratory Infection clinics and other clinics at The Everett Clinic between April 8th and 22nd, 2020 provided two nasal swab samples, which were tested for SARS-CoV-2 using the ID NOW platform and an RT-PCR platform. Patients were excluded if they were unable to demonstrate an understanding of the study, unwilling to commit to having all samples collected, had a history of nosebleed in the past 24 hours, nasal surgery in the past two weeks, chemotherapy treatment with documented low platelet and low white blood cell counts, or acute facial trauma. The sensitivity for each platform was compared with a composite reference standard based upon all tests. In addition, a systematic review (subset of review CRD420202044410 registered on PROSPERO) was conducted using papers identified by searching PubMed, bioRxiv and medRxiv for investigations in which at least 20 subjects were simultaneously tested using ID NOW and RT-PCR, and which appeared between January 1, 2020 and August 16, 2020. Bias was assessed using the QUADAS2 instrument. Meta-analysis was conducted in which the results of this evaluation were combined with those of results from the systematic review to estimate the performance of ID NOW by comparison with RT-PCR. Results: The study enrolled 785 symptomatic patients, 21 of whom tested positive for SARS-CoV-2 by both the ID NOW and RT-PCR assays, and 2 of whom tested positive only with the RT-PCR assay. In addition, the study enrolled 189 asymptomatic patients, none of whom tested positive by either ID NOW or RT-PCR. An invalid ID NOW assay result was reported for 9 subjects (2 asymptomatic, 7 symptomatic), all of whom tested negative by RT-PCR. Thus, the positive percent agreement between the ID NOW assay and the RT-PCR assay was 91.3%, and the negative percent agreement was 100%. The meta-analysis, which included the results of this evaluation together with results from our systematic review, allows us to estimate the sensitivity of the ID NOW assay to be 84% (95% CI 55-96%), and identifies patients with viral loads most likely to be associated with transmissible infections. Discussion: This clinical study and meta-analysis show that although the ID NOW platform is not as sensitive as RT-PCR for identification of SARS-CoV-2, it nevertheless provides a high positive and negative predictive value in many populations. Conclusions are limited by the relatively small sizes of many of the studies included in the systematic review and meta-analysis, together with the heterogeneity of populations enrolled and nucleic acid amplification tests utilized for comparison.