Clinical Evaluation and Utilization of Multiple Molecular In Vitro Diagnostic Assays for the Detection of SARS-CoV-2

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>To evaluate the clinical performance of 3 molecular assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We used 184 nasopharyngeal swab specimens to compare Abbott ID NOW COVID-19 (Abbott ID NOW), DiaSorin Molecular Simplexa COVID-19 Direct (DiaSorin Simplexa), and Roche cobas 6800 SARS-CoV-2 (Roche cobas) assays. In a separate analysis, 3 specimens (nasopharyngeal, oropharyngeal, and nasal) were collected from 182 unique patients presenting to the emergency department with suspicion of coronavirus disease 2019 and were tested utilizing Abbott ID NOW. To further characterize each assay, relative limits of detection were evaluated utilizing positive nasopharyngeal patient samples.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The positive percent agreement was 91% (95% confidence interval [CI], 0.76-0.97) for Abbott ID NOW and 100% (95% CI, 0.90-1.00) for DiaSorin Simplexa and Roche cobas. The negative percent agreement was 100% (95% CI, 0.98-1.00) for all 3 assays. All swab types tested with the Abbott assay produced concordant results. Polymerase chain reaction assays had approximately 10 to 100 times lower limits of detection than Abbott ID NOW.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Based on these evaluations, a multiplatform testing approach is proposed, depending on patient population and assay sensitivity, to address testing needs during a public health emergency.</jats:p> </jats:sec>

Nucleic acid amplification tests on respiratory samples for the diagnosis of coronavirus infections: a systematic review and meta-analysis

“… 43 Altogether the 51 studies analyzed 18,923 persons, of them 10,181 persons (22 studies) before COVID-19 and 8,742 persons for SARS-CoV-2 (29 studies). 7 , 9 , 13 , 14 , 17 , 18 , 19 , 22 , 23 , 25 , 26 , 27 , 34 , 35 , 36 , 38 , 39 , 41 , 43 , 45 , 46 , 47 , 50 , 51 , 53 , 54 , 55 , 56 The studies evaluated mostly patients with non-specific ILI or suspected COVID-19, the latter including both upper ARTI and pneumonia. Five studies included only children <2 years 16 , 21 , 31 , 32 , 48 , 25 studies included a mixed age range and 21 did not address patients' age.…”

The estimation of diagnostic accuracy of tests for COVID-19: A scoping review

“…Three studies determined the accuracy or agreement of rRT-PCR or automated rRT-PCR platforms/instruments compared to a reference standard based on the results of several tests as a "composite reference standard" ( Table 3 ). [18][19][20] There were between 58 and 184 patients per study. Suo et al considered a positive result of either repeated measurements of rRT-PCR or serology to indicate a positive test according to the reference standard; reported sensitivity of initial rRT-PCR result was 40%, rSp 100%, rPPV 100%, and rNPV 16%.…”

“…While Abbott ID NOW had a rPPA of 91%, the Roche cobas 6800 and Diasorin Simplexa assays had a rPPA of 100%. 18 These studies either did not report how samples were selected for evaluation (Supplementary Table 3), 19 , 20 or reported that only samples which had sufficient residual volume and had been properly stored were selected. 18 Cradic et al and Zhen & Mangi et al…”

Comparative study of four SARS-CoV-2 Nucleic Acid Amplification Test (NAAT) platforms demonstrates that ID NOW performance is impaired substantially by patient and specimen type

“…In the absence of clinical trials and a gold standard for COVID-19 diagnosis, the clinical performance of SARS-CoV-2 assays is unclear. Anecdotal claims of poor NAAT performance exist in the lay press, and limited studies have shown variable performance of rapid POC tests ( Cradic et al, 2020 ; Harrington et al, 2020 ; Mitchell and George, 2020 ; Moore et al, 2020 ; Rhoads et al, 2020 ; Smithgall et al, 2020 ; Visseaux et al, 2020 ; Wolters et al, 2020 ; Zhen et al, 2020 ). As a surrogate for a gold standard, a composite reference standard (CRS) can be used to determine the consensus of comparable assays and identify outlier assays in terms of clinical performance ( Schiaffino et al, 2020 ).…”