A Final Laboratory Validation Study and Comparative Performance Evaluation of The Abbott ID NOWTM COVID-19 Assay in A Coastal California Tertiary Care Medical Center

ABSTRACT

The Abbott ID NOWTM COVID-19 assay is a rapid molecular diagnostic test particularly designed for on-site, rapid turnaround point of care (POC) testing. The utilization of rapid diagnostic tests is integral to optimizing workflow within the hospital and/or procedural-based clinics. The capability to provide both rapid disposition and correct patient classification during this COVID-19 pandemic is critically important with broad infection control implications for both patients and healthcare staff. A tightly controlled, extended laboratory validation was performed at our medical center to determine the negative test agreement of the Abbott ID NOWTM compared with the BD MAXTM analyzer and/or Hologic PantherTM, laboratory-based, two target, molecular analyzers with a sensitive level of detection (LoD). This article is a follow-on evaluation from a preliminary smaller data-set study in which 117 patient’s results were included. The current data set includes a sample size of 1304 patients (over a 10-fold increase) allowing for a more robust statistical power analysis. There was strict adoption of the procedures listed in the Abbott ID NOWTM Instruction for Use (IFU) [1] insert delineating preferred practices for “optimal test performance” that also incorporates the revised Emergency Use Authorization (EUA) amendment of 17 September 2020 allowing for the use of dry nasopharyngeal (NP) swabs. Our institutional experience demonstrates an overall negative agreement of 1163 of 1178 (98.7%). Of interest, however, 11 of the original discordant results in the April to August time frame were able to be retested and 55% of the original ID NOWTM false negatives with nasal swabs that were retested with NP swabs proved to be positive, and 45% that remained false negatives (FN) even with NP swabs had Ct values > 35. As such, one could hypothesize that if dry NP swabs had been implemented months ago, that the negative test agreement could be as high as 99.4%, which equates to a 99.1% concordance similar to a previously reported correlation study [2]. It also demonstrates a LoD cutoff inflection point where sensitivity diminishes appears to be a Ct value around 35.

INTRODUCTION

The Abbott ID NOWTM COVID-19 assay, which received Food and Drug Administration Emergency Use Authorization (FDA EUA) approval on 27 March 2020, is a rapid molecular diagnostic test particularly designed for on-site, rapid turnaround point of care (POC) testing. The analyzer uses isothermal nucleic acid amplification of a single unique region of the RNA-dependent RNA polymerase (RdRp) genome using a self-contained, combined collection and testing kit. By mid-April 2020, Cottage Health (CH) adopted the use of the Abbott ID NOWTM analyzer and validated utilizing archived positive and negative specimens in viral transport media (VTM) as well as direct smears from known positive and negative patients. Our validation with direct smears demonstrated 100% concordance; however, there was only 80% concordance with the archived VTM specimens. Our analysis of this false negative discordance was coincident with the published studies from Northwell Health [3] and media reports about Cleveland Clinic [4] highlighting this issue. Given the proposed use of the Abbott ID NOWTM to test predominantly symptomatic hospital admissions in the context of the uncertainty imparted by these studies, Cottage Health purposely designed a process using dry swabs only with immediate on-site testing to comprehensively ascertain the actual negative test performance of the Abbott ID NOWTM.

STUDY DESIGN AND METHODS

The key conceptual elements of this prospective validation study were originally designed by CH senior infectious disease physicians and operationalized by emergency department (ED) and laboratory leadership. This study was initiated with the general design to test all COVID-19 prospective hospital admissions in the ED with the Abbott ID NOWTM and, if negative, recollect expeditiously and test on a laboratory-based molecular analyzer. The medical center in which this study was performed is a major referral center for Santa Barbara and adjoining counties in midcoastal California. At the inception of this extended validation study, the county had just reached its peak and the laboratory-tabulated prevalence of COVID-19 was slightly above 10%, which according to the Infectious Disease Society of America (IDSA) guidelines [5] would have been classified as high prevalence. As the peak subsided the final average over the time interval of the study vacillated in the intermediate to low prevalence [5]. As such, the Abbott ID NOWTM with their proprietary nasal swabs was the frontline testing platform and the Becton Dickinson BD MAXTM and/or Hologic PantherTM selected as the laboratory-based platforms. To optimize clinical test sensitivity, the decision was made to adopt the practice of collecting nasopharyngeal (NP) swabs and occasionally an additional oropharyngeal (OP) swab. Another important design feature is that the Abbott ID NOWTM was collected and tested immediately on-site in the ED diminishing any significant testing delay and reducing any potential RNA degradation associated with room-temperature, dry swab storage. Finally, a cardinal design feature to this prospective study was the deliberate recollection to occur within a short time interval (measured predominantly in single digit hours but all less than 24 hours) in order to focus specifically on testing the negative agreement concordance between the Abbott ID NOWTM and two mainline platforms rather than test clinical sensitivity variability associated with different swabs types. Our initial study was designed to specifically focus on the comparative performance of the different testing analyzers, but we also wanted to ascertain through retesting the second specimen, whether an NP swab had some degree of enhanced sensitivity compared with a nasal swab.

RESULTS

From 16 April 2020 to 27 September 2020, a total of 1304 patients were collected and the patients ranged from 11 to 97 years. There was a significant negative percent agreement with 1163 out of 1178 patients correlating for a 98.7% concordance. In this nearly 6-month time interval, 15 out of 1178 specimens were determined to be FN (Table1). In the 15 discordant FN specimens, we had enough sample for 11 of the 15 to retest on the Abbott ID NOWTM. In other words, we took an aliquot from 11 recollected samples with NP swabs in viral transport media (VTM) that tested positive with one of the two mainline analyzers and retested the sample with the Abbott ID NOWTM. We recognized that these could result negative due to VTM dilutional effect as noted earlier [3,4]; however, 6 of the 11 (55%) repeated as positive essentially confirming that NP swabs have a higher sensitivity than nasal swabs (ultimately confirming the rationale for the amended FDA EUA to include dry NP swabs as an acceptable source). Of interest, we found that 5 of the 11 (45%) that remained negative on the Abbott ID NOWTM had Ct values > 35. If we had used dry NP swabs from the inception of the study, hypothetically our final discordant rate could have been 7 out of 1170 translating into a negative concordance rate of 99.4%.

CONCLUSION

Our institutional results are correlated with a previously reported correlation study [2] performed from 8-22 April 2020 at the Everett Clinic, Washington in which the Abbott ID NOWTM was compared to the Hologic Panther Fusion®, a laboratory-based, two target, molecular analyzer. The concordance rate of negative results was determined to be 99.8% with 932 out of 934 Abbott ID NOWTM negative results concurring with the comparator platform, relatively similar to our concordance rate of 98.7% and even closer to a hypothetical concordance of 99.4% if dry swabs were to have been used rather than nasal swabs. A possible conclusion to our institutional laboratory validation is that dry NP swabs, which are tested immediately upon or shortly after collection, enhances the sensitivity and reduces the FN rate. Similar to the Abbott Binax NOWTM that has a cutoff Ct value (Ct = 33) representing an inflection point with decreased analytic sensitivity [6] due to LoD limitations of a POC instrument compared with mainline analyzers, the cutoff Ct value for the Abbott ID NOWTM in our limited sample size appears to be 35.

ACKNOWLEDGEMENT

The following clinical leaders from Cottage Health Infectious Disease, Emergency Medicine and Laboratory Departments provided invaluable insights and support that operationalized this prospective, extended laboratory validation study. Lynn Fitzgibbons MD (Infectious Disease, Santa Barbara Cottage Hospital); Brett Wilson MD and Bridget Crooks RN, MSN (Emergency Medicine Department, Santa Barbara Cottage Hospital); Lynette Hansen PhD, CLS, MT (ASCP), Charlene Fernandez CLS, MT (ASCP), Allison Reitz, CLS, MT (ASCP) and Jane Choe MBA, CLS, MT (ASCP) (Laboratory Department, Santa Barbara Cottage Hospital and Pacific Diagnostic Laboratories).

FUNDING/SPONSOR

There is no funding beyond the normal and customary costs associated with performing required laboratory validation studies, which is supported by the performing laboratory test (Cottage Health - Pacific Diagnostic Laboratories).

REFERENCES

  1. US Food and Drug Administration (2020) Coronavirus disease (COVID-19) emergency use authorizations for medical devices - In Vitro Diagnostics EUAs for SARS-CoV-2, on US FDA.
  2. Interim study by Tu YP, O’Leary TJ (2020) Sample collection and molecular diagnosis of SARS-CoV-2 infection presented at the association of molecular pathology 48(11): 1680-1689.
  3. Zhen W, Smith E, Manji R, Schron D, Berry GJ, et al. (2020). Clinical evaluation of three sample-to-answer platforms for the detection of SARSCoV- 2. J Clin Microbiol 58(8): e00783-00820.
  4. Stein R (2020) Study raises questions about false negatives from quick COVID-19 test, p In National Public Radio (NPR).
  5. Hanson KE, Caliendo AM, Arias CA, Englund JA, Lee MJ, et al. (2020) Infectious diseases society of America guidelines on the diagnosis of COVID-19 (IDSA). Ciaa 760.
  6. Basu A, Zinger T, Inglima K, Woo KM, Atie O, et al. (2020) Performance of the rapid nucleic acid amplification by Abbott ID NOW COVID-19 in nasopharyngeal swabs transported in viral media and dry nasal swabs in a New York City academic institution. 58(8): e01136-01220.

Article Type

Short Communication

Publication history

Received date: November 17, 2020
Published date: January 28, 2021

Address for correspondence

Stewart Comer, Santa Barbara Cottage Hospital, Laboratory Department, USA

Copyright

©2021 Open Access Journal of Biomedical Science, All rights reserved. No part of this content may be reproduced or transmitted in any form or by any means as per the standard guidelines of fair use. Open Access Journal of Biomedical Science is licensed under a Creative Commons Attribution 4.0 International License

How to cite this article

Stewart C, David F. A Final Laboratory Validation Study and Comparative Performance Evaluation of The Abbott ID NOWTM COVID-19 Assay in A Coastal California Tertiary Care Medical Center. 2021- 3(1) OAJBS.ID.000250.

Author Info

Stewart Comer1* and David Fisk2

1Santa Barbara Cottage Hospital, Laboratory Department, USA
2Santa Barbara Cottage Hospital, Infection Control Physician, USA

Table 1:

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