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

Kendall Cradic, PhD; Marie Lockhart, PhD; Patrick Ozbolt, MLS(ASCP); Lisa Fatica, MT(ASCP); Lorie Landon, SM(ASCP); Michael Lieber, MS; David Yang, MT(ASCP); Juanita Swickard, MBA; Nicholas Wongchaowart, MD; Susan Fuhrman, MD; Stella Antonara, PhD, D(ABMM)

Disclosures

Am J Clin Pathol. 2020;154(2):201-207. 

In This Article

Abstract and Introduction

Abstract

Objectives: To evaluate the clinical performance of 3 molecular assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: 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.

Results: 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.

Conclusions: 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.

Introduction

In December 2019, an outbreak of viral pneumonia with severe acute respiratory syndrome coronavirus-like (SARS-CoV) symptoms emerged in the Hubei province of China. The unknown virus spread rapidly throughout mainland China and ultimately to nearly every country in the world.[1,2] The etiological agent of this outbreak was later identified as a novel human virus, named SARS-CoV-2, causing coronavirus disease 2019 (COVID-19).[2,3] SARS-CoV-2 (COVID-19) was declared to be a pandemic by the World Health Organization and has caused more than 3 million infections and 210,000 deaths globally[4,5] at the time of this study. During the early stages of the pandemic, China, Italy, and Iran suffered from the greatest number of SARS-CoV-2 infections and subsequently had high numbers of casualties.

The virus traveled to the United States (US) early on during the outbreak, with the first reported cases coming from the state of Washington on January 19, 2020.[6] Due to the rapid spread of the virus in the US, the Secretary of Health and Human Services declared a public health emergency on February 4, 2020, which facilitated the development and emergency use authorization (EUA) of in vitro diagnostic tests for SARS-CoV-2. SARS-CoV-2 has not spread uniformly across the US, although all 50 states have reported cases of COVID-19 to the Centers for Disease Control and Prevention (CDC).[7] The coastal regions, including New York, California, and Louisiana, became epicenters of infection, likely due to community spread exacerbated by the high population densities in those areas. The rapid spread of COVID-19 coupled with the need for widespread testing has resulted in shortages of essential components of COVID-19 test kits, including reagents, nasopharyngeal swabs, and universal viral transport medium (UVT).

The clinical presentation of COVID-19 encompasses a broad spectrum of illness, ranging from the asymptomatic to those with mild to severe respiratory illness. Symptoms at the onset can include fever, cough, shortness of breath, chills, and loss of taste or smell.[8] While it is thought that the majority of cases are asymptomatic or mild, the infection can progress rapidly and cause severe disease, especially in older adults, patients with serious underlying medical conditions, and those requiring mechanical ventilation.[9] Although other human coronaviruses have been capable of causing devastating outbreaks, including SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 seems to be more efficiently and rapidly transmitted between humans, resulting in a massive global pandemic.[10–13]

Timely and accurate laboratory diagnosis of SARS-CoV-2 can significantly impact patient management, which is critically important to infection control measures aimed to curb the pandemic within communities and hospitals. Due to the rapid timeframe for assay development under the Food and Drug Administration (FDA) EUA and the lack of reference materials, it remains unclear how each assay performs relative to the others. Many clinical laboratories have implemented multiple assays for molecular testing of SARS-CoV-2 in an effort to meet testing demand. It is left to each laboratory to understand the differences between any testing platforms that they choose to implement, and to guide patient care based on the respective results.

In the present study, we evaluated the clinical performance of 3 SARS-CoV-2 assays: 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) using nasopharyngeal swabs from symptomatic patients. The equivalency of samples collected in UVT vs dry swabs tested on Abbott ID NOW was also assessed. In addition, we analyzed the analytical sensitivity of those 3 assays. This information may aid health care providers and public health officials as they decide how and where to implement the testing platforms available within their systems. The importance of obtaining rapid, reliable results is more critical than ever and will have a large impact on states across the country that are in danger of becoming COVID-19 epicenters.

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