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Impact of coronavirus disease 2019 (COVID-19) pre-test probability on positive predictive value of high cycle threshold severe acute respiratory coronavirus virus 2 (SARS-CoV-2) real-time reverse transcription polymerase chain reaction (RT-PCR) test results

Published online by Cambridge University Press:  09 August 2021

Jonathan B. Gubbay*
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
Heather Rilkoff
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada
Heather L. Kristjanson
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada
Jessica D. Forbes
Affiliation:
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Michelle Murti
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
AliReza Eshaghi
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada
George Broukhanski
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Antoine Corbeil
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Nahuel Fittipaldi
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Jessica P. Hopkins
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
Erik Kristjanson
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada
Julianne V. Kus
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Liane Macdonald
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Anna Majury
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Pathology and Molecular Medicine, Queens University, Kingston, Ontario, Canada
Gustavo V Mallo
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada
Tony Mazzulli
Affiliation:
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Department of Microbiology, Sinai Health/University Health Network, Toronto, Ontario, Canada
Roberto G. Melano
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Romy Olsha
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada
Stephen J. Perusini
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada
Vanessa Tran
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Vanessa G. Allen
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Samir N. Patel
Affiliation:
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
*
Author for correspondence: Jonathan B. Gubbay, E-mail: jonathan.gubbay@oahpp.ca

Abstract

Objectives:

Performance characteristics of SARS-CoV-2 nucleic acid detection assays are understudied within contexts of low pre-test probability, including screening asymptomatic persons without epidemiological links to confirmed cases, or asymptomatic surveillance testing. SARS-CoV-2 detection without symptoms may represent presymptomatic or asymptomatic infection, resolved infection with persistent RNA shedding, or a false-positive test. This study assessed the positive predictive value of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) assays by retesting positive specimens from 5 pre-test probability groups ranging from high to low with an alternate assay.

Methods:

In total, 122 rRT-PCR positive specimens collected from unique patients between March and July 2020 were retested using a laboratory-developed nested RT-PCR assay targeting the RNA-dependent RNA polymerase (RdRp) gene followed by Sanger sequencing.

Results:

Significantly fewer (15.6%) positive results in the lowest pre-test probability group (facilities with institution-wide screening having ≤3 positive asymptomatic cases) were reproduced with the nested RdRp gene RT-PCR assay than in each of the 4 groups with higher pre-test probability (individual group range, 50.0%–85.0%).

Conclusions:

Large-scale SARS-CoV-2 screening testing initiatives among low pre-test probability populations should be evaluated thoroughly prior to implementation given the risk of false-positive results and consequent potential for harm at the individual and population level.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

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Footnotes

PREVIOUS PRESENTATION: This manuscript was posted as a preprint to medRxiv.org, the preprint server for health sciences (https://www.medrxiv.org/content/10.1101/2021.03.02.21252768v1). These findings were also shared as a “Focus On” informational document on the Public Health Ontario website in September 2020 titled “An Overview of Cycle Threshold Values and their Role in SARS-CoV-2 Real-Time PCR Test Interpretation.”

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Impact of coronavirus disease 2019 (COVID-19) pre-test probability on positive predictive value of high cycle threshold severe acute respiratory coronavirus virus 2 (SARS-CoV-2) real-time reverse transcription polymerase chain reaction (RT-PCR) test results
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