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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

Part of: SARS-CoV-2/COVID-19

Published online by Cambridge University Press:  09 August 2021

Jonathan B. Gubbay Open the ORCID record for Jonathan B. Gubbay [Opens in a new window] ,
Heather Rilkoff ,
Heather L. Kristjanson ,
Jessica D. Forbes ,
Michelle Murti ,
AliReza Eshaghi ,
George Broukhanski ,
Antoine Corbeil ,
Nahuel Fittipaldi  and
Jessica P. Hopkins
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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
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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
Information
Infection Control & Hospital Epidemiology , Volume 43 , Issue 9 , September 2022 , pp. 1179 - 1183
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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.”

References

Management of cases and contacts of COVID-19 in Ontario; May 6, 2021 (version 12.0). Ontario Ministry of Health website. https://www.health.gov.on.ca/en/pro/programs/publichealth/coronavirus/docs/contact_mngmt/management_cases_contacts.pdf. Published May 6, 2021. Accessed July 7, 2021.Google Scholar
Real-time PCR cycle threshold (Ct) values: an overview of cycle threshold values and their role in SARS-CoV-2 real-time PCR test interpretation. Public Health Ontario website. https://www.publichealthontario.ca/-/media/documents/ncov/main/2020/09/cycle-threshold-values-sars-cov2-pcr.pdf?la=en. Published September 17, 2020. Accessed July 7, 2021.Google Scholar
Cohen, AN, Kessel, B, Milgroom, MG. Diagnosing SARS-CoV-2 infection: the danger of over-reliance on positive test results. medRxiv 2020. doi: 10.1101/2020.04.26.20080911.Google Scholar
Liu, Y, Yan, LM, Wan, L, et al. Viral dynamics in mild and severe cases of CoVID-19. Lancet Infect Dis 2020;20:656–657.CrossRefGoogle ScholarPubMed
Arons, MM, Hatfield, KM, Reddy, SC, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med 2020;382:2081–2090.CrossRefGoogle Scholar
Long, QX, Tang, XJ, Shi, QL, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020;26:1200–1204.CrossRefGoogle ScholarPubMed
Singanayagam, A, Patel, M, Charlett, A, et al. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19—England, January to May 2020. Euro Surveill 2020;25:2001483.CrossRefGoogle ScholarPubMed
Zhou, R, Li, F, Chen, F, et al. Viral dynamics in asymptomatic patients with COVID-19. Int J Infect Dis 2020;96:288–290.CrossRefGoogle ScholarPubMed
Tom, MR, Mina, MJ. To interpret the SARS-CoV-2 test, consider the cycle threshold value. Clin Infect Dis 2020;71:2252–2254.CrossRefGoogle ScholarPubMed
Table 17-10-0005-01 population estimates on July 1st, by age and sex. Statistics Canada website. https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1710000501. Accessed November 9, 2020.Google Scholar
Marchand-Senécal, M, Kozak, R, Mubareka, S, et al. Diagnosis and management of first case of COVID-19 in Canada: lessons applied from SARS-CoV-1. Clin Infect Dis 2020;71:2207–2210.CrossRefGoogle ScholarPubMed
Ontario COVID-19 data tool. Public Health Ontario website. https://www.publichealthontario.ca/en/data-and-analysis/infectious-disease/covid-19-data-surveillance/covid-19-data-tool. Published 2020. Accessed November 9, 2020.Google Scholar
Corman, VM, Landt, O, Kaiser, M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill 2020;25:2000045.CrossRefGoogle ScholarPubMed
Case definition—coronavirus disease (COVID-19). Ontario Ministry of Health website. https://www.health.gov.on.ca/en/pro/programs/publichealth/coronavirus/docs/2019_case_definition.pdf. Published 2020. Accessed July 11, 2021.Google Scholar
Jaafar, R, Aherfi, S, Wurtz, N, et al. Correlation between 3790 qPCR positives samples and positive cell cultures including 1941 SARS-CoV-2 isolates. Clin Infect Dis 2021;72:e921.Google Scholar
Corman, VM, Müller, MA, Costabel, U, et al. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Euro Surveill 2012;17:20334.CrossRefGoogle ScholarPubMed
SAS Institute. SAS Enterprise Guide 8.2: User’s Guide. Cary, NC: SAS Institute; 2019.Google Scholar
PHO’s COVID-19 serosurveillance initiative. Public Health Ontario website. https://www.publichealthontario.ca/en/data-and-analysis/infectious-disease/covid-19-data-surveillance/covid-19-serosurveillance. Published 2020. Accessed November 9, 2020.Google Scholar
Gudbjartsson, DF, Helgason, A, Jonsson, H, et al. Spread of SARS-CoV-2 in the Icelandic population. N Engl J Med 2020;382:2302–2315.CrossRefGoogle ScholarPubMed
Vodičar, PM, Valenčak, AO, Zupan, B, et al. Low prevalence of active COVID-19 in Slovenia: a nationwide population study on a probability-based sample. Microbiol Infect 2020;26:1514–1519.Google Scholar
Randazzo, W, Truchado, P, Cuevas-Ferrando, E, et al. SARS-CoV-2 RNA in wastewater anticipated COVID-19 occurrence in a low prevalence area. Water Res 2020;181:115942.CrossRefGoogle Scholar
Bendavid, E, Mulaney, B, Sood, N, et al. COVID-19 antibody seroprevalence in Santa Clara County, California. Int J Epidemiol 2021;50:410–419.CrossRefGoogle Scholar