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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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.
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SciScore for 10.1101/2021.03.02.21252768: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All analyses were conducted using SAS Enterprise Guide 8.3.17The PHO Ethics Review Board determined that this project is exempt from research ethics committee review, as it describes analyses that were completed at PHO Laboratory as part of routine clinical respiratory testing during the first wave of the COVID-19 pandemic in Ontario and are therefore considered public health practice, not research. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are …
SciScore for 10.1101/2021.03.02.21252768: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All analyses were conducted using SAS Enterprise Guide 8.3.17The PHO Ethics Review Board determined that this project is exempt from research ethics committee review, as it describes analyses that were completed at PHO Laboratory as part of routine clinical respiratory testing during the first wave of the COVID-19 pandemic in Ontario and are therefore considered public health practice, not research. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of this study include small sample size and use of a non-randomized sampling method that may limit generalizability of findings. Additionally, all specimens from Groups 2 to 5 included in the study were indicated as the individual’s first positive specimen tested by PHO. However, because PHO Laboratory only conducts a subset of Ontario’s testing (approximately 25%), it is possible that patients had additional positive tests processed at other laboratories, which would increase the pre-test probability of the specimen regardless of the group to which the individual’s sample was assigned. For similar reasons, it is possible that not all positive cases from individual institutions were captured in our study if some testing for additional cases was done at other laboratories or individuals declined testing. To substantiate that the low-prevalence institutional settings had no more than three cases, validation was conducted against provincially reported outbreak-related cases associated with these settings within a three week period. It was assumed that if the number of cases identified by the asymptomatic screening program became greater than 3, an outbreak would be declared and any additional cases would be captured as part of the outbreak. A further limitation of this study involves changes to government testing guidelines as the pandemic evolved: changes occurred in both the population incidence of COVID-19 as well as guidelines indicating who should be tested duri...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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