Diagnostic accuracy of RT-PCR for detection of SARS-CoV-2 compared to a “composite reference standard” in hospitalized patients
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Abstract
Background
COVID-19 caused by the novel coronavirus SARS-CoV-2 has caused the greatest public health emergency of our time. Accurate laboratory detection of the virus is critical in order to contain the spread. Although real-time polymerase chain reaction (PCR) has been the cornerstone of laboratory diagnosis, there have been conflicting reports on the diagnostic accuracy of this method.
Methods
A retrospective review was performed on all hospitalized patients tested for SARS-CoV-2 (at St. Pauls Hospital in Vancouver, BC) from March 13 – April 12, 2020. Diagnostic accuracy of initial PCR on nasopharyngeal (NP) swabs was determined against a composite reference standard which included a clinical assessment of the likelihood of COVID-19 by medical experts, initial and repeat PCR, and post-hoc serological testing.
Results
A total of 323 patients were included in the study, 33 (10.2%) tested positive and 290 (89.8%) tested negative by initial PCR. Patients testing positive were more likely to exhibit features of cough (66.7% vs 39.3%), shortness of breath (63.6% vs 35.9%), fever (72.7% vs 27.6%), radiographic findings (83.3% vs 39.6%) and severe outcomes including ICU admission (24.2% vs 9.7%) and mortality (21.2% vs 6.2%) compared to patients testing negative. Serology was performed on 90 patients and correlation between serology and PCR was 98.9%. There were 90 patients included in the composite reference standard. Compared to the composite reference standard, initial PCR had sensitivity of 94.7% (95% CI 74.0 to 99.9%), specificity of 100% (95% CI 94.9 to 100%), positive predictive value of 100% (95% CI 81.5 to 100%) and a negative predictive value of 98.6% (95% CI 92.5 to 100%).
Discussion
Our study showed high sensitivity of PCR on NP swab specimens when compared to composite reference standard in hospitalized patients. High correlation of PCR with serological testing further increased confidence in the diagnostic reliability of properly collected NP swabs.
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SciScore for 10.1101/2021.02.18.21252016: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was approved by the Research Ethics Board, University of British Columbia. Randomization not detected. Blinding Reviewers were not blinded to the PCR test result as it was reported in the electronic medical chart but were blinded to the serological result. 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:The limitations of …
SciScore for 10.1101/2021.02.18.21252016: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was approved by the Research Ethics Board, University of British Columbia. Randomization not detected. Blinding Reviewers were not blinded to the PCR test result as it was reported in the electronic medical chart but were blinded to the serological result. 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:The limitations of our study are the retrospective design and selection bias due to a hospital setting. Our data on clinical sensitivity applies to sicker, hospitalized patients who tend to have greater viral shedding, possibly leading to improved rates of PCR detection [46] [37]. Clinical assessment of COVID-19 likelihood was not blinded to PCR results as reviewers had access via an electronic medical record. Additionally, we have included the initial PCR test under evaluation as part of the composite reference standard. Even though we have expanded the reference standard to include any subsequent PCR results, this could have artificially enhanced the diagnostic performance of the index PCR and introduced a bias. The proposed reference standard has not been yet fully validated but reflects a practical approach utilizing currently available diagnostic modalities. The presence of a clear alternative diagnosis was used to assign lower likelihood of COVID-19 infection and although unlikely, there may have been cases of dual diagnoses. Furthermore, we were only able to obtain serology on a subset of patients as many were discharged from hospital prior to the time required to develop antibodies and had no subsequent bloodwork. Similar to PCR, false negative serology on patients could have overestimated PCR sensitivity, but in our data set, this is a rare occurrence which primarily applies to highly immunocompromised individuals.
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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