Estimating the false-negative test probability of SARS-CoV-2 by RT-PCR
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Abstract
Reverse-transcription PCR (RT-PCR) assays are used to test for infection with the SARS-CoV-2 virus. RT-PCR tests are highly specific and the probability of false positives is low, but false negatives are possible depending on swab type and time since symptom onset.
Aim
To determine how the probability of obtaining a false-negative test in infected patients is affected by time since symptom onset and swab type.
Methods
We used generalised additive mixed models to analyse publicly available data from patients who received multiple RT-PCR tests and were identified as SARS-CoV-2 positive at least once.
Results
The probability of a positive test decreased with time since symptom onset, with oropharyngeal (OP) samples less likely to yield a positive result than nasopharyngeal (NP) samples. The probability of incorrectly identifying an uninfected individual due to a false-negative test was considerably reduced if negative tests were repeated 24 hours later. For a small false-positive test probability (<0.5%), the true number of infected individuals was larger than the number of positive tests. For a higher false-positive test probability, the true number of infected individuals was smaller than the number of positive tests.
Conclusion
NP samples are more sensitive than OP samples. The later an infected individual is tested after symptom onset, the less likely they are to test positive. This has implications for identifying infected patients, contact tracing and discharging convalescing patients who are potentially still infectious.
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SciScore for 10.1101/2020.04.05.20053355: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: First, more data exists than we have been able to analyse. Many of the studies cited here (& others - e.g. [39]) have longitudinal data from more patients but which is not currently publicly available and we were unable to obtain, or is not disaggregated by swab type. Inclusion of this data would provide superior estimates, in particular if it is disaggregated into tests done from different samples via different routes in the same …
SciScore for 10.1101/2020.04.05.20053355: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: First, more data exists than we have been able to analyse. Many of the studies cited here (& others - e.g. [39]) have longitudinal data from more patients but which is not currently publicly available and we were unable to obtain, or is not disaggregated by swab type. Inclusion of this data would provide superior estimates, in particular if it is disaggregated into tests done from different samples via different routes in the same patient. Moreover, explicit reporting of dates when tests are performed in all patients (and not just those who test positive) would be especially useful to any subsequent similar analyses for SARS-CoV-2 or other emerging viruses. We thus advocate for such data to be made available more readily in publications and preprints. Second, we have attempted to account for possible differences among labs performing RT-PCR tests and although we do not find any evidence in favour of this being relevant, nor is there enough evidence to rule it out. There may also be variation in terms of the gene that is targeted, or method of RT-PCR performed, which we have also not been able to consider due to lack of available data (e.g. some target / assay combinations may be more sensitive than others [40,41]). We have also assumed that all the patients have been correctly identified as infected in each study and that the specificity of the test is perfect; it is likely to be extremely high but perhaps not 100% and may similarly vary with assay type [42]. Thi...
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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