Accepted manuscript
T Jefferson ,Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter
, Oxford
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E A Spencer ,Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter
, Oxford
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J Brassey ,Search for other works by this author on:
C HeneghanNuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter
, Oxford
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Received:
06 October 2020
Published:
03 December 2020
Objective
to review the evidence from studies relating SARS-CoV-2 culture with the results of reverse transcriptase polymerase chain reaction (RT-PCR) and other variables which may influence the interpretation of the test, such as time from symptom onset
Methods
We searched LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database for Covid-19 to 10 September 2020. We included studies attempting to culture or observe SARS-CoV-2 in specimens with RT-PCR positivity. Studies were dual extracted and the data summarised narratively by specimen type. Where necessary we contacted corresponding authors of included papers for additional information. We assessed quality using a modified QUADAS 2 risk of bias tool.
Results
We included 29 studies reporting attempts at culturing, or observing tissue infection by, SARS-CoV-2 in sputum, nasopharyngeal or oropharyngeal, urine, stool, blood and environmental specimens. The quality of the studies was moderate with lack of standardised reporting. The data suggest a relationship between the time from onset of symptom to the timing of the specimen test, cycle threshold (Ct) and symptom severity. Twelve studies reported that Ct values were significantly lower and log copies higher in specimens producing live virus culture. Two studies reported the odds of live virus culture reduced by approximately 33% for every one unit increase in Ct. Six of eight studies reported detectable RNA for longer than 14 days but infectious potential declined after day 8 even among cases with ongoing high viral loads. Four studies reported viral culture from stool specimens.
Conclusion
Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high cycle threshold are unlikely to have infectious potential.
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