Viral cultures for coronavirus disease 2019 infectivity assessment: A systematic review

<strong>Background</strong> We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of...

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Main Authors: Jefferson, T, Spencer, EA, Brassey, J, Heneghan, C
Format: Journal article
Language:English
Published: Oxford University Press 2020
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author Jefferson, T
Spencer, EA
Brassey, J
Heneghan, C
author_facet Jefferson, T
Spencer, EA
Brassey, J
Heneghan, C
author_sort Jefferson, T
collection OXFORD
description <strong>Background</strong> We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of the test, such as time from symptom onset. <br> <strong>Methods</strong> We searched LitCovid, medRxiv, Google Scholar, and the World Health Organization coronavirus disease 2019 (COVID-19) database for COVID-19 up 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 summarized narratively by specimen type. Where necessary, we contacted corresponding authors of included papers for additional information. We assessed quality using a modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) risk-of-bias tool. <br> <strong>Results</strong> 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 standardized 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 that the odds of live virus culture were reduced by approximately 33% for every 1-unit increase in Ct. Six of 8 studies reported detectable RNA for >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. <br> <strong>Conclusions</strong> 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 Ct are unlikely to have infectious potential.
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spelling oxford-uuid:9ddb866e-89c8-47b0-9d52-7b9641b7b3482022-06-07T11:52:59ZViral cultures for coronavirus disease 2019 infectivity assessment: A systematic reviewJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9ddb866e-89c8-47b0-9d52-7b9641b7b348EnglishSymplectic ElementsOxford University Press2020Jefferson, TSpencer, EABrassey, JHeneghan, C<strong>Background</strong> We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of the test, such as time from symptom onset. <br> <strong>Methods</strong> We searched LitCovid, medRxiv, Google Scholar, and the World Health Organization coronavirus disease 2019 (COVID-19) database for COVID-19 up 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 summarized narratively by specimen type. Where necessary, we contacted corresponding authors of included papers for additional information. We assessed quality using a modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) risk-of-bias tool. <br> <strong>Results</strong> 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 standardized 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 that the odds of live virus culture were reduced by approximately 33% for every 1-unit increase in Ct. Six of 8 studies reported detectable RNA for >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. <br> <strong>Conclusions</strong> 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 Ct are unlikely to have infectious potential.
spellingShingle Jefferson, T
Spencer, EA
Brassey, J
Heneghan, C
Viral cultures for coronavirus disease 2019 infectivity assessment: A systematic review
title Viral cultures for coronavirus disease 2019 infectivity assessment: A systematic review
title_full Viral cultures for coronavirus disease 2019 infectivity assessment: A systematic review
title_fullStr Viral cultures for coronavirus disease 2019 infectivity assessment: A systematic review
title_full_unstemmed Viral cultures for coronavirus disease 2019 infectivity assessment: A systematic review
title_short Viral cultures for coronavirus disease 2019 infectivity assessment: A systematic review
title_sort viral cultures for coronavirus disease 2019 infectivity assessment a systematic review
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AT spencerea viralculturesforcoronavirusdisease2019infectivityassessmentasystematicreview
AT brasseyj viralculturesforcoronavirusdisease2019infectivityassessmentasystematicreview
AT heneghanc viralculturesforcoronavirusdisease2019infectivityassessmentasystematicreview