Viral Cultures for Coronavirus Disease 2019 Infectivity Assessment: A Systematic Review
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Abstract
Background
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.
Methods
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.
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 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.
Conclusions
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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SciScore for 10.1101/2020.08.04.20167932: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources We searched four main databases: LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database for Covid-19 using the terms ‘viral culture’ or ‘viral replication’ and associated synonyms. Google Scholarsuggested: (Google Scholar, RRID:SCR_008878)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: An explicit section about the …SciScore for 10.1101/2020.08.04.20167932: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources We searched four main databases: LitCovid, medRxiv, Google Scholar and the WHO Covid-19 database for Covid-19 using the terms ‘viral culture’ or ‘viral replication’ and associated synonyms. Google Scholarsuggested: (Google Scholar, RRID:SCR_008878)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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.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.
- No funding statement was detected.
- No protocol registration statement was detected.
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