Department of Continuing Education, University of Oxford, Oxford, United Kingdom.
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Clin Infect Dis. 2021 Dec 6;73(11):e3884-e3899. doi: 10.1093/cid/ciaa1764.
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.
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.
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.
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.
我们旨在回顾与严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）培养相关的研究证据，以及可能影响检测结果解释的逆转录聚合酶链反应（RT-PCR）和其他变量，例如从症状发作到检测的时间。
我们检索了 LitCovid、medRxiv、Google Scholar 和世界卫生组织 2019 年冠状病毒病（COVID-19）数据库中截至 2020 年 9 月 10 日的 COVID-19 相关研究。我们纳入了试图在 RT-PCR 阳性标本中培养或观察 SARS-CoV-2 的研究。对研究进行了双重提取，并按标本类型进行了叙述性数据汇总。在必要时，我们联系了纳入研究的通讯作者以获取更多信息。我们使用改良的诊断准确性研究质量评估工具 2（QUADAS 2）对偏倚风险进行了评估。
我们纳入了 29 项研究，这些研究报告了尝试在痰、鼻咽或口咽、尿液、粪便、血液和环境标本中培养或观察 SARS-CoV-2 组织感染的情况。研究质量为中等，缺乏标准化报告。这些数据表明，从症状发作到标本检测时间、循环阈值（Ct）和症状严重程度之间存在关系。12 项研究报告称，在产生活病毒培养的标本中，Ct 值显著较低，对数拷贝数较高。两项研究报告称，Ct 值每增加 1 个单位，活病毒培养的可能性就会降低约 33%。8 项研究中的 6 项报告称，可检测到的 RNA 超过 14 天，但即使在病毒载量持续较高的情况下，感染潜力也会在第 8 天后下降。四项研究报告称从粪便标本中分离出病毒培养物。
完整的活病毒是传播所必需的，而不是 PCR 鉴定的片段。应该对参考和培养标本进行前瞻性常规检测，并将其与症状、体征和患者伴随因素相关联，以确定 PCR 评估感染潜力的可靠性。Ct 值较高者不太可能具有感染潜力。
