Division of Hospital Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Division of Infectious Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
J Infect Dis. 2021 Oct 28;224(8):1287-1293. doi: 10.1093/infdis/jiab215.
Previous studies demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected for weeks after infection. The significance of this finding is unclear and, in most patients, does not represent active infection. Detection of subgenomic RNA has been proposed to represent productive infection and may be a useful marker for monitoring infectivity.
We used quantitative reverse-transcription polymerase chain reaction (RT-qPCR) to quantify total and subgenomic nucleocapsid (sgN) and envelope (sgE) transcripts in 185 SARS-CoV-2-positive nasopharyngeal swab samples collected on hospital admission and to relate to symptom duration.
We find that all transcripts decline at the same rate; however, sgE becomes undetectable before other transcripts. The median duration of symptoms to a negative test is 14 days for sgE and 25 days for sgN. There is a linear decline in subgenomic compared to total RNA, suggesting that subgenomic transcript copy number is dependent on copy number of total transcripts. The mean difference between total and sgN is 16-fold and the mean difference between total and sgE is 137-fold. This relationship is constant over duration of symptoms, allowing prediction of subgenomic copy number from total copy number.
Subgenomic RNA may be no more useful in determining infectivity than a copy number threshold determined for total RNA.
先前的研究表明,严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的 RNA 可在感染后数周被检测到。这一发现的意义尚不清楚,而且在大多数患者中,这并不代表活跃的感染。亚基因组 RNA 的检测被提出代表有感染性,可能是监测传染性的有用标志物。
我们使用定量逆转录聚合酶链反应(RT-qPCR),对入院时采集的 185 份 SARS-CoV-2 阳性鼻咽拭子样本中的总亚基因组核衣壳(sgN)和包膜(sgE)转录本进行定量,并与症状持续时间相关。
我们发现所有转录本的下降速度相同;然而,sgE 在其他转录本之前变得不可检测。sgE 检测阴性的症状中位持续时间为 14 天,sgN 为 25 天。与总 RNA 相比,亚基因组的下降呈线性趋势,表明亚基因组转录本的拷贝数依赖于总转录本的拷贝数。总 RNA 与 sgN 之间的平均差异为 16 倍,总 RNA 与 sgE 之间的平均差异为 137 倍。这种关系在症状持续时间内是恒定的,允许从总拷贝数预测亚基因组拷贝数。
亚基因组 RNA 在确定传染性方面可能并不比总 RNA 的拷贝数阈值更有用。