今日《自然》新冠论文：9位患者的 SARS-CoV-2 病毒排出

2020 年 4 月 2 日 学术头条

《自然》杂志今天在线发表的一篇新冠病毒最新研究论文。来自德国的科研团队通过对来自慕尼黑的新冠肺炎患者进行详细病毒学分析，研究了 9 名新冠肺炎确诊中青年患者的病毒排出情况。

这些患者呼吸道疾病症状相对较轻，在慕尼黑的同一家医院接受上呼吸道轻微症状的治疗。研究人员分析了患者的咽拭子和肺组织标本、痰液（呼吸道分泌的粘液），以及在他们临床病程中采集的粪便、血液和尿液，发现新冠病毒在患者上呼吸道的复制较为活跃，说明病毒可能在症状出现后的第一周内“排毒”水平较高。

随着症状逐渐减轻，研究人员在症状出现后的第 8 天依然能从患者的咽拭子和肺组织标本中分离出具有传染性的毒株。其中两位有肺炎早期迹象的患者，其痰液在第 10 天或第 11 天时仍持续有高水平的病毒排出。症状消失后，痰液中仍旧可以检测到病毒 RNA。

研究人员指出，在所分析的患者中新冠病毒与 SARS 病毒展现出了截然不同的病毒学特征。 对 SARS 病毒而言，一般在出现症状的 7-10 天后，RNA 水平才会达到峰值。而新冠病毒看似“出道即巅峰”，在出现症状的 5 天内，RNA 水平就达到了峰值。而且相较 SARS 病毒，该峰值可以高出 1000 倍！

此外，研究人员在血样或尿样中未检测到病毒，在粪便样本中也未发现病毒复制，但能检测到高浓度的病毒 RNA。 这一结果支持病毒或不会通过粪便传播的理论。

不过，仍需开展样本量更大的研究，对这一可能传播途径做进一步调查。 综合来看，这些初步结果表明，在患者症状还较轻的早期，SARS-CoV-2 在上呼吸道的病毒排出能力也最强。 作者认为，后续研究或有助于评估患者出现症状一周后的病毒载量增加是否能预示症状的加重。

论文摘要：
Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 2019. Initial outbreaks in China involved 13.8% cases with severe, and 6.1% with critical courses. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung. By causing an early onset of severe symptoms, this same receptor tropism is thought to have determined pathogenicity, but also aided the control, of severe acute respiratory syndrome (SARS) in 2003. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting the potential for pre- or oligosymptomatic transmission. There is an urgent need for information on body site-specific virus replication, immunity, and infectivity. Here we provide a detailed virological analysis of nine cases, providing proof of active virus replication in upper respiratory tract tissues. Pharyngeal virus shedding was very high during the first week of symptoms. Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples, in spite of high virus RNA concentration. Blood and urine never yielded virus. Active replication in the throat was confirmed by viral replicative RNA intermediates in throat samples. Sequence-distinct virus populations were consistently detected in throat and lung samples from the same patient, proving independent replication. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (14 days in all), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild upper respiratory tract illness. Active virus replication in the upper respiratory tract puts the prospects of COVID-19 containment in perspective.

论文全文：
https://www.nature.com/articles/s41586-020-2196-x

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