Virological assessment of hospitalized patients with COVID-2019
Virological assessment of hospitalized patients with COVID-2019
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DOI：
10.1038/s41586-020-2196-x
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发表时间：
2020-04-01
期刊：
影响因子：
64.8
通讯作者：
Wendtner, Clemens
中科院分区：
文献类型：
--
作者：
Woelfel, Roman;Corman, Victor M.;Wendtner, Clemens
对 9 例 2019 冠状病毒病 (COVID-19) 病例的详细病毒学分析提供了 SARS-CoV-2 病毒在上呼吸道组织中活跃复制的证据。2019 冠状病毒病 (COVID-19) 是 2019 年底出现的一种急性呼吸道感染(1,2)。中国的首次暴发涉及13.8%的重症病例和6.1%的重症病例(3)。这种严重的表现可能是由于病毒使用主要在肺部表达的病毒受体所致(2,4)；据认为，相同的受体趋向性决定了 2003 年严重急性呼吸系统综合症 (SARS) 的致病性，同时也有助于控制该疾病(5)。然而，有报告称，患者表现出轻微上呼吸道症状的 COVID-19 病例，这表明存在症状前传播或寡症状传播的可能性(6-8)。迫切需要有关病毒在身体特定部位的复制、免疫和传染性的信息。在此，我们报告了对 9 例 COVID-19 病例的详细病毒学分析，提供了病毒在上呼吸道组织中活跃复制的证据。在出现症状的第一周，咽部病毒的排出量非常高，第 4 天每个咽拭子的 RNA 拷贝数达到峰值。感染性病毒很容易从喉咙或肺部的样本中分离出来，但不能从粪便样本中分离出来——尽管病毒 RNA 浓度很高。血液和尿液样本从未检测出病毒。喉咙样本中病毒复制 RNA 中间体的存在证实了喉咙中的活跃复制。我们在一名患者的喉咙和肺部样本中一致检测到序列不同的病毒群体，证明了病毒的独立复制。痰中病毒 RNA 的脱落持续到症状结束后。 50% 的患者在 7 天后发生血清转化（所有患者在第 14 天发生），但随后病毒载量并未迅速下降。 COVID-19 可能表现为一种轻微的上呼吸道疾病。确认上呼吸道病毒活跃复制对于遏制 COVID-19 具有重要意义。
Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019(1,2). Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses(3). This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung(2,4); the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 2003(5). However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission(6-8). There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 x 10(8) RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.