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近日,德国科学家团队以慕尼黑的9名患者为病例,对新冠病毒的病毒学特征进行详细研究,相关陈果发表于著名期刊Nature杂志。本文揭示了新冠病毒与以往SARS病毒的不同,并涉及了“无症状者具有感染性”的观点,强调应以“所有人都是潜在感染者”为标准,做好疫情的防控工作。在科学层面提及无症状感染,以往报道的案例并不多见。
本文中患者的口咽拭子或鼻咽拭子样本最早可以追溯到出现症状的第一天。此时,他们的症状往往还非常轻微。需要注意的是,在出现症状的头5天,患者的拭子样本均呈现阳性,且新冠病毒的RNA水平处于高位。此外在患者的痰液中,研究人员们同样检测出了新冠病毒的RNA。
为了明确患者在刚出现症状的时候是否具有潜在的传染性,科学家们进一步从患者的样本里尝试分离和培养病毒。后续结果表明,在出现症状的头一周里,患者的拭子样本和痰液样本中均能分离出病毒。而从第8天起,尽管患者的样本里还能检出较高的病毒载量,但未能成功分离出病毒。通过特异性检测病毒的sgRNA结果表明,在出现症状的头5天里,新冠病毒可在咽部活跃复制。
在另一些研究里,科学家们也发现了新冠病毒的一些奇怪特点。他们指出,在这9名患者里,有6人的粪便和痰液样本,在3周之后依旧可以检测出新冠病毒的RNA。此时,他们的症状早已完全消失了。由此作者指出在让患者出院时,我们需要遵循严格的标准(如出现症状后已经过了10天,或病毒拷贝数每毫升不超过10万个),这样才能最大程度地降低风险。
▲症状消失后,患者的痰液样本(橙色)和粪便样本(灰色)里,依旧可以检测出病毒RNA
研究发现,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,能从咽部样本中分离出新冠病毒,相比之下,SARS病毒的分离工作罕有成功。
总之,这些结果表明新冠病毒能在上呼吸道组织中进行活跃的复制,且在症状不明显之际就能达到很高的水平。等到患者出现症状之际,病毒在上呼吸道的峰值甚至可能已经过去了。为此,为了控制新冠疫情,我们需要比防治SARS病毒更为严格有效的手段。
附文献信息:PDF全文可通过点击文末的阅读原文获得
Title:Virological assessment of hospitalized patients with COVID-2019
DOI:10.1038/s41586-020-2196-x
Abstract
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 (peak at 7.11 × 108 RNA copies per throat swab, day 4). 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.
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本期编辑:hantavirus |
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