Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study
Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study
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DOI：
10.1016/s2666-5247(20)30004-5
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发表时间：
2020-05-01
期刊：
影响因子：
38.2
通讯作者：
Yuen, Kwok-Yung
中科院分区：
文献类型：
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作者：
Chu, Hin;Chan, Jasper Fuk-Woo;Yuen, Kwok-Yung
2020年1月，中国报告了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。SARS-CoV-2在人与人之间有效传播，在两个月内，已在46个国家造成超过82，000例实验室确诊的2019冠状病毒病（COVID-19）病例和2，800例死亡。病例和死亡总数已超过2003年严重急性呼吸道综合征冠状病毒（SARS-CoV）。尽管COVID-19和严重急性呼吸系统综合征（SARS）都表现为肺炎，但COVID-19显然与更有效的传播、更少的腹泻病例、更高的精神混乱和更低的粗死亡率有关。然而，潜在的病毒-宿主相互作用的特点，赋予这些观察的传播性和临床表现的COVID-19仍然是未知的。方法我们系统地研究了细胞的易感性，种嗜性，复制动力学，细胞损伤的SARS-CoV-2，并比较结果与SARS-CoV。我们用单因素方差分析比较了SARS-CoV-2和SARS-CoV在不同细胞系中的复制。对于在Calu 3（肺）和Caco 2（肠）细胞中SARS-CoV-2和SARS-CoV复制之间的曲线下面积比较，我们使用学生t检验。我们分析了SARS-CoV-2和SARS-CoV诱导的细胞损伤与one-way AN0VA.Findings SARS-CoV-2感染和复制到相当的水平在人类Caco 2细胞和Calu 3细胞在一段时间内的120小时（p=0.52）。相比之下，SARS-CoV感染和复制更有效地在Caco 2细胞比Calu 3细胞在相同的感染复数（p=0.0098）。SARS-CoV-2，而不是SARS-CoV，在U251（神经元）细胞中适度复制（p=0.036）。对于动物物种细胞嗜性，SARS-CoV和SARS-CoV-2都在非人灵长类动物、猫、兔和猪细胞中复制。SARS-CoV，而非SARS-CoV-2在中华菊头蝠肾细胞中感染并复制。SARS-CoV-2在非人灵长类动物细胞中持续诱导比SARS-CoV显著延迟且较轻水平的细胞损伤（VeroE 6，p=0.016; FRhK 4，p=0.0004）。这些数据提供了关于SARS-CoV-2与SARS-CoV相比的发病机制和高传播性的新见解，即COVID-19患者的腹泻发生率较低，疾病严重程度降低，死亡率降低。版权所有（C）2020作者。爱思唯尔有限公司出版
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted from person to person and, in 2 months, has caused more than 82 000 laboratory-confirmed cases of coronavirus disease 2019 (COVID-19) and 2800 deaths in 46 countries. The total number of cases and deaths has surpassed that of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV). Although both COVID-19 and severe acute respiratory syndrome (SARS) manifest as pneumonia, COVID-19 is associated with apparently more efficient transmission, fewer cases of diarrhoea, increased mental confusion, and a lower crude fatality rate. However, the underlying virus-host interactive characteristics conferring these observations on transmissibility and clinical manifestations of COVID-19 remain unknown.Methods We systematically investigated the cellular susceptibility, species tropism, replication kinetics, and cell damage of SARS-CoV-2 and compared findings with those for SARS-CoV. We compared SARS-CoV-2 and SARS-CoV replication in different cell lines with one-way ANOVA. For the area under the curve comparison between SARS-CoV-2 and SARS-CoV replication in Calu3 (pulmonary) and Caco2 (intestinal) cells, we used Student's t test. We analysed cell damage induced by SARS-CoV-2 and SARS-CoV with one-way ANOVA.Findings SARS-CoV-2 infected and replicated to comparable levels in human Caco2 cells and Calu3 cells over a period of 120 h (p=0.52). By contrast, SARS-CoV infected and replicated more efficiently in Caco2 cells than in Calu3 cells under the same multiplicity of infection (p=0.0098). SARS-CoV-2, but not SARS-CoV, replicated modestly in U251 (neuronal) cells (p=0.036). For animal species cell tropism, both SARS-CoV and SARS-CoV-2 replicated in non-human primate, cat, rabbit, and pig cells. SARS-CoV, but not SARS-CoV-2, infected and replicated in Rhinolophus sinicus bat kidney cells. SARS-CoV-2 consistently induced significantly delayed and milder levels of cell damage than did SARS-CoV in non-human primate cells (VeroE6, p=0.016; FRhK4, p=0.0004).Interpretation As far as we know, our study presents the first quantitative data for tropism, replication kinetics, and cell damage of SARS-CoV-2. These data provide novel insights into the lower incidence of diarrhoea, decreased disease severity, and reduced mortality in patients with COVID-19, with respect to the pathogenesis and high transmissibility of SARS-CoV-2 compared with SARS-CoV. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.