SARS-CoV-2 和 SARS-CoV 在人肺中的比较复制和免疫激活特征：一项具有 COVID-19 发病机制意义的离体研究。

Comparative Replication and Immune Activation Profiles of SARS-CoV-2 and SARS-CoV in Human Lungs: An Ex Vivo Study With Implications for the Pathogenesis of COVID-19.

机构信息

State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.

Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China.

出版信息

Clin Infect Dis. 2020 Sep 12;71(6):1400-1409. doi: 10.1093/cid/ciaa410.

DOI:10.1093/cid/ciaa410

PMID:32270184

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7184390/

Abstract

BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that has resulted in more than 2 000 000 laboratory-confirmed cases including over 145 000 deaths. Although SARS-CoV-2 and SARS-CoV share a number of common clinical manifestations, SARS-CoV-2 appears to be highly efficient in person-to-person transmission and frequently causes asymptomatic or presymptomatic infections. However, the underlying mechanisms that confer these viral characteristics of high transmissibility and asymptomatic infection remain incompletely understood.

METHODS

We comprehensively investigated the replication, cell tropism, and immune activation profile of SARS-CoV-2 infection in human lung tissues with SARS-CoV included as a comparison.

RESULTS

SARS-CoV-2 infected and replicated in human lung tissues more efficiently than SARS-CoV. Within the 48-hour interval, SARS-CoV-2 generated 3.20-fold more infectious virus particles than did SARS-CoV from the infected lung tissues (P < .024). SARS-CoV-2 and SARS-CoV were similar in cell tropism, with both targeting types I and II pneumocytes and alveolar macrophages. Importantly, despite the more efficient virus replication, SARS-CoV-2 did not significantly induce types I, II, or III interferons in the infected human lung tissues. In addition, while SARS-CoV infection upregulated the expression of 11 out of 13 (84.62%) representative proinflammatory cytokines/chemokines, SARS-CoV-2 infection only upregulated 5 of these 13 (38.46%) key inflammatory mediators despite replicating more efficiently.

CONCLUSIONS

Our study provides the first quantitative data on the comparative replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Our results provide important insights into the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2.

摘要

背景

严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是一种新兴的冠状病毒，已经导致超过 200 万例实验室确诊病例，包括超过 14.5 万例死亡。虽然 SARS-CoV-2 和 SARS-CoV 有许多共同的临床表现，但 SARS-CoV-2 在人与人之间的传播效率似乎非常高，并且经常导致无症状或症状前感染。然而，赋予这些病毒高传染性和无症状感染特征的潜在机制仍不完全清楚。

方法

我们全面研究了 SARS-CoV-2 感染在人类肺部组织中的复制、细胞嗜性和免疫激活特征，并将 SARS-CoV 作为比较。

结果

SARS-CoV-2 在人类肺部组织中的感染和复制效率高于 SARS-CoV。在 48 小时的时间间隔内，SARS-CoV-2 从感染的肺部组织中产生的传染性病毒颗粒比 SARS-CoV 多 3.20 倍（P <.024）。SARS-CoV-2 和 SARS-CoV 的细胞嗜性相似，均靶向 I 型和 II 型肺泡细胞和肺泡巨噬细胞。重要的是，尽管病毒复制效率更高，但 SARS-CoV-2 并没有在感染的人类肺部组织中显著诱导 I 型、II 型或 III 型干扰素。此外，虽然 SARS-CoV 感染上调了 13 个代表性促炎细胞因子/趋化因子中的 11 个（84.62%）的表达，但 SARS-CoV-2 感染仅上调了这 13 个中的 5 个（38.46%）关键炎症介质，尽管复制效率更高。