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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
Chu Hin.
Chan Jasper Fuk-Woo.
Wang Yixin.
Yuen Terrence Tsz-Tai.
Chai Yue.
Hou Yuxin.
Shuai Huiping.
Yang Dong.
Hu Binjie.
Huang Xiner.
Zhang Xi.
Cai Jian-Piao.
Zhou Jie.
Yuan Shuofeng.
Kok Kin-Hang.
To Kelvin Kai-Wang.
Chan Ivy Hau-Yee.
Zhang Anna Jinxia.
Sit Ko-Yung.
Au Wing-Kuk.
Yuen Kwok-Yung.
Acceso Abierto
Atribución-NoComercial-SinDerivadas
10.1093/cid/ciaa410
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that has resulted in nearly 1,000,000 laboratory-confirmed cases including over 50,000 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 cause asymptomatic infections. However, the underlying mechanism that confers these viral characteristics on 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 that of SARS-CoV. Within the 48-hour interval, SARS-CoV-2 generated 3.20 folds more infectious virus particles than that of SARS-CoV from the infected lung tissues (P<0.024). 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 pro-inflammatory cytokines/chemokines, SARS-CoV-2 infection only upregulated 5 of these 13 (38.46%) key inflammatory mediators despite replicating more efficiently. Conclusions Our study provided 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 provided important insights on the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2.
Clinical Infectious Diseases
2020
Artículo
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184390/pdf/main.pdf
Inglés
VIRUS RESPIRATORIOS
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