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

Hin Chu, Jasper Fuk-Woo Chan, Yixin Wang, Terrence Tsz-Tai Yuen, Yue Chai, Yuxin Hou, Huiping Shuai, Dong Yang, Bingjie Hu, Xiner Huang, Xi Zhang, Jian-Piao Cai, Jie Zhou, Shuofeng Yuan, Kin-Hang Kok, Kelvin Kai-Wang To, Ivy Hau-Yee Chan, Anna Jinxia Zhang, Ko-Yung Sit, Wing-Kuk Au, Kwok-Yung Yuen
Clinical Infectious Diseases 2020 September 12, 71 (6): 1400-1409

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.

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