[Clinical Infectious Disease] 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

Clinical Infectious Disease, 9 Apr 2020

Hin Chu, Jasper Fuk-Woo Chan, Yixin Wang, Terrence Tsz-Tai Yuen, Yue Chai, Yuxin Hou, Huiping Shuai, Dong Yang, Binjie 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


  • HKU established the world’s first ex vivo human lung tissue culture model for studying the pathogenesis and testing treatments for COVID-19. The team found that SARS-CoV-2 infected and replicated in human lung tissues more efficiently than that of SARS-CoV. Despite the more efficient virus replication, SARS-CoV-2 activated less interferon and pro-inflammatory response in the infected human lung tissues than that of SARS-CoV.
  • The underlying mechanism that confers these viral characteristics on high transmissibility and asymptomatic infection remain incompletely understood.
  • 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
  • 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.
  • 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.
  • The low degree of innate immune activation could also account for the mild or even lack of symptoms in many COVID-19 patients who were not even tested and unknowingly spreading the virus in both community and hospital settings, making the pandemic control much more difficult than SARS.
  • In addition to hand washing and social distancing, universal masking was recommended in East
    Asia as a key epidemiological control measure to prevent virus shedding from subclinical
    patient sources and to prevent infection of susceptible individuals in the community.
  • The results provided important insights on the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2.

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