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

By Hin Chu, J. Chan, Yixin Wang, T. Yuen, Yue Chai, Yuxin Hou, H. Shuai, Dong Yang, Binjie Hu, Xiner Huang and 11 more. Clinical Infectious Diseases, 2020

634 citations recorded by the source corpus.

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.

Subfields: Infectious Diseases, Neurology

View Paper: https://www.semanticscholar.org/paper/d07e78fcc691e65adb79a2b988caf9a14eb556ee

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Citations in the corpus

Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19 (2020, neutral): “An imbalance between type I IFN and inflammatory responses could also be favored by the highly efficient replication of SARS-CoV-2 in human tissues (Chu et al., 2020) and by the IFN-neutralizing effects of structural and non-structural viral components shared between SARS-CoV-2 and other virulent hu”
The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system (2020, neutral): “while the opposite was observed for CXCL10 [97].”
Mechanisms of SARS-CoV-2 Transmission and Pathogenesis (2020, positive): “In light of these findings, SARS-CoV-2 has replicated more efficiently than SARS-CoV in ex vivo human lung explants, possibly through the greater suppression of IFN-I/III cytokines [111]; further work will be needed to discern whether the suppressive nature of SARS-CoV-2 can impact virus transmissio”
Immune Response, Inflammation, and the Clinical Spectrum of COVID-19 (2020, result): “(57) compared the in vitro infection of human lung explants with SARS-CoV and SARS-CoV-2 and demonstrated that both viruses can equally infect type-I and -II pneumocytes, plus alveolar macrophages, although SARS-CoV2 had a better capacity to replicate in pulmonary tissues.”
The Role of Imaging in the Detection and Management of COVID-19: A Review (2020, background): “Chu et al. [46] found that the SARS-CoV-2 infection caused inﬂammatory and signiﬁcantly upregulated ﬁve inﬂammatory mediators.”