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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.
- Source :
-
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2020 Sep 12; Vol. 71 (6), pp. 1400-1409. - Publication Year :
- 2020
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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.<br />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.<br />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.<br />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.<br /> (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Subjects :
- COVID-19
Chemokines immunology
Coronavirus Infections virology
Cytokines immunology
Humans
Interferons immunology
Lung immunology
Lung virology
Pandemics
Pneumonia, Viral virology
SARS-CoV-2
Betacoronavirus physiology
Coronavirus Infections immunology
Immunity, Innate immunology
Pneumonia, Viral immunology
Severe acute respiratory syndrome-related coronavirus physiology
Virus Replication immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6591
- Volume :
- 71
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
- Publication Type :
- Academic Journal
- Accession number :
- 32270184
- Full Text :
- https://doi.org/10.1093/cid/ciaa410