The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi

Louisa L. Y. Chan (), Danielle E. Anderson, Hong Sheng Cheng, Fransiskus Xaverius Ivan, Si Chen, Adrian E. Z. Kang, Randy Foo, Akshamal M. Gamage, Pei Yee Tiew, Mariko Siyue Koh, Ken Cheah Hooi Lee, Kristy Nichol, Prabuddha S. Pathinayake, Yik Lung Chan, Tsin Wen Yeo, Brian G. Oliver, Peter A. B. Wark, Linbo Liu, Nguan Soon Tan, Lin-Fa Wang and Sanjay H. Chotirmall ()
Additional contact information
Louisa L. Y. Chan: Nanyang Technological University
Danielle E. Anderson: Duke-NUS Medical School
Hong Sheng Cheng: Nanyang Technological University
Fransiskus Xaverius Ivan: Nanyang Technological University
Si Chen: Nanyang Technological University
Adrian E. Z. Kang: Duke-NUS Medical School
Randy Foo: Duke-NUS Medical School
Akshamal M. Gamage: Duke-NUS Medical School
Pei Yee Tiew: Nanyang Technological University
Mariko Siyue Koh: Singapore General Hospital
Ken Cheah Hooi Lee: Singapore General Hospital
Kristy Nichol: University of Newcastle
Prabuddha S. Pathinayake: University of Newcastle
Yik Lung Chan: University of Technology Sydney
Tsin Wen Yeo: Nanyang Technological University
Brian G. Oliver: University of Technology Sydney
Peter A. B. Wark: University of Newcastle
Linbo Liu: Nanyang Technological University
Nguan Soon Tan: Nanyang Technological University
Lin-Fa Wang: Duke-NUS Medical School
Sanjay H. Chotirmall: Nanyang Technological University

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy individuals and COPD that recapitulate disease at the individual level. In contrast to healthy organoids, goblet cell hyperplasia and reduced ciliary beat frequency were observed in COPD organoids, hallmark features of the disease. Single-cell transcriptomics uncovered evidence for altered cellular differentiation trajectories in COPD organoids. SARS-CoV-2 infection of COPD organoids revealed more productive replication in bronchi, the key site of infection in severe COVID-19. Viral and bacterial exposure of organoids induced greater pro-inflammatory responses in COPD organoids. In summary, we present an organoid model that recapitulates the in vivo physiological lung microenvironment at the individual level and is amenable to the study of host-pathogen interaction and emerging infectious disease.

Date: 2022
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DOI: 10.1038/s41467-022-35253-x

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