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Tropism of the Novel Coronavirus SARS-CoV-2 in Human Respiratory Tract: An Analysis in Ex Vivo and In Vitro Cultures

25 Pages Posted: 25 Mar 2020

See all articles by Kenrie PY Hui

Kenrie PY Hui

The University of Hong Kong - School of Public Health

Man-Chun Cheung

The University of Hong Kong - School of Public Health

Ranawaka APM Perera

The University of Hong Kong - School of Public Health

Ka-Chun Ng

The University of Hong Kong - School of Public Health

Christine BT Bui

The University of Hong Kong - School of Public Health

John CW Ho

The University of Hong Kong - School of Public Health

Mandy MT Ng

The University of Hong Kong - School of Public Health

Denise IT Kuok

The University of Hong Kong - School of Public Health

Kendrick C. Shih

The University of Hong Kong - Department of Ophthalmology

SW Tsao

The University of Hong Kong - School of Biomedical Sciences

Leo LM Poon

The University of Hong Kong - School of Public Health

Malik Peiris

The University of Hong Kong - School of Public Health

John M. Nicholls

The University of Hong Kong - Department of Pathology

Michael CW Chan

The University of Hong Kong - School of Public Health

More...

Abstract

Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, to cause a respiratory disease (COVID-19) of varying severity in Wuhan China, subsequently spreading to other parts of China and beyond.

Methods: We infected ex vivo explant cultures of the human conjunctiva, bronchus and lung, and in vitro cultures of primary human alveolar epithelial cells and macrophages with SARS-CoV-2, and assessed viral tropism, replication competence and innate immune responses, in comparison with SARS-CoV, MERS-CoV, and the 2009 pandemic influenza H1N1 (pdmH1N1) virus.

Findings: SARS-CoV-2 infected ciliated, mucus secreting and club cells of bronchial epithelium, spindled morphologically type I pneumocytes in the lung, and the conjunctival mucosa. Virus replication competence of SARS-CoV-2 in the bronchus was higher than that of SARS-CoV but lower than pdmH1N1. SARS-CoV-2 replication was comparable with SARS-CoV and pdmH1N1 in the lung but was lower than MERS-CoV. SARS-CoV-2 virus was a less potent inducer of pro-inflammatory cytokines compared with H5N1 and MERS-CoV. Influenza virus infection of alveolar epithelial cells increased ACE2 expression.

Interpretation: The conjunctival epithelium and the conducting airways appear to be potential portals of infection of SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated comparably in the alveolar epithelium explaining the progression of infection to a primary viral pneumonia.

Funding Statement: US National Institute of Allergy and Infectious Diseases (NIAID) under Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract no. HHSN272201400006C and the Theme Based Research Scheme (Ref: T11-705/14N), Hong Kong Special Administrative Region.

Declaration of Interests: There is no conflict of interest for all authors.

Ethics Approval Statement: All experiments were carried out in a Bio-safety level 3 (BSL-3) facility. Informed consent was obtained from all subjects and approval was granted by the Institutional Review Board (IRB) of the University of Hong Kong and the Hospital Authority (Hong Kong West) (approval no: UW 20-167).

Keywords: SARS-CoV-2; COVID-19; tropism; ex vivo; explants; respiratory tract; conjunctiva; pathogenesis; risk assessment; transmissibility

Suggested Citation

Hui, Kenrie PY and Cheung, Man-Chun and Perera, Ranawaka APM and Ng, Ka-Chun and Bui, Christine BT and Ho, John CW and Ng, Mandy MT and Kuok, Denise IT and Shih, Kendrick C. and Tsao, SW and Poon, Leo LM and Peiris, Malik and Nicholls, John M. and Chan, Michael CW, Tropism of the Novel Coronavirus SARS-CoV-2 in Human Respiratory Tract: An Analysis in Ex Vivo and In Vitro Cultures (3/10/2020). Available at SSRN: https://ssrn.com/abstract=3552870 or http://dx.doi.org/10.2139/ssrn.3552870

Kenrie PY Hui

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

Man-Chun Cheung

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

Ranawaka APM Perera

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

Ka-Chun Ng

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

Christine BT Bui

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

John CW Ho

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

Mandy MT Ng

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

Denise IT Kuok

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

Kendrick C. Shih

The University of Hong Kong - Department of Ophthalmology

Hong Kong, Pokfulam
China

SW Tsao

The University of Hong Kong - School of Biomedical Sciences

Pokfulam Road
Hong Kong, +852-2559-0468 HK
China

Leo LM Poon

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

Malik Peiris

The University of Hong Kong - School of Public Health

Hong Kong, Pokfulam
China

John M. Nicholls

The University of Hong Kong - Department of Pathology

Hong Kong
China

Michael CW Chan (Contact Author)

The University of Hong Kong - School of Public Health ( email )

Hong Kong, Pokfulam
China
(852) 3917-9800 (Phone)
(852) 2855-9587 (Fax)

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