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Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses

32 Pages Posted: 1 Jun 2020 Sneak Peek Status: Under Review

See all articles by Runhong Zhou

Runhong Zhou

The University of Hong Kong - AIDS Institute

Kelvin Kai-Wang To

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Yik-Chun Wong

The University of Hong Kong - AIDS Institute

Li Liu

The University of Hong Kong - AIDS Institute

Biao Zhou

The University of Hong Kong - AIDS Institute

Xin Li

The University of Hong Kong - AIDS Institute

Haode Huang

The University of Hong Kong - AIDS Institute

Yufei Mo

The University of Hong Kong - AIDS Institute

Tsz-Yat Luk

The University of Hong Kong - AIDS Institute

Thomas Tsz-Kan Lau

The University of Hong Kong - AIDS Institute

Pauline Yeung

The University of Hong Kong - Department of Intensive Care

Wai-Ming Chan

Queen Mary Hospital - Department of Adult Intensive Care

Alan Ka-Lun Wu

Pamela Youde Nethersole Eastern Hospital - Department of Clinical Pathology; Government of the Hong Kong Special Administrative Region

Kwok-Cheung Lung

Pamela Youde Nethersole Eastern Hospital - Department of Medicine

Owen Tak-Yin Tsang

Princess Margaret Hospital - Department of Medicine

Wai-Shing Leung

Princess Margaret Hospital - Department of Medicine; Hong Kong Special Administrative Region (HKSAR)

Ivan Fan-Ngai Hung

The University of Hong Kong - Department of Medicine

Kwok-Yung Yuen

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Zhiwei Chen

The University of Hong Kong - AIDS Institute

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Abstract

SARS-CoV-2 pandemic has resulted in over 4 million infections yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By evaluating 15 acute and 24 convalescent patients’ immune profile, we report herein acute SARS-CoV-2 infection resulted in broad immune cell reduction including T cells, NK cell, monocytes and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and cDC/pDC ratios were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated, there were insufficient receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks post symptoms onset. Moreover, acute RBD- and NP-specific T cell responses were mainly CD4 but not CD8 T cells with effector memory dominance. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses might contribute to acute COVID-19 pathogenesis and have implications to vaccine development.

Funding: This work was partly supported by Theme-Based Research Scheme (T11-706/18-N to ZC) of the Hong Kong Research Grants Council, University Development Fund and Li Ka Shing Faculty of Medicine Matching Fund from HKU to AIDS Institute. Funding supports to KY include the donations of the Shaw Foundation Hong Kong, Richard Yu and Carol Yu, May Tam Mak Mei Yin, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, the Jessie & George Ho Charitable Foundation, Perfect Shape Medical Limited, and Kai Chong Tong; and funding from the Health and Medical Research Fund (grant no. COVID190121 and CPVOD1901123), the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region; the National Program on Key Research Project of China (grant no. 2020YFA0707500 and 2020YFA0707504); the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Hong Kong Special Administrative Region Government; the Theme-Based Research Scheme (T11/707/15) of the Research Grants Council, Hong Kong Special Administrative Region; Sanming Project of Medicine in Shenzhen, China (No. SZSM201911014); and the High Level-Hospital Program, Health Commission of Guangdong Province, China.

Conflict of Interest: The authors declare no competing interests.

Ethical Approval: This study was approved by the Institutional Review Board of University of Hong Kong/Hospital Authority Hong Kong West Cluster, Hong Kong East Cluster Research Ethics Committee, and Kowloon West Cluster Research Ethics Committee (UW 13-265, HKECREC-2018-068, KW/EX-20-038[144-26]).

Keywords: SARS-CoV-2, COVID-19, acute infection, convalescent, dendritic cell, receptor-binding domain, nucleocapsid protein, neutralizing antibody, T cell immune response

Suggested Citation

Zhou, Runhong and To, Kelvin Kai-Wang and Wong, Yik-Chun and Liu, Li and Zhou, Biao and Li, Xin and Huang, Haode and Mo, Yufei and Luk, Tsz-Yat and Lau, Thomas Tsz-Kan and Yeung, Pauline and Chan, Wai-Ming and Wu, Alan Ka-Lun and Lung, Kwok-Cheung and Tsang, Owen Tak-Yin and Leung, Wai-Shing and Hung, Ivan Fan-Ngai and Yuen, Kwok-Yung and Chen, Zhiwei, Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses. Available at SSRN: https://ssrn.com/abstract=3614132 or http://dx.doi.org/10.2139/ssrn.3614132
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Runhong Zhou

The University of Hong Kong - AIDS Institute ( email )

China

Kelvin Kai-Wang To

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Pokfulam Road
Hong Kong, Pokfulam HK
China

Yik-Chun Wong

The University of Hong Kong - AIDS Institute ( email )

China

Li Liu

The University of Hong Kong - AIDS Institute

China

Biao Zhou

The University of Hong Kong - AIDS Institute

China

Xin Li

The University of Hong Kong - AIDS Institute

China

Haode Huang

The University of Hong Kong - AIDS Institute ( email )

China

Yufei Mo

The University of Hong Kong - AIDS Institute ( email )

China

Tsz-Yat Luk

The University of Hong Kong - AIDS Institute ( email )

China

Thomas Tsz-Kan Lau

The University of Hong Kong - AIDS Institute ( email )

China

Pauline Yeung

The University of Hong Kong - Department of Intensive Care ( email )

Pokfulam Road
Hong Kong, Pokfulam HK
China

Wai-Ming Chan

Queen Mary Hospital - Department of Adult Intensive Care ( email )

Hong Kong
China

Alan Ka-Lun Wu

Pamela Youde Nethersole Eastern Hospital - Department of Clinical Pathology

Hong Kong

Government of the Hong Kong Special Administrative Region

Hong Kong

Kwok-Cheung Lung

Pamela Youde Nethersole Eastern Hospital - Department of Medicine ( email )

Hong Kong

Owen Tak-Yin Tsang

Princess Margaret Hospital - Department of Medicine ( email )

China

Wai-Shing Leung

Princess Margaret Hospital - Department of Medicine

China

Hong Kong Special Administrative Region (HKSAR)

Hong Kong

Ivan Fan-Ngai Hung

The University of Hong Kong - Department of Medicine ( email )

Pokfulam Road
Hong Kong, Pokfulam HK
China

Kwok-Yung Yuen

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Pokfulam Road
Hong Kong, Pokfulam HK
China

Zhiwei Chen (Contact Author)

The University of Hong Kong - AIDS Institute ( email )

China

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