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

Runhong Zhou; Kelvin Kai-Wang To; Yik-Chun Wong; Li Liu; Biao Zhou; Xin Li; Haode Huang; Yufei Mo; Tsz-Yat Luk; Thomas Tsz-Kan Lau; Pauline Yeung; Wai-Ming Chan; Alan Ka-Lun Wu; Kwok-Cheung Lung; Owen Tak-Yin Tsang; Wai-Shing Leung; Ivan Fan-Ngai Hung; Kwok-Yung Yuen; Zhiwei Chen

doi:10.1016/j.immuni.2020.07.026

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

Immunity. 2020 Oct 13;53(4):864-877.e5. doi: 10.1016/j.immuni.2020.07.026. Epub 2020 Aug 4.

Authors

Runhong Zhou¹, Kelvin Kai-Wang To², Yik-Chun Wong¹, Li Liu¹, Biao Zhou¹, Xin Li³, Haode Huang³, Yufei Mo¹, Tsz-Yat Luk³, Thomas Tsz-Kan Lau³, Pauline Yeung⁴, Wai-Ming Chan⁵, Alan Ka-Lun Wu⁶, Kwok-Cheung Lung⁷, Owen Tak-Yin Tsang⁸, Wai-Shing Leung⁸, Ivan Fan-Ngai Hung⁹, Kwok-Yung Yuen¹⁰, Zhiwei Chen¹¹

Affiliations

¹ AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), People's Republic of China; Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
² Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
³ AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), People's Republic of China.
⁴ Department of Intensive Care, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
⁵ Department of Adult Intensive Care, Queen Mary Hospital, Hong Kong SAR, People's Republic of China.
⁶ Department of Microbiology, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, People's Republic of China.
⁷ Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, People's Republic of China.
⁸ Department of Medicine, Princess Margaret Hospital, Hong Kong SAR, People's Republic of China.
⁹ Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
¹⁰ Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China. Electronic address: kyyuen@hku.hk.
¹¹ AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), People's Republic of China; Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China. Electronic address: zchenai@hku.hk.

Abstract

The SARS-CoV-2 pandemic has resulted in millions of infections, yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, natural killer, monocyte, and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and ratios of conventional DCs to plasmacytoid DCs were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks after symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, could contribute to acute COVID-19 pathogenesis and have implications for vaccine development.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antibodies, Neutralizing / biosynthesis
Antibodies, Viral / biosynthesis
Betacoronavirus / immunology
Betacoronavirus / pathogenicity*
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / pathology
CD4-Positive T-Lymphocytes / virology
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / pathology
CD8-Positive T-Lymphocytes / virology
COVID-19
Convalescence
Coronavirus Infections / complications
Coronavirus Infections / diagnosis
Coronavirus Infections / immunology*
Coronavirus Infections / virology
Dendritic Cells / immunology*
Dendritic Cells / pathology
Dendritic Cells / virology
Diabetes Complications
Diabetes Mellitus / diagnosis
Diabetes Mellitus / immunology*
Diabetes Mellitus / virology
Disease Progression
Female
Humans
Hypertension / complications
Hypertension / diagnosis
Hypertension / immunology*
Hypertension / virology
Killer Cells, Natural / immunology
Killer Cells, Natural / pathology
Killer Cells, Natural / virology
Lymphocyte Activation
Lymphocyte Count
Male
Middle Aged
Monocytes / immunology
Monocytes / pathology
Monocytes / virology
Pandemics
Pneumonia, Viral / complications
Pneumonia, Viral / diagnosis
Pneumonia, Viral / immunology*
Pneumonia, Viral / virology
SARS-CoV-2
Severity of Illness Index

Substances

Antibodies, Neutralizing
Antibodies, Viral