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HKUMed discovers that acute SARS-CoV-2 infection impairs human immune defences: significant implications for viral transmission, disease severity and vaccine research

06 August 2020

Researchers at the AIDS Institute, Department of Microbiology and State Key Laboratory of Emerging Infectious Diseases, LKS Faculty of Medicine of The University of Hong Kong (HKUMed), in collaboration with clinicians at Queen Mary Hospital, Pamela Youde Nethersole Eastern Hospital and Princess Margaret Hospital, conducted a study for determining the role of human immune responses in acute SARS-CoV-2 infection (within 3 weeks after infection) by investigating 17 acute and 24 convalescent COVID-19 patients as compared with healthy people in Hong Kong. The study demonstrated that acute SARS-CoV-2 infection impairs dendritic cell and T cell function, allowing the virus to evade host innate and adaptive defences for more efficient transmission and severe clinical diseases. The full research article is now published in one of world’s leading journals Immunity [link to the publication].

The COVID-19 pandemic has resulted in over 17 million of infections, yet why host immune responses are insufficient in controlling early transmission and pathogenesis of SARS-CoV-2 remains unclear. The study found that acute SARS-CoV-2 infection resulted quickly in broad immune cell reduction including T, Natural Killer (NK), monocyte and dendritic cell (DC). DCs were significantly reduced with functional impairment, and cDC:pDC (Conventional Dendritic Cells : Plasmacytoid Dendritic Cells) ratios were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed viral receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first three weeks post symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 helper T cells than CD8 killer T cells. The findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell immune responses, may contribute to acute COVID-19 pathogenesis and have significant implications for vaccine development.

“The findings suggested that jump-starting the immune response with early use of drugs with both immune boosting or antiviral activity such as interferon beta-1b could be important in reducing morbidity and mortality of COVID-19”, said co-corresponding author, Professor Yuen Kwok-yung, Henry Fok Professor in Infectious Diseases and Chair of Infectious Diseases, Department of Microbiology, HKUMed.

“The major challenge for COVID-19 vaccine development is that we do not know the immune correlates of protection. In other words, we do not know what kind of vaccine-induced immune responses are needed for protection. We, therefore, aimed to learn from patients naturally infected by SARS-CoV-2. We reported earlier that significantly higher amount of neutralizing antibodies, that were induced supposedly to kill the virus, was actually found in severe COVID-19 patients in intensive care unit than that in mild patients. In this study, we further demonstrated that functionally impaired dendritic cells might underly the delayed killer T cell responses that are essential for eliminating SARS-CoV-2-infected cells. Therefore, an effective vaccine should induce balanced antibody and killer T cells for protection,” said Professor Chen Zhiwei, Director of the AIDS Institute, Professor of Department of Microbiology, HKUMed, who led the research. 

Based on their findings, he and his colleagues have made two COVID-19 vaccines that have already entered the large scale of Good Manufacturing Practice (GMP) production for upcoming human trials.   

 

About the research team

The research was conducted primarily by Dr Zhou Runhong and Dr Wong Yik-chun, Post-doctoral Fellows, Dr Liu Li, Research Assistant Professor, Mr Zhou Biao, PhD candidate, at the AIDS Institute, HKUMed, and Dr Kelvin To Kai-wang, Clinical Associate Professor, Department of Microbiology, HKUMed, who share the first authorship. This team is led by Professor Chen Zhiwei, Director of the AIDS Institute, Professor of Department of Microbiology, HKUMed, and Professor Yuen Kwok-yung, Henry Fok Professor in Infectious Diseases and Chair of Infectious Diseases, Department of Microbiology, HKUMed, in collaboration with Professor Ivan Hung Fan-ngai, Ru Chien and Helen Lieh Professor in Health Sciences Pedagogy, Chief of Infectious Diseases Division and Clinical Professor at Department of Medicine and Assistant Dean (Admissions), HKUMed. 

The research was supported by the Theme-Based Research Scheme (T11-706/18-N) from Hong Kong Research Grants Council and Health and Medical Research Fund (COVID190123) from the Government of the Hong Kong Special Administrative Region.

 

About the AIDS Institute, HKUMed

Established in 2007, the AIDS Institute, LKS Faculty of Medicine of The University of Hong Kong (HKUAI) has a long and distinguished history in HIV/AIDS education and research. Currently, HKUAI is leading the undergraduate course of Infection and Immunity for the Bachelor of Biomedical Sciences programme and is chairing the Hong Kong Society for Immunology. HKUAI is also leading the Theme-Based Research Scheme on HIV-1 Vaccine and Cure granted by the Hong Kong Research Grants Council. HKUAI has made significant contributions through its research and advocacy to improve the health of populations and individuals in the fight against the AIDS pandemic, which led to the winning of 2019 Knowledge Exchange Awards of LKS Faculty of Medicine and The University of Hong Kong, respectively. 

To promote knowledge exchange, research activities at HKUAI can be viewed through https://www.med.hku.hk/aidsinst/.

 

Media enquiries

Please contact LKS Faculty of Medicine of The University of Hong Kong by email (medmedia@hku.hk).

The study found that acute SARS-CoV-2 infection resulted quickly in broad immune cell reduction including T, Natural Killer (NK), monocyte and dendritic cell (DC). The study provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell immune responses, may contribute to acute COVID-19 pathogenesis and have significant implications for vaccine development.

From left to right: Dr Liu Li, Research Assistant Professor at the AIDS Institute, HKUMed; Dr Kelvin To Kai-wang, Clinical Associate Professor, Department of Microbiology, HKUMed; Professor Chen Zhiwei, Director of the AIDS Institute, Professor of Department of Microbiology, HKUMed; Professor Yuen Kwok-yung, Henry Fok Professor in Infectious Diseases and Chair of Infectious Diseases, Department of Microbiology, HKUMed; and Dr Zhou Runhong, Post-doctoral Fellow and Mr Zhou Biao, PhD candidate at the AIDS Institute, HKUMed.