On Aug. 6, 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 was published in one of worldﾒs leading journals Immunity.

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 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.