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

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.

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