Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses

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

Summary 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, NK, monocyte and dendritic cell (DC). 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 in patients, there were delayed 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 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, may contribute to acute COVID-19 pathogenesis and have implications for vaccine development.