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.

SARS-CoV-2大流行已导致数百万次感染，但宿主免疫反应在早期COVID-19发病机理中的作用仍不清楚。通过调查17名急性和24名康复中的患者，我们发现急性SARS-CoV-2感染导致广泛的免疫细胞减少，包括T，自然杀伤细胞，单核细胞和树突状细胞（DC）。DCs随功能障碍而显着降低，并且在急性重症患者中常规DC与浆细胞样DC的比率增加。除了淋巴细胞减少症，尽管在患者中迅速大量产生了中和抗体，但在症状发作后的前三周内，受体结合域（RBD）和核衣壳蛋白（NP）特异性T细胞反应有所延迟。此外，急性RBD和NP特异性T细胞应答比CD8 T细胞包括相对更多的CD4 T细胞。我们的发现提供了证据，即受损的DC以及及时倒置的强抗体但CD8 T细胞应答较弱，可能会导致急性COVID-19发病，并可能影响疫苗的开发。