SARS-CoV-2-induced immune activation and death of monocyte-derived human macrophages and dendritic cells

Zheng, Jian; Wang, Yuhang; Li, Kun; Meyerholz, David K; Allamargot, Chantal; Perlman, Stanley

Studies of SARS-CoV-2-infected patients and experimentally infected animals indicate a critical role for augmented expression of pro-inflammatory chemokines and cytokines in severe disease. Here, we demonstrate that SARS-CoV-2 infection of human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) was abortive, but induced the production of multiple antiviral and pro-inflammatory cytokines (IFN-α, IFN-β, TNF, IL-1β, IL-6 and IL-10) and a chemokine (CXCL10). Despite the lack of efficient replication in MDMs, SARS-CoV-2 induced profound IFN-mediated cell death of host cells. Macrophage activation and death was not enhanced by exposure to low levels of convalescent plasma, suggesting that antibody-dependent enhancement of infection does not contribute to cell death. Together, these results indicate that infection of macrophages and dendritic cells potentially plays a major role in COVID-19 pathogenesis, even in the absence of productive infection.