The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing
Gang Xu, Furong Qi, Hanjie Li, Qianting Yang, Haiyan Wang, Xin Wang, Xiaoju Liu, Juanjuan Zhao, Xuejiao Liao, Yang Liu, Lei Liu, Shuye Zhang, Zheng Zhang
Abstract
Abstract Understanding the mechanism that leads to immune dysfunction in severe coronavirus disease 2019 (COVID-19) is crucial for the development of effective treatment. Here, using single-cell RNA sequencing, we characterized the peripheral blood mononuclear cells (PBMCs) from uninfected controls and COVID-19 patients and cells in paired broncho-alveolar lavage fluid (BALF). We found a close association of decreased dendritic cells (DCs) and increased monocytes resembling myeloid-derived suppressor cells (MDSCs), which correlated with lymphopenia and inflammation in the blood of severe COVID-19 patients. Those MDSC-like monocytes were immune-paralyzed. In contrast, monocyte-macrophages in BALFs of COVID-19 patients produced massive amounts of cytokines and chemokines, but secreted little interferons. The frequencies of peripheral T cells and NK cells were significantly decreased in severe COVID-19 patients, especially for innate-like T and various CD8 + T cell subsets, compared to healthy controls. In contrast, the proportions of various activated CD4 + T cell subsets among the T cell compartment, including Th1, Th2, and Th17-like cells were increased and more clonally expanded in severe COVID-19 patients. Patients’ peripheral T cells showed no sign of exhaustion or augmented cell death, whereas T cells in BALFs produced higher levels of IFNG , TNF , CCL4 , CCL5 , etc. Paired TCR tracking indicated abundant recruitment of peripheral T cells to the severe patients’ lung. Together, this study comprehensively depicts how the immune cell landscape is perturbed in severe COVID-19.