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

doi:10.1038/s41421-020-00225-2

The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing

Cell Discov. 2020 Oct 20:6:73. doi: 10.1038/s41421-020-00225-2. eCollection 2020.

Authors

Gang Xu^#¹, Furong Qi^#¹, Hanjie Li^#², Qianting Yang¹, Haiyan Wang¹, Xin Wang¹, Xiaoju Liu³, Juanjuan Zhao¹, Xuejiao Liao¹, Yang Liu¹, Lei Liu¹, Shuye Zhang⁴, Zheng Zhang¹

Affiliations

¹ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518112 China.
² CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055 China.
³ Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515 China.
⁴ Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.

^# Contributed equally.

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.

Keywords: Bioinformatics; Immunology.