The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing

Minfeng Liao; Yang Liu; Jin Yuan; Yanling Wen; Gang Xu; Juanjuan Zhao; Lin Chen; Jinxiu Li; Xin Wang; Fuxiang Wang; Lei Liu; Shuye Zhang; Zheng Zhang

Expanded anti-viral T cell clones may exert protective or pathogenic functions during viral infections dependent on different situations. Here, we took advantages of single-cell TCR-seq to assess the status of clonal expansions in the BALF of patients. As expected, CCR7 + T cells as naive or central memory cells, showed little clonal expansion, while CD8 + effector T cells showed the highest expansion levels among different T cell subsets ( Figure 4A and S5). Proliferating T cells and Treg cells also showed some expansion, but were less pervasive. Next, we examined the proportions of expanded clones between COVID-19 patients with mild and severe diseases. We found that the expansion levels in both total T and CD8 + T cells were significantly higher in mild disease group than the severe patients ( Figure 4B and 4C, S5). In average, more than 50% CD8 + T cells in mild group were expanded clones, which likely represented the SARS-CoV-2-specific T cells. They also showed higher amplification index than those from severe patients ( Figure 4C ). At the individual levels, we also found the higher T cell clonality was consistently remained in the 3 mild patients as compared to the 3 severe patients ( Figure 4D ), supporting that highly expanded CD8 + T cell participated in resolving the SARS-CoV-2 infection. To confirm the functional status of expanded T cell clones, we performed GEX analysis between expanded CD8 + T cells versus non-expanded cells. We found increased expression of signaling and tissue resident genes including XCL1, XCL2, ZNF683, HOPX, CXCR6 and ITGAE, etc., which further supports a superior All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.