Dynamic blood single-cell immune responses in patients with COVID-19

Lulin Huang; Yi Shi; Bo Gong; Li Jiang; Zhixin Zhang; Xiaoqi Liu; Jialiang Yang; Yongquan He; Zhilin Jiang; Ling Zhong; Juan Tang; Chunfang You; Qi Jiang; Bo Long; Tao Zeng; Mei Luo; Fanwei Zeng; Fanxin Zeng; Shuqiang Wang; Xingxiang Yang; Zhenglin Yang

doi:10.1038/s41392-021-00526-2

Signal Transduction and Targeted Therapy (Mar 2021)

Dynamic blood single-cell immune responses in patients with COVID-19

Lulin Huang,
Yi Shi,
Bo Gong,
Li Jiang,
Zhixin Zhang,
Xiaoqi Liu,
Jialiang Yang,
Yongquan He,
Zhilin Jiang,
Ling Zhong,
Juan Tang,
Chunfang You,
Qi Jiang,
Bo Long,
Tao Zeng,
Mei Luo,
Fanwei Zeng,
Fanxin Zeng,
Shuqiang Wang,
Xingxiang Yang,
Zhenglin Yang

Affiliations

Lulin Huang: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Yi Shi: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Bo Gong: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Li Jiang: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Zhixin Zhang: Institute of Health Management, Health Management Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Xiaoqi Liu: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Jialiang Yang: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Yongquan He: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Zhilin Jiang: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Ling Zhong: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Juan Tang: Department of Infection Disease, Zigong First People’s Hospital
Chunfang You: Department of Infection Disease, Zigong First People’s Hospital
Qi Jiang: Department of Infection Disease, Mianyang No. 404 Hospital
Bo Long: Department of Infection Disease, Mianyang No. 404 Hospital
Tao Zeng: Infectious diseases laboratory, Public Health and Clinical Center of Chengdu
Mei Luo: Infectious diseases laboratory, Public Health and Clinical Center of Chengdu
Fanwei Zeng: Sichuan Dazhou Central Hosptical
Fanxin Zeng: Sichuan Dazhou Central Hosptical
Shuqiang Wang: Department of Infection Disease, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Xingxiang Yang: Department of Infection Disease, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Zhenglin Yang: The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China

DOI: https://doi.org/10.1038/s41392-021-00526-2
Journal volume & issue: Vol. 6, no. 1
pp. 1 – 12

Abstract

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Abstract The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus’ pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5’ gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.

Published in Signal Transduction and Targeted Therapy

ISSN: 2059-3635 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: http://www.nature.com/sigtrans/

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