Profiling of the immune repertoire in COVID-19 patients with mild, severe, convalescent, or retesting-positive status

Yonggang Zhou; Jinhe Zhang; Dongyao Wang; Dong Wang; Wuxiang Guan; Jingkun Qin; Xiuxiu Xu; Jingwen Fang; Binqing Fu; Xiaohu Zheng; Dongsheng Wang; Hong Zhao; Xianxiang Chen; Zhigang Tian; Xiaoling Xu; Guiqiang Wang; Haiming Wei

doi:10.1016/j.jaut.2021.102596

Profiling of the immune repertoire in COVID-19 patients with mild, severe, convalescent, or retesting-positive status

J Autoimmun. 2021 Mar:118:102596. doi: 10.1016/j.jaut.2021.102596. Epub 2021 Jan 14.

Authors

Yonggang Zhou¹, Jinhe Zhang², Dongyao Wang¹, Dong Wang², Wuxiang Guan³, Jingkun Qin², Xiuxiu Xu¹, Jingwen Fang⁴, Binqing Fu¹, Xiaohu Zheng², Dongsheng Wang⁵, Hong Zhao⁶, Xianxiang Chen⁷, Zhigang Tian², Xiaoling Xu⁵, Guiqiang Wang⁸, Haiming Wei⁹

Affiliations

¹ Respiratory and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China; Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; Institute of Immunology, University of Science and Technology of China, Hefei, 230027, China.
² Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; Institute of Immunology, University of Science and Technology of China, Hefei, 230027, China.
³ Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China.
⁴ HanGene Biotech, Xiaoshan Innovation Polis, Hangzhou, Zhejiang, 311200, China.
⁵ Respiratory and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
⁶ Department of Infectious Diseases, Peking University First Hospital, Beijing, 100034, China.
⁷ Department of Tuberculosis, Wuhan Pulmonary Hospital, Wuhan, 430030, China.
⁸ Department of Infectious Diseases, Peking University First Hospital, Beijing, 100034, China. Electronic address: john131212@sina.com.
⁹ Respiratory and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China; Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; Institute of Immunology, University of Science and Technology of China, Hefei, 230027, China. Electronic address: ustcwhm@ustc.edu.cn.

Abstract

Forty-seven samples of peripheral blood mononuclear cells from four groups of coronavirus disease (COVID)-19 patients (mild, severe, convalescent, retesting-positive) and healthy controls were applied to profile the immune repertoire of COVID-19 patients in acute infection or convalescence by transcriptome sequencing and immune-receptor repertoire (IRR) sequencing. Transcriptome analyses showed that genes within principal component group 1 (PC1) were associated with infection and disease severity whereas genes within PC2 were associated with recovery from COVID-19. A "dual-injury mechanism" of COVID-19 severity was related to an increased number of proinflammatory pathways and activated hypercoagulable pathways. A machine-learning model based on the genes associated with inflammatory and hypercoagulable pathways had the potential to be employed to monitor COVID-19 severity. Signature analyses of B-cell receptors (BCRs) and T-cell receptors (TCRs) revealed the dominant selection of longer V-J pairs (e.g., IGHV3-9-IGHJ6 and IGHV3-23-IGHJ6) and continuous tyrosine motifs in BCRs and lower diversity of TCRs. These findings provide potential predictors for COVID-19 outcomes, and new potential targets for COVID-19 treatment.

Keywords: BCR; COVID-19 predictor; Dual-injury mechanism; Immune repertoire; TCR.

MeSH terms

Adult
COVID-19 / genetics*
COVID-19 / immunology
COVID-19 Drug Treatment
Female
Humans
Male
Middle Aged
Receptors, Antigen, B-Cell / genetics*
Receptors, Antigen, B-Cell / immunology
Receptors, Antigen, T-Cell / genetics*
Receptors, Antigen, T-Cell / immunology

Substances

Receptors, Antigen, B-Cell
Receptors, Antigen, T-Cell