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Transcriptomic characteristics and impaired immune function of patients who retest positive for SARS-CoV-2 RNA
Dongyao Wang1,2,3,† , Dong Wang2,3,† , Min Huang4,† , Xiaohu Zhen2,3 , Yiqing Shen2,3 , Binqing Fu1,2,3 , Hong Zhao5 , Xianxiang Chen6 , Peng Peng6 , Qi Zhu6 , Yonggang Zhou1,2,3 , Jinghe Zhang2,3 , Zhigang Tian1,2,3 , Wuxiang Guan7,* , Guiqiang Wang5,8,* , Haiming Wei1,2,3,*
1Division of Life Sciences and Medicine, Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei 230001, China
2Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medicine and Medical Center, University of Science and Technology of China, Hefei 230001, China
3Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230001, China
4Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, HuaZhong University of Science and Technology, Wuhan 430030, China
5Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
6Department of Tuberculosis, Wuhan Pulmonary Hospital, Wuhan 430030, China
7Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
8Peking University International Hospital, Beijing 100034, China
These authors contributed equally to this work.
*Correspondence to:Wuxiang Guan , Email:guanwx@wh.iov.cn Guiqiang Wang , Email:john131212@sina.com Haiming Wei , Email:ustcwhm@ustc.edu.cn
J Mol Cell Biol, Volume 13, Issue 10, October 2021, 748-759,  https://doi.org/10.1093/jmcb/mjab067
Keyword: COVID-19, CD8+, T cells, NK cells, RTP patients, immune function

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global public health crisis. Some patients who have recovered from COVID-19 subsequently test positive again for SARS-CoV-2 RNA after discharge from hospital. How such retest-positive (RTP) patients become infected again is not known. In this study, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for the analysis of immunological characteristics of their peripheral blood mononuclear cells. We found that absolute numbers of CD4+ T cells, CD8+ T cells, and natural killer cells were not substantially decreased in RTP patients, but the expression of activation markers on these cells was significantly reduced. The percentage of granzyme B-producing T cells was also lower in RTP patients than in convalescent patients. Through transcriptome sequencing, we demonstrated that high expression of inhibitor of differentiation 1 (ID1) and low expression of interferon-induced transmembrane protein 10 (IFITM10) were associated with insufficient activation of immune cells and the occurrence of RTP. These findings provide insight into the impaired immune function associated with COVID-19 and the pathogenesis of RTP, which may contribute to a better understanding of the mechanisms underlying RTP.