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Immune cell profiling of COVID-19 patients in the recovery stageby single-cell sequencing

Wen Wen1National Center for Liver Cancer, Second Military Medical University, 200438 Shanghai, ChinaWenru Su2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060 Guangzhou, ChinaHao Tang3Department of Respiratory and Critical Care Medicine, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, ChinaWenqing LeDepartment of Critical Care, Wuhan Hankou Hospital, 430000 Wuhan, Hubei ChinaXiaopeng Zhang6Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, 100071 Beijing, ChinaYingfeng Zheng2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060 Guangzhou, ChinaXiuxing Liu2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060 Guangzhou, ChinaLihui Xie2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060 Guangzhou, ChinaJianmin Li6Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, 100071 Beijing, ChinaJinguo Ye2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060 Guangzhou, ChinaLiwei Dong1National Center for Liver Cancer, Second Military Medical University, 200438 Shanghai, ChinaXiuliang Cui1National Center for Liver Cancer, Second Military Medical University, 200438 Shanghai, ChinaYushan Miao3Department of Respiratory and Critical Care Medicine, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, ChinaDepeng WangGrandOmics Diagnosis Co. Ltd., 430014 Wuhan, Hubei ChinaJiantao DongBerry Genomics Co. Ltd., 102206 Beijing, ChinaChuan‐Le Xiao2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060 Guangzhou, ChinaWei Chen6Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, 100071 Beijing, ChinaHongyang Wang10Ministry of Education (MOE) Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, 200433 Shanghai, China
2020en
ABI

Аннотация

Abstract COVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000 people and killed more than 60,000. The key immune cell subsets change and their states during the course of COVID-19 remain unclear. We sought to comprehensively characterize the transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It was found that T cells decreased remarkably, whereas monocytes increased in patients in the early recovery stage (ERS) of COVID-19. There was an increased ratio of classical CD14 ++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14 ++ IL1β + monocytes in the ERS. CD4 + T cells and CD8 + T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naïve B cells decreased. Several novel B cell-receptor (BCR) changes were identified, such as IGHV3-23 and IGHV3-7, and isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development were confirmed. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity, which had not been reported yet. Furthermore, integrated analysis predicted that IL-1β and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2, and IL-4 may be beneficial for the recovery of COVID-19 patients. Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting COVID-19 patients are still vulnerable after hospital discharge. Identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19.

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