Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing
Authors: Lihui Xie
Jianmin Li
Hongyang Wang
Wei Chen
Yushan Miao
Yingfeng Zheng
Chuanle Xiao
Liwei Dong
Xiuliang Cui
Jinguo Ye
Hao Tang
Depeng Wang
Wenqing Le
Xiaopeng Zhang
Jiantao Dong
Wenru Su
Xiuxing Liu
Wen Wen
Journal: Cell Discovery (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Immunology; Mechanisms of disease.
Affiliations: 1National Center for Liver Cancer, Second Military Medical University, 200438 Shanghai, China., 2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060 Guangzhou, China., 3Department of Respiratory and Critical Care Medicine, Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China., Department of Critical Care, Wuhan Huoshenshan Hospital, 430113 Wuhan, Hubei China., Department of Critical Care, Wuhan Hankou Hospital, 430000 Wuhan, Hubei China., 6Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, 100071 Beijing, China., GrandOmics Diagnosis Co. Ltd., 430014 Wuhan, Hubei China., Berry Genomics Co. Ltd., 102206 Beijing, China., 9Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 200438 Shanghai, China., 10Ministry of Education (MOE) Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, 200433 Shanghai, China.

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. 

Retracted: No

PubPeer comments:
 Fig. 6C and 6E contains dataset that is much more similar than expected. Could the authors check it please? ![file] , 
 Thank you for your question. The data is similar due to the scale of the graphs. A sum of granulocytes (Fig. 6D), which represents only 2% of the total population of Anopheles aquasalis hemocytes, practically does not alter the graphical representation of total hemocytes (Fig. 6C) from the populations of prohemocytes and oenocytes (Fig. 6E). ,