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.
【저자키워드】 immunology, Mechanisms of disease, 【초록키워드】 COVID-19, Treatment, SARS-CoV-2, Vaccine, Vaccine development, Gene Expression, antibody, B cells, virus, CD4, CD8, Single-cell RNA sequencing, monocyte, Peripheral blood, specificity, T cell, Patient, change, Plasma cell, COVID-19 patients, monoclonal, IL-2, BCR, IL-4, IL-1β, Signaling, Evidence, Analysis, Inflammatory, Immune cell, COVID-19 patient, identification, target gene, early recovery, mononuclear cell, frequencies, isotype, hospital discharge, CD14, inflammatory storm, IL1β, IL-18, M-CSF, immune signature, Course, greater, classical, predicted, affected, caused, significantly, reported, indicated, provide, expressed, subset, transcriptional change, IGHV3-15, IGHV3-23, IGHV3-30, IGHV3-7, IGKV3-11, inflammatory gene, naïve B cell, TNFSF13, 【제목키워드】 Sequencing, single-cell, COVID-19 patient, Cell,