Immune Cell Profiling of COVID-19 Patients in the Recovery Stage by Single-Cell Sequencing

Wen Wen; Wenru Su; Hao Tang; Wenqing Le; Xiaopeng Zhang; Yingfeng Zheng; XiuXing Liu; Lihui Xie; Jianmin Li; Jinguo Ye; Xiuliang Cui; Yushan Miao; Depeng Wang; Jiantao Dong; Chuan-Le Xiao; Wei Chen; Hongyang Wang

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03. 23.20039362 doi: medRxiv preprint of CD14 + monocytes exclusively expressed IL1β, which was predicted to bind to IL1RAP expressed by T cells. T cell-monocyte interaction may enhance immune response and be exclusive to COVID-19 patients. (Fig. 7A, B) . Furthermore, we found that monocytes highly expressed the poliovirus receptor, which serves as a cellular receptor for poliovirus in the first step of poliovirus replication and induction of the NF-kappa B signaling pathway. From the B cell-monocyte and B cell-T cell interactions, we found that B cells could secrete a large number of IL-6, LTA, and LTB, which are combined with IL-6R, LTAR, and LTBR expressed in monocytes, and a large amount of IL-6 was applied to T cells to promote the secretion of IFN-γ, IL-1β, and other inflammatory cytokines and chemokines. Thus, a cascade signature of inflammatory monocytes with high expression of IL-6 and their progeny were formed in the peak incidence of ERS COVID-19 patients (Fig. 7C) . These activated immune cells may enter the circulation in the lung and other organs in large numbers and play an immune-damaging role. In LRS COVID-19 patients, DC ligands were predicted to interact with B and T cell receptors involved in cell proliferation and the production of antibodies. We discovered that the peripheral blood of LRS patients contains a diversity of antibodies ; we found that IL18-IL18RAP, TNFSF13-TNFRSF13B, TNFSF13-TNFRSF17, TNFSF13B-TNFRSF17, TNFSF13B-TNFRSF13B , and TNFSF13B-TNFRSF13C were highly expressed in our analysis of DC-B cell interaction (Fig. 7D) . Thus, we speculate that DCs produce IL-18, TNFSF13, and TNFSF13B to promote the proliferation of B cells and then secrete many antibodies into the blood in ERS. From the DC-T and T cell-B cell interactions, we discovered that DCs produce not only IL-18 but also IL-7 to promote the proliferation of T cells; moreover, T cells produce IL-2 (to promote the proliferation of B cells) and antibodies (Fig. 7D) . Thus, cell-to-cell interactions help us to understand why COVID-19 patients manifested high rates of monocytes and low rates of lymphocytes and why the proportion of lymphocytes gradually increased in the peripheral blood of recovering patients.