1 inflammatory storm incited by monocyte centric immune interactions 2 revealed by single-cell analysis 3 4 ABSTRACT 40 41Coronavirus disease 2019 has caused more than 40,000 deaths 42 worldwide 1 . Approximately 14% of patients with COVID-19 experienced severe 43 disease and 5% were critically ill 2 . Studies have shown that dysregulation of the 44 COVID-19 patients' immune system may lead to inflammatory storm and cause severe 45 illness and even death 3,4 . Tocilizumab treatment targeting interleukin 6 receptor has 46shown inspiring clinical results of severe COVID-19 patients 5 . However, the immune 47 network with Tocilizumab treatment at single cell resolution has not been uncovered. 48Here, we profiled the single-cell transcriptomes of 13,289 peripheral blood 49 mononuclear cells isolated at three longitudinal stages from two severe COVID-19 50 patients treated with Tocilizumab. We identified a severe stage-specific monocyte 51 subpopulation and these cells centric immune cell interaction network connected by the 52 inflammatory cytokines and their receptors. The over-activated inflammatory immune 53 response was attenuated after Tocilizumab treatment, yet immune cells including 54 plasma B cells and CD8 + T cells still exhibited an intense humoral and cell-mediated 55 anti-virus immune response in recovered COVID-19 patients. These results provided 56 critical insights into the immunopathogenesis of severe COVID-19 and revealed 57 fundamentals of effectiveness in Tocilizumab treatment. 58 59 60 61Keywords : Coronavirus disease 2019 (COVID-19); Severe acute respiratory 62 syndrome coronavirus 2 (SARS-CoV-2); Tocilizumab; Single-cell RNA sequencing 63(scRNA-seq); Inflammatory storm; Monocyte 64 65 (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.