Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an in vitro Model of Inflammation

• Main Authors: Arya Zarinsefat, George Hartoularos, Dmitry Rychkov, Priyanka Rashmi, Sindhu Chandran, Flavio Vincenti, Chun J. Yee, Minnie M. Sarwal
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-01-01
• Series: Frontiers in Genetics
• Subjects: single cell RNA seq; COVID-19; tocilizumab (IL-6 inhibitor); kidney transplantation; transcriptomics; bioinformatics and computational biology
• Online Access: https://www.frontiersin.org/articles/10.3389/fgene.2020.610682/full

COVID-19 has posed a significant threat to global health. Early data has revealed that IL-6, a key regulatory cytokine, plays an important role in the cytokine storm of COVID-19. Multiple trials are therefore looking at the effects of Tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activity, on treatment of COVID-19, with promising findings. As part of a clinical trial looking at the effects of Tocilizumab treatment on kidney transplant recipients with subclinical rejection, we performed single-cell RNA sequencing of comparing stimulated PBMCs before and after Tocilizumab treatment. We leveraged this data to create an in vitro cytokine storm model, to better understand the effects of Tocilizumab in the presence of inflammation. Tocilizumab-treated cells had reduced expression of inflammatory-mediated genes and biologic pathways, particularly amongst monocytes. These results support the hypothesis that Tocilizumab may hinder the cytokine storm of COVID-19, through a demonstration of biologic impact at the single-cell level.