Background:Coronavirus disease (COVID-19) caused by SARS-COV2 represents an unprecedented global public health concern with a particular burden on patients with chronic diseases and those on immune-modulating drugs. It is especially worrisome to patients with rheumatoid arthritis (RA) who are on immune suppression regimens[1]. On the other side, many reports showed and recommended the use of some Disease-Modifying Drugs commonly used to treat rheumatic diseases like hydroxychloroquine. However, the general understanding of COVID-19 characteristics in this population and the mechanism of action of these drugs in COVID-19 is still unknown[2].Objectives:Explore publicly available transcriptomic dataset of patients infected with SARS-COV2 compared to uninfected to identify differentially expressed genes (DEGs) related to the immune system that might be pathogenic in RA synovium. Then explore the effect of Disease-Modifying Drugs on their local expression that might give hints about their possible mechanism of action.Methods:RNAseq dataset (GSE147507) were retrieved using the Gene Expression Omnibus (GEO) and used to identify DEGs between infected and uninfected lung samples using BioJupies tools [3]. The DEGs were explored for common pathways using Metascape online tool (http://metascape.org) [10], as shown in figure (1). The chemokines genes were filtered out, and their common receptor (CR) was identified. The immune cells that express a higher level of the identified receptor were explored using DICE project tool (https://dice-database.org/). The expression of CR was searched in a microarray dataset (GSE77298) of synovial biopsies of RA and healthy controls. RNAseq dataset (GSE97165) of synovial biopsies taken from 19 early RA patients at baseline and after six months of Triple Disease-Modifying Anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine, and hydroxychloroquine) treatment.Results:84 DEGs were identified between uninfected and COVID-19 infected lung samples. These DEGs were enriched in pathways specific to (response to the virus, response to interferon, leukocyte activation, and chemotaxis). Interestingly, SARS-COV-2 infected lungs express more CCL4, CCL8, and CCL11; the three ligands shared the same receptor, which is CCR5. Top immune cells that express CCR5 were CD4 T memory T reg cells, Th17, Th1, and monocytes. CCR5 was significantly upregulated in RA compared to healthy controls synovium (p=0.04) and was dramatically downregulated after six months of tDMARD treatment (p=0.004), as shown in figure (2).Conclusion:Using publicly available transcriptomic datasets properly highlighted the possible beneficiary effect of DMARDs in patients with COVID-19, which can block CCR5 rich immune cells recruitment.References:[1]Favalli, E.G., et al.,COVID-19 infection and rheumatoid arthritis: Faraway, so close!Autoimmun Rev, 2020. 19(5): p. 102523.[2]Gianfrancesco, M.A., et al.,Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.The Lancet Rheumatology, 2020. 2(5): p. e250-e253.[3]Torre, D., A. Lachmann, and A. Ma’ayan,BioJupies: Automated Generation of Interactive Notebooks for RNA-Seq Data Analysis in the Cloud.Cell Systems, 2018. 7(5): p. 556-561.e3.Figure 1.Flowchart of transcriptomic analysisFigure 2.(A) Top immune cells that express CCR5 (B) CCR5 expression in synovial biopsies of RA and control (C) CCR5 expression at baseline and after 6 months of tDMARD treatment.Disclosure of Interests:None declared
CO0005 C-C CHEMOKINE RECEPTOR TYPE 5 AND ITS LIGANDS CCL4, 8 AND 11 CAN LINK COVID-19, RHEUMATOID ARTHRITIS AND HYDROXYCHLOROQUINE
