C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis

Transl Med Commun. 2020;5(1):14. doi: 10.1186/s41231-020-00066-x. Epub 2020 Sep 9.


Patients with rheumatoid arthritis (RA) represent one of the fragile patient groups that might be susceptible to the critical form of the coronavirus disease - 19 (COVID-19). On the other side, RA patients have been found not to have an increased risk of COVID-19 infection. Moreover, some of the Disease-Modifying Anti-Rheumatic Drugs (DMARDS) commonly used to treat rheumatic diseases like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID-19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases at the molecular side. In this research, we used the in silico approach to investigate the transcriptomic profile of RA synovium to identify shared molecular pathways with that of severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) infected lung tissue. Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases; RA and COVID-19. Moreover, our results also highlighted a possible mechanism through which HCQ, which can be used as a monotherapy in mild RA or as one of the triple-DMARDs therapy (tDMARDs; methotrexate, sulphasalazine, and HCQ), might interfere with the COVID-19 infection. This might be achieved through the ability of HCQ to upregulate specific immune cell populations like activated natural killer (NK) cells, which were found to be significantly reduced in COVID-19 infection. In addition to its ability to block CCR5 rich immune cell recruitment that also was upregulated in the SARS-COV-2 infected lungs. This might explain some of the reports that showed beneficial effects.