Comparative in vitro transcriptomic analyses of COVID-19 candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes.

Michael Jay Corley; Christopher Sugai; Michael Schotsaert; Robert E. Schwartz; Lishomwa C Ndhlovu

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.13.039263 doi: bioRxiv preprint biosynthetic process, GO molecular function chemokine activity, and GO cellular component integral component of plasma membrane (Fig.3a-c, Supplemental Data 1) . Specifically, HCQ altered expression of LDLR, CXCL6, CCL18, CCL5, and CXCL3 genes (Fig.3d-h) . To extend our findings of HCQ impacting immune chemokine activity in innate immune cells, we examined transcriptomes of plasmacytoid dendritic cells (pDC) from four healthy individuals that had been either stimulated with RNA-IC for 6 hours only or stimulated with RNA-IC for 6 hours in the presence of HCQ (Supplementary Table 1) . We observed that CXCL10, CXCL11, CCL4, and CXCL9 genes were significantly downregulated in stimulated HCQ treatment compared to the only stimulated condition (Supplemental Figure 4) . Together, our findings in macrophages and pDC cells suggest HCQ impacts certain cell type specific chemokine signaling pathways and likely modulates immune inflammation.