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

In this study, we observed that in vitro HCQ treatment of immune cells alters gene transcription which is likely cell type-specific and context dependent. Notably, these alterations were more apparent in macrophage cells compared with bulk PBMC cells treated with HCQ. Our study is a start to address mechanisms of action for whether HCQ is an effective therapy for COVID-19. While these findings are of interest to studies of HCQ and COVID-19, transcriptional studies need to be conducted on in vivo treatment of COVID-19 participants before and after HCQ treatment. The mechanisms of action of HCQ in the setting of viral infection remains an area still under investigation and a research area containing contrasting findings. This is supported by previous HCQ research in the setting of HIV that reported HCQ treatment drastically reduced immune activation in HIVinfected individuals [32] . In contrast to these findings, a randomized double blind placebo controlled trial of 400 mg of HCQ failed to find any difference in T cell activation and reported increased viral replication [33] . While in vitro data of SARS-CoV-2 provide compelling rationale for suggesting clinical efficacy of HCQ [4, 34] , in vivo data and randomized double blinded placebo COVID-19 studies of HCQ are needed to account of contextdependent effects of the host being administered HCQ. Further work will need to determine whether the mechanism of action of HCQ is directly impacting SARS-CoV-2 or indirectly impacting the immune system and hence indiscriminately improving COVID-19 clinical outcomes. Unfortunately, at this moment HCQ is not a panacea for COVID-19 and alternative therapies are urgently needed. author/funder. All rights reserved. No reuse allowed without permission.