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The copyright holder for this preprint (which was not peer-reviewed) is the .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 PBMC cells are not a main target for SARS-CoV-2 infection and viral replication. We preliminarily confirmed that PBMC cells do not harbor SARS-CoV-2 virus by mapping RNA-Seq reads from COVID-19 PBMC samples and identifying no significant reads aligning to the SARS-CoV-2 reference (Supplemental Figure 3b) . This was also observed by Xiong et al. [20] . In contrast, we observed viral mapping of reads in the Blanco-Melo et al. in vitro SARS-CoV-2 infection dataset of A549 and NHBE cells (Supplemental Figure 3c,d) . Notably, the in vitro SARS-CoV-2 infection dataset contains a 3' bias of read alignment compared to the COVID-19 PBMC dataset. Recent in vitro work suggest SARS-CoV-2 infects T lymphocytes [26] . Whether this is observable in COVID-19 patient remains to be determined. We assume HCQ treatment of A549 or NHBE cells during SARS-CoV-2 infection would dramatically reduce the viral mapping detected by RNA-Seq. Our observations of overlapping transcriptional changes provides candidate genes to further study for addressing host immune-related mechanisms of action of HCQ in the setting of COVID-19.