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 our comparative analyses for the macrophage HCQ dataset, we first examined whether the HCQ- Table 1 ). This comparative analysis identified 15 overlapping genes including LDLR, CXCL6, GPNMB, HMGCS1, IDI1, C1S, FDPS, MMP1, PLAU, MAFF, ITGB3, BHLHE40, TNC, CXCL3, SLC7A8 (Fig.4a) . Next, we sought to compare the HCQ-related transcriptional changes in human primary macrophage cells with transcriptional data from COVID-19 participants and in a similar cell type. Hence, we analyzed transcriptome data from bronchoalveolar lavage samples obtained from two individuals with COVID-19 and three uninfected individuals (Supplemental Table 1 ). Bronchoalveolar lavage (BAL) samples predominantly contain macrophages with only a minor population of neutrophils, lymphocytes, and eosinophils. We used CIBERSORT to confirm that the majority population in the transcriptome dataset was macrophage cell types (Supplemental Figure 5) . Additionally, we confirmed that the BAL transcriptome dataset from COVID-19 participants contained high levels of SARS-CoV-2 virus by mapping reads to the viral reference (Supplemental Figure 3a) . The bronchoalveolar lavage COVID-19 transcriptome dataset contained 5,304 differentially expressed genes comparing COVID-19 to author/funder. All rights reserved. No reuse allowed without permission.