Limited impact of ivermectin on immune response and transcriptional profiles in mild COVID-19

Ivermectin (IVM) was tested as a treatment for COVID-19 due to its in vitro antiviral activity and possible immunomodulatory properties. Here, we studied the immunomodulatory effects in a clinical trial involving 24 mild COVID-19 patients who received IVM within 72 h of symptoms onset by comprehensively analyzing immune responses over 28 days. The IVM group had statistically significant increased levels of IgG against the SARS-CoV-2 nucleocapsid compared to the control group at days 4 and 7 post-treatment. IVM did not affect the kinetics of leukocyte subsets or SARS-CoV-2-specific T cells, despite a decrease in naïve CD4 + T cells, which was non-significant after adjusting for multiple comparisons. Although differential gene expression was not observed between IVM-treated and placebo groups, blood transcriptional module analysis revealed statistically significant decreases in innate and antiviral signatures and increases in adaptive signatures over time, with 10 modules upregulated (related to innate responses) and 15 modules downregulated (related to T cells and cell cycle) in the IVM-treated group compared to placebo. In conclusion, despite some weak differences in IVM treated participants, our detailed analyses do not support significant immunomodulatory effects that could benefit disease progression.