RNA Sequencing Identifies T Effector Subset Changes in Foralumab-Treated Subjects.
inflammation, hypercytokinemia
CORONAVIRUS, BLOOD, PATHOGENESIS, INFLAMMATION
To investigate the transcriptomic changes in immune cells following nasal Foralumab treatment in SARS-CoV-2-infected patients, we Fluorescence-activated cell sorting (FACS)sorted CD3Compositional Analysis Shows Reduction of Effector T Cell Subsets in Foralumab-Treated subjects. Study design. Subjects were treated with 100 µg of nasal Foralumab given daily for 10 consecutive days. Blood was collected on day -2 and day 10. For bulk RNA-seq, CD3We then compared CD3We next investigated the effect of nasal Foralumab on gene expression in T cells, B cells, and monocytes by comparing pre- treatment (day-2) vs. follow-up (day 10) in Foralumab-treated vs. untreated subjects. IPA of the differentially expressed genes (DEGs) before and after treatment showed downregulation of inflammatory pathways such as hypercytokinemia and interferon signaling pathway in both groups. We also identified a coronavirus pathogenesis pathway that were downregulated in the Foralumab group but not in untreated controls (We thus analyzed the effect of nasal Foralumab on gene expression in B cells by comparing pre-treatment vs. day 10 in Foralumab-treated vs. untreated subjects Our bulk RNA-seq analysis suggested that nasal administration of Foralumab led to the downregulation of genes related to inflammation and coronavirus pathogenesis and that its immunomodulatory effects were mostly pronounced in CD3+ T cells, although we could find some evidence for changes indirectly affecting both monocytes and B cells.We also performed droplet-based 10x CellRanger sequencing in FACS sorted cells from healthy controls, untreated COVID-19 subjects, and Foralumab-treated COVID-19 subjects (We next compared gene expression of total CD3Because anti-CD3 activates T cells, we next investigated the cell state score of predefined gene sets associated to T cell exhaustion and activation in COVID-19 (