Professor Duke University Durham, NC, United States
Introduction: Chronic olfactory dysfunction persists in a subset of patients years after initial COVID-19 infection. Evidence suggests this may be due to persistent immune infiltration in the olfactory epithelium. Here we further investigate potential mechanisms of immune dysregulation within human olfactory mucosal biopsies in patients with long-COVID smell loss.
Methods: Olfactory cleft surgical or brush biopsies were collected from patients reporting smell loss shortly after COVID-19 infection that lasted for more than 3 months, confirmed by the SIT, following an approved Duke University IRB protocol. Cells were processed for flow cytometry to quantify differences in immune cell types compared to normosmic controls. Sorted CD45+-immune cells were then cultured and stimulated in a CD3/CD28-dependent manner to measure pro-inflammatory cytokine levels in the harvested supernatant at 4h, 24h, and 96h time points.
Results: In agreement with prior single cell RNA-seq analysis, olfactory mucosa from long-COVID hyposmics trended toward more CD45+ immune cells versus normosmic controls (p < 0.07, n=3 per group). While statistically significant increases in cytokines were not identified, certain pro-inflammatory compounds were detectable in vitro.
Conclusions: Our findings support a role for persistent immune changes within the olfactory epithelium of those with long-COVID hyposmia, including an increase in CD8+ T cell subset population, a decrease in anti-inflammatory M2 macrophages, as well as possible increases in pro-inflammatory cytokines. Understanding mechanisms of long-COVID olfactory dysfunction is necessary to guide future therapeutic strategies.
