Nasal cytological evidence of chronic inflammation in the olfactory cleft in post-viral olfactory dysfunction

Abstract

Purpose: This study investigated nasal cytological alterations in patients with persistent post-viral olfactory dysfunction. The primary objective was to evaluate the role of immune dysregulation and chronic local inflammation within the nasal mucosa in sustaining long-term olfactory impairment.

Methods: An observational case-control study was conducted at the Otorhinolaryngology Department of the University of Rome Tor Vergata. Thirty-six patients with persistent olfactory dysfunction were compared to two control groups: one comprised subjects recovered from SARS-CoV-2 infection without olfactory impairment, and the other included individuals without a history of COVID-19 or olfactory dysfunction. Psychophysical olfactory function was assessed using the TDI (Threshold, Discrimination, and Identification) test. Nasal cytology samples were obtained via nasal brushing at the level of the olfactory cleft and stained using the May-Grunwald-Giemsa technique. Cellular alterations were evaluated using a semiquantitative grading system.

Results: Patients with persistent olfactory dysfunction exhibited increased lymphocytes and neutrophils compared to both control groups, indicating ongoing local inflammation. Ciliocytophthoria was notably present in a significant portion of the olfactory dysfunction group, while absent or minimally present in controls. Eosinophils and mast cells were rare across all groups.

Conclusion: Persistent post-viral olfactory dysfunction is associated with sustained immune activation and epithelial damage localized to the olfactory cleft. Elevated lymphocytes, neutrophils, and ciliocytophthoria emphasize the role of chronic inflammation in the pathogenesis of prolonged olfactory deficits. These findings highlight the potential utility of targeted therapies to modulate immune responses and promote olfactory recovery in affected patients.

Keywords: Ciliocytophthoria; Long COVID; Lymphocytes; Nasal cytology; Olfactory dysfunction; Post-Viral.

Fig. 1

Comparison of Nasal Cytology Grading for Lymphocytes and Neutrophils Across Study Groups Violin plots illustrating the grading distribution of lymphocytes and neutrophils across the olfactory dysfunction (OD), control group 1 (CG1), and control group 2 (CG2) study groups. The y-axis represents the grading scale used in the semiquantitative nasal cytology analysis. For lymphocytes, the OD group shows a significantly higher grading compared to both CG1 and CG2, as indicated by **** (p < 0.0001) and * (p < 0.05). For neutrophils, the OD group also demonstrates significantly higher grading than both CG1 and CG2, with ** (p < 0.01), while no significant difference (ns) is observed between CG1 and CG2

Fig. 2

Nasal cytology in the olfactory dysfunction (OD) group, stained with May–Grunwald–Giemsa (MGG) at ×1000 magnification. (a) Lymphocytes; (b) Lymphocytes in an active functional state with pseudopodia formation (red arrows); (c) Neutrophils; (d) Ciliated cells in various stages: some retain the hyperchromatic supranuclear stria (black arrows), while others show signs of degeneration, including loss of the supranuclear stria, rarefaction of apical cilia, initial apical decapitation, and vacuole depletion (green arrow), indicative of ciliocytophthoria