Dysfunction of Olfaction After COVID-19 Infection: Morphological and Histomolecular Investigation

Not Applicable

Recruiting

• Conditions: Olfactory Dysfunction; Covid19
• Interventions: Procedure: Biopsy and Cytobrush

• Registration Number: NCT06482138
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

Brief Summary

Investigation of the mechanisms of persistent SARS-CoV-2 associated olfactory dysfunction (OD) in patients with well-documented olfactory function. The investigators plan to collect olfactory cleft biopsies and cytobrushes in COVID-19 patients and controls.

Detailed Description

An explorative prospective clinical study using human body materials of living post-COVID-19 patients with and without OD, to study the mechanisms of persisting olfactory dysfunction. Patients consult ENT specialist for medical purposes and undergo standard-of-care diagnostics and management. The collected tissues from the olfactory cleft mucosa will be analyzed using single cell RNA sequencing and RNAscope combined with immunohistochemistry.

Study Timeline

• Study Start: 2024-01-24
• Study First Submitted: 2024-02-19
• Study First Submitted QC: 2024-06-28
• Study First Posted: 2024-07-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-07
• Last Update Posted: 2025-03-12
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• Olfactory Dysfunction group: Presence of evident OD (Parosmia, Threshold-Discrimination-Identification (TDI)-score ≤24, Subjective abnormal quantitative olfactory function; measured by a visual analogue score (VAS) of smell impairment ≥5/10
• Control group: No OD (TDI-score >30.5.)

Exclusion Criteria

• Presence of concomitant nasal mucosal pathology that might affect olfactory function or bias the study investigations
• Use of anticoagulation therapy
• Allergy to local anesthetics

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Olfactory Dysfunction	Biopsy and Cytobrush	Biopsy and cytobrush during consultation in local anesthesia
Control	Biopsy and Cytobrush	Biopsy and cytobrush during a scheduled structural intervention in general anesthesia

Primary Outcome Measures

Name	Time	Method
Analysis of olfactory cleft biopsies	From enrollment of 1 patient until analyzed, 1 month	Morphological and histomolecular differences between OD and control patients; * Evaluating tissue pathology: * Metaplasia; * hypertrophy; * aberrant scar formation; * apoptosis; * presence of inflammatory cells \[H\&E, CD68 and CD3 stainings, RNAscope\]; * Presence of SARS-CoV-2 RNA; * Percentage of OSNs versus sustentacular cells; maturation of OSNs
Analysis of olfactory cytobrushes	From enrollment of 1 patient until analyzed, 1 month	Morphological and histomolecular differences between OD and control patients; * Evaluating tissue pathology: * Metaplasia; * hypertrophy; * aberrant scar formation; * apoptosis; * presence of inflammatory cells \[H\&E, CD68 and CD3 stainings, RNAscope\]; * Presence of SARS-CoV-2 RNA; * In the olfactory epithelium: percentage of OSNs versus sustentacular cells; maturation of OSNs

Trial Locations

Locations (7)

UZ/KU Leuven; 🇧🇪 Leuven, Vlaams-Brabant, Belgium

Max Planck Research Unit for Neurogenetics; 🇩🇪 Frankfurt am Main, Frankfurt, Germany

AZ Sint-Jan Brugge; 🇧🇪 Brugge, West-Vlaanderen, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

University Hospital Carl Gustav Carus; 🇩🇪 Dresden, Germany

University of Zurich and University Hospital Zurich; 🇨🇭 Zürich, Switzerland

Hôpitaux Universitaires de Genève; 🇨🇭 Genève, Switzerland