Olfactory Training in COVID-19 Associated Loss of Smell

A Randomized Controlled Trial of the Effectiveness of Olfactory Training on Loss of Smell Related to COVID-19 (SMELL)

Olfactory dysfunction (OD) like hyposmia or anosmia has been realized as a common symptom or even cardinal sign of the disease and can be persisting after recovering.

There are two different hypotheses on the pathogenesis of OD in past COVID-19: The central hypothesis, which speculates on neurotrophic abilities on olfactory receptors in the neuroepithelium, and the peripheral hypothesis, which speculates on damage of the sensory olfactory epithelium.

Potential treatment strategies aim for the unique neural plasticity of the olfactory system and its potential for recovery.

Clinical studies and case reports have shown a promising effect of olfactory training (OT) by frequent sniffing and/or exposure to odors 2-4 times a day for several weeks.

The main objective of the study is to assess the effects of olfactory training in patients with COVID-19 related OD on:

1. objective olfactory testing with the Sniffin' sticks test (identification and discrimination),
2. subjective OD and its impact on the daily life,
3. other clinical scales and questionnaires referring to OD-related mood and quality of life,
4. gender differences in COVID-19 related OD. Approach / methods OT will be performed twice a day with a 4-odor training set for 12 weeks. Effects of OT on COVID-19 related OD will be measured with objective and subjective efficacy variables.

The sense of smell is an important function for social relationships and is therefore a challenging clinical problem with few proven therapeutic options.

With this new approach, we want to investigate a possible simple treatment for an impedimental symptom of COVID-19, but also learn more about the pathomechanism of post-infectious OD.

To our knowledge, this will be the first study comparing patients with COVID-19 associated OD with and without OT in clinical outcomes.

Inclusion Criteria:

• The subject is aged over 18 years;
• confirmed diagnosis of COVID-19 at least three months ago (history of positive PCR-testing required) or positive serum nucleocapsid antibody titer against SARS-CoV2;
• post-infectious COVID-19 related olfactory dysfunction persisting for at least three months with abnormal Sniffin' sticks test (<13/16 items correct in the identification part);
• the patient is willing to undergo odor training over 12 weeks;
• written ICF is obtained.

Exclusion Criteria:

• History of olfactory dysfunction prior to COVID-19 infection due to other conditions e.g. status post traumatic brain injury, Parkinson's disease, allergic rhinitis, etc.;
• Nasal pathology not related to COVID-19 in the systematic otorhinolaryngological examination including endoscopy.
• the participant is pregnant