Insights into the molecular triggers of parosmia based on gas chromatography olfactometry

Background Parosmia is a debilitating condition in which familiar smells become distorted and disgusting, with consequences for diet and mental health. It is a feature of post-infectious olfactory loss, particularly resulting from COVID-19. There is currently little understanding of its pathophysiology, and the prevailing hypothesis for the underlying mechanism is aberrant growth of regenerating olfactory sensory neurons after damage. Methods We use gas-chromatograph olfactometry to individually present components of a complex olfactory mixture as a rapid screening tool for assessment of both quantitative and qualitative olfactory dysfunction in those with and without parosmia. This allows them to report the associated sensory effects and to identify those molecules which are altered or parosmic in nature. Results Here we show 15 different molecular triggers of this symptom. These trigger molecules are common to many in the parosmic volunteer group and share certain characteristics such as extremely low olfactory threshold and common molecular structure Conclusions We posit that specific highly odour-active molecules are the cause of the parosmic symptom in most cases and initiate the sense of disgust, suggesting that parosmia is, at least in part, a receptor-level phenomenon. Parker et al. determine the aroma compounds responsible for the distortions experienced by those with the olfactory disorder parosmia, by applying a technique normally used in flavour chemistry, GC-Olfactometry. The authors show that a group of 15 highly odour-active compounds are common triggers of distortion and individually elicit the perception of disgust. Plain language summary During the recovery from smell loss, caused by infection or injury, sometimes certain smells can become revolting – a condition called parosmia. We used a technique that separates out the chemicals that make up the smell of instant coffee and let several people with parosmia after infection smell them one at a time. Most of these people picked out the same chemicals as smelling disgusting and setting off their parosmia. These chemicals are known to have strong smells to humans and can be grouped into four classes based on their chemical shape and the elements they contain. These findings help in the understanding of what chemical compounds trigger parosmia, which may help in developing diagnostics and therapies for this condition in the future.