RESUMEN
Background/Objectives: Chemosensory dysfunction is a hallmark of SARS-CoV-2 infection;nevertheless, the genetic factors predisposing to long-term smell and taste loss are still unknown. This study aims to identify candidate genes possibly involved in persistent smell/taste loss through Whole Genome Sequencing (WGS) analysis of a large cohort of 130 fully characterised Italian individuals, previously diagnosed with COVID-19. Method(s): DNA of all analysed patients was used to perform WGS analysis, and a detailed personal anamnesis was collected. Moreover, orthonasal function was assessed through the extended Sniffin' Sticks test, retronasal function was tested with 20 powdered tasteless aromas, and taste was determined with validated Taste Strips. Self-reported smell and taste alterations were assessed via Visual Analog Scales plus questionnaires. Result(s): The clinical evaluation allowed to classify the patients in two groups: 88 cases affected by persistent smell dysfunction (median age, 49) and 42 controls (median age, 51). Among cases, 26.1% (n = 23) were functionally anosmic and 73.9% (n = 65) were hyposmic. Within cases, 77 underwent the taste strip test: 53.2% (n = 41) presented hypogeusia and 46.8% (n = 36) were normogeusic. Preliminary WGS results on a first subset of 76 samples confirmed the important role of UGT2A1 gene, previously described as involved in smell loss. Interestingly, we identified a nonsense variant (rs111696697, MAF 0.046) significantly associated with anosmia in males (p-value: 0.0183). Conclusion(s): Here, for the first time a large cohort of patients, fully characterised through a comprehensive psychophysical evaluation of smell and taste, have been analysed to better define the genetic bases of COVID-19-related persistent chemosensory dysfunction.