Olfactory dysfunction in post-acute COVID-19: clinical characterization, hedonic asymmetry, and machine-learningbased...

Olfactory dysfunction (OD) is among the most prevalent features of post-acute sequelae of COVID-19 (PASC) and frequently co-occurs with cognitive and neuropsychiatric symptoms. The specific predictors of objective olfactory impairment severity and its relation to systematic shifts in hedonic odor perception remain underexplored. Here, we used data-driven approaches to identify and rank predictors of objective OD severity and examined hedonic valence ratings in patients with and without olfactory impairment.

We examined 144 patients with confirmed PASC diagnoses at 15-63 months post-infection using psychophysical testing (Sniffin' Sticks), standardized cognitive tests for verbal fluency, working memory, attention, and working speed, and patient-reported outcome measures for other symptoms of PASC. Predictors were identified using LASSO regression with voting and random forest variable importance ranking. Hedonic valence ratings from the identification subtest were examined at the group and individual odor level.

Olfactory function was significantly below normative population values. Verbal fluency emerged as the most robust predictor of olfactory dysfunction severity, converging across both LASSO regression and random forest analyses, and remained significant after controlling for respiratory symptoms. Parosmia, respiratory symptoms, working memory, and somatic symptom burden were also consistently selected. Hyposmic patients showed significantly reduced maximal valence ratings independent of parosmia and anhedonia, while minimal ratings were preserved, with garlic and coffee remaining significant after correction.

Verbal fluency emerged as the strongest predictor of OD severity in long-term PASC patients. Beyond reduced olfactory sensitivity, hyposmic patients showed asymmetric hedonic impairment, pointing to differential involvement beyond peripheral olfactory loss.