Reduced Olfactory Bulb Volume Accompanies Olfactory Dysfunction After Mild SARS-CoV-2 Infection

SUMMARY Background Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Methodology/Principal Data of non-vaccinated COVID-19 convalescents recruited within the framework of the Hamburg City Health Study COVID Program between March and December 2020 were analyzed. On average 8 months after recruitment,, participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022 olfactory function was assessed at an additional timepoint including quantitative olfactometric testing with Sniffin’ Sticks. Results This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute olfactory dysfunction had a significantly lower olfactory bulb volume at scan-time than normally smelling individuals. Olfactory bulb volume predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Conclusions Our work demonstrates an association of long-term smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.