Reduced Olfactory Bulb Volume Accompanies Smelling Dysfunction After Mild SARS-CoV-2 Infection: The Hamburg City Health Study COVID Program (preprint)

BackgroundDespite its high prevalence, the determinants of smelling impairment in COVID-19 remain opaque. Olfactory bulb volumetry has been previously established as a promising surrogate marker of smelling function in multiple otorhinolaryngological diseases. In this work, we aimed to elucidate the correspondence between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment. Therefore, we conducted a large-scale magnetic resonance imaging (MRI)-based investigation of individuals recovered from mainly mild to moderate COVID-19. MethodsData of 233 COVID-19 convalescents from the Hamburg City Health Study COVID Program were analyzed. Upon recruitment, patients underwent cranial MR imaging and assessment of neuropsychological testing. Automated olfactory bulb volumetry was performed on T2-weighted MR imaging data. Olfactory function was assessed longitudinally after recruitment and at follow-up via a structured questionnaire. Follow-up assessment included quantitative olfactometric testing with Sniffin Sticks. Group comparisons of olfactory bulb volume and olfactometric scores were performed between individuals with and without smelling impairment. The associations of olfactory bulb volume and neuropsychological as well as olfactometric scores were assessed via multiple linear regression. ResultsLongitudinal assessment demonstrated a declining prevalence of olfactory dysfunction from 67.6% at acute infection, 21.0% at baseline examination (on average 8.31 {+/-} 2.77 months post infection) and 17.5% at follow-up (21.8 {+/-} 3.61 months post infection). Participants with post-acute olfactory dysfunction had a significantly lower olfactory bulb volume [mm3] at scan-time than normally smelling individuals (mean {+/-} SD, baseline: 40.76 {+/-} 13.08 vs. 46.74 {+/-} 13.66, f=4.07, p=0.046; follow-up: 40.45 {+/-} 12.59 vs. 46.55 {+/-} 13.76, f=4.50, p=0.036). Olfactory bulb volume successfully predicted olfactometric scores at follow-up (rsp = 0.154, p = 0.025). Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. ConclusionsOur work demonstrates the association of smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Olfactory bulb volume was demonstrably lower in individuals with sustained smelling impairment and predicted smelling function longitudinally. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.

Brain imaging and neuropsychological assessment of individuals recovered from mild to moderate SARS-CoV-2 infection (preprint)

Importance: As SARS-CoV-2 infections have been shown to affect the central nervous system, it is crucial to investigate associated alterations of brain structure and neuropsychological sequelae to help address future health care needs. Objective: To determine whether a mild to moderate SARS-CoV-2 infection is associated with alteration of brain structure detected by magnetic resonance imaging (MRI) and neuropsychological deficits. Design, Setting and Participants: Following a case-control design, 223 non-vaccinated individuals with a positive polymerase chain reaction test (PCR) for SARS-CoV-2 obtained between 1 March and 31 December 2020 received MRI and neuropsychological assessments within the framework of the Hamburg City Health Study (median 9.7 months after testing). Two hundred twenty-three healthy controls, examined prior to the SARS-CoV-2 pandemic, were drawn from the main study and matched for age, sex, education and cardiovascular risk factors. Exposure: Infection with SARS-CoV-2 confirmed by a positive PCR. Main Outcomes and Measures: Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load and neuropsychological test scores. Results: The present analysis included 223 individuals recovered from mainly mild to moderate SARS-CoV-2 infections (100 female/123 male, age [years], mean +- SD, 55.54 +- 7.07) and 223 matched healthy controls (93 female/130 male, 55.74 +- 6.60). Among all 11 MR imaging markers tested, significant differences between groups were found in global measures of mean diffusivity and extracellular free-water which were both elevated in the white matter of post-SARS-CoV-2 individuals comparing to matched controls (free-water: 0.148 +- 0.018 vs. 0.142 +- 0.017, P