Late olfactory bulb involvement in COVID-19

Transient or persistent hypo-anosmia is common in SARS‑CoV‑2 infection but olfactory pathway late-term morphometric changes are still under investigation. We evaluated late olfactory bulb (OB) imaging changes and their correlates with the olfactory function in otherwise neurologically asymptomatic COVID-19 patients. Eighty-three subjects (mean-age 43 ± 14 yr; 54 females; time-interval infection/MRI: 129±68 d) were affected by asymptomatic to mild COVID-19 in 2020 and 25 healthy controls (mean-age 40 ± 13 yr; 9 females) underwent 3T-MRI and olfactory function evaluation through anamnestic questionnaire and Sniffin' Sticks. Exclusion criteria were intensive care treatment or neurological involvement other than olfaction. Maximal OB area was measured blindly on high-resolution coronal T2w images by 2 observers. Patients were subdivided into (i) persistently hypo/anosmic, (ii) recovered normosmic, and (iii) never complaining smell dysfunction with proven normal olfactory function. No significant differences were observed among patients' subgroups (P = 0.76). Intraobserver and interobserver reliability were high (r = 0.96 and 0.86). Former COronaVIrus Disease 19 (COVID-19) patients had decreased mean maximal OB area than controls (6.52 ± 1.11 mm2 vs. 7.26 ± 1.17 mm2, P = 0.008) even when considering persistently hypo-anosmic (6.46 ± 0.90, P = 0.006) or normosmic patients at MRI (6.57 ± 1.25, P = 0.04). SARS-CoV-2 infection is associated with mid/late-term morphological changes in the OB, regardless of presence or persistence of olfactory dysfunction. The long-term consequences on olfactory aging need to be further investigated including possible links with neurodegenerative disorders.