Mapping the Olfactory Brain: A Systematic Review of Structural and Functional Magnetic Resonance Imaging Changes Following COVID-19 Smell Loss.

Publication date: Jun 27, 2025

Olfactory dysfunction (OD)-including anosmia and hyposmia-is a common and often persistent outcome of viral infections. This systematic review consolidates findings from structural and functional MRI studies to explore how COVID-19 SARS-CoV-2-induced smell loss alters the brain. Considerable heterogeneity was observed across studies, influenced by differences in methodology, population characteristics, imaging timelines, and OD classification. Following PRISMA guidelines, we conducted a systematic search of PubMed/MEDLINE, Scopus, and Web of Science to identify MRI-based studies examining COVID-19’s SARS-CoV-2 OD. Twenty-four studies were included and categorized based on imaging focus: (1) olfactory bulb (OB), (2) olfactory sulcus (OS), (3) grey and white matter changes, (4) task-based brain activation, and (5) resting-state functional connectivity. Demographic and imaging data were extracted and analyzed accordingly. Structural imaging revealed consistent reductions in olfactory bulb volume (OBV) and olfactory sulcus depth (OSD), especially among individuals with OD persisting beyond three months, suggestive of inflammation and neurodegeneration in olfactory-associated regions like the orbitofrontal cortex and thalamus. Functional MRI studies showed increased connectivity in early-stage OD within regions such as the piriform and orbitofrontal cortices, possibly reflecting compensatory activity. In contrast, prolonged OD was associated with reduced activation and diminished connectivity, indicating a decline in olfactory processing capacity. Disruptions in the default mode network (DMN) and limbic areas further point to secondary cognitive and emotional effects. Diffusion tensor imaging (DTI) findings-such as decreased fractional anisotropy (FA) and increased mean diffusivity (MD)-highlight white matter microstructural compromise in individuals with long-term OD. COVID-19’s SARS-CoV-2 olfactory dysfunction is associated with a range of cerebral alterations that evolve with the duration and severity of smell loss. Persistent dysfunction correlates with greater neural damage, underscoring the need for longitudinal neuroimaging studies to better understand recovery dynamics and guide therapeutic strategies.

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Concepts Keywords
Months brain connectivity
Mri DTI
Olfactory olfactory bulb volume
Stage olfactory dysfunction
Viral olfactory sulcus depth
rs-fMRI
task-based fMRI

Semantics

Type Source Name
disease MESH COVID-19
disease MESH Smell Loss
disease MESH viral infections
disease MESH inflammation
drug DRUGBANK Tropicamide
drug DRUGBANK Coenzyme M
disease IDO intervention
pathway REACTOME Sensory Perception
disease IDO blood
disease MESH infections
disease MESH olfactory impairment
disease IDO process
drug DRUGBANK Trestolone
disease IDO history
disease IDO infection
drug DRUGBANK Water
drug DRUGBANK Zalcitabine
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Gadolinium
disease MESH hypogeusia
disease MESH edema
disease MESH cortical thinning
disease MESH symptom burden
disease MESH long COVID
disease IDO symptom
disease MESH sequelae
disease MESH abnormalities
disease MESH neurological disorders
disease MESH cognitive disorders
disease MESH encephalitis
disease MESH nasal obstruction
disease MESH atrophy
disease IDO susceptibility
disease MESH sensory deprivation
disease MESH pus
disease MESH uncertainty
disease MESH physiological stress
disease MESH neuroinflammation
disease MESH hypoxia
disease MESH syndrome
disease IDO acute infection
disease MESH psychological stress
disease MESH neurodegenerative diseases
pathway REACTOME Neurodegenerative Diseases
disease MESH Alzheimer’s disease
disease MESH metabolic diseases
disease MESH psychiatric illnesses
disease IDO object
disease MESH Allergy
drug DRUGBANK Flunarizine
disease MESH rhinosinusitis
disease MESH Brain Tumor
disease MESH Cancers
disease MESH Neurologic Symptoms
disease MESH mood disorders

Original Article

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