COVID-19 And Olfactory Dysfunction: Neuroimaging Insights And Cognitive Implications

Acute olfactory dysfunction emerges as one of the earliest and most prevalent symptoms linked with COVID-19, affecting up to 75% of cases. This dysfunction can manifest in various degrees, ranging from diminished or distorted perception to a complete loss of smell and/or taste.

In the context of COVID-19, acute olfactory dysfunction refers to the altered sense of smell lasting for 14 days or less. Typically, this dysfunction arises approximately three days after initial infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with complete recovery of smell perception occurring within four to six weeks. However, around 27% of COVID-19 patients may continue to experience altered smell perception for up to four months, with 21.3% reporting persistent changes for up to a year.

While COVID-19 stands out for its high prevalence of olfactory dysfunction, other viral infections, traumas, neurodegenerative processes, and sinus diseases can also contribute to this condition. Despite its frequency, few studies have explored the neuroimaging abnormalities associated with COVID-19-related olfactory dysfunction, particularly those affecting the olfactory bulb (OB), olfactory sulcus (OS), olfactory cleft, and olfactory tract (OT).
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In a recent study, researchers conducted a literature review focusing on OB changes observed in patients with confirmed olfactory dysfunction following COVID-19 diagnosis. They also examined current treatments for COVID-19-associated olfactory dysfunction. Through an extensive search of databases like PubMed, Scopus, and Google Scholar, the researchers identified 12 observational studies and one case report for analysis.

SARS-CoV-2 is recognized as neurotropic, neuroinvasive, and neurovirulent, with certain viral variants displaying a higher affinity for the central nervous system (CNS) than others. Despite numerous studies, the precise pathogenesis and molecular mechanisms underlying COVID-19-related olfactory dysfunction remain unclear. Proposed hypotheses include mechanical obstruction due to congestion and rhinitis, as well as direct damage to olfactory neurons by SARS-CoV-2.

MRI findings in COVID-19 patients have revealed volumetric abnormalities and altered signal intensity of OBs, changes in OS depth, abnormalities within the olfactory cortex, and irregularities of neuron filia. Reduced OB volume and OS depth have been observed in both sides of hospitalized COVID-19 patients, indicating direct damage to olfactory neuronal pathways.
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Moreover, up to one-third of recovered COVID-19 patients report neurological symptoms such as brain fog, insomnia, headache, depression, anxiety, and mental fatigue. Prolonged olfactory dysfunction has been associated with severe cognitive consequences in COVID-19 cases, likely due to inflammation, altered olfactory system neurogenesis, and functional brain structure changes.