February 22, 2024

COVID-19’s lasting impact on smell and brain health revealed

This is evident from a recent study published in the journal Diagnostics, researchers are investigating the relationship between olfactory disorders associated with the coronavirus disease 2019 (COVID-19) and subsequent neurocognitive disorders.

Study: A comprehensive review of COVID-19-related olfactory deficiency: unraveling associations with neurocognitive disorders and magnetic resonance imaging findings. Image credits: Mariia Boiko / Shutterstock.com


Acute olfactory dysfunction is one of the earliest and most common symptoms associated with COVID-19, with an incidence of up to 75%. The manifestation of both smell and taste disorders in COVID-19 can range from reduced or distorted perception to a complete loss of smell and/or taste.

In the context of COVID-19, acute olfactory dysfunction is defined as the altered sense of smell lasting fourteen days or less. Typically, olfactory dysfunction develops around the third day after initial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with odor perception disappearing completely within four to six weeks. However, up to 27% of COVID-19 patients will experience altered olfactory perception for up to four months, with 21.3% of patients reporting an altered sense of smell for up to a year.

In addition to COVID-19, several other viral infections can lead to olfactory disorders, in addition to trauma, neurodegenerative pathological processes and the secondary effects of sinus diseases. Despite the high prevalence of COVID-19-related olfactory disorders, few studies have discussed neuroimaging abnormalities associated with this symptom, including abnormalities that may affect the olfactory bulb (OB), olfactory sulcus (OS), olfactory cleft, and olfactory tract (OT). affect. ).

About the study

In the current study, researchers conducted a literature review of OB changes observed in patients with clinically confirmed olfactory disorders after a diagnosis of COVID-19. They also discussed current treatments for olfactory disorders associated with COVID-19.

To this end, the researchers searched multiple databases, including PubMed, Scopus and Google Scholar, until December 5, 2023, using keywords such as ‘COVID-19’, ‘olfactory deficit’, ‘anosmia’, ‘imaging’, ‘SARS-CoV-2, ”magnetic resonance imaging (MRI),’ ‘olfactory bulbs’, ‘neurocognitive deficits’, ‘mood disorders’, ‘neuropsychiatric consequences’ and ‘treatments.’ This search resulted in a total of twelve observational studies and one case report included in the analysis.

How does SARS-CoV-2 cause olfactory disorders?

SARS-CoV-2 is considered neurotropic, neuroinvasive, and neurovirulent, with some viral variants associated with greater affinity for the central nervous system (CNS) than others. In particular, the ancestral D614G strain, followed by the Gamma, Delta, and Omicron BA1 variants, have been associated with the greatest neurotropism in descending order.

Despite several studies evaluating the impact of SARS-CoV-2 infection on the sense of smell, the precise pathogenesis and molecular mechanisms responsible for this dysfunction remain unclear. Some proposed hypotheses include mechanical obstruction due to congestion and rhinitis, which may compromise airflow and transport of odorants for odor perception. However, this hypothesis has been refuted, as several studies have found that olfactory disturbances often last longer than respiratory symptoms, with many COVID-19 patients experiencing olfactory disturbances without the associated nasal congestion necessary to support this theory.

Researchers have also hypothesized that SARS-CoV-2 causes direct damage to olfactory neurons, which then leads to olfactory disorders. Despite the absence of both angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) on olfactory neurons, both of which are crucial for virus entry into cells, SARS-CoV-2 may use other pathways, such as Basigin. BSG), neuropilin-1 (NRP1), TMPRSS11A and furin receptors to infect the olfactory system and cause dysfunction.

MRI imaging to elucidate olfactory disorders in COVID-19

The reviewed studies included various descriptions of MRI findings in patients with COVID-19, such as volumetric abnormalities and altered signal intensity of OBs, altered depth of OS, olfactory cortex abnormalities, and neuron filia irregularities.

Measuring OB volume (OBV) and OS depth is the most common approach to evaluating the olfactory system. To this end, reduced OBV and OS depth on both the right and left sides of hospitalized COVID-19 patients have been observed in several studies, indicating that SARS-CoV-2 causes direct damage to olfactory neuronal pathways.

Up to a third of patients who have recovered from COVID-19 report neurological symptoms, including brain fog, insomnia, headaches, depression, anxiety and mental fatigue. In COVID-19, prolonged olfactory function has been associated with severe cognitive consequences, which can be attributed to inflammation, altered neurogenesis of the olfactory system, and functional changes in brain structures.

Treatment of olfactory disorders in COVID-19

Although olfactory disorders often resolve spontaneously in COVID-19 patients, a significant proportion of these individuals experience chronic olfactory disorders. Thus, a wide range of treatment approaches have been proposed for the treatment of COVID-19-related olfactory disorders, some of which include corticosteroids and intranasal insulin, the intake of various dietary supplements, and olfactory training.

Future studies are needed to determine the efficacy of combining these treatment strategies to restore olfactory function.

Magazine reference:

  • Simonini, L., Frijia, F., Ait Ali, L., et al. (2023). A comprehensive review of COVID-19-related olfactory deficiency: unraveling associations with neurocognitive disorders and magnetic resonance imaging findings. Diagnostics 14(4); 359. doi:10.3390/diagnostics14040359

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