Long-Term Smell Loss in COVID-19 Linked to Damage in Brain’s Olfactory Bulb

In COVID-19 one of the most prevalent non-respiratory symptoms is olfactory dysfunction, which can be of variable severity, including anosmia, hyposmia, and parosmia. It reportedly affects 30-70% of patients with COVID-19. 

The prevalence of olfactory dysfunction has prompted US Centers for Disease Control and Prevention to list new loss of smell as a cardinal symptom of COVID-19 on its webpage. Olfactory dysfunction occurs early in the course of infection and has no direct association with disease severity or viral loads.

In most cases, the symptoms spontaneously resolve within 3 to 4 weeks, but a subset of patients developed persistent olfactory impairment up to 12 months postinfection, suggesting that the injury to the olfactory system may be severe or permanent. 

In a recently published study, researchers performed a postmortem study to characterize the olfactory pathology associated with COVID-19. The study appears in the journal JAMA Neurology. 

Long-Term Smell Loss and Olfactory Bulb Damage 

The postmortem cohort study was conducted from April 7, 2020, to September 11, 2021, and included deceased patients with COVID-19 (23) and control individuals (14).

There was also no obvious increase in lymphocytic infiltrates, microglia, or reactive astrocytes in COVID-19 olfactory tissue. Conversely, semithin section and ultrastructural analyses by electron microscopy demonstrated a spectrum of axon pathology ranging from mild changes to severe axonal injury and axonal losses. 

Compared with controls, individuals who died from COVID-19 showed significantly worse olfactory axonal damage. Overall, individuals with reported smell alterations had significantly more severe olfactory axon pathology than cases with an intact smell. 

The team didn’t find evidence of viral infection in the olfactory bulbs of most patients. Therefore, the axon and microvascular pathology were most likely not caused by direct viral injury. The results suggested that local inflammation in the upper respiratory tract may be sufficient to cause endothelial and axonal damage in the olfactory pathway.

According to the researchers, it appears that the smell alterations in a lot of COVID-19 patients, mainly those with severe pathology can be permanent. 


Cheng-Ying Ho, et al. Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients With COVID-19. 2022. JAMA Neurol. doi:10.1001/jamaneurol.2022.0154 

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