Patterns in Olfactory Injury Among Patients Who Died From COVID-19 – Neurology Advisor

Among patients who died with COVID-19 infection, more severe axon pathology, axon losses, and microvasculopathy were found in the olfactory tissue than in those who died without COVID-19 infection, suggesting COVID-19 olfactory dysfunction may be permanent. These are the findings of a postmortem study published in JAMA Neurology.

SARS-CoV-2 is associated with a range of symptoms with the most common nonrespiratory symptom presenting as olfactory dysfunction. As the pandemic is still recent, it remains unclear how long COVID-19 symptoms may persist.

To evaluate the severity of damage to the olfactory system from COVID-19, postmortem tissues and premortem symptoms were collected from 23 COVID-19 cases and 14 non-SARS-CoV-2 control individuals. Autopsies were performed between 2020 and 2021 at the University of Maryland Medical Center or Orlando Health. Tissues were evaluated by histology analysis, immunohistochemistry, and electron microscopy.

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The COVID-19 cohort and control individuals were aged median 62 (range, 28-93) and 53.5 (range, 20-77) years at death and 60.9% and 50% were men, respectively.

Brain tissues from 6 individuals of the COVID-19 group and 8 individuals of the control group showed significant brain pathology.

Histopathology did not reveal obvious olfactory abnormalities among tissues from the COVID-19 group. However, electron microscopy demonstrated axon pathology ranging from mild to severe axonal injury and loss.

Compared with control individuals, the tissues of patients with COVID-19 had greater axon pathology scores (mean, 1.921 vs 1.198; P <.001) and decreased axon density in the lateral olfactory tract (mean, 2.973 vs 3.867 104/mm2; P =.002).

The subset of patients who reported alterations to their smell had higher axon pathology scores (mean, 2.26 vs 1.63; P =.002) compared with patients who had intact smell. Among both patient groups, however, no differences in axon density were observed (mean, 3.272 vs 2.693 104/mm2; P =.28).

Patients with COVID-19 were frequently observed to have endothelial injury of the microvasculature with mean microvasculopathy scores of 1.907 compared with 1.405 among the control individuals (P <.001). Patients with olfactory-related symptoms had poorer microvascular pathology scores than patients without olfactory symptoms (mean, 2.154 vs 1.694; P =.02).

The researchers noted that olfactory axon and microvascular pathology did not appear to be related with severity of SARS-CoV-2 infection.

After controlling for age, COVID-19 remained associated with increased axonal pathology scores (b, 0.774; 95% CI, 0.439-1.110; P <.001), increased vascular pathology scores (b, 0.522; 95% CI, 0.222-0.822; P =.001), and reduced axonal densities (b, -0.661; 95% CI, -1.209 to -0.114; P =.02).

Overall, COVID-19 was not associated with more severe age-related tau pathology in brain or olfactory tissues compared with control individuals

This study may have been limited by the range in times between death and autopsy.

These data indicated that COVID-19 infection caused axonal injury and microvasculopathy in olfactory tissue. “The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 infection may be severe and permanent,” the researchers concluded.


Ho C-Y, Salimian M, Hegert J, et al. Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients With COVID-19. JAMA Neurol. Published online April 11, 2022. doi:10.1001/jamaneurol.2022.0154