COVID-19 infection was associated with axon pathology and microvasculopathy in the olfactory bulb and tract region, particularly in patients whose sense of smell was altered, according to results from a study published in JAMA Neurology on April 11.
“Olfactory dysfunction of variable severity, including anosmia, hyposmia, and parosmia, reportedly affect 30 to 70 percent of patients with COVID-19," wrote lead study author Cheng-Ying Ho, MD, PhD, an associate professor of pathology at Johns Hopkins University School of Medicine, and colleagues. “Olfactory dysfunction occurs early in the course of infection and has no direct association with disease severity or viral loads. The mechanism underlying olfactory dysfunction in COVID-19 is currently unknown."
To characterize the olfactory pathology associated with COVID-19 infection, the researchers performed an ultrastructural and histopathological analysis of 23 deceased patients with COVID-19 and 14 age and disease severity–compatible deceased controls.
The median age of the COVID-19 study group was 62 years old and the cohort was 60.9 percent men. The control group's median age was 53.5 years and included seven men and seven women. The multicenter postmortem study was conducted from April 7, 2020, to September 11, 2021, and the data analysis was conducted from February 7 to October 19, 2021.
The mean axon pathology score (range: 1-3) was 1.921 in patients with COVID-19 and 1.198 in controls, whereas axon density was 2.973 in patients with COVID-19 and 3.867 (0.670) in controls.
Concomitant endothelial injury of the microvasculature was also noted in olfactory tissue. The mean microvasculopathy score (range: 1-3) was 1.907 in patients with COVID-19 and 1.405 in control individuals.
Both the axon and microvascular pathology was worse in patients with COVID-19 with smell alterations than those with intact smell (mean axon pathology score was 2.260 versus 1.63; mean microvasculopathy score was 2.154 versus 1.694), but the researchers reported that it was not associated with clinical severity, timing of infection, or presence of the virus.
These findings suggested that local inflammation in the upper respiratory tract may be sufficient to cause endothelial and axonal damage in the olfactory pathway.
“Although we did not see an obvious overall increase in inflammatory cells in our cohort, it remained possible that focal or perivascular infiltrates may have a role in axonal or microvascular injuries associated with COVID-19 infection," the study authors wrote.
The researchers added that the striking axonal pathology in some cases within the cohort indicated that olfactory dysfunction in COVID-19 infection may be severe and permanent.
Limitations of the study included possible inaccuracies in olfactory function due to self-reporting and the study authors were not able to assess how pathologic changes in nasal mucosa may contribute to smell alterations in COVID-19 infection.
Dr. Ho did not report any disclosures. See the study for a full list of disclosures.
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Ho CY, Salimian M, Hegert J, et al. Postmortem assessment of olfactory tissue degeneration and microvasculopathy in patients with COVID-19. JAMA Neurol 2022; Epub 2022 Apr 11.