by Dr. Juliette Dufour
For June 2022, we have selected Cheng-Ying Ho et al, Covid-19 Paper of the month: Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients with COVID-19. JAMA Neurology, 2022, DOI: 10.1001/jamaneurol.2022.0154.
Loss of smell is an early and common presentation of COVID-19 infection. Indeed, olfactory dysfunction of variable severity, including anosmia, hyposmia, and parosmia, reportedly affect 30% to 70% of patients with COVID-19. A subset of patients developed persistent olfactory impairment up to 12 months post infection suggesting that injury to the olfactory system may be severe or permanent. The mechanism underlying olfactory dysfunction in COVID-19 is currently unknown. The most notable theory is SARS-CoV-2 infection of olfactory receptor neurons (ORNs) through nasal mucosa. However, there is conflicting evidence as to whether SARS-CoV-2 is capable of infecting ORNs.
To evaluate the association of COVID-19 infection with olfactory bulb, our authors of the month conducted this multicenter postmortem cohort study, using ultrastructural and histopathological analysis. They included 23 deceased COVID-19 patients (median age, 62 [49-69] years) and 14 control individuals (median age, 53.5 [33.25-65] years) from April 7, 2020, to September 11, 2021.
The results were as follows:
- The mean (SD) axon pathology score (range, 1-3) was 1.921 (0.569) in patients with COVID-19 and 1.198 (0.208) in controls (P < .001), whereas axon density was 2.973 (0.963) × 104/mm2 in patients with COVID-19 and 3.867 (0.670) × 104/mm2 in controls (P = .002).
- Concomitant endothelial injury of the microvasculature was also noted in olfactory tissue. The mean (SD) microvasculopathy score (range, 1-3) was 1.907 (0.490) in patients with COVID-19 and 1.405 (0.233) in control individuals (P < .001).
Both the axon and microvascular pathology was worse in patients with COVID-19 with smell alterations than those with intact smell (mean [SD] axon pathology score, 2.260 [0.457] vs 1.63 [0.426]; P = .002; mean [SD] microvasculopathy score, 2.154 [0.528] vs 1.694 [0.329]; P = .02) but was not associated with clinical severity, timing of infection, or presence of virus.
Moreover, patients with COVID-19 did not have more severe age-related tau pathology in brain or olfactory tissue than control Individuals.
This cohort study was the first to examine the ultrastructural changes of olfactory bulb and olfactory tract in COVID-19 infection. Results of this study demonstrate how the pathologic findings were associated with smell alterations in patients with COVID-19. There was no evidence of direct viral infection in olfactory bulb, therefore, the axon and microvascular pathology in olfactory tract were most likely not caused by direct viral injury.
Our authors of the month concluded that COVID-19 infection is associated with axon injuries and microvasculopathy in olfactory tissue. Overall, patients with smell alterations had more severe olfactory pathology than those with intact smell. The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 infection may be severe and permanent.
