Histopathological changes in the olfactory pathway in COVID-19: An autopsy-based case-control study

Area of Science:

• Neuropathology
• Central Nervous System (CNS) Disorders
• Infectious Disease Pathology

Background:

• Coronavirus disease 2019 (COVID-19) often presents with neurological symptoms like anosmia, prompting investigation into central nervous system (CNS) involvement.
• Previous neuropathological studies on COVID-19 have yielded inconsistent results, with debate on direct viral effects versus indirect systemic responses.

Purpose of the Study:

• To investigate neuropathological changes in the CNS of COVID-19 decedents.
• To differentiate between direct viral effects and indirect mechanisms contributing to CNS alterations in COVID-19.

Main Methods:

• An autopsy-based case-control study comparing 16 COVID-19-positive decedents with 15 age- and sex-matched controls.
• Histopathological analysis of the olfactory bulb, olfactory tract, and frontal cortex, assessing reactive gliosis, microglial activation, inflammation, and vascular injury.

Main Results:

• COVID-19 cases showed increased reactive gliosis and microglial activation in the olfactory bulb and mild perivascular inflammation in the frontal cortex.
• No direct viral cytopathic changes or encephalitis were identified; systemic findings indicated severe multisystem disease.
• Corpora amylacea and petechial hemorrhages were common in both groups, indicating nonspecific changes.

Conclusions:

• COVID-19 is linked to CNS alterations characterized by reactive and vascular changes, not direct encephalitic processes.
• The study highlights that many reported histological findings are nonspecific background changes.
• Findings support indirect, reactive, and vascular mechanisms as primary drivers of CNS involvement in COVID-19.