SARS-CoV-2 infection in the mouse olfactory system.

Area of Science:

• Virology
• Neuroscience
• Immunology

Background:

• Olfactory dysfunction is a common COVID-19 symptom, but its mechanism is unclear.
• Understanding SARS-CoV-2's impact on the olfactory system is crucial for treating extrapulmonary manifestations.

Purpose of the Study:

• To investigate the mechanism of SARS-CoV-2-induced olfactory dysfunction.
• To establish a mouse model that recapitulates COVID-19-related smell loss.

Main Methods:

• Intranasal inoculation of SARS-CoV-2 in humanized ACE2 (hACE2) mice.
• Analysis of viral replication in the olfactory epithelium (OE) and olfactory bulb (OB).
• Transcriptomic and proteomic analyses of infected OE.

Main Results:

• SARS-CoV-2 replicated in the OE, targeting sustentacular and Bowman's gland cells, leading to transient olfactory dysfunction.
• Significant OE structural damage, cell death, and immune cell infiltration were observed.
• Antiviral/inflammatory responses and downregulation of olfactory receptor genes occurred in the OE.

Conclusions:

• The hACE2 mouse model effectively mimics COVID-19 olfactory dysfunction.
• SARS-CoV-2 directly impacts OE structure and function, contributing to smell loss.
• Findings provide insights into the physiological basis of extrapulmonary COVID-19 symptoms.